Mood Disorders

Depressive Disorders

Dr. Ahmad Kamel

M.D., psychiatry
Consultant psychiatry
.Hail psychiatric Hospital K.S.A
– Ass. professor of psychiatry
Faculty of Medicine
AL-AZHAR UNIVERSITY – CAIRO - EGYPT
 Mood:
 Sustained emotional states not merely to external “affective”
expression of transitory emotional state.

 Mood v. Affect
 “Mood”
 a sustained emotional attitude typically garnered through pt
self-report
 “Affect”
 the way a pt’s emotional state is conveyed relates more to
others’ perception of the pt’s emotional state, responsiveness
Mood Disorders
 Mood disorders are disturbances of
emotions that are severe or prolonged
enough to cause impairment of
functioning.
 These conditions are magnifications of our
normal reactions.
 The magnified states in mood disorders are
mania and depression.
 Mania – a period of abnormally high emotion and
activity
 Depression – a period of extreme sadness and
helplessness
Types of Mood Disorders

Mood
Disorders

Major
Dysthymic Bipolar Cyclothymic
Depressive
Disorder Disorder Disorder
Disorder
Mood Disorders versus Mood Episodes

 Mood episodes are distinct periods of time in

which some abnormal mood is present. They
include depression, mania, and hypomania.
 Mood disorders are defined by their patterns of
mood episodes.
 They include major depressive disorder (MDD),
bipolar I disorder, bipolar II disorder, persistent
depressive disorder, and cyclothymic disorder.
 Some may have psychotic features (delusions or
hallucinations).
Depressive disorders
conditions where mood is primary, the
predominant problem
Major depressive disorder (MDD)
Persistent depressive disorder
Premenstrual dysphoric disorder
Disruptive mood dysregulation disorder
Major Depressive Disorder (Unipolar
Depression)
 The most common mood disorder, and
one of the more common psychological
disorders in general.
 Everyone gets depressed, so how do
we know when normal depression
crosses the line into major depressive
disorder?
Major Depressive Disorder
Epidemiology:
 Incidence & Prevalence
 Leading cause of disability among adults under 45y of age
 lifetime prevalence of 12% in ♂, 20% in ♀
 incidence peaks in 20s (but onset in late life not uncommon)
 mean age 40Y “20-50y”

 Sex:
 MDD 2:1 w:m
1. Hormonal diff.
2. Childbirth.
3. Psychological stressor.
 Marital status: without close interpersonal relation, divorce,
separated.
Major Depressive Disorder (cont.)
 A person may be suffering from major
depressive disorder when five of the following
nine symptoms have been present for two or
more weeks:
 Depressed mood most of the day, nearly every day
 Little interest or pleasure in almost all activities
 Significant changes in weight or appetite
 Sleeping more or less than usual
 Agitated or decreased level of activity
 Fatigue or loss of energy
 Feelings of worthlessness or inappropriate guilt
 Diminished ability to think or concentrate
 Recurrent thoughts of death or suicide
Major Depressive Disorder (cont.)
 The symptoms must also produce distress or
impaired functioning to qualify as indicators of
MDD.
 Also, with MDD, there is no apparent reason,
or trigger, for the emotions.
 EXCLUSIONS:
 not attributable to a substance/medication or
another medical condition
 no prior [endogenous] episodes of mania or
hypomania
Major Depressive Disorder (MDD)
 (MDD) is marked by episodes of
depressed mood associated with loss of
interest in daily activities.
 Diagnosis and DSM-5 Criteria
 At least one major depressive episode
 No history of manic or hypomanic episode.
Question:
When does a major depressive episode
(MDE) ≠ Major Depressive Disorder?

