TITLE OF THESIS: CAUSES, PREVALENCE AND THERAPEUTIC MANAGEMENT

OF DEPRESSION AMONG GENERAL POPULATION

THIS THESIS IS SUBMITTED TO DR. SAIRA SHEHNAZ

GROUP MEMBERS (BATCH 2018)

• WARDA JAVED(501-S18-031) • MAIRA KHAN(501-S18-040)

• LAVIEZAH FAREED(501-S18-006) • JAVERIA HUSSAIN (501-S18-

025)
• MAHNOOR KHAN (501-S18-049)

YEAR OF SUBMISSION: 2023

 NAZEER HUSSAIN UNIVERSITY

FACULTY OF PHARMACY

CERTIFICATE

This is to certify that the students of 5th Professional Year Batch-III (2018) have completed their
research on “CAUSES, PREVALENCE AND THERAPEUTIC MANAGEMENT OF
DEPRESSION AMONG GENERAL POPULATION”
Under the Cordial and Sincere Supervision of DR. SAIRA SHEHNAZ.

RESEARCH CONDUCTED BY:

• WARDA JAVED

• LAVIEZAH FAREED

• MAHNOOR KHAN

• MAIRA KHAN

• JAVERIA HUSSAIN

Dr. Saira Shehnaz

Assistant Professor
Department of Pharmacy
Practice
CAUSES, PREVALENCE AND THERAPEUTIC MANAGEMENT
OF
DEPRESSION AMONG GENERAL POPULATION
ACKNOWLEDGMENT

Praise is to Allah Almighty, who has blessed us with the ability to complete this study project. The
completion of this project would not have been possible without the support and assistance of
several people. First and first, we would like to express our gratitude to Nazeer Hussain University
for providing us with the opportunity to participate in this learning experience and for providing us
with various resources and academic guidance.
We'd like to express our sincere gratitude in the strongest possible terms TO DR. SAIRA
SHEHNAZ, our Research Supervisor, for choosing us to be the part of this innovative and
educational journey and providing us with a platform to show our skills, knowledge and abilities in
contributing our piece of work in research world and hope to serve our country in the most
beneficial way. Throughout the research, we are grateful for her kind assistance and guidance.
We'd also like to express our gratitude to the respondents (All healthcare professionals) including
general physicians, intensivists, pharmacists, nursing staff, paramedics, psychologists, and general
public without their sincere responses, this study project would be impossible to complete.
We are honorable to public and private hospitals to give us opportunities.
We wholeheartedly thank them for letting us freely visit and enter their respective departments,
followed by all SOPs, so that we could conduct our research smoothly and successfully.
On this learning journey, me and the group members worked hard and did our best to fulfill our
role in this research project. Group members including Warda Javed, laviezah Fareed, Mahnoor
Khan, Maira Khan, Javeria Hussain contributed their untiring efforts and consistent hard work in
completing this innovative study.
When it comes to our family and friends, we are grateful for their unwavering support and
encouragement since they are always ready to guide and motivate us.
Finally, we would like to specially thank the front-line workers for cooperating with us during
this whole research project and those who have contributed directly or indirectly to the
completion of this project.
For this, our beloved Dean Dr. Nighat Rizvi had been a source of motivation to stay devoted to
this great research. Along with her, our faculty members including our coordinator Dr. Khawar
Khalid, our respected lecturers Dr. Tauseef Imtiaz, Dr.Yusra Khan, Dr. Shereen, and other staff
members were a great source of knowledge, advices, ideas and outstanding support. We are truly
thankful to all of them for giving us their valuable time.

4
DEDICATION

This Research is dedicated to our family and friends, who are willing to assist us at every stage of
the project's completion. We also dedicate this to all the front-line workers who have been doing
their best in this critical time of the country who are also being the victim of mental
instability/depression and stress during the pandemic, and we'd like to give special credit to DR.
SAIRA SHEHNAZ, our incredibly encouraging, friendly, and helpful supervisor, her words of
encouragement and determination are the constant source of inspiration and motivation for us.
This work is dedicated to her, and we thank her for being with us throughout this project.

5
Table of Contents

Acknowledgement.........................................................................................................................4

Dedication......................................................................................................................................6

Abbreviation.................................................................................................................................7

Abstract.........................................................................................................................................8

Introduction.................................................................................................................................11

 Definition.............................................................................................................................13

 Types….................................................................................................................................15

 Diagnosis Of Depression......................................................................................................16

 Prevalence.............................................................................................................................17

 Cause Of Depression.............................................................................................................18

 Therapeutic Management.....................................................................................................20

 Mood Stabilizers…...............................................................................................................33

 Alternate Method...................................................................................................................30

Literature Review.........................................................................................................................35

Methodology..................................................................................................................................42

 Duration of Study..................................................................................................................42

 Targeted Population...............................................................................................................42

 Sampling Technique..............................................................................................................42

 Sample Size...........................................................................................................................42

 Sample Selection...................................................................................................................42

 Inclusion Criteria.....................................................................................................................42

 Data Collection Procedure.....................................................................................................42

 Data Analysis….....................................................................................................................42
7
 Ethical Consideration............................................................................................................43

Results.............................................................................................................................................44

Discussion........................................................................................................................................

Conclusion........................................................................................................................................

