Consensus Treatment Guidelines Compendium of

on Major Depressive Philippine Medicine

20th Edition

Disorder in Adults

Philippine Psychiatric Association, Inc.

Suite 1011 Medical Plaza Ortigas Building
San Miguel Avenue, Ortigas Center, Pasig City 1600
Telephone No.: +63(2) 8635 9858
E-mail: philpsych.org@gmail.com
Website: https://philippinepsychiatricassociation.org/
Open-access dissemination of scientific and
medical knowledge now!
 r-'
- .7
J..l
a
CPMEW.:
Ippine [Cine

- .
Philippine Psychiatric Association, Inc.

-
z2
Suite 1011 Medical Plaza Ortigas Building
San Miguel Avenue, Ortigas Center, Pasig City 1600
Telephone No.: +63(2) 8635 9858
E-mail: philpsych.org@gmail.com

1a3
2
Website: https://philippinepsychiatricassociation.org/

Board of Directors

President Luzviminda S. Katigbak, MD, FPP A

Vice President Antonio C. Sison, MD, FPPA (Life)
� Belen M. Dimatatac, MD, FPPA (Life)

+3
Secretary
Treasurer Angelo Jesus Vicente V. Arias, MD, FPPA
Public Relations Officer Robert D. Buenaventura, MD, FPPA (Life)

-
Auditor Eufemio E. Sobrevega, MD, FPPA (Life)
2 Director for Luzon Amold Angelo M. Pineda, MD, FPP,A
Director for Visayas Valerie Heena D. Andora-Quilaton, MD, FPPA

--
Director for Mindanao Angela Jamelarin Espanola, MD, FPPA, FPSCAP
-3
Immediate Past President Amadeo A. Alinea, Jr., MD, FPPA

Legal Adviser Hon. Judge Rosalina L. Pison (Ret.)

a
.=a
=a
-a Steering Committee: PPA 2016 Committee on Standards of Care
a
-a Chair Mariano S. Hembra, MD, FPP A

---
-3 Members Lovie Hope Go-Chu, MD, FPPA
Eric George V. Cruz, MD, FPPA
Michael P. Sion7on, MD, FPP A
Myra Dee Lopez-Roces, MD, FPPA

1
-a
=-
--
-3

-3
-)
139
-E
Major Depressive Disorder
Consensus Treatment Guidelines
on Major Depressive Disorder
in Adults
INTRODUCTION
Depression is a global public health concern that
warrants immediate attention. An estimated 350
million people of all ages suffer from this condition
and thus it is deemed as the leading cause of
disability worldwide. It is also seen as the major
contributor to the overall global burden of disease.
In fact, depression is estimated to be the principal
cause of disease burden by the year 2030 (Mathers
et. al., 2008, WHO, 2016)
In the Philippines, the National Statistics Office
(NSO) listed mental health illnesses as the third
most common form of morbidity for Filipinos
(NSO, 2000). On the other hand, mood disorders,
which included depression, were the second most
prevalent mental disorder encountered in mental
health and community facilities (WHO, 2006). As
of this writing, a national registry or a multi-center
epidemiologic study onMajor Depressive Disorder
is still unavailable and hence, remains an area
worth investigating.
Major Depressive Disorder (MDD) is a chronic,
brain disorder characterized by low mood and
loss of interest that can affect a person's thoughts,
behavior, feelings, and social functioning (APA,
2013). As such, depression poses a great impact
to a person's relationships and productivity. It
may also complicate existing medical conditions
adding to the burden of chronic diseases and may
lead to possible suicide.Major Depressive Disorder
is a complex condition encompassing biological,
psychological, and social factors; hence it warrants
a multi-modal approach. Left untreated, MDD can
lead to physical and psychological disability.
Filipino psychiatrists continuously engage
in various efforts with the aim of increasing
depression awareness in the country. Due to lack
of this, there is a growing concern that many
individuals continue to struggle with depressive
disorders. Moreover, in a developing country such
as the Philippines, access to healthcare especially
in the field of mental health, is limited for many.
In addition to lack of awareness, shortage of
mental health care, poverty, and stigma are
common obstacles. Mental disorders remain to be
misunderstood and frowned upon by many due
to the stigma associated with psychiatric illnesses.
Psychiatrists believe few seek professional help
140
and even fewer patients are able to access, afford,
or adhere to treatment because of these. Hence,
the impact of these factors on the state of mental
health care in the country is an important area that
needs further investigation.
METHODOLOGY
The Philippine Psychiatric Association (PPA)
steering committee initiated the development
of guidelines for the management of psychiatric
disorders. The committee then assigned training
institutions to provide technical writing groups.
Makati Medical Center provided a technical writing
group for consensus treatment guideline of adults
with Major Depressive Disorder (MDD) comprised
of psychiatry specialists and psychiatry residents.
This consensus treatment guideline is intended for
use by psychiatrists practicing in the Philippines in
the management of adults with Major Depressive
Disorder. This does not address diagnosis and
treatment strategies for special populations such as
children and adolescents, pregnant and postpartum
women, the elderly, and those with common
medical illnesses. This treatment guideline also
emphasizes suicide as a medical emergency and
reviews essential steps in its assessment and
management. However, practice guidelines for
the evaluation and treatment of suicide in the
Philippines have yet to be developed.
Topics discussed in this guideline include princi-
ples of care, diagnosis, suicide, criteria for psychia-
tric hospitalization, psychosocial interventions,
pharmacologic treatments, adjunctive treatments,
electroconvulsive therapy, and other neuromodu-
lation therapies. An overview of complementary
and alternative medicine treatments was also in-
cluded.
Information on MDD disease burden specific to
the Philippines is limited. Still an effort to include
the latest epidemiologic data from the National
Statistics Office was taken into consideration.
Information from the World Health Organization
was also included when deemed appropriate.
The technical writing group underwent a
workshop conducted by the PPA to prepare for
the development of this guideline. Literature
search made use of Medline, PubMed, Cochrane,
and Google Scholar. Practice guidelines, more
specifically the latest ones, were subjected to
group appraisal using the online tool AGREE II
(Brouwers et al., 2010). The writing group held
CPM Compecdm>
--
of
pie . Medic
tipoine [Ce
various meetings and online conferences to discuss
the technical aspects of the treatment guidelines.
In terms of MDD diagnosis, diagnostic features
described in DSM-5 (APA, 2013) and 1CD-10
(WHO, 2010) were used. Pharmacologic treatments
for MDD were based on practice guidelines
(Bauer et al., 2013; Kennedy et al., 2016; Malhi et
al., 2013; APA, 2010; NICE, 2009) and followed
the established level of clinical evidence (Refer to
Appendix A) taking into consideration medications
Major Depressive Disorder
•
significant loss, which may include bereavement
or financial collapse, the presence of MDD must
be carefully considered using clinical judgment.
Several specifiers for a depressive episode include
various clinical presentations that are not in the
criteria for MDD (Figure 2). These dimensions have
implications on the course, prognosis, treatment,
response, and outcome (Refer to Appendix D)
r 'iingle j ---
ii(

1
that are not available in the country (Ping et al., Mtld
2016). Psychosocial treatments, electroconvulsive
J
Recurrent
therapy and other neuromodulation therapies Modcrat<·
><HJUS
are described and included in the treatment 0,stres,;

interventions. Alternative treatments were also

discussed in the guidelines despite having no
approved therapeutic benefits based on regulatory
standards (FDA Philippines; DOH Philippines).

Atypical
This consensus treatment guideline on the
Clinical Features Mood- ]
management of adults with MDD was subjected
to review by an expert panel (Refer to list of expert =---J,'J"•""' "'"•-a.. !fi,-" ,,,- em,,_,
Depressive] Moe4.
panel) and presented to stakeholders. Answers
to clinical questions that reached consensus are &zzzz/ coJ hors
i Features
mentioned in text boxes. reap»rm

me:
The technical writing group from MMC received f Onset

funding solely from PPA.

In Partial
DIAGNOSIS

What are the criteria in the diagnosis of Major

Depressive Disorder?

Two systems can be used in the diagnosis of MDD,

(1) the fifth edition of the Diagnostic Statistical
Manual (DSM-5) by the American Psychiatric
Association (APA, 2013), and (2) the tenth edition
of International Statistical Classification of
Diseases and Health Related Problems (CD-10) by
the World Health Organization (WHO, 2010).
MDD is included in the DSM-5 group of Depressive
Disorders (Refer to Appendix B). It is characterized
by either a depressed mood or loss of interest or
pleasure as the core symptoms, persisting for
at least 2 weeks and associated with a change
from previous functioning (APA, 2013). Aside
from these core symptoms, there must be at
least five other symptoms of depression (Refer
to Appendix C). Furthermore, these must have a
significant effect on the individual's functioning.
The symptoms must not be an effect of any
substance, medical condition, or other psychiatric
conditions specified in the criteria. Even in cases of
Figure 1. DSM-5 Specifiers forMajor Depressive Disorder
(APA, 2013)
In the International Code for Diseases (1CD-10),
Depressive Episode and Recurrent Depressive
Disorder are classified under Mood (Affective
Disorders), together with Bipolar Disorders
(Appendix E). A formal diagnosis using the ICD-
10 requires at least four out of ten depressive
symptoms to be considered as a depressive
episode. Similar to the DSM-5, symptoms should
be present for at least2 weeks with each symptom
present at sufficient severity for most of the day
every day (Appendix F). Unlike DSM-5, 1CD-10
requires at least two key symptoms (low mood,
loss of interest and pleasure, or loss of energy) to
be present. The depressive episode or the current
141

Major Depressive Disorder
episode of a recurrent depressive disorder is
further classified as mild, moderate, severe without
psychotic symptoms, and severe with psychotic
symptoms (Refer to Appendix G and H).
Clinical settings in the Philippines use either
DSM-5 or ICD-10 or both. The inclusion of
corresponding ICD-10 codes in DSM-5 is helpful
in achieving consistency in the use of diagnostic
criteria, particularly for depressive disorders and
its specifiers, and coding of depressive disorders
(Figure 2).
Mild 296.21 (0F32.0)
1 Moderate 296.22 0+32.1
s«a.l
j Severe 296.23 (F32.2)
Psychotic Features
Episode 296.24 0132.3)
In Partial Remission
en
296253 0132.4)
I
I
Full Remission
296.26 0132.5)
Unspecified 296.20 (F32.9)
'Major Depressive
Disorder (4)
' Mild 296.31 (F33.0)
I J Moderate 296.32 (F33.1)
Severe 296.33 (F33.2
\, "' "'
Episode
Psychotic Features
296.34 (F33.3)
In Partial Remission
;
296.35 (F33.41)
\ In Full Remission
26.36 (F33.42)
Unspecified 296.30 4F33.9
Figure 2. DSM-5 (APA, 2013) and 1CD-10 Codes (WHO,
2010) for Depressive Disorders
To date, there is no published data describing the
depressive symptoms of Filipinos or confirming
if they meet DSM-5 Major Depressive Disorder
criteria and its specifiers. Psychiatrists in the
country are familiar with DSM-5 which they
use this in their clinical practice. There is an
agreement within PPA that symptoms reported
by Filipinos are similar to the DSM-5 criteria of
Major Depressive Disorder and its specifiers.
Consensus Statement
142
o>room·' CPM
philippine Medicine .-.a.
What are the tools used in the diagnosis of MDD?
The screening of individuals suspected to have
clinical depression is necessary, especially in
patients with a history of depression and those
with existing chronic medical illness. A patient
presenting with insomnia or fatigue should
be examined further for the presence of other
depressive symptoms. The "2-question screen",
(1)"In the last month, have you been bothered by
little interest or pleasure in doing things?" and (2)
"In the last month, have you been feeling down,
depressed or hopeless?", has been reported as
an effective and simple approach for screening
a in clinical practice (Bosanquet et al., 2015). This
: tool, modified for use among Filipinos, includes
two questions: (1) on having little interest in
: doing things and (2) on feeling down, depressed,
or hopeless (Figure 3). An affirmative answer to
either question requires a detailed assessment and
consideration of other possible causes of depressive
symptoms like medical illness, medications, or use
of other substances. If initial screening indicates a
possible depression, a thorough biopsychosocial
'
]
assessment by a mental health professional is
warranted (Lam et al., 2016; NICE, 2009).
Screening
I
• In the last four weeks, have you been bothered
by little interest in doing things?
) Yes to at least one of the questions
J
Referral to a Mental Health Professional
l • Obtain a comprehensive biopsychosocial
assessment, including suicide assessment
I
• Assess other possible sources of depression,
including medical illness and medications
I Figure 3. Screening for MDD (Adapted from Bosanquet et
I
al., 2105)
Using a specific number of weeks to describe the
duration of symptoms, when screening Filipinos
for depression, was considered more effective.
PPA recommends the use of "four weeks" as
a criterion to indicate the duration or onset of
symptoms in the two-question screening tool
in the local setting. (Figure 3).
Consensus Statement
------------
A comprehensive inquiry of symptoms must be
done to the patient and if possible, with acquisition
of important collateral information (Lam et al.,
2016). The presence of disorders that have high
co-morbidity with major depression should also
CPM Compecdrn>of
p . Medic
a tipoine [Cine
be evaluated. Careful examination of possible
presence of bipolar disorder, anxiety disorders,
and substance use disorders, including alcohol
must be performed. Clinical rating scales (Refer
to Appendix I), which are useful in screening,
diagnosis, and monitoring, may be used if deemed
necessary (Lam et al., 2016). However, rating scales
must be used only as a supplement in the diagnosis
and should not replace clinical judgment (Lam et
al., 2016)
What are the examinations used in the diagnosis
of MDD?
The diagnosis of MDD is done through a clinical
examination by a psychiatrist or a trained health
professional. Physical examination may be done
depending upon the patient's clinical status at the
time of assessment (Refer to Appendix J. At present,
there are no laboratory examinations that can
diagnose MDD. However, there are several tests
(Refer to Appendix K) that may be used to screen for
conditions that mimic the symptoms of depressive
disorders (Malhi et al., 2015).
PRINCIPLES OF CARE
What are the general principles of care for MDD?
Several guidelines provide general principles of
care for MDD that will be useful in the Philippines'
setting (Bauer et al., 2013; Malhi et al., 2015; Lam
et al., 2016). These principles emphasize the
need to conduct a biopsychosocial assessment,
obtain collateral information whenever possible,
formulate a diagnosis and differential diagnosis,
establish therapeutic alliance, support education
and self-management, engage the patient and
his/her social support as partners, construct a
comprehensive treatment plan, deliver evidence-
based treatments, and monitor outcomes (Lam et
al., 2016; Malhi et al., 2015; Bauer et al., 2013).
Once a diagnosis of major depressive disorder is
established, a comprehensive treatment strategy is
essential, encompassing psychosocial interventions,
pharmacotherapy, and somatic treatments (NICE,
2010; Bauer et al., 2013; Malhi et al., 2015; Lam et al.,
2016). Principles of pharmacotherapy are discussed
in the section on pharmacological treatments.
In terms of measuring treatment outcome, the use
of validated rating clinical scales (Refer to Appendix
L) to monitor results and guide clinical decision-
making is important in the overall care (Lam et al.,
2016, Kennedy et al., 2016) according to reported
Major Depressive Disorder
- -'---- - - -- ......j
improved outcomes (Guo et al., 2015). However,
it is important to note that the use of rating scales
intends to supplement clinical monitoring and
decision-making, not take the place of clinical
judgment (Lam ct al., 2016).
What are the goals of treatment?
The main goal of the treatment of major depressive
disorder is the relief of symptoms or complete
remission to reduce risk for relapse (Bauer et
al., 2013; Malhi et al., 2015). Residual depressive
symptoms are negative predictors of long-term
outcome and are possible risk factors for relapse
(Lam et al., 2015). Treatment of MDD aims to
reduce morbidity and to limit disability, risk of
self-harm, and most especially the potential danger
of fatality with eventual recovery and return to
level of functioning before onset of disorder (Malhi
et al., 2015)
What are the stages of illness and the phases of
treatment?
Treatment phases have been identified as a two-
phase process (Patten et al, 2009) and as a three-
phase process (Kupfer, 2005; Malhi et al., 2009).
There are three stages of illness (Figure 4) that
correspond to three phases of treatment (Malhi
et al., 2015): (1) response, (2) remission, and (3)
recovery. These are often indistinguishable and are
difficult to delineate. The Diagnostic and Statistical
Manual of Mental Disorders 5" edition defines
full remission as absence of significant signs and
symptoms during the past two months (APA,
2013). The end of a major depressive episode or the
beginning of a stable, well state was shown to be
possible in the incidence of four consecutive weeks
of asymptomatic recovery. Reduction of residual
symptoms was also found to be a continuation of
the active state ofMDE (Judd et al., 2015).
Figure 4.Mood Disorders Stages of Illness and Phases of
Treatment (RAN7ZCP Malhi et al,, 2015)
The blue line represents a tendency towards
depression. Obtaining a response and remission is
the goal of the acute phase and continuation phase,
143
 core CpM ct
=
Major Depressive Disorder Philippine Medicine
-.r