 Major depressive episodes can be present in:

 major depressive disorder,
 persistent depressive disorder (dysthymia),
 bipolar I/II disorder,
 schizoaffective disorder.
 w/ seasonal pattern

w/ anxious distress w/ mood-[congruent, incongruent]

psychotic features

Major depressive disorder

w/ mixed features w/ peripartum onset

w/ catatonia

w/ atypical features w/ melancholic features

 w/ seasonal pattern
w/ mood-[congruent, incongruent]
w/ anxious distress
psychotic features

Major depressive disorder

w/ mixed features w/ peripartum onset

w/ catatonia
w/ atypical features w/ melancholic features

≥2 of the following:
• keyed-up/tense
• unusually restless
• can’t concentrate b/c of worry
• fear something awful may happen
• might lose control
 w/ seasonal pattern
w/ mood-[congruent, incongruent]
w/ anxious distress
psychotic features

Major depressive disorder

w/ mixed features w/ peripartum onset

w/ catatonia
w/ atypical features w/ melancholic features

≥3 of the following nearly everyday during an MDE:

[drawn from list of sxs for a manic/hypomanic episode, minus distractibility;
this list includes elevated/expansive mood…]
 w/ seasonal pattern
w/ mood-[congruent, incongruent]
w/ anxious distress
psychotic features

Major depressive disorder

w/ mixed features w/ peripartum onset

w/ catatonia
w/ atypical features w/ melancholic features

≥1 of the following during the most severe portion of the current episode:
• absolute anhedonia or absolute mood non-reactivity

plus ≥3 of the following:

• a distinct quality of depressed mood (e.g., worse than prior MDEs)
• worse in the AM
• early AM awakening (by at least 2h)
• marked PMA or PMR
• significant appetite or wt loss
• excessive guilt
 w/ seasonal pattern
w/ mood-[congruent, incongruent]
w/ anxious distress
psychotic features

Major depressive disorder

w/ mixed features w/ peripartum onset

w/ catatonia
w/ atypical features w/ melancholic features

• mood reactivity MAO-I’s (but SSRI’s still 1st line…)

plus ≥2 of the following:

• significant appetite or wt increase
• hypersomnia
• leaden paralysis
• long-standing interpersonal rejection sensitivity leading to social/work problems
 w/ seasonal pattern
w/ anxious distress w/ mood-[congruent, incongruent]
psychotic features

Major depressive disorder

w/ mixed features w/ peripartum onset

w/ catatonia
w/ atypical features w/ melancholic features

• delusions &/or hallucinations

• examples of congruent delusions: personal inadequacy, guilt, death, nihilism,

deserved punishment
 w/ seasonal pattern
w/ mood-[congruent, incongruent]
w/ anxious distress
psychotic features

Major depressive disorder

w/ mixed features w/ peripartum onset

w/ catatonia
w/ atypical features w/ melancholic features

during most of the episode, ≥3 of the

following:

• stupor • mannerism (odd cariacture of a

• catalepsy (passive induction of a posture normal action)
held against gravity) • stereotypy
• waxy flexibility • agitation (indep of external stimulus)
• mutism • grimacing
• negativism • echolalia or echopraxia
• posturing (spontaneous, maintenance
against gravity)
 w/ seasonal pattern
w/ mood-[congruent, incongruent]
w/ anxious distress
psychotic features

Major depressive disorder

w/ mixed features w/ peripartum onset

w/ catatonia
w/ atypical features w/ melancholic features

• during pregnancy or in the 4wks after delivery

 w/ seasonal pattern
w/ mood-[congruent, incongruent]
w/ anxious distress
psychotic features

Major depressive disorder

w/ mixed features w/ peripartum onset

w/ catatonia
w/ atypical features w/ melancholic features

• relapses and remissions occur at characteristic times of the year

• at least 2 seasonal MDE’s in the last 2y (and no non-seasonal MDEs during this
period)
• seasonal episodes outnumber non-seasonal episodes (lifetime)

If a patient always gets depressed with season unemployment (or the beginning
of the school year), would we call this ‘w/ seasonal pattern?’ No.
Etiology of Mood
Disorders
Possible Causes
Etiology