References.......................................................................................................................................58

7
ABBREVIATION:

ADHD=Attention deficit hyperactivity disorder

Adrs = adverse drug reaction
CFS = Chronic fatigue syndrome
CNS=central nervous system
CYP450= Cytochrome P450
DSM= Diagnostic and Statistical Manual of Mental Disorders.
MAO=mono amine oxidase inhibitor.
MDD= major depressive disorder
NDRIS=Norepinephrine and dopamine reuptake inhibitors.
NSAIDS=non-steroidal anti-inflammatory drugs
PMDD=Premenstrual dysphoric disorder.
REM= rapid eye movement
SAD =Seasonal affective disorder.
SNRIS=Serotonin and norepinephrine reuptake inhibitors.
SSRIS=Selective serotonin reuptake inhibitors.
t½=half life
TCA=tricyclic antidepressant.
MDP=manic depressive psychosis
CAD=Coronary artery disease

8
ABSTRACT

OBJECTIVE:
The goal of this research survey was to assess the leading cause of depression among general
population and their therapeutic approach and management toward depression

METHODOLOGY:

Cross-sectional web-based study is performed by following quantitative technique and data

is taken from public sector with the help of internet and online survey. Online structured
questionnaire is to provide the targeted audience over the internet generally by circulating
the survey form and then result is compiled in the form of percentage and frequencies of the
reported responses.
Duration of study: The duration of study was 6 months Type of Study: Cross-sectional type
Targeted population: Male and female of age angling from under 13 to 65+ Sample
selection: Both male and female were considered.

RESULT:

Aim of this study was to map the knowledge of global depression among adults of different
age groups by systemically analyzed the age, gender, marital status, employment status,
prevalence and therapeutic management they are being followed. Demographic details of
participant include in this research survey indicate that 70% of the response were recorded
from audience agedbetween18-25 in which 53% were females 5.6%Asians, 27.2%married,
70%single, 61.7%students, 18.3%job person.

9
CONCLUSION:

This research survey demonstrates that 15% of participants were diagnosed with depression
and nearly 16.1% of the participants received medical treatment.
the main reason contributing to their depression were relationship problems i.e
21%,17.8%financial problems,16.7%grief or loss,16.1%loneliness and islolation,11.7% due
to post trauma,7.2% were suffered from after effects of corona virus.
Despite some limitation, this study gives the evidence of rise of depression and anxiety
among young adults. Large percentage of population have been suffering from after effect of
pandemic, addition to academic and professional uncertainty financial crisis is majorly
contributing to rise in depression.

KEYWORDS: depression, Depressive disorder, anxiety, pharmaceutical care, prevalence

and therapeutic management

10
CHAPTER # 1: INTRODUCTION

11
INTRODUCTON:
DEFINITION:

Depressive disorders are characterized by sadness, loss of interest and pleasure, feelings
of guilt and low self-esteem, sleep and eating problems, fatigue, and difficulty
concentrating (1). Depression can be long-lasting or relapsing and can severely affect
functioning at work or school and the ability to cope with daily life. At worst, depression
can lead to suicide. (2) The word depression comes from the Latin “depression” which
means sinking. The person feels sunk with a weight on their existence. (3) It is a mood
disorder that varies from. Normal transient low mood in daily life itself to clinical
syndrome with severe and significant duration and associated signs and symptoms,
markedly different from normality.

Depression consists of a disease with decayed mood as its main symptomatology.(4) There
are also painful feelings, bad humor, anguish and panic attacks, performance decay of
various psychic and cognitive functions, tendency to isolation, demotivation, apathy,
abulia, difficulty to enjoy, hopelessness, motor inhibition, hypotonia and negative
thoughts, including possible delusions in cases of serious severity.(5)On the other hand, it
can present a very diverse associated somatic symptomatology, some organic alterations
often corresponding to larval or encapsulated ways of going through a depression.(6)It is
considered a mental disease consisting of a mood disorder, being its usual symptom a
state of dejection and unhappiness that may be transient or permanent.(7)In this sense, it is
defined as a mental disorder characterized by the presence of sadness, loss of pleasure,
feelings of guilt and low self-esteem, accompanied with alterations in the sleep pattern
and the appetite, lack of concentration, and feelings of being tired, which can become
chronic and recurrent, making the person dysfunctional in their daily activities; when it is
mild it can be treated with psychotherapy, but when it is moderate or severe,
pharmacological treatment may be needed. In the previous cited definitions of recent
data, it can be seen how depression is conceived at the same time as a “mental disorder
“and as a “mood disorder”, although both perspectives coincide in a subjective and
emphasizes the need to operationalize them symptoms. (7,8)

Vallejo indicated that the term depression is used in his three regions Symptoms,
12
Syndromes and Diseases. As a symptom of it may be accompanied by other psychiatric
disorders such as anxiety disorders. How Syndrome, sadness, inhibition, Outlined as
Guilt, Handicap, Lifeless Drive, and Illness as a disorder of biological origin.(9) The
WHO estimates that depression is projected to become the second most serious disease in
the world over the next decade, with 1 in 5 women and 1 in 12 men already suffering
from depression. I'm here. Not just adults, 2% of school children and 5% of her teens
suffer from depression, mostly unrecognized. (10)

Major depression is manifested by a combination of symptoms that affect the ability to

work, sleep, eat, and engage in once-pleasant activities. (11) These depressive episodes can
occur once, twice, or multiple times in a lifetime. (12) The explanation of impairment by
'significant social deterioration' can also be considered subjective, making these
symptoms manipulable. Vallejo notes that the term depression can uses in three different
ways. (10,12)

Symptoms, Syndromes and Diseases. As a symptom, it can accompany other psychic

disorders, such as anguish disorders; as a syndrome, it groups processes characterized by
sadness, inhibition, guilt, disability and loss of vital impulse, and as a disease, it is
outlined as a disorder of biological origin in which an etiology, a clinic, a course, a
prognosis and a specific treatment can be established(13).From the previous perspective, it
seems that depression, if considered a “disease” only to emphasize an organic etiology,
could lose both the entity of “disorder” and of “symptom”, in contrast to understanding
the human being as a biopsychosocial entity and the tripartite biological, psychological
and social composition of all alterations that could possibly affect it(14).Among other
confusions, Jimenez argues that “depression” is generally interpreted as “melancholy”,
however, they are different because the latter is more related to longing or memories of
the past, more accurately related to sadness of past time(s) “that will not return” while
“depression” would be more related to high levels of sadness, discomfort, loss of interest,
mental confusion and alterations in the execution of daily activities. Another confusion in
history has been the use of the term “depression” as a synonym of “sadness. (14,15).