respectively. In maintenance phase, achieving Table 2. Indications for Psychiatric Admission

a return to pre-morbid state or recovery is the (From RANZCP Malhi et al., 2015)
target and the ultimate goal in the management
of depression. These stages of illness are not
Severe depression with significant
disability
er
distinct and specifying an episode as a relapse or
recurrence is often difficult. (Malhi et al., 2015).
Suicidal ideations with seemingly
imminent risk
E

==
Clinical Medical risk factors such as inadequate
Presentation fluid intake
(Refer to Table 1. Stages of Illness and Phases of
Insight is severely limited to the extent
Treatment (From RANZCP Malhi et al., 2015) that outpatient treatment is not pos-
sible
Table 1. Stages of Illness and Phases of Treatment (From Significant psychotic symptoms
RANZCP Malhi et al., 2015)
€=
r Stage of Illness
and Phases of Goals and Clinical Features
Medical illness that influences the
course and treatment of depression
Co-morbidities Alcohol and other substance misuse G=
Treatment (particularlv stimulants, cannabis, hal-
lucinogens, and benzodiazepines)
G
Goal: Toobtain response to treatment
Lack of significant social support
G;i
Cl@cal features
• Response may appear as early as
Psychosocial
variables (eg recent loss of support)
Stressful home environment
g=
Stage of
Response and
the first 2 weeks
G
g
• Significant reduction in signs/symp- Inability to engage in community-
Acute Phase toms based care
of Treatment e% reduction in the total score on a Treatment Failure to respond to community-based
standardized rating scale, such as
the Hamilton Depression Rating
Variables care
Initiation of complex treatment €>
Scale (HAM-D) (Hamilton, 1960) (eg. electroconvulsive therapy) G5
c=

-
Goal: To achieve remission of symp-
toms with continued treatment How is suicide risk assessed?

Clinical features There is a high prevalence of suicide in MDD

(
• Continued amelioration ot symptoms (Borges et al., 2006; Bolton et al., 2008) and this

=
Stage of • If an adequate dose is effective,
constitutes an emergencv. Thus, the suicide risk
Remission and remission usually requires 6 weeks
of the patient should be assessed in every clinical

z
Continuation of treatment.
Phase of
Treatment
• Minimal residual signs/symptoms
• Defined as cut-off score of less than
encounter (Lam et al., 2016). Clinician-rated suicide
risk assessment tools such as SADPERSONS
g
5 on the HAM-D (Hamilton, 1960) (Warden et al., 2014; Bolton et al., 2012) and
or equivalent on the Montgomery- Columbia Suicide Severity Rating Scale (Giddens
Asberg Depression Scale (MADRS)
et al., 2014; Posner et al., 2011) can also be used.
(Montgomery and Asberg, 1979)
Although rating scales are not reliable in predicting
Goals: suicide attempts, these may aid in systematic
• To prevent recurrence with ongoing assessment and documentation (NICE, 2009). It GS,._,
«
z
Stage of treatment is important to consider the presence of suicidal
Recovery and To enhance resilience
ideations as a psychiatric emergency as it places
Maintenance
Phase of Clinical features: the individual at imminent risk, thereby requiring
Treatment • Regain complete functioning immediate hospitalization.
• Return to pre-morbid state

What are the indications for psychiatric admission TREATMENT

in MDD?
Life-threatening conditions, related to depression
as well as several clinical conditions, necessitate
immediate hospitalization.
:t
Psychosocial Treatment
Pharmacologic agents for depression remain as
the mainstay of treatment for depression in health

(Refer to Table 2. Indications for Psychiatric Admission
(From RANZCP Malhi et al., 2015).
144
?
care settings (Ellis, 2004). Despite proven efficacy
of pharmacologic therapy, there appears to be
issues in terms of treatment adherence remaining
low (van Geffen et al., 2009). Some of the reasons
stated were concerns with stigma, drug side cl
«.-
--PM
C Comper<llum of
p4,ti
.'thtpone CCC/ne 144,
effects, and possibility of dependence. Hence,
many patients opted for psychological intervention
as an alternative or adjunctive treatment option
(Churchill et al., 2001).
A biopsychosocial approach to management of MDD
is recommended by many guidelines (Kennedy et
al., 2009; Malhi et al., 2015; Lam et al., 2016) and
psychiatrists in the country. The combination
of psychotherapy and pharmacotherapy is
often initiated at the start of treatment, or
when the patient does not respond with initial
monotherapy using either pharmacologic therapy
or psychotherapy (Paykel et al., 1999; Frank et al.,
2000). This dual treatment combines advantages
of each modality (Hollon et al., 2005). Potential
benefits include improved treatment response,
reduced relapse rates, enhanced quality of life, and
increased adherence to pharmacotherapy (Segal
et al., 200I). Dual treatment was also shown to be
superior to psychotherapy or pharmacotherapy
alone (deMaat et al., 2008).
What psychological therapies are available for
Depression?
Psychological therapies are generally categorized
into four separate philosophical and theoretical
schools: (1) psychoanalytic/psychodynamic,
(2) behavioral, (3) humanistic, and (4) cognitive
(APA, 2010). They have different yet overlapping
psychotherapeutic approaches. Some make
use of integrative approach, such as cognitive-
analytic therapy, while other forms target-specific
characteristics considered specific to the disorder,
ie. Interpersonal Therapy for Depression (IPT)
(Parikh et al,, 2009). The best studied among
these are Cognitive Behavioral Therapy (CBT),
Behavioral Therapy, Interpersonal Therapy (IPT),
and Cognitive Behavioral Analysis System of
Psychotherapy (Parikh et al., 2009).
In the Philippines, psychiatrists often initiate
psychosocial interventions in combination with
pharmacologic treatment, primarily with the use of
psychoeducation and the principles of supportive
techniques that cater to the individual needs of
the patient.
Psychiatrists do not often use CBT, IPT, and
other cognitive-behavioral approaches due to
their limited access to training in these forms
of psychotherapy and limited availability of
CBT- or IPT-trained providers in the country.
Many psychiatrists bridge this gap by providing
a combination treatment of pharmacotherapy
and psychotherapy. However, most Filipino
Major Depressive Disorder
psychiatrists provide only basic supportive
techniques with psychoeducation and counseling.
The therapeutic benefits with this approach have
vet to be examined in our setting.
What are the limitations of psychological
management?
There is a comparatively small number of studies
involving psychotherapy which are limited by
problems with methodology (APA, 2010). In
terms of the practice of psychotherapy, clinical
considerations and patient factors determine the
type of therapy needed. Conduction also varies
according to the therapist's skills and training
(Parikh et al.,2009). Moreover, psychotherapies are
not without their side effects. For instance, lengthy
sessions may be poorly tolerated due to impatience
(APA, 2010). Sessions may also generate anxiety
and other strong feelings that may be difficult
to manage (APA, 2010). Thus, it is important to
consider the needs of the patients in determining
the type of psychotherapy that will be used.
Limited access to evidence- and manual-based
psychotherapies in the Philippines is also an
issue due to insufficient number of mental health
professionals properly trained in CBT and IT.
This is an ongoing challenge that the patients,
families, and psychiatrists need to face. Thus,
referral to a trained practitioner for a specific
type of psychosocial management is suggested
only if practicable or readily available. Other
psychotherapy forms (Refer to Appendix L) are not
yet available in our setting.
What is Psychoeducation?
Psvchoeducation is an intervention wherein in-
struction is offered to patients and their families
following a required consent before such informa-
tion can be shared to someone other than the pa-
tient (APA, 2010). It provides different advantages
such as being less expensive, more easily adminis-
tered, and more accessible than the conventional
pharmacologic and psychological interventions
(Donker et al., 2009). Psychoeducation is also a way
of obtaining informed consent from the patient and
the family before continuation of the management
(APA, 2010). Topics to discuss may include the set
of symptoms exhibited by the patient, course of
depression, and as an illness with available treat-
ment that is effective and necessary (APA, 2010). It
may also delve on general health promotion, such
as sleep hygiene (Donker et al., 2009).
Psvchoeducational interventions for depressive
145

Major Depressive Disorder
.
disorders show a small but significant effect on
-------'-------Ci-
depression compared to controls (Donker et aL.,
2009). However, for mild depressive episodes,
psychoeducation was one of the psychosocial
interventions recommended as an alternative to
antidepressants (Bauer et al., 2013).
svchoeducation was identified as a common
tool in engaging patients to actively participate in
treatment. It was also considered as an effective
psychological intervention among depressed
patients based on clinical experience. Aside from
this, treatment planning and discharge planning
involving the patient and family members
were also considered as useful psychosocial
interventions in clinical practice.
For those individuals with depressive disorders
who will benefit from these, PP A recommends
the use of psychoeducation and treatment/
discharge planning with the patient and the
family members as psychosocial interventions.
Consensus Statement
What is Supportive Psychotherapy?
Supportive psychotherapy has been defined
as an unstructured therapy without specific
psychological techniques excluding those found
in other approaches such as catharsis and
empathy. Others have also referred to it as simply
'counseling' (Cuijpers et al., 2008). Its main goal is to
focus and boost the patient's strength to overcome
the illness (Cuijpers et al 2008). Compared to other
therapeutic modalities, it was shown to be less
effective (Cuijpers et al 2008).
Still, many psychiatrists in the country use this
type of unstructured supportive psychotherapy
in their clinical practice
PPA did not reach a consensus on unstructured
supportive psychotherapy as an effective
psychosocial intervention, hence does not
recommend for use in clinical practice.
Consensus Statement
What is Cognitive Behavioral Therapy (CB1?
Since three decades ago, when it was first evaluated
for use in major depressive disorder, CBT has been
the most widely studied form of psychotherapy
(Dobson et al., 1989). It also has reasonably
robust sizes for meta-analyses (Blackburn et
al., 1997; Dobson et al,, 1989; Robinson et al.,
1990; Gaffan et al., 1995; Gloaguen et al., 1998).
Cognitive behavioral therapy is effective in
146
%-
cease Cpl G
Philippine Medicine z-r
preventing relapse in patients with recurrent
MDD (Teasdale et al, 2000). Several guidelines
recommend CBT for MDD (NICE, 2009 Parikh e'
al., 2009; APA, 2010; Malhi et al., 2015; Parikh et al.
2016).
Several studies that date back from 2009 prove
that CBT is the most established evidence-based
€=
€
=
first line treatment for depression both for acute
and maintenance management (Luty et al., 2007;
=
Hoffman et al., 2012; Cuijpers et al., 2013; Cuijpers
et al., 2015). It was also demonstrated that CBT is
as good as therapeutic medications while CBT-
plus-medications showed increased effectiveness €
...-
€=
than either treatment alone (Macgillivray et al.,
2001; Arrol et al., 2009; Panzer, 2005). Cognitive
behavioral therapy has level l evidence in terms of
efficacy in treating depression and thus, continues
to be the first line treatment for acute MDD (Parikh €
:
et al., 2009).
G
Other psychosocial interventions
Some psychiatrists in the country identified the
need for trauma-based psychosocial interventions
€
=
given that natural disasters, among other traumatic
stressors, occur frequently in the country. Some
psychiatrists are adopting Eye Movement
Desensitization and Reprocessing (EMDR) as a
treatment tool for of this.
PPA did not reach consensus on EMDR as an
effective psychosocial intervention and hence,
does not recommend its use in depression.
I
- Consensus Statement
Pharmacological Treatments
What are the principles of pharmacological
treatment of MDD?
Recommendations for pharmacologic treatment
were based on guidelines as well as their suggested
level of evidence (Bauer et al., 2013; Malhi et al.
2015; Kennedy et al., 2016). Medications used in
treating MDD consist mainly of antidepressants
which are classified according to structure
and neurotransmitter profile. Psychiatrists in
the Philippines continue to refer psychiatric
medications for MDD as" antidepressants" despite
the introduction of PPA last 2014 to its members
the ECNP nomenclature of psychiatric medications
(Zohar et al., 2013). For practical purposes, the drug
classification of " antidepressants" used by many
guidelines (Kennedy et al., 2016; Malhi et al., 2015;
Bauer et al., 2013) will be adapted. Adjunctive
treatments are also discussed.
Major Depressive Disorder
cream
Philippine Medicine
cpl
--cc