 The precise cause of depression is unknown,

but MDD is believed to be a heterogeneous
disease, with biological, genetic,
environmental, and psychosocial factors
contributing.
What causes mood disorders?
 Again, biology and environment interact
as possible contributors to mood
disorders.
 Stress also seems to play a role,
providing a trigger that sparks mood
disorders when other factors are present.
Biomedical Approach
 Heredity – First-degree relatives are two to four
times more likely to have MDD. Concordance rate
for monozygotic twins is <40%, and 10–20%for
dizygotic twins.
 Brain function – Depressed people have
depressed brains. Brain scans indicate that the
brain is less active during major depression.
 Also, certain neurotransmitters (serotonin and
norepinephrine) are lacking during times of
depression.
 Prozac and other antidepressant medications help
restore proper levels of these neurotransmitters.
 MDD is likely caused by neurotransmitter
abnormalities in the brain.
 Evidence for this is the following:
 Antidepressants exert their therapeutic effect by increasing
catecholamines;
 ↓ cerebrospinal fluid (CSF) levels of 5-hydroxyindolacetic
acid (5-HIAA), the main metabolite of serotonin, have been
found in depressed patients with impulsive and suicidal
behavior.
 Increased sensitivity of beta-adrenergic receptors in the brain .
 Biogenic amine
↓ Norepinephrine – Serotonin - Dopamine
“Parkinson's dis. & amphetamine”
↓’d GABAergic transmission
 Neuroendocrine regulation
Adrenal axis = 50% of dep. Pt. ↑ cortizol level

 High cortisol: Hyperactivity of hypothalamic-pituitary-adrenal axis,

as shown by failure to suppress cortisol levels in the
dexamethasone suppression test.
 Abnormal thyroid axis: Thyroid disorders are associated with
depressive symptoms.
 Decrease blood flow in cerebral cortex & specific
frontal lobe and neuroanatomical “limbic system, basal
ganglia, hypothalamus.
 Limbic → emotional
 Hypothalamus → sleep , appetite , sexual , biological
change in endocrine & immunology.
 Basal ganglia → stooped posture, motor slowness,
minor cognitive impairment.
The Depressed Brain
 PET scans show that brain energy consumption
rises and falls with manic and depressive
episodes.

Courtesy of Lewis Baxter an Michael E.

Phelps, UCLA School of Medicine
 Psychosocial
 Life even & environmental stress:
 Stressful event more often in first episode than sub
sequent.
 Long lasting changes in brain biology  loss
neuron & Dec. synaptic contact.
 Cognitive theory
1. -ve self precept.
2. -ve world perception as hostile, demand.
3. -ve future as suffer & failure.
 Learned helplessness =
Social-Cognitive Factors (cont.)
 Learned helplessness – People develop a
sense of helplessness when subjected to events
over which they have little or no control. As they
acquire this feeling of helplessness, they give up
and no longer try to improve their situation,
because they learned in the past that efforts to
improve the situation will not work. This, by
itself, can produce depression.
 Learned helplessness may also explain why
women suffer higher rates of depression than
men do. Women are more likely to be abused
and twice as likely to feel overwhelmed. This
may explain women’s higher levels of learned
helplessness and depression.
Social-Cognitive Perspective
The social-cognitive perspective suggests that
depression arises partly from self-defeating
beliefs and negative explanatory styles.
Course and Prognosis
 Early intervention→ early remission
 Untreated, depressive episodes are self-limiting but last
from 6 to 12 months.
 Generally, episodes occur more frequently as the
disorder progresses.
 The risk of recurrence is 50–60% within the first 2 years
after the first episode.
 Up to 15% of patients with MDD eventually commit
suicide.
 Approximately 60–70% of patients show a significant
response to antidepressants.
Course and Prognosis
 Development of manic episode
5-10% will have manic episode.6-10y after first episode
 Character  hypersomnia, psychomotor retardation,
psychotic symp. , post partum, F.H. of BADI, history of
antidep. Drug Induce hypomania.
 Prognosis =
 Chronic, relapse
 Less relapse on prophylactic R.X.
 Indicator 
 Good prog.  late onset, mild episode, absents of
psychotic symp. & comorbid dis. Or personality dis.,
only one admission, stable family function.
 Poor prog.  men, more than one admission,
dysthymic, alcohol, other substance, anxiety.
Diff. dig. Of MDD
PSYCHIATRIC
 Anxiety D/O’s (esp. GAD, PTSD)
 Schizoaffective D/O
 Delirium
 Dementia
 Personality D/O’s
 Adjustment D/O? develops in response to a stressor