In this regard, Jiménez states that sadness is a transient emotional state that varies in
intensity and duration, characterized by a pattern of responses that encompasses
13
 cognitive-subjective, physiological and motor observable level changes. (16) The sadness
response is usually triggered by unpleasant situations (real or imagined) that are
interpreted by the subject as losses, for which the subject generally believes that he or she
does not have coping capacity and/or exhausts this capacity, accepting the loss without
generating a resource-mobilizing response. In this sense, according to Jiménez, there is a
continuum with the poles “depression” and “non-depression”, passing by the emotion of
“sadness”, understanding the latter as a normal reaction of the human being, capable of
turning into a pathological. Prior to this distinction between ``sadness'' and
``depression,'' the criteria of ``intensity, frequency, and duration'' are used to distinguish,
but the boundaries between each other and the concept of depression as a ``normal
emotional response'' It remains unknown." For the purposes of this work, 'sadness' is
understood (like other emotions) as a fundamental unpleasant emotion with adaptive
functions in humans, and 'depression' is a maladaptive emotion. (14,15,16,17)

TYPES:

There are following 8 types of depression. (18)

1. Major Depressive disorder/Depressive disorder:

Depression is a mood disorder that causes persistent sadness and loss of interest. Also
known a
major depressive disorder or clinical depression, it affects feelings, thoughts and
behavior and can lead to a variety of emotional and physical problems. You may feel
worthless. (19)

2. Dysthymia
Dysthymia, a persistent or chronic form of mild depression. Symptoms of dysthymia are
similar. Depressive episodes progress but tend to be less severe and longer lasting. (19,20)

3. BIPOLAR DISORDER:

People with bipolar disorder, sometimes called "manic-depressive," have mood episodes
that range from high-energy extremes with "excited" moods to low-level "depressive"
episodes.
When you are in the lower stages, you have symptoms of major depression. (21)
14
 Medications can help control mood swings. Whether you're feeling high or low, your
doctor may recommend a mood stabilizer such as lithium (19,20)

4. SEASONAL AFFECTIVE DISORDER (SAD):

Seasonal Affective Disorder (SAD) is a form of depression associated with seasonal
changes. SAD begins and ends at approximately the same time each year. If you're like
most people with SAD, your symptoms start in the fall and last through the winter,
making you depleted of energy and moody. It often happens. Less commonly, SAD
causes depression in the spring or early summer and resolves in the fall or winter. (20,22)

5. PSYCHOTIC DEPRESSION:
Psychotic depression is a subtype of major depression that occurs when major depressive
disorder is accompanied by some form of psychosis. Psychosis can be hallucinations (eg,
hearing voices telling you that you are no good or worthless), delusions (eg, intense
feelings of worthlessness, failure, or guilt), or alternate realities. Can arise from a
disconnection from Psychotic depression affects about 1 in 4 people hospitalized with
depression. (21,22,23)

6. PSYCHOTIC DEPRESSION:

Psychotic depression is a subtype of major depression that occurs when major depressive
disorder is accompanied by some form of psychosis. Psychosis can be hallucinations
(e.g, hearing voices telling you that you are no good or worthless), delusions (e.g, intense
feelings of worthlessness, failure, or guilt), or alternate realities. Can arise from a
disconnection from Psychotic depression affects about 1 in 4 people hospitalized with
depression. (21,22,23)

7. PERINATAL (POSTPARTUM) DEPRESSION:

Perinatal depression is a mood disorder that can affect women during pregnancy and
after childbirth. The term “perinatal” refers to the period before and after the child is
born. Perinatal depression includes depression that develops during pregnancy (prenatal
depression) and depression that develops after childbirth (postpartum depression).
Mothers with perinatal depression may experience extreme sadness, anxiety, fatigue, and
15
 difficulty completing daily tasks, including caring for themselves and others. (23,24)

8. PREMENSTRUAL DYSPHORIC DISORDER (PMDD):

Premenstrual dysphoric disorder (PMDD) is similar to premenstrual syndrome (PMS)

but is a more serious health condition. PMDD causes severe irritability, depression, or
anxiety one to two weeks before menstruation. Symptoms usually go away 2-3 days after
your period starts. (24,25)

9. SITUATIONAL DEPRESSION:

Situational depression is short-term, stress-related depression. It can develop after

experiencing a traumatic event or series of events. Situational depression is a type of
adjustment disorder. After a traumatic event, you may find it difficult to adjust to your
daily routine. (26)

10. SITUATIONAL DEPRESSION:

Situational depression is short-term, stress-related depression. It can develop after

experiencing a traumatic event or series of events. Situational depression is a type of
adjustment disorder. After a traumatic event, you may find it difficult to adjust to your
daily routine. (26)

SIGNS AND SYMPTOMS:

SIGNS AND SYMPTOMS OF MAJOR DEPRESSIVE DISORDER:

 Feelings of sadness, tearfulness, vacancy, or hopelessness. (24)