Antidepressants (From CANMAT 2016 b Kennedy Table 3. Summary Recommendations for Anti-
et al, 2016) and Table 4. Summary of Antidepressant depressants (From CANMAT 2016 by Kennedy et al,
Use - Acute (Malhi et al., 2015)) 2016)

Antidepressants Mechanism Dose Range

Table 4. Summary of Antidepressant Use - Acute (Malhi
First Line (Level 1 Evidence)
et al.,, 2015)
<Please refer to Annex> Agomelatine MT, and MT, 25-50 mg
agonist; 5HT
antagonist
What medications are recommended for MDD
Bupropion" NDRI 150-300 mg
Clinical Specifiers?
Citalopram" SSRJ 20-40 mg
There is a common agreement that several factors Desvenlafaxine SNRJ 50-100 mg
can influence choice of antidepressant medication, Duloxetine SNRI 60 mg

particularly clinical features and dimensions Fscitalopram SSRJ 10-20 mg

of major depressive episode (Kennedy et al., Fluoxetine SSRI 20-60 mg
2016; Malhi et al., 2015). The fifth edition of the Fluvoxamine SSRI 100-300 mg
Diagnostic and Statistical Manual of Mental Mianserin Alpha-Adrenergie 60-120 mg
Disorders (APA, 2013) uses specifiers that are agonist; 5-HT
based on associated features and patterns or antagonist
course of clinical presentation of MDD. These .Milnacipran" SNRI 100 mg
depressive subtypes may respond to certain Alpha+-Adrenergie
antidepressants. Mirtazapine agonist; 5-HT: 15-45 mg
antagonist
(Refer to Table 5. Recommendations for Clinical Paroxetine SSRI 20-50 mg
25-62.5 mg
Speifiers and Dimensions of MDD)
for CR
version
What strategies can be used when switching Sertraline SSRI 50-200 mg
antidepressants?
Venlafaxine 75-225 mg
...............
Vortioxetine
SNRI
Serotonin reuptake 10-20 mg
Switching antidepressants is a common strategy inhibitor; 5-HT%
used in the treatment and management of MDD. If agonise; 5-HT,%
the initial antidepressant is poorly tolerated by the partial agonist;
patients due to its side effects, switching to another 5-HT.5-HT%
antidepressant within the same class may be done and 5-HT- agonist
with the use of a lower initial dose for the second Second Line (Level 1 Evidence)
medication especially for SSRIs (Malhi et al., 2015). Amitriptyline, TCA Various
More importantly, it is important to note that there clomipramine
is no conclusive evidence to support switching and others
to another antidepressant class compared to Levomilnacipran SNRI 40-120 mg
switching of treatment within the same class, Moclobemide Reversible inhibitor 300-600 mg
particularly for SSRIs (Lam et al., 2009). ofMAO-A
Quetiapine Atypical 150-300 mg
(Refer to Table 6. Strategies for Switching anti psychotic
Antidepressants From Malhi et al., 2015 (RANZCP, Selegiline IrreversibleMA0-B
2015). transdermal inhibitor 6-12 mg daily
I
transdermal
Trazodone Serotonin reuptake 150-300 mg
What is Adjunctive Treatment in MDD? inhibitor; 5-HT2
antagonist
Adjunctive treatment involves the addition of Vilazodone Serotonin reuptake 20-40 mg
a second medication to enhance treatment for inhibitor; S-HT% (titrate from
patients who do not respond to an adequate dose partial agonist 10 mg)
f----
of antidepressant (Kennedy et al., 2016). There are Third Line (Level 1 Evidence)
clinical factors to consider in choosing adjunctive I Phenelzine Irreversible MAO 45-90 mg
treatment (Refer to Appendix L) over switching inhibitor
to another antidepressant. Careful treatment Tranylypromine 20-60 mg
planning when considering adjunctive strategies Reboxetine" Noradrenaline 8-10 mg
is necessary with consideration on the co-existing reuptake inhibitor
148
CPMEE.
- -
·.Pitpie eCCfe

Table 5. Recommendations for Clinical Specifiers and Dimensions of MDD

(Adapted from CANMAT Kennedy et al, 2016)
Major Depressive Disorder
.-

--
Specifiers/Dimensions Recommendations Comments
(Level of Evidence)
With anxious distress Use of an antidepresssa «ukase kkcreace in efficacy t
bets«a,
in generalized anxiety disorder (Level 4), SSKIs, SNRIs and bupropion (Level 2)
wnu Penodi
catatonic features repines (Level3) No antidepressants have been studied
With melancholic features No specific antidepressants have TCA« and SNRIs have been studied

With atypical features

demonst rated superiority(1eel3)
No specific antidepressants have
]_
Other studies found MAO

__
..]demonstrated superiority (Level2) inhibitors superior to TCAs
With psychotic features Use antipsychotic and antidepressant Few studies involved atypical
cotreatment (Level 1) antipsvchotics
idose(devet2
weh mixed fest ' comparative stag
Ziprasidone (Level 3)
With seasonal pattern 1Nocene tdepressants have
demonstrated superiority (Level 2 and 3),
SSRIs, gomelatine bupropion and
moclobemide have been studied
"Not
available in the Philippines (Some SNRIs and TCAs are not available)
Table 6. Strategies for Switching Antidepressants From Malhi et al., 2015 (KANZCP, 2015)
------
Strategies for switching antidepressant medication
-.- --
A. Changes in dose of both medications are implemented
simultaneously
Eowe»e-sos
rttastir pa
vd
es0e

-
- Preferred for partial response.
• Advantages: I
- Individual is always under a medication
- Switching is achieved quickly
• Disadvantages:
- Increased chances of interactions and side effects

B Dose changes are only implemented in one medication al a time

while maintaining the initial medication dose constant until the.orcewaor rt at a
second medication has reached optimal dose. eouer a .at para ore
- Preferred for partial response.
• Advantages
- The cross-over helps retain any benefit achieved from the initial
medication.
- The cause of side effects is more easily identified, should side
effects emerge, because only one medication is modified at a time
Disadvantage
. There is an increased risk of interactions and side effects
because of overlapping of medications.
c-- -
C. Concurrent administration and sequential titration:
---
- The initial medication is tapered and once this has been fully
withdrawn, the new medication is gradually introduced and
titrated to optimal dosage.
G
- Preferred for non-response
•

/
$
!'+
• Advantages
- This is the safest strategy. 8
- This option has the least likelihood of causing any interactions. I
. ..
i
•
Disadvantages:
- This takes much longer especially if a washout period is included.
I
0
• ,••
n

This strategy increases the chance of worsening condition

b
because of the considerable period when medication is at a Ire
sub-therapeutic dose. - -- - -- J
reen dotted line depicts treatment response. Red line shows dose of initial (ongoing) antidepressant medication.
e line shows dose of second (added) antidepressant medication
149

Major Depressive Disorder
medical conditions of the patient and possible
drug-drug interactions (NICE, 2009). A review of
the existing guidelines on depression as well as
conducted clinical trials recommended addition
of lithium, second-generation antipsychotics,
sedative-hypnotics, or thyroid hormones for cases
of non-responders or partial responders (NICE,
2009; AP A, 2010; Bauer et al., 2013; Malhi cl al.,
2015; Kennedy et al., 2016).
(Refer to Table 7. Recommendations for Adjunctive
Medications for Non-response or Partial Response to
an Antidepressant (From CANMAT Kennedy et al.,
2016)).
What other pharmacologic agents may be used for
Adjunctive Treatment of MDD?
(Refer to Table 7. Recommendations for Adjunctive
Medications for Non-response or Partial Response to
an Antidepressant (From CANMAT Kennedy et al.,
2016)).
Lithium. Lithium augmentation is historically one
of the first and well-established approaches. It
has been documented to act synergistically with
a broad spectrum of antidepressants (Joffe et al.,
1993 Katona et al.,, 1995), with particular interest
is given on its ability to lower suicidal tendencies
(Cipriani et al., 2005). Serum levels of 0.6-0.8
mEq/L for at least2 weeks constitute an adequate
treatment trial (Bauer and Gitlin, 2016). Prior to
treatment, renal and thyroid function should be
evaluated, ideally monitored every 6 months with
regular observation for signs of toxicity (Refer to
Appendix N) (Crossley and Bauer, 2007). Positive
predictive response is associated with patients with
recurrent depression with 3 or more episodes and a
family history tor mood disorders (Sugawara et al.,
2010). Although augmentation with lithium was
associated with statistically significant treatment
response, there was no noteworthy difference
in terms of the acceleration of the said response
(Crossley and Bauer, 2007).
Second-Generation Antipsychotics. There is an
increased rate in response with the addition of
second-generation antipsychotics in the treatment
strategies for depression (Nelson and Papakostas,
2009). Atypical antipsychotics such as aripiprazole,
olanzapine, quetiapine, and risperidone have been
studied as adjunctive agents for MDD (Nelson
and Papakostas, 2009). Pharmacologie properties
such as 5-HT2A antagonism at low doses may
facilitate the efficacy of SSRIs by enhanced action
of serotonin at the 5-HT1A receptor (Komossa
et al., 2010). Although evidence proves their
150
coeou' CpM
- ---
Philippine Medicine ----
efficacy, atypical antipsychotics were linked with
adverse effects such as sedation, weight gain, and
hyperprolactinemia (Komossa et al., 2010).
Thyroid Hormones. Tr~iodothyronine /liothyronine
(T3) has been employed as an adjunctive agent
to antidepressant therapy even in euthyroid
patients (APA, 2010). Studies conducted focused
more on T3 and proved its efficacy compared to
placebo (Zhou et al,, 2015). Antidepressant effects
of thyroid hormones are related to their action on
the serotonergic system and to a lesser extent, to
the noradrenergic system (Newman et al., 2000).
T3 was proved to be comparable in efficacy with
lithium and generally more tolerated (Nierenberg
et al., 2006). Although there was evidence that this
can improve treatment, further studies are still
recommended to provide more decisive proof
(Cooper-Kazaz and Lerer, 2008).
Anxiolytics and Sedative-Hypnotics. Prescribing
benzodiazepines with antidepressants for
depressed patients with debilitating anxiety and
persistent insomnia is already a common clinical
practice (APA, 2010). Since the effect of the
antidepressant does not manifest for several weeks,
benzodiazepines are often added for immediate
relief of some depressive symptoms (Valenstein
et al., 2004). A low dose benzodiazepine can be
prescribed for a limited time period to lessen the
activation or agitation seen in the initial stages of
SSRI trial (Malhi et al., 2015). Careful consideration
should be in place in balancing benefits of
benzodiazepines against the potential harmful
effects such as dependence and increase risks in
accident (Furukawa et al., 2002).
Based on clinical practice, administration of
benzodiazepine at the start of the treatment in
combination with an antidepressant is beneficial
among patients with MDD with anxious
distress.
Consensus Statement
Other Agents. Several studies investigated the
potential added benefits from augmentation with
other pharmacological agents such as stimulants,
beta-blockers, and anticonvulsants (Kennedy et
al, 2016).
What are the side effects of antidepressants?
Tolerability in the use of antidepressant enhances
treatment adherence (Malhi et al., 2015). Rapid
dose increase is known to lead to higher likelihood
of side effects and treatment discontinuation
(Malhi et al., 2015). Side effects of antidepressants
C-PM Compecdlumof
--
---a philit . Medic Mippine 1cine Major Depressive Disorder
Table 7. Recommendations for Adjunctive Medications for Non-response or Partial Response to an Antidepressant
(From CANMAT Kennedy et al., 2016)
a

Recommendation Level of Evidence Adjunctive Treatment Dosing

2-15 mg
Aiipramole
Level1
First-Line 1eel1
Level 1
Quetiapine
Risperidone
150-300 mg
1-3mg
.
c-- Brexpiprazole" 1-3mg
�
Bupropion° 150-300 mg
600-1200 mg
Level 2 Lithium
(therapeutic serum levels)
Second-Line Mirtazapine
Level 2 Mianserine" 30-60 mg

Level 2 Modafinil 100-400 mg

�
Level 1 Olanzapine 2.5-10 mg
Level 2 Triiodothyronine 25-50 mcg
Various
Level 3
Other antidepressants Various
Level 3 Other sti mulants (methylphenidate)
Third-Line <----- --�---
Level 2 TCAs Various
Level 3 Ziprasidone 20-80 mg bid
--1---
Experimental Level1 Ketamine' 0.5 mg/kg. single IV dose
Not recommended
-
Not recommended Level 1 Pidolol (Lacks efficacy)

Not available in the Philippines

Methylphenidate is the only stimulant available in the Philippines

-----��-
Some TCAs are not available in the Philippines
Approved as an anesthetic agent in the Philippines (Pint et al., 2016)
may occur and may vary between classes (Bauer
et al., 2013). These must be monitored to foster
treatment adherence
The most frequent side effects of TCAs include
dry mouth, constipation, blurred vision, urinary
retention, alpha-adrenergic blockade, tachycardia,
orthostatic hypotension, bradyarrhythmias,
sedation, and weight gain (Bauer et al., 2013).
Compared to TCAs, SSRIs are better tolerated
(Anderson, 2009). The frequent side effects
associated with the use of SSRls are activation,
agitation or restlessness, sexual dysfunction in
both genders, gastrointestinal distress (nausea,
vomiting, diarrhea), and neurological problems
such as exacerbation of migraine headaches
and tension headaches (Bauer et al., 2013).
SSRIs may also affect platelet function; hence,
combination with other medications that have an
effect on platelet function will need monitoring
for bleeding time (Bauer et al., 2013). Other
risks associated with SSRls include low serum
sodium and prolonged QTe with high doses (e.g.
citalopram and escitalopram) (Bauer et al., 2013).
Meanwhile, weight gain and sedation are some
of the commonly seen side effects of mirtazapine
(Watanabe et al, 2011).
----
_J
Side effects may appear during the first two
weeks of antidepressant treatment but eventually
become tolerable and minimal, although some
individuals may experience persistence of side
effects. Patients who find these problematic must
be close monitoring of response and side effects
should be done once antidepressant treatment is
started (Malhi et al., 2015)
(Refer to Table 8. From Malhi et al., 2015 (RANZCP)
Common Side Effects of Antidepressants)
What is the association of suicidality with
antidepressants?
Suicidal ideation, thoughts of death, or suicide
attempts are common symptoms of MDD (APA,
2013). Concern for increased suicidal thoughts
and behaviors in adolescents and young adults,
shown in antidepressant clinical trials, prompted
regulatory agencies to issue "black box" warnings
in 2004. A comprehensive review showed that
antidepressants, including SSRls, carry a small risk
of inducing suicidal thoughts and suicide attempts,
in age groups below 25 years with decreasing risk
at the age of about 30 to 40 years (Moller et al.,
2008). Clinical decision-making should carefully
�--- 151
 cooed CpM
Major Depressive Disorder
---------- - -
Table 8. Common Side Effects of Antidepressants From Malhi et al., 2015 (RANZCP)

CNS effect
Philippine Medicine av.