(w/in 3mos)
 Bereavement, also known as simple grief, is a reaction
to a major loss, usually of a loved one, and it is not a
mental illness.
Diff. dig. Of MDD
Depressive, Related D/O d/t a Another Medical Condition

 Endocrine (e.g., thyroid, hypothalamic-pituitary-adrenal/HPA)

 Neurologic (e.g., multiple sclerosis, CVA, brain tumor, Parkinson’s,

Alzheimer’s/other dementia, Huntington’s, seizure d/o)

 Neoplastic (e.g., pancreas)

 Infectious (e.g., HIV, Syphilis) TBI

 Autoimmune (e.g., neuropsychiatric systemic lupus erythematosus /

NPSLE)

 Hematologic (e.g., acute intermittent porphyria / AIP)

 typically: anx/depr >> s/t Ψosis, mania (rare)
 acute abdominal pain, muscle weakness
 port wine-colored urine (porphobilinogen)
 transient damage to nerve cells

 Nutritional (e.g., B12)

Diff. dig. Of MDD
Substance/Medication-induced Depressive, Related D/O

ILLICITS
 can be from intoxication or withdrawal phases
 EtOH – typically depressive
 stimulants –

Prescription Rxs
 steroids
β-blockers
 antidepressants
 α-TB drugs
Mood D/O’s lab.

 CBC
 Chem panel
 TSH
 B12
 U-tox
 U-preg (dep on demographics)
 HIV-1,2 ELISA (lower threshold for BD patients…)
Treatment of MDD
 Consider:
1. Pt. safety.
2. Dig. Evaluation.
3. Treatment plan “symp & feature”.

 Hospitalization:
1. Need for dig.
2. Suicide & homicide.
3. Dec. ability to get food or shelter.
4. History of rapid progressive
Treatment of MDD
 Pharmacotherapy
 SSRI  fluoxetine, paroxetine, fluvoxamine.
 SNRI venlafaxine
 Tricyclic  amitriptyline, imipramine, clomipramine
 Takes 3-4 week.
 Symp. Improve appetite & sleep then agitation, anxiety
& dep..
 Max. dose 4-5 w OR less if get improve.
 duration  6m. Or length of previous episode.
 Taper over 1-2 w.
 augmentation
Treatment of MDD
 Adjunct medications:
 Atypical (second-generation) antipsychotics
along with antidepressants are first-line
treatment in patients with MDD with psychotic
features.
 Resistant/refractory MDD:
 Atypical (second-generation) antipsychotics
 Triiodothyronine (T3), levothyroxine (T4)
 Lithium
 Stimulants (such as methylphenidate) may be
used in certain patients (e.g., geriatric and
terminally ill patients)
MDD tx options
 tricyclic antidepressants (TCADs)
 selective serotonin reuptake
amitriptyline  nortriptyline
inhibitors (SSRIs)
 fluoxetine (PROZAC), 20-80 mg/d imipramine  desipramine
 citalopram (CELEXA), 20-40 mg/d  monoamine oxidase inhibitors (MAO-Is
 escitalopram (LEXAPRO), 10-20 mg/d  typically, non-selective & irreversible
 sertraline (ZOLOFT), 50-200 mg/d  MAO-A (NE, EPI, 5HT, DA)
 paroxetine (PAXIL), 20-50 mg/d  MAO-B (trace amines, DA)
 why we “wash-out”
 serotonin-norepinephrine reuptake
 5HT syndrome
inhibitors (SNRIs)
 HTNsive crisis
 venlafaxine XR (EFFEXOR XR),
 selegiline (EMSAM)
37.5-225 mg/d
 desvenlafaxine (PRISTIQ)
 duloxetine (CYMBALTA), 30-120 mg/d  [additional] augmenting agents
 Li+
 others  T3, 25 mcg/d
 bupropion SR, XL (WELLBUTRIN)  buspirone (BuSPAR), 5-30 mg BID
100-200 mg BID (SR)  atypical antipsychotics
150-450 mg/d (XL)
 mirtazapine (REMERON), 15-45 mg/d
 trazodone, 50-200mg/noc (for sleep)
 nefazodone
Treatment of MDD
• Psychotherapy
• cognitive bx therapy (CBT)
• interpersonal therapy (IPT)
• psychodynamic therapy
• family/couples therapy

May be used alone or in conjunction with pharmacotherapy.