 Angry outbursts, irritability or frustration, even over small topics (22)

 Loss of hobby or satisfaction in maximum or all everyday sports, along with sex,
pastimes or sports activities (26)

 Sleep disturbances, together with insomnia or snoozing an excessive amount of

Tiredness and absence of energy (27)

16
 Anxiety, agitation, or restlessness (24)

 Slowed thinking, talking or frame moves (22)

 Feelings of worthlessness or guilt, fixating on beyond screw ups or self-blame (20)

 Trouble thinking, concentrating, making choices, and remembering matters (21)

 Suicidal mind, suicide tries or suicide (27)

 Unexplained bodily issues, along with again ache or complications (21)

SIGNS AND SYMPTOMS OF DYSTHYMIA:

Symptoms of persistent depressive disorder usually come and go over years and may
change in intensity over time This is sometimes called double depression, persistent
depressive disorder can be severely debilitating and include (24,25,26,27,28):

 Loss of interest in daily activities 24

 Sadness, emptiness, or depression 25

 Disappointment 26

 Fatigue and lack of energy 26

 Low self-esteem, self-criticism, feelings of helplessness 27

 Difficulty concentrating and making decisions 27

 Irritability or excessive anger 24

 Reduced activity, effectiveness, and productivity 25

 Avoidance of social activities 24

 Guilt and worry about the past 24

 Anorexia or overeating 26

 Sleeping disorder 25

 In children, symptoms of persistent depressive disorder include low mood and

irritability. 27

17
 The main symptom of PDD is a sad, low or dark mood. 28

 Other signs may include (28):

 Malaise. 28

 Hopelessness, worthlessness, isolation. 28

 Poor appetite or overeating. 28

 Concentrate a little. Limited energy.

 Low self-esteem. 28

 Problems at work or school. 29

 Having trouble falling asleep or sleeping too much. 29

 Most people with PDD have had at least one major depression at some point,
sometimes called "double depression." 29

SIGNS AND SYMPTOMS OF BIPOLAR DISORDER:

In bipolar disorder, dramatic episodes of highs and lows. These episodes can occur over
weeks, months, and sometimes years (29).

 Excessive Happiness, Hope, and Excitement 29

 Sudden change from joy to irritability, anger, or hostility 29

 Restlessness 29

 Speaks quickly and lacks concentration 29

 Need for more energy and less sleep 29

 Abnormally high libido 29

 Make big, unrealistic plans 29

 Show bad judgment 29

 Loss of appetite 29

 Greater confidence and happiness 29 18

SIGNS AND SYMPTOMS OF SEASONAL AFFECTIVE DISORDER (30):
The signs and symptoms of SAD include those associated with major depression and
some specific symptoms that differ between winter and summer SAD. Not all SAD
patients experience all of the symptoms listed below.

SYMPTOMS OF MAJOR DEPRESSION INCLUDE (27, 28, 29, 30)

 Feeling depressed most of the day, almost every day

 Loss of interest in activities once enjoyed

 Changes in appetite or weight

 Have trouble sleeping

 Feeling sluggish or upset

 Low energy

 Feeling hopeless or worthless

 Can't concentrate

 Frequent thoughts of death or suicide

 In winter-type SAD, additional specific symptoms may include:

 Oversleeping (hypersomnia)

 Overeating, especially carbohydrate cravings

 Weight gain

 Hikikomori (hibernation)

 Specific symptoms of summer-type SAD include:

 Sleep disturbance (insomnia)

 Anorexia leading to weight loss

 Restlessness and excitement

19
 Fear

 Episodes of violence

SIGNS AND SYMPTOMS OF PSYCHOTIC DEPRESSION (31):

People with psychotic depression experience a combination of depressive symptoms,

including:

 Melancholy mood

 Decreased interest or pleasure in previously enjoyed activities

 Fatigue or lack of energy

 Feelings of worthlessness or guilt

 Can't concentrate

 Significant changes in weight and appetite

 Difficulty sleeping

 Thoughts of death or suicide

 In addition to the above symptoms, people with psychotic depression also

experience
delusions and hallucinations (28).

SIGNS AND SYMPTOMS OF PERINATAL (POSTPARTUM) DEPRESSION

(30,31,32)

 Persistent sad, anxious, or “empty” temper 32

 Irritability 32

 Feelings of guilt, worthlessness, hopelessness, or helplessness 31

 Loss of hobby or pride in pastimes and sports 30

 Fatigue or unusual lower in strength 32

20
 Feeling stressed or having problem sitting nonetheless 32

Difficulty concentrating, remembering, or making selections31 Trouble bonding or

forming an emotional attachment with the brand-new child
Persistent doubts approximately the cap potential to take care of the brand- new child
Thoughts approximately death, suicide, or harming oneself or the child (31,32,)

SIGNS AND SYMPTOMS OF PREMENSTRUAL DYSPHORIC DISORDER (33):

 Persistent irritability or anger that can affect others

 Feelings of sadness, despair, or even suicidal thoughts

 Feeling nervous or anxious

 Panic attacks

 Mood swings and frequent crying

 Lack of interest in daily activities and relationships

 Difficulty thinking or concentrating

 Fatigue or low energy

 Craving or binge eating

 Sleeping disorder

 Feeling out of control

 Physical symptoms such as cramps, bloating, breast tenderness, headaches, and

joint
and muscle pain.