Weight gain r Sexual (e.g. sedation, Anticholinergie

effect (e.g. dry GI distress

..
dysfunction fatigue or
mouth, tremor)
agitation)
SSRI • 4 ++ ••
SM
NARI ..• •
#
•
...
•
4

•
++•
++
Na$SA ++ •• ++ •
Melatonergic agonist + + • • +
NDRI
SNRp
++
4 ...• 44

4
•
4
•
H
TCA- ++
L
• +H H+ +
MAOp • # • • +
SARI • + I +++ + d
'
KEY: + <10%, ++ 10-30%, 4++ 30%. SSRI, selective serotonin reuptake inhibitor; SM, serotonin modulator; NARI
noradrenaline reuptake inhibitor; Na5SA, noradrenaline and specific serotonerg antidepressant; NDRI, noradrenaline-
dopamine reuptake inhibitor; SNRI serotonin noradrenaline reuptake inhibitor; TCA, tricyclic antidepressant; MAOL,
monoamine oxidase inhibitor; SARI, serotonin antagonist and reuptake inhibitor.
Not available in the Philippines
Some SNRI and TC As are not available in the Philippines
Some combination of MAOls with other drugs can be fatal. Dietary restrictions are necessary to prevent hypertensive
cr1SIS

balance this potential risk against the well-known
beneficial effects of antidepressants on depressive
and other symptoms (anxiety, panic, obsessive-
compulsive symptoms), including suicidality and
suicidal behavior (Moller et al., 2008; Bauer et al.,
2013). Close observation of the patient's symptoms
during the first 2 to 4 weeks of treatment should
be considered upon initiation of the antidepressant
(Bauer et al., 2013; Malhi et al., 2015). The patient
and family members or caregivers should be
advised about small chances of suicidal thoughts
in the early phase of antidepressant treatment
(Malhi et al., 2015).
Electroconvulsive Therapy and other
Neuromodulation Therapies
What is Electroconvulsive Therapy?
Electroconvulsive Therapy (ECT) is a neuro-
modulation technique employed to treat certain
psychiatric conditions. In basic terms, it involves
the application of an electrical current to the brain
to evoke a seizure. Psychiatrists have utilized ECT
since its introduction in the 1930s but, to date, the
exact mechanism of action of ECT remained elusive
(APA, 2001). Almost every facet of the ECT has
been discussed, from its efficacy and indications
to its physiological, psychological, and adverse
effects. In fact, there are detailed guidelines for its
152
pplication (APA, 2001). Though theories on its
action have surfaced focusing on seizure-induced
changes in neurotransmitters, neuroplasticity, and
functional connectivity, an evidence-based and
universally acceptable explanation is still lacking.
In an era of momentous medical advancement
and research focused especially on the brain, it is
anticipated that the mechanism of action of this
therapy will finally be unveiled.
The most common indication for ECT is MDD since
it is the fastest and most effective therapy available
(Sadock et al., 2015). According to Bauer et al., the
efficacy of ECT is a well-established fact backed
up by a number of studies (Bauer et al., 2013). A
response rate of 70-90% has been found in MDD
patients administered with ECT (APA, 2010). ECT
is indicated for all subtypes of MOD including
atypical depression, bipolar depression, psychotic
depression, and depression with prominent
suicidal ideation (Kennedy et al, 2009).
Mental health professionals consider ECT as a safe
and effective treatment, however, certain patient
groups were opinionated about its obsolete and
seemingly-harmful process (NICE, 2009). Since the
advent of novel antidepressants, the use of ECT has
declined. The less controversial use of drugs and its
accessibility renders it more preferable over ECT. A
survey conducted among psychiatrists suggested

that ECT is now being used only after an adequate
trial of medications has proven ineffective or that
ECT be added to the treatment regimen as an
adjunctive approach (APA, 2001).
In the Philippine culture, where patients still
suffer from the stigma associated with psychiatric
disorders, including depression, many psychiatrists
have encountered the common experience where
most patients and their families have the perception
that ECT is an indicator of a severe or terminal illness.
What are the indications, contraindications and
adverse effects of ECT?
A review of the existing guidelines on depression
recommended that ECT be used as first-line
treatment if an immediate improvement of
severe, life threatening symptoms of depression
is warranted, as in cases with psychotic features,
catatonia, suicide risk, and nutritional compromise
(Husain et al, 2004).
Electroconvulsive therapy is a recommended
second-line management for treatment-resistant
depression and patients who were unable to
tolerate the adverse effects of medications (Husain
et al, 2004)
The decision to use ECT should be arrived at after
a complete psychiatric, physical, neurological, and
pre-anesthesia examination. A thorough medical
history, cognitive assessment, and indicated
diagnostic procedures are compulsory information
in order to weigh the benefits against the risks of
the procedure (Refer to Appendix O)
Although there is no absolute contraindication for
ECT, caution is given for patients with unstable
or severe cardiovascular conditions, aneurysms
or vascular malformations, increased intracranial
pressure (as may occur with some brain tumors
or other space-occupying lesions), recent cerebral
infarction, pulmonary conditions (e.g. severe
chronic obstructive pulmonary disease, asthma,
or pneumonia) and anesthetic risk rated as ASA
level 4 or 5 (Beyer et al., 1998).
Adverse reactions such as cardiac dysrhythmias,
cognitive impairment, confusion, disorientation
spontaneous seizures, or seizures occurring
outside the treatment setting may be attributed to
the induced seizures or the anesthetic drugs used
in the procedure (APA, 2001). Other symptoms
like headaches, muscle soreness, and nausea are
transient and may be treated symptomatically
(Milev et al., 2016)
Major Depressive Disorder
Can ECT be used for relapse prevention?
Major Depressive Disorder is a highly recurrent
condition with relapse rates of 50% after a first
episode and 80% for the succeeding episodes
(APA, 2013). Similar outcomes were exhibited by
patients treated successfully with ECT. Without
active treatment, patients relapse within 6
months after discontinuation of the ECT (Sackeim
et al., 2001). Thus, maintenance treatment is
highly recommended (Milev et al., 2016). Oral
antidepressants lowered the risk of recurrence
by 50%. Despite the limited evidence for newer
antidepressants and popular augmentation
strategies, tricyclic antidepressants are proven to
be effective (Jelovac et al, 2013). Continuation and
maintenance ECT are also useful treatment strategies
for the prevention of relapse (Petrides et al., 2011).
Electroconvulsive therapy remains a valuable
treatment option in the treatment for depression
For the past 80 years since its discovery, its efficacy
and safety has been well established (Milev et al.
2016; Malhi et al,, 2015; APA, 2010; NICE, 2009;
Bauer et al., 2015). ECT is still unsurpassed in
terms of its onset of action (APA, 2001). Though
its use has declined due to the advent of newer
psychotropic medications and psychotherapies, it
is still highly recommended bv literature (Milev et
al., 2016; Malhi et al., 2015; APA, 2010, NICE, 2009;
Bauer et al., 2015). Revisiting a treatment with an
outstanding track record would be prudent.
What other Neuromodulation Therapies may be
used for MDD?
Recent advances in the field of Neurosciences
brought about a renewed interest in neuromodu-
lation therapies for psychiatric conditions, spe-
cifically depression (Refer to Appendix P) (Hoy and
Fitzgerald, 2010). Research focused on these topics
revealed promising results (Carpenter et al., 2011).
Though these alternative treatment modalities
have limited availability in the country at present,
it may be judicious to list them down.
(Refer to Table 9. Other Neuromodulation Therapies for
MDD Adapted from Hoy, KE and Fitzgerald PB. Brain
stimulation in psychiatry and its effects on cognition.
Nature Reviews Neurology. April 2010.)
Novel Treatments
What Novel Treatments can be considered to
manageMDD?
Ketamine (Refer to Appendix Q) is an N-Methyl-
153
 Phi'�.deM � or CPM
-
Major Depressive Disorder Doirer
-
Cine --F

Table 9. Other Neuromodulation Therapies for MDD. Adapted from Hoy, KE and Fitzgerald PB. Brain stimulation
in psychiatry and its effects on cognition. Nature Reviews Neurology. April 2010.

T«hnique Adnnt;ages __
-_-_-_-_-_-c-
---0-..,-,-.-,-.-
. ,-.-6----
, �

,
I Transcranial direct
current stimulation
• Non-invasive and non-convulsive
• High tolerability
·Lacks evidence for degree of efficacy
compared with other techniques
(tDCS) ·Low cost and potential applkability in
developing countries
·No cognitive adverse effects; possibly
[enhances cognition
A considerable amount of further
research required
I
magnetic stimulation Some evidence for efficacy in treatment- results
TMS) resistant depression Lacks evidence of efficacy for other
• No evidence of cognitive adverse effects psychiatric indications
·Further research required to
optmze response
• Definitive«evidence required of efficacy
in treatment-resistant depression
�Deep brain shmulat1on
DBS)
• Provide!> continual stimulation
·Provides direct and targeted
Invasive surgical procedure
·Restricted to treatment-refractory
1
stimulation of deep brain structures patients
·No evidence of cognitive adverse effects
---- -- -- -+-��-
"''"'"' s,i,ure lhernpy
(MST) 1 •·Seems
'""'""'""
to lack cognitive adverse effects
Requires anesthetic
Head-to-head trials with ECT
required to establish efficacy
simulation
Vagal nerve • Minimally invasive ·Initially approved for treatmc
(VNS) ·Some evidence for efficacy in treatment- resistant epilepsy, approval for