 80-90% remission rate

 50-80% relapse rate (6mos out)
• Interventional treatment:  SEs: musculoskeletal, headache,
• electroconvulsive therapy (ECT) cognitive
• transcranial magnetic stimulation (TMS)  mania, catatonia, NMS (other
• vagal nerve stimulation (VNS) indixn’s)
• deep brain stimulation (DBS)

• Other
• light box therapy (mostly for MDD w/ seasonal features)
Persistent depressive disorder (dysthymia)
 2y of depressed mood (1y in children/adolescents) most of the day, more days than
not, plus 2 of the following:
 appetite disturbance (↓ or ↑) veg
 sleep disturbance (↓ or ↑) veg
 ↓energy E
 ↓esteem E
 poor [ ] C
 hopeless H

 never sx-free for more than 2mos at a time

 overlapping dx of MDD is now allowed
 there has never been mania, hypomania, or cyclothymia

 w/ persistent MDE
 MDD specifiers can also be used for dysthymia
 additionally:  w/ intermittent MDE’s, w/ current e
early onset (before age 21)  w/ intermittent MDE’s, w/o current
late onset (at age 21 or older)
w/ pure dysthymic syndrome --these last 3 are essentially a co-dx of MDD, but
captured within the specifier…

from DSM-5
Persistent depressive disorder (dysthymia)
 Epidemiology
 Twelve-month prevalence: 2%.
 More common in women.
 Onset often in childhood, adolescence, and early adulthood.
 Course and Prognosis
 Early and insidious onset, with a chronic course.
 Depressive symptoms much less likely to resolve than in
MDD.
 Treatment
 Combination treatment with psychotherapy and
pharmacotherapy CYCLOTHYMIC DISORDER
Premenstrual dysphoric d/o
Criterion A. In most menstrual cycles, ≥5 sxs in the final week before
onset of menses,
w/ improvement w/in a few days after onset of menses, and near-
absent in the weekpost-menses
 At least one of the following symptoms is present: affective lability,
irritability/anger, depressed mood, anxiety/tension.
 At least one of the following symptoms is present (for total of at least
five symptoms when combined with above):
anhedonia, problems concentrating, anergia, appetite changes/food
cravings, hypersomnia/insomnia, feeling overwhelmed/out of
control, physical symptoms (e.g., breast tenderness/swelling,
joint/muscle pain, bloating, weight gain).
Premenstrual dysphoric d/o
 Epidemiology/Etiology
 Prevalence: 1.8%.
 Onset can occur at any time after menarche.
 Has been observed worldwide.
 Environmental and genetic factors contribute.
 Course and Prognosis
 Symptoms may worsen prior to menopause but cease after menopause.
 Treatment
 SSRIs are first-line treatment, either as daily therapy or luteal phase-only
treatment
 Oral contraceptives may reduce symptoms.
 Gonadotropinreleasing hormone (GnRH) agonists have also been used,
and,
 in rare, severe cases, bilateral oophorectomy with hysterectomy will
resolve symptoms.
DISRUPTIVE MOOD DYSREGULATION
DISORDER (DMDD)
 Chronic, severe, persistent irritability occurring in childhood and
adolescence.
 Symptoms for at least 1 year, and no more than 3 months
without symptoms.
 Symptoms must have started before age 10, but diagnosis
can be made from ages 6 to 18.

 Treatment
 Psychotherapy, such as parent management training,
 Medications should be used to treat comorbid disorders.
 Stimulants, SSRIs, mood stabilizers, and second-generation
antipsychotics
Other Types of “Depressions”
 Seasonal Affective Disorder
 Double Depression (Dysthymia + Major
Depression)
 Post-partum depression