SIGNS AND SYMPTOMS OF SITUATIONAL DEPRESSION (34)

 Sorrow

 Disappointment

 Lack of pleasure in usual activities

21
 Regular crying

 Constantly worrying or feeling anxious or stressed

 Difficulty sleeping

 Indifference to food

 Out of focus

 Difficulties in everyday life

 Feeling overwhelmed

 Avoidance of social situations and interactions

 Don't bother with important issues like paying bills or going to work suicidal
ideation
or attempted suicide

DIAGNOSIS OF DEPRESSION:

DSM-5 Diagnostic Criteria of Major depressive disorder. (34,35):

Major depressive disorder is associated with high mortality, much of which is accounted
for by suicide. The latest edition of the Diagnostic and Statistical Manual of Mental
Disorders (DSM), the DSM-5, added two specifiers to further classify diagnoses (34,35).
With Anxious Distress – The presence of anxiety in patients may affect prognosis,
treatment options, and the patient’s response to them.
Clinicians will need to assess whether the individual experiencing depression also
presents with anxious distress. (34,35)
A person suffering from depression feels sad and hopeless about everything. This person
may have every reason to be happy, but they lose the ability to experience joy and
enjoyment. Even the activities they once

enjoyed are no longer interesting or enjoyable (35,36). In addition, experiencing sadness

caused by something specific can help keep you motivated and wanting to sleep and do
things as usual (36,37). It is associated with severe confusion and the desire not to get out of
bed all day. In grief, you may feel regret and remorse for what you said or did, but the
feeling of worthlessness and guilt doesn't last as long as it does in depression. One of the
22
diagnostic hallmarks of depression is this type of self-restrictive negative thought pattern.
Finally, self-harm and suicidal thoughts do not arise from non-depressive grief. People
suffering from major depression may have thoughts of self-harm, death, or suicide, or
may have suicidal plans (36,37).

PREVALANCE:

The survey was conducted in the capital city of Sindh Karachi, this survey was
conducted among the generalized population. The responses were concluded as (36,37):
It was the most common psychiatric disorder recorded in OPD and general clinical
settings it is also most common in youth (18-25) was more common in women more than
men and among students the population were recorded to have a traumatic and
unpleasant event that lead to the progression of depression. Women with marital un-
satisfaction and spousal conflicts were reported more than usua (40).
Additional research needs to be carried out for the evaluation of points like
expenditure, behavior and conduction towards treatment, compliance and biological
correlation (41). The further study on the determination for the exact period of treatment
and should estimate the economical methods towards the treatment that should be readily
accessible in the first line of treatment functionally in the treatment of major depressive
disorder. (41,42)

CAUSES OF DEPRESSION:

The causes of depression that influence us environmentally are listed below (42) :-
Anyone among the population can face such situation in their daily life practices or
routine. These may be called as external factors, according to the study of modern times
these circumstances can effected a person’s mental health & stability (40)
The past experiences of the life influence the processing of thoughts and feelings and the
life practices. The events may be concluded as failed relationships, early childhood crisis.
The main role in progression of depression among numerous people appears to the way
they conduct themselves in day to day life. And may vary from person to person.(40,41,42)

STRESS:
23
It seems a much compounded correlation to oppressive circumstances. Conduction of an
entities mindset and of a human body towards pressure and the progression of depression
is linked with an any unpleasant or pressure building event for many people studying
regarding the pressure of the situation can be distinguished between positive and
negative factors (43).

EARLY CHILDHOOD TRAUMA:

Majority patients of clinical depression are the ones who have difficulty in childhood or
had abusive or traumatic childhood inclusive of sexual / emotional / domestic or physical
abuse, separated parents, dysfunctional family, and toxic household and psychiatric
issues with anyone or both of them (44).

HORMONAL IMBALANCES:

Taking ecp emergency contraceptive pills cause hormonal imbalance that leads to
occurrence of depression some other times the hormonal disorders such as pcos and pcod
gives miserable moods to the suffering female with these major depressive episodes if
not treated progression towards depression another factor is fdemales are more prone to
depression as they usually face pms as well as some of them faces premenstural
dysphoric disorder (45).

SEXUAL ASSAULT / ABUSE:

A sexual assault is the key that leads to clinical depression, an assault after effects are
loss of apetite , flashbacks , nightmares inability of falling asleep , panic attacks the
worsening condition leading towards extremely low mood and depression the victims of
assault are diagnosed with ptsd and are suicidal. (43,44,45)

ENVIRONMENTAL FACTORS:

The environment of high school and institutions influence the mental health of young
ones the factors are bullying, competition to be ahead of everyone every time leads to
loneliness and clinical depression. (44)

24
DRUG THERAPY TO TREAT DEPRESSION:

Depression is a widespread mood condition that has a significant impact on the general
population. Under diagnosis is common, which can result in missed opportunities for
therapy. In terms of biochemistry, it is linked to the complicated and poorly understood
depletion of the brain monoamines 5-HT and NA (45).
One of the significant developments in psychopharmacology over the past few years is
the effective treatment of depression with medication. Several medications are now
available that are classified as "antidepressants," sometimes known as "psychoanaleptics"
or "mood lifters" in some cases. They work by making more monoamines (NA, 5-HT)
available intra-synoptically in the brain. This is accomplished in one of three ways:
(43,44,45)
1. blocking the neural reuptake of such amines
2. blocking receptors
3. impeding amine metabolism with enzyme inhibitors like MAOI. As a result,
medications can be divided into:

1. INHIBITORS OF MONOAMINE OXIDASE (MAOI)

 Irreversible

Hydrazine MAOIS, such as Phenelzine, Iso-carboxazid, and Iproniazid. (45)

Non hydrazine, such as tranylcypromine. (45)

 Reversible, such as moclobemide

2. TRICYCLIC ANTIDEPRESSANTS (TCA)

They can be grouped into:

NA-reuptake inhibitors, such as desipramine and amitriptyline such as protriptyline. (45)

Inhibitors of 5-HT reuptake, such as clomipramine. (45)

3. SSRIS (SELECTIVE SEROTONIN (5-HT) REUPTAKE INHIBITORS)

25
It includes Fluoxetine, Paroxetine, Fluvoxamine, Sertraline, Citalopram, and
Escitalopram. (44,45)

4. SNRIS (SELECTIVE 5-HT-NA REUPTAKE INHIBITORS):

Venlafaxine, Duloxetine, and Milnacipran. (45)

5.NOREPINEPHRINE AND DOPAMINE REUPTAKE INHIBITORS (NDRIS):

bupropion. (45)

6.MOOD STABILIZER: Lithium carbonate. (45)

MONOAMINE OXIDASE INHIBITORS (MAOI)

MECHANISM OF ACTION:

The hypothalamus and other subcortical areas of the brain contain relatively high
concentrations of 5-HT and NA. These amines are kept in the neurons granules and
released in response to neuronal inputs. Since the enzyme MAO instantly breaks down
the active amines, they do not accumulate but instead act on the postsynaptic receptors.
Most tissues, especially the CNS, stomach, and liver, contain it intracellularly. The
human body's metabolism of neurotransmitters is impacted differently by the two kinds
of MAO, MAO-A and MAO-B (45,46).
Inhibition of the MAO-A: NA and 5-HT are less likely to be deaminated when the
MAO-A is inhibited. This results in a rise in local NA and 5-HT, which is linked to
interactions with sympathomimetic medicines and foods containing tyramine associated
with hypertensive effects as well as antidepressant effects. Accumulation of these amines
is connected to excitation and increased motor activity in animal tests (44,45,46).
Selective inhibition of MAO-B: which primarily reduces dopamine deamination, is
helpful in treating parkinsonism but is not connected to antidepressant or hypertensive
activity. Because of their high concentration in portal circulation these medications have
a significant impact on liver MAO enzymes when taken orally (45,46).

PHARMACOLOGICAL ACTIONS:

26
Behavioral effects: These medications have a mood-lifting impact on depressed people.
Subjects report feeling more alert, energized, and fresh. Suicidal ruminating becomes
less common. Agitation, chattiness, and restlessness may occasionally happen. After a
latent period of a few days to three to four weeks, the action is visible. (45,46,47)
Cardiovascular effects: some MAOI may result in hypotension.

Reserpine reversal: reserpine administration causes agitation and excitation because of

amine buildup. The term is called "reserpine reversal" (46,47)
Miscellaneous: These medications delay the metabolism of numerous medications and
lengthen their effects by inhibiting MAO and other liver enzymes. This could cause
toxicity to arise. They effectively prevent REM sleep (47).

ABSORPTION, FATE AND EXCRETION:

Oral absorption of all substances is efficient. Although there is insufficient knowledge

regarding their human metabolism, the effects of MAOI last for 10 to 14 days after the
medicine has been stopped. This is because of their irreversible impact on the MAO
enzyme, whose level may return to normal after more than two weeks (42,44).

ADVERSE REACTIONS:

Behavioral effects: These symptoms include headaches, elation, agitation,

hallucinations, and sleep disturbance. These medications have the potential to trigger
latent psychosis, thus using them by itself in schizophrenia cases is not advised (46).
CNS effects: As evidenced by tremors, twitches, ataxia, hyperreflexia, hyperthermia, and
even convulsions, they may stimulate the CNS and produce sleeplessness. Iproniazid and
isocarboxacid can occasionally result in peripheral neuritis that can be treated with
pyridoxine (44,45,46).
Hypertensive crisis: Concurrent use of sympathomimetic pressor amines, such as
amphetamine and ephedrine, might cause this. Even subarachnoid haemorrhage may
result from a sudden spike in blood pressure. If individuals on MAOI consume tyramine-
containing foods like cheese or red wine, a hypertensive crisis may also develop.
Tyramine is typically broken down in the liver by MAO enzymes. Infusion of sodium
nitroprusside should be used to treat a hypertensive crisis. (45,46,47)
Autonomic effects: Antimuscarinic effects from hydrazine compounds include
27
constipation, dry mouth, blurred vision, impotence, difficulty urinating, and orthostatic
hypotension (48).
Miscellaneous effects: They make you put on weight. Hepatocellular jaundice may be
brought on by hydrazine substances, particularly iproniazid. (47,48)

MOCLOBEMIDE:

This medication works by selectively inhibiting the MAO-A enzyme, which is why it is
known as a reversible inhibitor of MAO (RIMA). Compared to irreversible MAOI, it
lessens the potentiation of pressor amines and reduces the likelihood of medication
interactions. Since the intestinal MAO is primarily MAO-B, rigorous dietary restrictions
are not necessary (45).

TRICYCLIC ANTIDEPRESSANTS (TCA):

The well-researched tricyclic antidepressant (TCA), IMIPRAMINE, a dibenzazepine

derivative, is suggested as a prototype. It is structurally distinct from phenothiazines
ethylene bond takes the place of the Sulfur. (49)

MECHANISM OF ACTION:

All medications that treat depression or mania have unique effects on 5- HT, NA, and/or
DA reuptake. Typically, a significant percentage of the 5HT/NA released at the nerve
ends is re-absorbable into its storage sites, where it is rendered inactive. (48,49)
By attaching to their transporters, neuronal NA and, to varying degrees, 5-HT reuptake
are inhibited in the brain. As a result, the synaptic gap experiences a localised rise in
NA/5-HT levels. (49)
Block α1 and, to a lesser extent α2 presynaptic adrenoreceptors in a varied manner; and
have anti-muscarinic effects in the brain. (49)

Additionally, various TCA inhibit dopamine, histamine ach, and also other
neurotransmitters to varying degrees (49).