---- resistant depression

D-aspartate (NMDA) receptor antagonist that is

depression is still controversial

literature dedicated on this topic (Dela Cruz et

US FDA approved. It acts as an anaesthetic agent
for procedures that do not require skeletal muscle
relaxation, for the induction of anaesthesia and
for supplementation of low-potency anaesthetic
agents (Mathew et al., 2012). A number of trials
demonstrated rapid antidepressant and anti-
suicidal effects with infusion of ketamine (Caddy
et al., 2014).
Although ketamine's efficacy as an antidepressant
presents a promising possibility, a review of the
studies done resulted in limited evidence. The
practicality of administration and safety profile
also warrants further longer-term investigations
(Caddy et al., 2015). Ketamine may provide
newer insights on the neurobiology of depression
and may eventually lead to the development of
glutamatergic antidepressants (Abel et al., 2003).
Complementary and Alternative Treatments
What Complementary and Alternative Treatments
are available for MDD?
Complementary and alternative medicine refers
to a culturally-influenced set of knowledge,
beliefs, and practices related to health, including
diagnosis, treatment, and prevention of diseases
(WHO, 2016). Philippines is supportive in this
field of medicine as evidenced by numerous
154
al., 2006). Despite this, there is lack of data on its
application on depression or even mental disorders
as a whole
A review of existing guidelines on the management
of depression yielded several complementary and
alternative treatments (Refer to Appendix R) options
backed up by studies (APA, 2010; Mahli et al., 2015;
Ravindran et al,2016). Recommended physical or
meditative therapies with a good level of evidence
for management of mild to moderate MDD include
exercise, yoga, and acupuncture. Among the
natural health products, St. John's Wort, omega-3
fatty acids, and S-adenosyl-methionine (SAMe)
have been proven to be beneficial. However these
health products have no approved therapeutic
benefits in the country and are not included in
the list of approved herbal treatments (FDA
Philippines, DOH Philippines).
References
I. Abel KM, Allin MPG, Kucharsla-Pietura K David A et
al. Ketamine alters neural processing of facial emotion
recognition in healthy men an tMRI study. NeurolReport.
2003; 14.387-91.
2 AllanCL, Ebmeier KP The Use of ECT and MST in treating
depression. International Review ot Psychiatry, 2011;
23400--412
3. American Psychiatric Association The practice of
electroconvulsive therapy: Recommendations for
treatment, training. and privileging (A Task Force Report
of the American Psychiatric Association), 20012'ed
4. American Psychiatric Association: Practice guideline
 Compendium of
- Philippine Medicine
for the treatment of patients with major depressive
disorder Am J Psychiatry. 2010 3° ed. http://www.
psychiatryonline.com/pracGuide/ pracGuide Topi_
7.aspx.
5 American Psychiatric Association: Diagnostic and
Statistical Manual oft Mental Disorders, Fifth Edition
Arlington, VA, American Psychiatric Association, 2013.
6. Autry AE Adachi M, Nosyreva E, Na ES et al. NMDA
receptor blockade at rest triggers rapid behavioural
antidepressant responses. Nature. 2011, 475. 91-95
Anderson IM. Selective serotonin reuptake inhibitors
versus tricvclic antidepressants: a meta-analvsis of efficacy
and tolerability. J Affect Disord. 2000,58:19-36.
8 Arroll B, Eley CR, Fishman I, Goodyear-Smith FA,
Kenealy T, Blashlki G. Antidepressants versus placebo
for depression in primary care.. Cochrane Database of
Swstematic Reviews 2009,Issue 3. DX¥ 10, 1002/14651858
Do0954
9 Azorin JM Kaladjian A, Adida M, et al. Self-assessment
ad characteristics of mixed depression in the French
national EPIDEP study.J Affect Discord. 2012143:109-117.
Bauer M and Gitlin M. 2016. The Essential Guide to
Lithium Treatment. Springer International Publishing
Switzerland.
It. Baer M, Pfennig A, Severus E, Whybrow PC et al
World Federation of Societies of Biological Psychiatry
(wpsBP) Guidelines for Biological Treatment of Unipolar
Depressive Disorders, Part I Update 2013 on the acute
ad continuation treatment. World1 Biol Psychiatry. 2013;
14334-385
2 Blackburn RG: Controlled acute and follow-up trial of
cognitive IM, Moore therapy and pharmacotherapy in
out-patients with recurrent depression. Br I Psychiatry
1997 171328--334
3. Bever JL. Weiner RD, GlennMD: Electroconvulsive
therapy. a programmed text. Arlington, VA, American
Psychiatric Press, Inc. 1998
4 Bolton JM, Beik SL, Cox BJ, et al. Exploring the
correlates of suicide attempts among individuals with
major depressive disorder. findings from the National
Epidemiologic Survey on Alcohol and Related Conditions.
JC Psychiatry. 2008, 69.1139-1149.
15. Bolton JM Spiwak R, Sareen J. Predicting suicide attempts
with the SAD PERSONS scale: a longitudinal analysis. Chin
Psychiatry. 2012, 73.e735-e741.
• Brouwers M. Kho ME, Browman GP, Burgers JS, Cluzeau
F FederG, Fervers B, Graham ID, Grimshaw J, Hanna5
Littlejohns P, MakarskiJ, Zitzelsberger L for the AGREE
Next Steps Consortium. AGREE IE Advancing guideline
development, reporting and evaluation in healthcare
Can Med Assoc . 2010. Available online July 5, 2010
dot10.1503/cmaj.090449
L7 Brunoni AR et al. 2015. Ie Escitalopram versus Electric
Current Therapy for Treating Depression Clinical Study
(ELECT-TDCS): rationale and study design of a non-
inferiority, triple-arm, placebo-controlled clinical trial.
Sao PauloMed J. 2015; 13303)252-63. DOE 10.1590/1516-
3180.2014.00351712
8. Brunoni AR Nitsche MA, Bolognini N, et al. 2012. Clinical
research with transcranial direct current stimulation
(tDCS challenges and future directions. Brain Stimul
2012, 5031175-95
19. Caddy et al. 2014. Ketamine as the prototype glutamatergie
antidepressant: pharmacodynamic actions, and a
systematic review and meta-analysis of efficacy
Therapeutic Advances in Psychopharmacology 2014, Vol
402) 75-99
20. Caddy et al, 2015. Ketamine and other glutamate receptor
modulators for depression in adults (Review). Cochrane
Database of Systematic Reviews 2015, lssue9. Art. No.
CD011612.
21. Carpenter, L, Megna,L., Herrera-Rojas, M. & Siddiqui, U.
201i.When medication fails: Neurostimulation therapies
for depression. Clinical Neuropsychiatry, 8, 61 - 80.
22.Charlson F, Siskind D, Doi SA, et al. 2012.ECT efficacy and
treatment course a systematic review and meta-analysis
of twice vs thrice weekly schedules. ] Affect Disord. 2012;
138.1-8
23. Churchill RR, Hunot V, Corey R. Knapp M,McGuire H,
Major Depressive Disorder
Tvlee A,et al. A systematic review of controlled trials of the
effectiveness and cost-effectiveness of brief psychological
treatments for depression. Health Technology Assessment
2001, 50351-173
24. Cipriani A, Pretty H, Hawton K, Geddes JR. 2005. Lithium
in the prevention of suicidal behavior and al-cause
mortality in patients with mood disorders: a systematic
review ot randomized trials. American Journal of
Psychiatry 162-1805--1819
25. Cooper-Kaaua R and Lerer B. 2008. Efficacy and safety
of triiodothv- ronine supplementation in patients
with major depressive disorder treated with specific
serotonin reuptake inhibitors. International Journal of
Neuropsychopharmacology 11:685-699
26. Crosley NA and Bauer M. 2007 Acceleration and
augmentation of antidepressants with lithium for
depressive disorders: two meta-analyses of randomized,
placebo-controlled trials. Journal of Clinical Psychiatry
68935-940.
27. Cuijpers, P et al 2008. Psychotherapy for depression in
adults: A meta-analysis ot comparative outcome studies
Journal of consulting and clinical psychology. Vol. 76, no
6. 909.922
28. Cuijpers P Berking M, Andersson G, Quigley L, Kleiboer
A Dobson K. A Meta-Analysis of Cognitive-behavioural
Therapy for Adult Depression, Alone and in Comparison
with Other Treatments. Can J Psychiatry 2013 58 376-
385
29. Cuijpers P. Psychotherapies for adult depression recent
developments. Curr Opinion Psychiatry. 2015,22824-29
30. Dela Cruz P and AG Ramos, 2006. Indigenous
Health Knowledge Systems in the Philippines: A
Literature Survey. TIh CONSAL Conference, Manila,
Philippines
31. Department of Health http://www.doh.gov.ph/
32. De Maat S, Dekker J, Schoevers R, van Aalst G,
Gijsbers-van Wilk C, Hendriksen M, Kool S, Peen J,
Van R, de Jonghe F: Short psychodynami supportive
psychotherapy, antidepressants, and their combination in
the treatment of major depression: a mega-analysis based
on three randomized clinical trials. Depress Anxiety 2008,
25.565-574
33. Dobson KS, Hollon SD, Dimidjian S, Schmaling Kl,
Kohlenberg RJ, Gallop R], Rizvi SL, Gollan JK, Dunner DL,
Jacobson NS: Randomized trial of behavioral activation,
cognitive therapy, and antidepressant medication in the
prevention ot relapse and recurrence in major depression
J Consult Cin sychol 2008 76468-477
34. Donker T, Griffiths K, Cujipers P.Psychoeducation for
Depression, Anxiety, and Psychological Distress A Meta
Analysis.BMCMedicine.2009.7-79.
35. Dunne RA, McLaughlin DM. 2012. Systematic review
and meta- analvsis of bifrontal electroconvulsive therapy
versus bilateral and unilateral electro@convulsive therapy
in depression. World J Biol Psychiatry. 2012, 13.248-258.
36. Ellis P. Australian and New Zealand clinical practice
guidelines for the treatment of depression. Australian and
New Zealand Journal of Psychiatry 2004: 38;389-407.
37. Fava M, Alpert JE, Carmin CN, Wisniewski SR, Trivedi
MH, Biggs MM, Shores-Wilson K, Morgan D, Schwart
T, Balasubramani GK Rush A]: Clinical correlates and
symptom patterns of anxious depression among patients
with major depressive disorder in STARD. Psychol Med
2004 341299-13068
38. Food and Drug Administration Philippines. http://www
fda gov.ph/
39. Frank E, ThaseME, Spanier C, Cyranowski JM, Siegel
Psychotherapy of affective disorders. In: Helmchen H,
Henn F, Lauter H, Sartorius. Contemporary Psychiatry
2003. Vol. 3. Springer, Heidelberg pp 348-363
40. Furukawa TA et al. 2002. Antidepressant and
benzodiazepine for major depression. Cochrane Database
of Systematic Reviews.
41. Gaffan EA, Tsaousis I, Kemp-Wheeler SM: Researcher
allegiance and meta-analysis: the case of cognitive therapy
for depression. J Consult Cin Psychol 1995, 63.966--980
42 Gelziniene G, SeeckM. 2005. Vagus nerve stimulation in
depression. Epileptologie 2005 22: 177- 180
43. George MS. 2010. Iranscranial magnetic stimulation
155
Major Depressive Disorder
for the treatment of depression. Expert Review of
Neurotherapeutics 10- 17611772
44. George MS. 1998. Why would you ever want to? Toward
understanding the antidepressant effect of prefrontal
rIMS. Hum. Psychopharmacol. 15, 307--313 (1998)
45. Giacobbe, P., Mayberg, H. S. & Lozano, A. M. 2009.
Treatment resistant depression as a failure of brain
homeostatic mechanisms: implications for deep brain
stimulation. Exp. Neurol. 219, 44--52 02009)
46. Giddens JM, Sheehan KH, Sheehan DV. The Columbia-
Suicide Severity Rating Scale (C-SSRS): has the "gold
standard" become a liabilitv? Innov Cin Neurosci. 2014
1166-80.
47. Gloaguen V, Cottraux J, Cucherat M, Blackburn IM
A meta-analysis of the effects of cognitive therapy in
depressed patients. J Affect Disord 1998, 49.5972
48. Goldberg JE. Mixed depression: a farewell to differential
diagnosis? JClin Psychiatry. 2015,76e378-e380
49. Guo T, Xiang YT, Xiao L et al. Measurement-based care
versus standard care for major depression a randomized
controlled trial with blind raters. Am ] Psychiatry, 2015;
1721004-1013.
50. Hamilton M. Development of a rating scale for primary
depressive illness. Br I Sc Clin Psychopharmacol 1967;
6.278-296.
51. Hoffman S, Asnaani A, Vonk I, Sawyer A, Fang A. The
Efficacy of Cognitive Behavioral Therapy. A Review of
Meta Analyses. Cogrit Ther Res 2012; 3605), 427-440
52. Hollon SD, DeRubeis RJ, Shelton RC, Amsterdam JD,
Salomon RM, O'Reardon JP, Lovett ML, Young PR,
Haman KL, Freeman BB, Gallop R: Prevention of relapse
following cognitive therapy vs medications in moderate
to severe depression. Arch Gen Psychiatry 2005, 62417--
422
53. Hoy KE, Fitgerald PB. 2010. Introducing magnetic
seizure therapy: A novel therapy tor treatment resistant
depression. Australian and New Zealand Journal of
Psychiatry. 2010, 44-591--598. [Pub Med 20560846]
54. Ho, KE and Fitzgerald PB. 2010. Brain stimulation in
psychiatry and its effects on cognition. Nature Reviews
Neurology. April 2010.
55. Hung O. Lithium. 2014. In: Marx [A, Hock.berger RS, Walls
RM, et al, eds. Kosen's Emergency Medicine: Concepts
and Clinical Practice. 8 ed. Philadelphia, PA: Elsevier
Saunders: chap 16f
56. Husain MM et al. 2004. Speed of response and remission
in major depressive disorder with acute electroconvulsive
therapy (CD a Consortiu for Research in ECT (CORE)
report. J Cin Psychiatry 2004, 65485-491
57 Jelovac A, Kolshus F, McLoughlin DM. 2013. Relapse
following successful electroconvulsive therapy for major
depression: a meta-analysis. Neuropsychopharmacology.
2013; 38: 2467-2474
58. Joffe RT, Singer W, Levitt AJ, MacDonald €. 1993.
A placebo-controlled comparison of lithium and
triiodothyronine augmentation of tricvchic antidepressants
in unipolar refractory depression. Archives of General
Psychiatry 50:387-393
59. Johnson MD et al. 2008. Mechanisms and targets
of deep brain stimulation in movement disorders.
Neurotherapeutics 5, 294--308
60. Judd LL, Schettler P], Rush AJ, Coryell WH, Fiedorowicz
JG, Solomon DA. A new empirical definition of major
depressive episode recovery and its positive impact on
future course of illness. J Cin Psychiatry. 2015. dx.doi.
0rg/10,4088/1CP.15m09918
61. Katona CL, Abou-Saleh MT, Harrison DA, Nairac BA,
Edwards DR, Lock T, et al, 1995. Placebo-controlled trial
of lithium augmentation of fluoxetine and lotepramine
British Journal of Psychiatry 166.80-86.
62. Kennedy S, Lam R, Parikh S, Patten S, Ravindran A.
Canadian Network for Mood and Anxiety Treatments
Clinical guidelines for the management of major depres-
sive disorder in adults. J Affect Disord. 2009 1175$1.$2
P,
63. Kennedy SH, Milev RR, Giacobbe Ramasubbu K. Lam
RWet al Canadian Network for Mood and Anxietv
Treatments (CANMAT) Clinical guidelines for the man-
agement of major depressive disorder in adults: neuro-
stimulation therapies. ] Affect Disord. 2009, 117-S44$53
156
64. Kennedy SH, Lam RW,McIntyre RS, Tourjman SV et al.
Canadian Network for Mood and Anxiety Treatment
(CANMAT) 2016 clinical guidelines for the management
of adults with major depressive disorder. pharmacological
treatments. Can J Psychiatry. 2016,1-21 DOE 10.1177/070
6743716659417
65. Kennedy SH et al. 2016.Canadian Network for Mood and
Anxiety Treatments (CANMAT) 2016 clinical guidelines
for the management of adults with major depressive
disorder: neurostimulation treatments. 2016. Can J of
Psychiatry. 2016; 1-15. DOE 10.1177/0706743716660033
66. Koike H, Lijima M, Chaki S. Involvement of AMP A
receptor in both the rapid and sustained antidepressant-
like effects of ketamine in animal models of depression.
Behav Brain Res. 2011, 224107-11.
67. Komossa K Depping AM, Gaudchau A, et al. 2010,
Second-generation antipsychotics for major depressive
disorder and dysthymia. Cochrane Database of Systematic
Reviews. 2010, (12)
68. Kudlow PA, Mcintyre RS, Lam RW. Early switching
strategies in antidepressant non-responders: current
evidence and future reseanch directions. CNS Drugs. 2014;
28:601-609
69. Kupfer D. The pharmacological management of
depression. Dialogues Clin Neurosci. 2005; 71191-205
70. Lam RW, Kennedy SH, Grigoriadis S, Mcintyre RS, et
al. Canadian Network for Mood and Arxiet Treatment
(CANMAT) 200 clinical guidelines for the management of
major depressive disorder in adults: III. Pharmacotherapy.
J Affect Disord. 2009. DOE 10.1016/j.jad.2009.06.041
71. Lam RW, Mcintosh D, Wang JL, Enns MW et al. Canadian
Network forMood and Anxiety Treatment (CANMAT)
2016 clinical guideline for the management of adults
with major depressive disorder. disease of burden and
principles of care. Can J Psychiatry. 2016. DOE 10.1177 /0
706743716659416.
72 Lerer B, Shapira B, CaleA, Tubi N et al. Antidepressant
and cognitive effects of twice- versus three-times-weekly
ECT. Am J Psychiatry. 1995, 152.564-570
73. Li N, Lee B, Liu R, Banasr M, Dwyer JM et al. 2010.
mTOR-dependent synapse formation underlies the rapid
antidepressant effects of NMDA antagonists. Science
2010; 329.959-964
74. Lisanby SH. 2007 Electroconvulsive therapy for
depression. New England Journal of Medicine 2007,
357:19391945
75. Luty SE, Carter JD, McKenzie JM et al. Randomized
controlled trial of interpersonal therapy and cognitive
behavioral therapy for depression. Br I Psychiatry, 2007,
190.496-502.
76. Macgillivray S, Arroll B, Hatcher S, Ogston S, Reid I,
Sullivan F, Williams B, Crombie I: Efficacy and tolerability
of selective serotonin reuptake inhibitors compared with
tricyclic antidepressants in depression treated in primary
care: systematic review and meta-analysis. BM] 2003;
326.1014
77 Malhi GS, Bassett D, Boyce P, Bryant R et al. Royal
Australian and New Zealand College of Psychiatrists
clinical practice guidelines for mood disorders. Australian
& New Zealand Journal of Psychiatry. 2015, 49:1087-
1206.
78. Mathers, C Fat, D. M, Boerma, J. T., & World Health
Organization. The global burden of disease: 2004 update.
Geneva, Switzerland: World Health Organization
79. Mathew et al. 2012. Ketamine for Treatment-Resistant
Unipolar Depression. CNS Drugs. 2012 March 1 26(3)
189-204.
80. Mcclintock SM, Tirmizi 0, Chansard M et al. 2011
A systematic review ot the neurocognitive effects of
magnetic seizure therapy. Int Rev Psychiatry.2011,23413-
423
81. McIntyre RS, Socrynska JK, Cha DS, et al. The prevalence
and illness characteristics of DSM-S-defined "nixed
feature specifier"in adults with major depressive disorder
and bipolar disorder. results from the International Mood
Disorders Collaborative Project. ] Affect Disord. 2014
172C 2539-264.
82. Mile RV, Giacobbe P, Kennedy SH, Blumberger DM,
Daskalakis Z et al, 2016. Canadian Network for Mood and
 Compendium of
CPM
--- Philippine Medicine
Anxiety Treatments (CANMAT) 2016 clinical guidelines
for the management of adults with major depressive
disorder: neurostimulation treatments. Can
Psychiatry.
2016 1-15 DOE 10.1177/0706743716660033
83. Moller HJ, Baldwin DS, Goodwin G, Kasper S, Okasha
A, Stein DJ et al. WPA Section on Pharmacopsychiatry:
consensus statement. Eur Arch Psychiatry Clin Neurosci.
2008. DO1 10.1007,/ s00-406-008-3002-1
84 Montgomery SA and Asberg M. A new depression scale
designed to be sensitive to change. The British Journal of
Psychiatry. 1979 134382-389.
85. National Statistics Office. 2000. Census of population and
housing. Manila.
86. National Institute for Health and Care Excellence.
Depression in adults: the treatment and management of
depression in adults. NICE Guideline [CG90]. 2009.
$7 Nelson JC and Papakostas GI Atypical Antipsychotic
Augmentation in Major Depressive Disorder. A Meta-
Analvsis of Placebo-Controlled Randomized Trials. Am
J Psychiatry. 2009, 166-980-991.
88. Nereroff CB, Mayberg HS, Krahl SE, McNamara J Frazer
A et al. VNS therapy in treatment-resistant depression:
Clinical evidence and putative neurobiological mecha-
nisms. Neuropsychopharmacology. 2006; 3E 1345-1355
89 Newman ME, Agid O, Gur E & Lerer B. 2000.
Pharmacological mechanisms of T3 augmentation
of antidepressant action. International Journal of
Neuropsychopharmacology 3187--191.
90 Nierenberg AA, Fava M, Trivedi MH, Wisniewski
SR. Thase ME et al. A comparison of lithium and T(3)
augmentation following two failed medication treatments
for depression: a STAR'D report. Am ] Psychiatry, 2006,
1631519.1530
91. Nitsche MA, Paulus W. 2000. Excitability changes induced
in the human motor cortex by weak transcrarial direct
current stimulation. J Physiol, 2000, 527633-639. [Pub.Med:
10990547]
92 Panzer ME: Are SSRls really more effective for anxious
depression? Ann CLin Psychiatry. 2005, 17.23-29
93 Parikh SV, Segal ZV, Grigoriadis S, Ravindran AV,
Kennedv SH et al. Canadian Network for Mood and
Anxiety Treatment (CANMAT) 2009 clinical guidelines
for the management of adults with major depressive
disorder. psychotherapy alone or in combination with
antidepressant treatment. J Affect Disord, 2009. DOE
10.1016/j jad.2009.06.042
94 Parikh SV, Quilty LC, Ravitz P, Rosenbluth M, Pavlova
B, Grigoriadis Set al. Canadian Network for Mood and
Anxiety Treatment (CANMAT2016 clinical guidelines for
the management of adults with major depressive disorder.
psychological treatments. Can J Psychiatry. 2016. DOE
10.1177/0706743716659418
95. Patten SB, Kennedy SH Lam RW,et al. Canadian Network
for Mood and Anxiety Treatment (CANMAT) clinical
guidelines for the management of major depressive
disorder in adults: I. Classification, burden and principles
of management. J Affect Disord. 2009 117 (Suppl 1:S5-
514.
96. Pavkel ES, Scott J, Teasdale JD, Johnson AL, Garland A,
Moore R, Jenaway A, Cornwall PL, Hayhurst H, Abbott
R.Pope M. Prevention of relapse in residual depression by
cognitive therapy. A controlled trial. Arch Gen Psychiatry.
199.56 829-835
97. Perugi G, Angst I, Azorin JM, et al. Mixed features in
patients with a major depressive episode the BRIDGE-
II-MIX study.I Clin Psychiatry. 2015 76.e351-e358.
98. Petrides G, Tobias KG, Kellner CH, et al. Continuation
and maintenance electroconvulsive therapy for mood
disorders: review of the literature. Neuropsvchobiology.
2011, 64: 129-140.
99. Ping N, Lim C, Dela Pena L, Tamolang S. Romano
M, Patriarca A, Mejia E, et. al. MIMS Drug Reference
Concise Prescribing Information. 2016; 147 ed.
100. Posner K, Brown GK, Stanley B et al. The Columbia-
Suicide Severity Rating Scale: initial validity and internal
consistency findings from three multisite studies with
adolescents and adults. Am[Psychiatry.20l1,1681266-127,
I0L. Prudic J, Olfson M, Marcus SC, Fuller RB &Sackeim HA.
Effectiveness of electroconvulsive therapy in community
-----�
Major Depressive Disorder
settings. Biological Psychiatry. 2004; 55.301-312
102. Ravindran AV, Balneaves LG, Faulkner G, Ortiz A,
-
McIntosh D et al. Canadian Network for Mood and
Anxiety Treatments (CANMAT) 2016 Clinical Guidelines
for the Management of Adults with Major Depressive
Disorder: Complementary and Alternative Medicine
Treatments. Can J Psychiatry. 2016,1-12 DOE 10,1177/07
06743716660290
103. Rizvi 5], Donovan M, Giacobbe P, et al. Neurostimulation
therapies for treatment resistant depression: A focus on
vagus nerve stimulation and deep brain stimulation.
International Review of Psychiatry. 2011, 23. 424-436
104. Robinson RG, Starkstein SE: Current research in affective
disorders following stroke. J Neuropsychiatry Clin
Neurosei 1902-14
105. Sackeim HA, Haskett RF, Mulsant BIL, Thase ME,Mann
JJ et al. 2001. Continuation pharmacotherapy in the
prevention of relapse following electroconvulsive therapy:
a randomized controlled trial. JAMA. 2001,285-12991307
[PubMed: 11255384]
106. Sadock, B. J., Sadock, V A., & Ruiz, P 2015. Kaplan &
Sadock's synopsis of psychiatry: Behavioral sciences
clinical psychiatry (l edition.) 2015. Philadelphia
Wolters Kluwer
107. Seo HJ, Jung YE, Kim TS, et al. Distinctive clinical
characteristics and suicidal tendencies of patients with
anxious depression. J Nervy Ment Dis. 2011, 19942-48
108. Stagg8 CJ, Best JG, Stephenson MC, O'Shea J, Wylezinska
M et al. 200. Polarity -sensitive modulation of cortical
neurotransmitters by transcranial stimulation. J Neuro-
sci, 2009 Apr 22 29016)-52025206. [Pub Med. 19386916]
109. Suga wara H, Sakamoto K, Harada T et al. Predictors of
efficacy in lithium augmentation for treatment-resistant
depression. Journal of Affective Disord. 2010, 125: 165--168
110. Teasdale JD, Segal ZV, Williams JM, Ridgeway VA,
Soulsby JM, La MA: Prevention of relapse/recurrence in
major depression by mindfulness-based cognitive therapy
J Consult Clin Psychol 2000, 68615-623
111. Valenstein M, Taylor KK, Austin K, Kales HC, McCarthy IF
et al. 2004. Benzodiazepine use among depressed patients
treated in mental health settings. Am JI'sychiatry. 2004
161654-661
12. van Getfen EC, Gardarsdottir H, van Hulten RR, van Dijk
L, Egberts AC, Heerdink ER. Initiation of antidepressant
therapy: do patients follow the GP's prescription?. British
Journal of General Practice 2009, 59.81-7
113. Vollenweider F, Leenders KL, Scharfetter C, Antonini A,
Maguire P et al. Metabolic hyperfrontality and psychopa-
thology in the ketamine model of psychosis using positron
emission tomography (PET and [I8F] fluorodeoxyglucose
(FDG). European Neuropsychopharmacology. 1997 79-
24
114. Warden S, Spiwak R, Sareen Jet al. The SAD PERSONS
scale for suicide risk assessment. a systematic review. Arch
Suicide Res. 2014; 18.313-326
115. Watanabe N, Omori IM, Nakagawa A Cipriani A, Barbu
C, Churchill R, et al.2011. Mirtazapine versus other
antidepressive agents for depression. Cochrane Database
Syst Rev 12.CD006528.
116. World Health Organization. 2016. Depression (fact sheet).
http:/ /www.who.int/mediacentre /factsheets/'fs369/en/
11 World Health Organization. International Statistical
Classification of Diseases and Related Health Problems
Instruction Manual. 2010; vol. 2. 10 revision
1I8. World Health Organization. 2006. WHO- AIMS Report
onMental Health System in The Philippines. WHO and
Department of 1 Health, Manila, the Philippines. WHOPress
119. World Health Organization. 2016. Traditional Medicine
Definitions. Retrieved from: http://www.who.int/
medicines/areas/traditional/definitions/en/
120. Zhou X, Ravindran AV, Qin B, Del GiovaneC, Li Q et al
Comparative efficacy, acceptability, and tolerability of
augmentation agents in treatment-resistant depression:
systematic review and network meta-analysis. Journal of
Clinical Psychiatry. 2015;76e487-9%8
121. Zohar ], Nutt DJ, Kupfer DJ,Moller H et al. A proposal for
an updated neuropsychopharmacological nomenclature.
European Neuropsychopharmacology.2013 http://
du.doi.org/10.1016/j.euroneur0,2013.08.004
157