PHARMACOLOGICAL ACTIONS:

Behavioral effects: While imipramine and MAOI have similar antidepressant effects,
28
their respective mechanisms of action are distinct. Without regenerating brain
monoamines, the medication can counteract the depressive effects of reserpine.
Additionally, it acts as a mild anxiolytic. (47,48)

Central nervous system: In normal persons, a single dose of 100 mg results in

sleepiness and a sense of lightheadedness. It induces moderate drowsiness, improves
sleep, and stops compulsive thinking. The medication increases stage 4 sleep while
suppressing REM sleep.
Repeated treatment may result in memory and attention problems, it should only be used
with people who have a history of seizures. (46,45,48)

29
ABSORPTION, FATE AND EXCRETION:

TCA are readily absorbed when taken orally. They are broadly dispersed, very lipophilic, and
firmly linked to proteins in many tissues. In general, hepatic CYP3A4 and CYP2D6 metabolise
antidepressants, and some of them are changed into an active metabolite with a prolonged half-
life. (50)

ADVERSE REACTIONS:

The endocrine side effects, such as galactorrhoea after taking clomipramine, amoxapine,
trimipramine, etc., are caused by blocking of the D2 receptor. TCA are often well tolerated.

 Allergic symptoms such photosensitivity, urticaria, and skin rashes(48,49,50).

 Antimuscarinic effects: TCA's most common and problematic side effects are
antimuscarinic effects. These include dry mouth, trouble sleeping, tachycardia,
constipation, problems urinating, impotence, delayed ejaculation, and, in rare cases,
hyperpyrexia. Patients with glaucoma or an enlarged prostate should use the medication
with caution. It can sporadically result in paralytic ileus. Confusion, disorientation, or
psychosis may be brought on by central antimuscarinic activity(50).

 Central nervous system: Fatigue, sluggishness, headaches, and weight gain may be
seen. Potent sedatives that can induce sleep include amitriptyline, trimipramine,
doxepin, trazodone, and mirtazepine. These medications, like MAOI, can lead to
tremors, muscle jerking, ataxia, and hyperreflexia. It is recommended to avoid them
when an epileptic (47).

 Cardiovascular system: Following long-term therapy, postural hypotension,

cardiomyopathy, and heart failure have been documented. Rarely, amitriptyline and
imipramine can both result in a flattened or inverted T wave, a prolonged QT interval,
and a depressed ST segment in the ECG. They have the ability to cause cardiac
arrhythmias when taken in excess(48).

 Miscellaneous: Similar to chlorpromazine, imipramine can result in

30
 edoema, agranulocytosis, and cholestatic jaundice. The heterocyclic drug trazodone can
cause priapism. Tricyclic antidepressants can cause hyperexcitability, jitteriness,
suckling issues, and in rare cases, heart arrhythmias in the newborn. Rarely, abruptly
stopping TCA can cause a cholinergic crisis and a flu-like illness(48).

 Tricyclic acute poisoning can cause convulsions, coma, hyperpyrexia, hypertension or

hypotension, and convulsions. Arrhythmias of the heart could be present. Additionally,
metabolic acidosis may result. The remedy only addresses symptoms. Anticholinergic
CNS symptoms are treated with parenterally administered doses of 1-4 mg of
physostigmine salicylate per hour (49).

 THERAPEUTIC USES:

 Major depression (44)

 Social phobias, anxiety disorders, and acute panic attacks (44)

 Obsessive compulsive neurosis (45)

 Migraine (46)

 Deafferentiation pain (45)

 ADHD (Attention deficit hyperactivity disorder) (44)

 CFS (Chronic fatigue syndrome) (45)

 Nonspecific fibromyalgias. (45)

SELECTIVE SEROTONIN (5-HT) REUPTAKE INHIBITORS (50):

The introduction of tricyclic antidepressants (TCAS) and monoamine oxidase

inhibitors in the 1950s revolutionized the treatment of MDD (major depressive
disorder). Since then, the search for more selective drug has continued. (51) This
movement of rational drug development gave birth to selective serotonin reuptake
inhibitors (SSRIS) and becoming the first-line drugs for the treatment of
MDD.SSRI are generally safer than the TCA in the elderly, because repeated
administration of TCA leads to gradual desensitisation of autoreceptor after
prolonged used of TCA for several week. (51)
31
MECHANISM OF ACTION:

SSRIS drug bind to the serotonin transporter (SERT) at a site other than the
binding site of 5-HT and inhibit the transporter. They act mainly by inhibiting the
reuptake of serotonin by the tryptaminergic neurons.
Because of their selective receptor actions they are as effective as TCA in
moderate depression but may be less effective in the severely depressed patients,
they may also cause. (49,50)

 Low grade anti-muscarinic effects. (50)

 Low grade antihistaminic effects, with less sedation. (49,50)

 Fewer cardiovascular effects (bradycardia, hypotension, conduction disturbances). (50)

THERAPEUTIC USES:

Only indicated in those patients who

 SSRI are clinically effective and also have better safety and tolerability profile than
tricyclics, mostly given at morning hour due to their stimulant effect. (49)

 These drugs are also preferred in the depressed geriatric patients as the TCA can cause
dizziness, postural hypotension, constipation and difficulty in micturition. (47,49,50)

COMMON SIDE EFFECT: (51)

 GASTROINTESTINAL (nausea, vomiting bleeding). 49

 Hepatotoxicity and hypersensitivity reaction (dermatologic and vascular

manifestation). 50

 Weight gain and metabolic disturbance. 50

 Cardiovascular (qt. interval prolongation, basal heart rate prolongation and HRV,
hypertension, orthostatic hypotension). 50

32
 Genitourinary (urinary retention, incontinence) 50

 Sexual dysfunction 50

 Hyponatremia 50

 Osteoporosis and fracture 49

 Bleeding 49

 Central nervous system (seizures threshold extra pyramidal side effects

 Sweating 50

PHARMACOKINETIC OF DRUG:

SSRI are well absorbed orally and have long half-lives which indicate that
elimination time of drug is prolonged and single dose is sufficient to produce
(49)
optimum therapeutic effect.