Major Depressive Disorder
APPENDIX A -----·---
Criteria for Level of Evidence and Line of Treat-
ment (CANMAT 2016)
Table A.I. Criteria for Level of Evidence and Line of
Treatment (Lam et al.,., 2016)
Criteria
Level of Evidence
I
I Meta-an.ilysis with narrow confidence
intervals and/or 2 or more RCTs with
adequate sample size, preferably placebo
controlled
2 Depressive Disorder
Meta-analysis with wide confidence
intervals and/or I or more RCTs with
adequate sample size
3 Small-sample RCTs or nonrandomized,
controlled prospective studies or case se-
4
ries or high-quality retrospective studies
Expert opinion/consensus
Line of Treatment
First line Level I or Level 2 Evidence, plus clinical
support"
Second Line Level 3 Evidence or higher, plus clinical
ma
support
Level 4 Evidence or higher, plus clinical
support , APPENDIX C
RCT, randomized clinical trial.
Nate that Level 1 an 2idenee refer specifically to treatment
studies in which randomized comparisons are available. Recom-
mendations involving epidemiological or risk factors primarilv
arise trom observational studies, and hence the highest level of
evidence is usually Level 3. Higher order recommendations (e.g.
principles of care) reflect higher level judgment of the strength of
evidence from various data sources and therefore are primarily
Level4 Evidence
Clinical support refers to application of expert opinion of the
Canadian Network for Mood and Anxiety Treatment committees
to ensure that evidence-supported interventions are feasible and
relevant to clinical practice. Therefore, treatments with higher
levels of evidence may be downgraded to lower lines of treatment
due to clinical issues such as side effect or safety profile
Levels of Evidence for Intervention Studies
(RANZCP, 2015)
Table B.2. Levels of Evidence for Intervention Studies
(Malhi et al., 2015)
Level Design
- count or observation).
I A systematic review of level II studies
IT A randomized controlled trial (RCT)
III A pseudo-randomized controlled trial (i.e.
alternate allocation or some other method)
A com rative study with concurrent controls
Non-randomized, ex rimental trial - • Psvchomotor agitation or retardation nearly every
Cohort studv
Case-control studv
Interrupted time series with a control group
A comparative study without concurrent con-
trols:
Historical control study
Two or more single arm studies
Interrupted time series without a parallel con-
trol group
IV A case series with either post-test or pre-test/
post-test outcomes
-
coo· CpM
philippine Medicine
APPENDIX B
a.
i Oi,,rupllvt, Mood Dy sregulation
ore
h Persistent Depressive Disorder
'
Depression due to General
e
i
l\VL_oo.
] __··-""- =•=Ucp"--_"_"_
Disorder
Unspecified Depressive Disorder
Figure B.1. DSM-5 Classification of Depressive Disorders
(APA, 2013)
Table C.1. DSM-5 Diagnostic Criteria tor MDD
DSM-5Di+nostic Criteria for MDD
A. Five (or more) of the following symptoms have
been present during the same 2-week period and
represent a change from previous functioning: at
least one of the symptoms is either (I) depressed
mood or (2) loss of interest or pleasure
Note: Do not include symptoms that are clearly
attributable to another medical condition.
1. Depressed mood most of the day, nearly every
day, as indicated by either subjective report (e.g.
feels sad, empty, hopeless) or observation made
by others(e.g appears tearful). (Note: In children
and adolescents, can be irritable mood.)
2. Markedly diminished interest or pleasure in all,
or almost all, activities most of the day, nearly
every day (as indicated by either subjective ac-
3. Significant weight loss when not dieting or
weight gain (e.g., a change of more than 5% of
body weight in a month), or decrease or increase
in appetite nearly every day. (Note: In children,
consider failure to make expected weight gain.)
4. Insomnia or hypersomnia nearly every day.
day (observable by others, not merely subjective
feelings of restlessness or being slowed down)
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive or inap-
propriate guilt (which may be delusional) nearly
every day (not merely self-reproach or guilt about
being sick).
8. Diminished ability to think or concentrate, or
indecisiveness, nearly every day (either by subjec-
tive account or as observed by others).
9. Recurrent thoughts of death (not just fear of dy-
ing), recurrent suicidal ideation without a specific
 Compendium of
Philippine Medicine
Lan, or a suicide attempt or a specific plan for
, committing suicide.
B The symptoms cause clinically significant distress
or impairment in social, occupational, or other
important areas of functioning-
C. The episode is not attributable to the physiological
effects of a substance or to another medical condi-
on
Note: Criteria A-C represent a major depressive
episode.
Note. Responses to a significant loss (e.g., bereave-
ment, financial ruin, losses from a natural disaster,
a serious medical illness or disability) may include
the feelings of intense sadness, rumination about
the loss, insomnia, poor appetite, and weight loss
noted in Criterion A, which may resemble a depres-
sive episode. Although such symptoms may be
understandable or considered appropriate to the
loss, the presence of a major depressive episode in
addition to the normal response to a significant loss
should also be carefully considered. This decision
inevitably requires the exercise of clinical judgment
based on the individual's history and the cultural
norms for the expression of distress in the context
of loss.
D The occurrence of the major depressive episode is
not better explained by schizoaffective disorder,
schizophrenia, schizophreniform disorder, delu-
sional disorder, or other specified and unspecified
schizophrenia spectrum and other psychotic dis-
orders.
F There has never been a manic episode or a hypo-
manic episode.
Note This exclusion does not apply if all of the
manic-like or hypomanic-like episodes are sub-
stance--induced or are attributable to the physiologi-
cal effects of another medical condition
APPENDIX 0
DSM-5 Specifiers of Depressive Disorders (APA,
2013
The different clinical features included in the specifiers
are the following: with arxious distress, with mixed
features, with melancholic features, with atypical
features, with psychotic features, with catatonia, with
peripartum onset, and with seasonal pattern.
Forty-six percent of individuals with depression presents
with features of anxiety (Fava et al., 2004). In DSM- S,
aoous distress is considered when at least two of the
following symptoms are met: feeling keyed up or tense,
feeling unusually restless, difficulty concentrating
because of worry, fear that something awful may happen,
or feeling that the individual might lose control of himself
or herself. The severity is rated based on the number of
symptoms that are present in the patient. It is considered
mild if with two symptoms, moderate if with three, and
moderate-severe if with four to five symptoms. laving
four to five symptoms in the presence of motor agitation
qualifies as a severe type. The assessment of anxious
distress and its severity is important because high anxiety
is associated with higher suicide risk, non-response to
treatment, and longer duration of illness (Seo et al., 2011)
and hence, must be considered in treatment planning
Major Depressive Disorder
and monitoring.
One third of patients with MDD have mixed features
(Mcintyre et al., 2014; Perugi et al., 2015). The specifier
on mixed feature allows for the diagnosis of MDD
in a clinically depressed individual presenting with
symptoms of mania or hypomaria. At least three of the
following manic or hypomanic symptoms should be
present nearly every day during the majority of the days
of major depressive episode: elevated or expansive mood,
inflated self-esteem or grandiosity, being more talkative
than usual or having pressure to keep on talking, flight
of ideas or racing of thoughts, increased energy or goal-
directed activity, increased involvement in activities with
high potential for harmful results, or decreased need
for sleep. There must be a change in the person's usual
behavior that is observable to others. Individuals that
meet the full criteria of mania and hypomania should
be diagnosed either as bipolar I or bipolar II disorder.
The effect of substances, medication or any treatment
should also be ruled out. This specifier must be noted in
treatment planning and monitoring. A study of Azorin
(2012) showed that it is more common in younger
patients, with more severe presentation and higher
suicide risk. However, this specifier on mixed feature
remains to be controversial (Goldberg, 2015)
The diagnosis of melancholic features (APA, 2013)
requires that one of the following is present during the
most severe period of the current episode: loss ot pleasure
in all, almost all activities or lack of reactivity to usually
pleasurable stimuli. Furthermore, three or more of the
following should be seen in the individual; a distinct
quality of mood characterized by profound despondency
despair, moroseness or empty mood, depression that is
worse in the morning, early morning awakening (at least 2
hours before the usual awakening), marked psychomotor
agitation or retardation, significant anorexia or weight
loss, and an excessive or inappropriate guilt.
The melancholic feature specifier is applied in the most
severe stage of the episode, where there is near- complete
absence of the capacity for pleasure, Even highly desired
event does not bring about marked uplifting of the mood.
The depressed mood is distinctly different from a non-
melancholic episode. Moreover, psychomotor agitation
or retardation is present most of the time. There is a small
tendency to repeat in succeeding episodes.
The atypical feature specifier (APA, 2013) is applied
when mood reactivity predominates during the majority
of the days in a current episode of major depression
Mood reactivity may include brightening of the mood
in response to an event. It can be euthymic (normal
non-depressed mood) over extended periods, leading
to increase in food intake and weight gain, This
specifier also includes two or more of the following
symptoms: significant weight gain or increase in
appetite, hypersomnia, leaden paralysis, and a long
standing pattern of interpersonal sensitivity resulting to
a significant socio-occupational impairment. The criteria
for melanchohc features and catatonia should not be met
within the same episode
The specifier on psychotic features (APA, 2013) is
included when delusions or hallucinations are present.
Contents of delusions and hallucinations related to the
depressive themes are considered to be with mood-
159

I
Major Depressive Disorder
congruent. Meanwhile, the presence of delusions or
hallucinations that are not consistent with depressive
themes of inadequacy, guilt, disease, death, and nihilism
are considered to be with mood-incongruent psychotic
features. This feature specifier is also used if there is a
combination of mood-congruent and mood-incongruent
features in the same episode. The diagnosis of psychotic
features has important implication in the management
of depression.
Catatonia (APA, 2013) can occur in several disorders
including major depressive disorders. The psychomotor
features that may happen in a major depressive
episode are stupor, catalepsy, waxy flexibility, mutism,
negativism, posturing, mannerisms, stereotypy,
agitation, grimacing, echolalia, and echopraxia. The
specifier on catatoma is present if there are three out of
the twelve psychomotor features noted
The specifier on peripartum onset (APA, 2013) may
be applied if the start of mood changes occurs during
pregnancy and until four weeks after the delivery. Three
to 6%of women experience the onset of major depressive
disorder during pregnancy and after the delivery. Fifty
percent of the cases actually begin prior to delivery.
The episodes of peripartum depression have more
pronounced anxiety and even panic attacks. The risk
of postpartum episode is higher in women with mood
and anxiety symptoms and to those experiencing baby
blues. Psychotic features can happen in an MDE with
peripartum onset. This occurs in 1 in 500 to 1 in 1,000
deliveries, which occurs more on women bearing a child
for the first time. The risk of postpartum episode with
psychotic feature is higher in women with postpartum
mood episode, with history of depressive or bipolar
disorders and those with family history of bipolar
disorders. The risk of recurrence in succeeding deliveries
is as high as 30-50%. Infanticide or killing of the infant
may happen in a postpartum psychotic episode due to
command hallucinations and delusions that their infant
is possessed.
The seasonal pattern specifier (APA, 2013) applies
to recurrent major depressive episodes, where there
is an established temporal relationship between the
onset ot depression and the remission that occur in a
particular time of the year. This excludes situations that
may be explained by seasonally linked psychosocial
stressors. This may be established if two episodes of
major depression have occurred in the last two years
Throughout the patient's lifetime, the number of seasonal
major depressive episode outnumbers the non-seasonal
episodes. Hypersomnia, overeating, weight gain,
cravings for carbohydrates, and prominent energy occurs
in episodes with seasonal pattern. There are currently no
studies on the presence of seasonal pattern of depression
in the country.
Partial remission is established if the symptoms of the
major depressive episode are present but could no longer
fulfill the criteria or if the patient has no significant
symptoms for less than two months after an episode. If
the patient remains asymptomatic after two months, the
patient is considered to be in full remission
Symptom severity is also incorporated in the specifiers
A case is considered mild if only few symptoms are
present in excess of those required by the criteria. The
'
Compendium of
Philippine Medicine CPM
---
symptoms are distressing but manageable with minor
impairment only in socio-occupational functioning.
Meanwhile, the number of symptoms in severe cases
is substantially in excess of what is required to make a
diagnosis. Depressive symptoms are unmanageable and
distressing and there is marked effect on the patient's
socio-occupational functioning. Cases wherein the
number of symptoms, distress and impairment of socio-
occupational functioning fall between mild and severe
are considered moderate
APPENDIX E
Manic Episode
Bipolar Affective Disorder
Mood (Affective)
Disorders
'' Persistent Mood (Affective)
'
a..es
l/
\
Disorder
D1son:i<'I"
Figure E.1. CD-1 Classification of Mood Disorders
APPENDIX F
Table F.1. CD-10 Depressive Episode
F32 Depressive episode
In typical mild, moderate, or severe depressive
episodes, the patient suffers from lowering of
mood, reduction of energy, and decrease in activity.
Capacity for enjoyment, interest, and concentration is
reduced, and marked tiredness after even minimum
effort is common. Sleep is usually disturbed and
appetite diminished. Self-esteem and self-confidence
are almost always reduced and, even in the mild
form, some ideas ot guilt or worthlessness are often
present. The lowered mood varies little from day
to day, is unresponsive to circumstances and may
be accompanied by so-called "somatic" symptoms,
such as loss of interest and pleasurable feelings,
waking in the morning several hours before the
usual time, depression worst in the morning, marked
psychomotor retardation, agitation, loss of appetite,
weight loss, and loss of libido. Depending upon the
number and severity of the symptoms, a depressive
episode may be specified as mild, moderate or severe
Incl.:
single episodes of
• depressive reaction
1 •psychogenic depression
• reactive depression
 Compendium of

�--=�-:--- -
Philippine Medicine Major Depressive Disorder

APPENDIX G
Excl.:

-
adjustment disorder (F43.2)
recurrent depressive disorder (F33.-) Mild
when associated with conduct disorders in
(92.0)
Moderate
F32.0
Mild depressive episode Severe Depressive Episode
Two or three of the above symptoms are usually without Psychotic Symptoms
present. The patient is usually distressed by these
but will probably be able to continue with most Severe Depressive Episode
with Psychotic Symptoms
activities.
F321
Moderate depressive episode
Four or more of the above symptoms are usually'
\l Other Dcprcs>1ve Ep,sode
J
present and the patient is likely to have great difficulty
in continuing with ordinary activities.
l Depressive Episode,

Figure G.1. ICD-IO Depressive Episode

Unspecified I
F322
Severe depressive episode without psychoti c
symptoms
An episode of depression in which several of the above
APPENDIX H
symptoms are marked and distressing typically loss
of self-esteem and ideas of worthlessness or guilt
Suicidal thoughts and acts are common and a number
of somatic"symptoms are usually present.
j Recurttnt Depressive Disorder,
Current Episode Mild
�
Agitated depression single episode without
I Recurrent Depressive Disorder,
Major depression
Vital depression
psychotic symptoms

,
I Current Episode Moderate

geeurrent Depressive Disorder,

F323 Current Episode Severe Without
Severe depressive episode with psychotic symptoms I Psychotic Symptoms
I
An episode of depression as described in F32.2
but with the presence of hallucinations, delusions
psychomotor retardation, or stupor so severe tha t
'

ordinarv social activities are impossible; there mav be

'
Recurrent Depressive l
Recurrent �pre,;sive D,;,order,
Current Episode Severe With
Psychotic Symptoms
l
to
danger life from suicide, dehydration, or starvation Disorder �
The hallucinations and delusions may or may not be \\ Recurrent Depressive Disorder,
Currently in Remission
mood-congruent )
Single episodes of:
major depression with psychotic symptoms
psychogenic depressive psychosis ' Other Recurrent Deprc;&ve
Disorder
)

psychotic depression
reactive depressive psychosis
F32.8
Other depressive episodes
Atypical depression
I
[·cl pecitied

Figure H.1. ICD-I0 Classification of Recurrent Depressive

Single episodes of masked" depression NOS Disorder
F32.9
Depressive episode, unspecified
Depression NOS
Depressive disorder NOS
Adapted from 1CD-10

161
 CPM
-
Phi!ComperdumicdeM of
Major Depressive Disorder I0pine ine s..

APPENDIX I APPENDIX K
Table I.1. Suggested Rating Scales Table K.1. Ancillary /Diagnostic Examinations
/ I Clinicbn---.-,-,.-.- 1-•-,-,;- -,- Rated Ancilla, /Dia gnostic Examinations
Symptoms Hamilton Depression Patient Health Complete blood count
Rating Scale (HAM-D) Questionnaire Urea, electrolytes and liver function tests
Montgomery-Asberg (PHQ-9), Electrocardiogram
Rating Scale (MADRS) including the Thvroid function tests and autothyroid antibodies
Inventory of Depressive Filipino
Inflammatory markers and microbial serology
Symptomatology (IDS) version
Vitamin levels
Clinically Useful
Depression Sexually transmitted disease testing
Outcome Pregnancy testing (beta-HCG)
]Sale(CUDOS) Urine and blood drug screen
-------
Functioning WHO Disability Assess- [Sheehan Adapted from RANZCP 2015 (Malhi et al, 2015)
ment Scale Disability
(WHO-DAS) Scale (SDS)
Social and Occupational
Functioning and APPENDIX L
Assessment Scale
(SOFAS) Table L.1. Recommendations for Psychological
Treatments for Acute and Maintenance Treatment of
Side UKU Side Effect Rating Frequency, Major Depressive Disorder (Parikh et al, 2016) (From
Effects Scale Intensity and CANMAT 2016)
Burden of

l
Side Effects Maintenance
Acute Phase
Rating Scale Phase
(1BSER) First-line •Cognitive lk-havioral •Cogmt1vc
Quality of Quality of Life Interview Psycho- Therapy (CBT) [level 1] Behavioral
Life (00LI) therapy Interpersonal Therapy (CBTy
Adapted from CANMAT 2016 (Lam et al, 2016) Choice Therapy (PT) [level 1]
--
±ace.le'
Second-
lh.Em-
·Bibliotherapy [level 1] ·Interpersonal
line ·Behavioral Activation Therapy (PT)
APPENDIX J Psycho- [level2] [level 2]
therapy Computer-Assisted • Behavioral
Table J.1. Physical Examination Choice CBT [level2] Activation
• Telephone-delivered [level 2]
Endocnne disorders
Oinical features obseTYed that
may be seen in goiter, hyper-
thyroidism, hypothyroidism
I CBI and IPT
·Cognitive Behavioral
·Cognitive
Behavioral
andCushing's syndrome Analysis System of Analysis System
Psychotherapy of Psycho-
Respiratory disorders Signs and symptoms of sleep
[level 2] therapy
apnea/snoring, restless leg
syndrome, COPD features, [level 2]
wheeze/lung malignaney Third-line Psychodynamic None with
Neurological disorders Signs and symptoms of parkin- Psycho- Therapy [level2] evidence

I
sonism, motor or sensory defi- therapy • Emotion-focmcd
cits,cerebrovascular disease Choice Therapy (level 21

Organ insufficiency
features/stroke, motor tics
Jaundice, arteriovenous fis-
tula for dialysis, dyspnea
I
·Acceptance and
Commitment Therapy
[level 3]
Motivational Inter-
and peripheral edema may
be resent viewing [level4] ]
Adapted from RANZCP 2015 (Malhi et al, 2015 Adapted from CANMAT 2016

162
 Compendium of
cPM
-- Philippine Medicine Major Depressive Disorder

APPENDIX M APPENDIX 0

Table M.1. Factors to consider in choosing between Administration of ECT

switching to another antidepressant monotherapy or
adding an adjunctive medication (Level 3 Evidence)
(Kennedy et al., 2016) (From CANMAT 2016)
nsider switching to another antidepressant when
It is the first antidepressant trial
There are poorly tolerated side effects to the initial
antidepressant
There is no response (25% improvement) to the
initial antidepressant
There is more time to wait for a response (less se-
vere, less functional impairment)
Patient prefers to switch to another antidepres-
sant
Consider an adjunctive medication when:
• There have been 2 or more antidepressant trials
• The initial antidepressant is well tolerated
·There is partial response (>25% improvement) to
the initial antidepressant
·There are specific residual symptoms or side effects
to the initial antidepressant that can be targeted
There is less time to wait for a response (more se-
vere, more functional impairment)
Patient prefers to add on another medication
After careful consideration of the risks and benefits,
the decision to proceed with ECT should follow a
full disclosure discussion with the patient and/or the
relatives. ECT is administered in a controlled clinical
setting. The patient is placed under general anesthesia
Delivery of electrical current to the brain is accomplished
through electrodes. Electrode placement may be right
unilateral, bitemporal, or bifrontal (Lisanby, 2007)
Stimulus applied should transcend the seizure threshold
to achieve an effective seizure, Bilateral treatments
use stimulus 1.5-2 times the seizure threshold while
unilateral placement required 6-8 times the threshold
(Malhi et al, 2015). A systematic review of the different
electrode placements yielded equivocal results in terms
of efficacy but different profiles in affecting the memory
domain (Dunne et al, 2012). An adequate generalized
seizure should last for at least 20 seconds. Re-stimulation
at higher intensities should immediately be done until
an effective seizure is achieved. CT is administered
2-3times per week totaling 6-15 sessions. Twice weekly
ECT is as efficacious as more frequent administration
and is associated with less memory impairment
(Charlson et al, 2012). Thrice weekly ECT is indicated

--
E For the initial antidepressant trial. In subsequent tri- if a more immediate response is warranted (Lerer et al,
als, lack of response (25% improvement) may not be 1995). Continued treatment sessions are essential until
a factor for choosing between switch and adjunctive symptom remission or if improvement plateaued as its
premature discontinuation may lead to higher relapse
�a leg"-'�-'
, -. _
-) rates and poorer overall prognosis (Prudi et al, 2004)
Risk Factors to consider longer term (2 years or longer
maintenance treatment with antidepressant (level 3
APPENDIX P

-
and 4 evidence) (Kennedy et al., 2016) (From CA.NMAT
E- 2016)
Frequent, recurrent episodes
Other Neuromodulation Therapies
Severe episodes (psychosis, severe impairment, Trantscranial Direct Current Stimulation (tDCS)
suicidality)
Chronic episodes tDCSis a non-invasive neuromodulation therapy which
Presence of comorbid psychiatric or other medical utilizes weak electrical currents to effect changes in
conditions brain activity (Malhi et al., 2015). With the use of scalp
Presence of residual symptoms electrodes, a constant flow of currents is delivered to
Difficult-to-treat episodes specific regions of the cerebral cortex (Brunoni et al.,
2012). Stimulus polarity determines the subthreshold
modulation of resting membrane potential (Nitsche et al.,

-=
2009). Following the principles of basic neurophysiology,
APPENDIX N anodal stimulation results in cortical excitability through
neuronal depolarization while cathodal stimulation
Signs and Symptoms of Lithium Toxicity (Hung. 2014) causes the opposite (Nitsche et al., 2000). Further
=) • Diarrhea research also showed that tDCS may effect changes
in neurotransmitters as well. Excitatory effects are
• Dizziness
mediated by reduction in GABAergie inhibition and
Nausea NMDA-related processes whereas inhibitory effects

±= • Stomach pains
• Vomiting
follow the reduction in glutamatergic activity (Stagg et
al., 2009). Being such, tDCS may be beneficial to address

±- Weakness the depressive state associated with hypoactivity of the

• ·Coma (decreased level of consciousness, lack of re- left dorsolateral prefrontal cortex (DLPFC (Brunoni et al.,

-
sponsiveness) 2015). Studies conducted on its efficacy so far have mixed
rn
results owing possibly to the differences in procedures

-
• Hand tremors
and patient population.
• Lack of coordination of arms and legs
• Muscle twitches Repetitive Transcranial Magnetic Stimulation (rTMS)
Seizures
,s:-a • Slurred speech
• Uncontrollable eye movement
eT\MS is a non-invasive, non-convulsive therapeutic
brain stimulation technique. This method employs

163
Major Depressive Disorder
the basic principle of electromagnetism wherein a
pulsed magnetic field induces an electrical current in a
conductive substance (Carpenter et al,, 2011). Pulsating
magnetic fields are delivered to brain with the use of
TMS device and an inductor coil placed on the scalp
(Malhi et al., 2015). Then, electrical currents that are
induced will alter brain activity depending on the region
stimulated and stimulus parameters (George, 2010). It
was suggested that stimulation would be beneficial to
address the neuroimaging findings of patients suffering
from depression (George, 1998). All in all, TMS is a
safe and well-tolerated procedure with no cognitive
impairment. It does not require anesthesia and can be
done on an outpatient basis.
Deep Brain Stimulation (DBS)
DBS is an invasive neurosurgical procedure initially
developed for neurological conditions. Guided by MRI
specific brain regions are implanted with electrodes that
deliver continuous stimulation from a pulse generator.
Stimulation parameters mav be accessed or programmed
remotely (Hoy and Fitzgerald, 2010). Recently there has
been an influx of research focused on the application
of DBS to psychiatric disorders. Target brain structures
relevant to depression are being explored including the
subgenual cingulate cortex, nucleus accumbens, and
the ventral caudate or ventral striatum (Glacobbe et
al., 2009). The therapeutic mechanism of DBS is related
to alterations in neuronal activity and firing pattern
produced by continuous stimulation (Johnson et al.,
2008).
Magnetic Seizure Therapy (MST)
MST is an alternative non-invasive convulsive therapy.
Under general anesthesia, a transcranial stimulation
device delivers stimulation through a coil in direct
contact with the skull (Milev et al., 2016). Magnetic
fields induce electrical currents, which in turn causes
neuronal depolarization and subsequent seizures in the
superficial regions of the cortex (Carpenter et al., 20I1).
Specific regions and circuits in the brain associated with
the pathogenesis of depression are targeted (Allan and
Fbmeier, 2011). This will produce a more focal seizure,
sparing the deeper brain structures, resulting in lesser
cognitive adverse effects (Hoy et al., 2010). MST ie
conceptualized to be a hybrid combining the proven
efficacy of FCT and the safety profile of TMS (McClintock
et al., 2011)
Vagus Nerve Stimulation (VNS)
VNS is a minimally invasive procedure initially
approved for the treatment of refractory epilepsy. Due
to clinical observations of mood improvement in study
patients, VNS was evaluated and later on approved
for treatment of resistant depression (Nemeroff et al.,
2006). VNS entails the implantation of two electrodes
wrapped around the left vagus nerve through an
incision in the neck, connected to a pulse generator in
the left chest wall. Stimulus parameters are controlled
remotely by the use of a software device (Gelziniene
and Seeck, 2005). The antidepressant effects of VNS are
theorized to be attributed to alterations in neurotrophie
and neurotransmitter function in specific brain areas
implicated in mood regulation (Rizvi et al., 2011).
APPENDIX
Ketamine
Clinical investigations attributed the antidepressant ef-
fect of ketamine to various mechanisms. These include
o-amino--hydroxy-methyl-4-isoxazolepropionic acid
(AMPA) receptor activation (Koike et al., 2011), increased
hipporampal brain-derived neurotrophic factor (BDNF),
increased tropomyosin receptor kinase B(TrkB) phospho-
rylation (Autry et al., 2011) and activation of the mam-
malian target of rapamycin (mTOR) pathway (Li et al,
2010). Imaging studies further support ketamine's effect
on the brain as evidenced by increased metabolic activ-
ity in the frontomedial and anterior cingulate cortex in
positron emission tomography(PET)scan (Vollenweider
et al., 1997) and decreased limbic responses to emotional
stimuli in functional magnetic resonance imaging (Abel
et al., 2003).

APPENDIX R
Table R.1. Complementary and Alternative Treatments
Therapy/Agent Indication Recommendation
Physical/Meditative
Mild to Moderate MDD line (Level I evidence)
Exercise
Moderate to SevereMDD 2'line (Level 1 evidence)
Yoga Mild to Moderate MDD 2'line (Level 2 evidence)
Acupuncture Mild toModerate MDD 3Le (Level 2 evidence)
Natural Health Products
Mild toModerate MDD 1line(Level 1 evidence)
St. John's wort
Moderate to Severe MDD 2line (Level 2 evidence)
Mild to Moderate MDD 2°'line (Level 1 evidence)
Omega-3 fatty acids
Moderate to Severe MDD 2'line (Level 2 evidence)
Mild to ModerateMDD 2'Line (Level l evidence)
S-adenosy!-methionine (SAMe
I Moderate to Severe MD[ 2"line (Level 2 evidence) I
Adapted from Ravindran et al. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical
Guidelines for the Management of Adults with Major Depressive Disorder. Section 5. Complementary and Alternative
Medicine Treatments. The Canadian Journal of Psychiatry 1-12

164
 of
CPM Compencfium
-
Ph-,.�-·� l liLhlthhlff@

STATEMENT OF INTEREST
Major Depressive Disorder

All the members of the Technical Writing Group declare no conflict of interest.

DISCLAIMER

This consensus guideline represents the view of the Technical Writing Group and the Philippine
Psychiatric Associations' steering committee, expert panel members and stakeholders, which was arrived
at after careful consideration and review of the evidence available at the time. Healthcare providers
are recommended to take it fully into account when exercising their clinical judgment. However, these
guidelines do not override the individual responsibility of the healthcare professional to make decisions
deemed appropriate to the circumstances of the individual patient, in consultation with the patient and/
or guardian of the patient, and informed by the summary of product characteristics of any drugs that
they are considering. Treatment and care for the individual patient should take into account individual
needs and preferences. Patients should have the opportunity to make informed decisions concerning their
treatment and management in partnership with the healthcare providers. For all the recommendations,
the group highly recommends that a discussion with the patient and/or with the guardian of the patient
be done regarding the risks and benefits of the interventions, as well as their values and preferences.

ACKNOWLEDGMENT

a The Philippine Psychiatric Association Steering Committee would like to recognize the significant
contribution of the Technical Writing Group - Elaine Angela O. Leynes, MD, FPPA, Anna Marie G
Lantano,MD, FPPA, Reinald Francis. Joseph T. Castaneda, MD, FPPA, Rose Anne C. Roque, MD, Marife
P. Mararang, MD and David Raymund J. Valderrama, MD, and to the Expert Panel Group - Edgardo

E- Juan L. Tolentino Jr.,MD, FPPA (Life), Japhet G. Fernandez De Leon, MD, FPSCAP, FPPA (Life), Jocelyn
Nieva Yatco-Bautista, MD, FPSCAP, FPPA (Life), Constantine D. Della, MD, FPPA (Life), Alma L.
Jimenez, MD, FPP A (Life), and Felicitas A. Soriano, MD, FPPA (Life) - for providing assistance in the
finalization of the development of the guidelines.

--2
-2
The Committee likewise acknowledges the contribution of international consultant Roger S. McIntyre,
MD, FRCPC for his invaluable input in reviewing this guideline. The recommendations hence put forth
do not necessarily reflect the opinion of Dr. McIntyre.

Steering Committee: PPA 2016 Committee on Standards of Care

-
-2 Chair Mariano S. Hembra, MD, FPP A
Members: Lovie Hope Go-Chu, MD, FPP A

---
Eric George V. Cruz,MD, FPPA
-2 Michael P. Sionzon, MD, FPP A
Myra Dee Lopez-Roces, MD, FPPA

--
Our sincere gratitude for the valuable contributions to all those who helped complete the documents.
Without their continued efforts and support, we would have not been able to bring the work to a
successful completion.

--»
The preparation, development, and finalization of these recommendation statements were facilitated
through technical assistance of the following:

-2 Carl Abelardo T. Antonio, MD, MPH

Amiel Nazer C. Bermudez, MD, MPH
Kun L. Cochon, MSPH, RND
College of Public Health University of the Philippines, Manila
--2 165
-3
Major Depressive Disorder
Compendium of
philippine Medicine CPM
--
Index of Drugs Referred to in the Guideline
This index lists the products of interest and/or their therapeutic classifications related to the guideline.
This index is not part of the guideline. For the doctor's convenience, brands available in the PPD references
are listed under each of the classes. For drug information, refer to the PPD references, namely: PPD,
PPD Clinic App, and www.TheFilipinoDoctor.com.

Olandus ODT
Selective Serotonin Olanpresor
Reuptake Inhibitors Olave
Olauzin
Escitalopram OLadin
Escinal Salveo
Escivex Tolan
Fscitalo yprexa
Feliz S
[ovia Quetiapie
Lexapro QWin
Lexdin Qtipine
Neito Quetadin
Rhea Escitalopram Serota
S-Celepra Vietus
Zescita
Zvtapram isperidone
floe tine Aspidon
Drafzin Renuvie
Motivest Residon
Prodin Risdin
Risperdal
Paroxetire Risperdal Consta
et 20 Kisperdal Oral Solution
Kisponz
sertraline ------
Deperin Lithium Antipychotic
Exulten
Serenata Litleiwrm carboarte
Zolodin Litcab
7oloft
CNS Stimulants
Noradrenergie and Specific
Serotonengie Antide- Methlphen±date
press.ant (NASS4) Concerta
Ritalin
Mirtazapie
Menelat 30
Mirazep

Serotonin Modulator and

Simulator (5MS)

Vortioxetie hydrochloride
Brintellix

fewlics; Norepinephrine-
Reuptake Inhibitors

Desvenlafaxime succinate
Pristiq SK
Duloetine
Cymbalta

Atypical Antipsychotics
Aripiprazole
Abdin
Ability
Abilifv Maintena
Ariz0press
Bis0za
Rhea Aripiprazole
Ola zapine
Oland us

166