SEROTONERGIC SYNDROME:

Hyperstimulation of 5-HT1A receptors in brain stem leads to

seretonergicsyndrome. The treatment is symptomatic. The administration of an
MAOI concurrently with or immediately prior to one of these drugs. Proper drug
monitoring is being performed when serotonergic drugs is used in combination.
Sign and symptoms of serotonergic syndrome are (51,52):

 Cognitive-behavioral symptoms: mainly agitation, insomnia, anxiety hypomania and

seizures. (51)

 Autonomic symptoms: nausea, salivation, diaphoresis, diarrhea, abdominal cramps,

flushed skin, hypertension and hyperthermia. (52)

 Neuromuscular symptoms: hyperreflexia, shivering, twitching, rigidity. (52)

 Rhabdomyolysis, secondary to severe rigidity and hyperthermia, may occur. (52)

33
WITHDRAWAL EFFECT:

SSRIS can produce withdrawal symptoms such as anxiety,agitation, confusion, insomnia,

sweating, tremor, vomiting and shock like syndrome. May cause mania when used in
patients with undiagnosed bipolar depression.eg: Fluoxetine with a longer t½ is less likely
to cause these symptoms. (53)

DOSE:

FLUOXETINE DOSING INTERVAL:

Fluoxetine is used initially in the dose of 20 mg once a day, in the morning, increased by
20 mg once in several weeks, to a maximum of 80 mg daily (less in the elderly). Doses
higher than 20 mg should be given in two divided doses in the morning and at noon. (52,53)

DRUG OF CHOICE:

Choice of SSRI: All SSRIS are almost equally effective in the treatment of depression.
Hepatic metabolism plays keen role in the efficacy of drug because of their selective
profile, they may be useful in matching individual patient’s needs in terms of efficacy and
tolerability.

 Fluoxetine is currently considered the drug of choice for routine use (54).

 Paroxetine exerts more anti-muscarinic effects, may cause more weight gain as well
as pose a high risk of mood changes and withdrawal syndrome (55).

 Sertraline has relatively lower risk of drug interaction than the former drugs while
citalopram and escitalopram carry no such risk (56).

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS):

SNRI were first introduced in the mid-1990s as a class of antidepressant drugs. SNRI are
selectively act on (serotonin and nor epinephrine) sometimes called as dual reuptake
inhibitors or dual-acting antidepressants. Serotonin is the key hormone that stabilizes mood,
while norepinephrine influences emotions, alertness, and energy. (54,55,56)
SNRIS are used for those patients who are not responsive to SSRIS drug therapy typically

34
used to treat depression, for people having severe anxiety, nowadays SSRI AND SNRI are
considered as first drug of choice to treat psychiatrist symptoms as well as depressive
illness.
Sometimes the combination of SSRIS with tricyclic antidepressants is given to those
patients diagnosed with treatment-resistant depression with monotherapy. (56)

MECHANISM OF ACTION:

Serotonin is sometimes called a “feel-good” chemical because it’s associated with positive
feelings of well-being. Norepinephrine is related to alertness and energy. when these two
neurotransmitter are not present in sufficient quantity, this term is associated with a medical
illness known as depression. SNRIS block the reuptake of these two neurotransmitter back
into the brain cells which stabilize mood and ultimately relief depression. SNRIS helps treat
depression by balancing the levels of these two chemical messengers in your brain. (55,56,57)
INDICATION:

SNRIS can also help treat some chronic pain conditions, including fibromyalgia, chronic
musculoskeletal pain, and diabetic peripheral neuropathic pain. (57)

DRUG-INDUCED HEPATOTOXICITY:

 The elevation of alanine aminotransferase levels in liver above 3 times the upper
normal limit provides an indication (i.e. A ‘red flag') of hepatotoxicity. 58

 Drug-induced liver toxicity among patients taking SSRIS and SNRIS ranges from
0.5 to 1% and this risk seems to be more prevailing among patients exposed to
nefazodone, bupropion, agomelatine and duloxetine. 58

 Liver toxicity may occur within days to about 6 months after antidepressant
treatment initiation Antidepressant-induced liver injury is generally dose-dependent,
with higher doses being more likely to cause liver injury, which is life threatening to
the patients. 59

 In addition, polypharmacy, especially with the concomitant administration of

multiple compounds metabolized by the same CYP450 isoenzymes, is an important
risk factor for DILI. For example, the concomitant use of duloxetine plus trazodone,
duloxetine, fluoxetine, duloxetine, mirtazapine, venlafaxine and trazodone have
been associated with severe liver injury. 59

35
DOSE MONITORING:

Thus, clinicians should regularly monitor liver function while treating patients with
antidepressants, particularly if using agomelatine and duloxetine. Baseline liver function
tests should be tested prior to treatment initiation and thereafter following dose increments.
Special care should be taken when treating patients with preexisting liver disease and, if
possible drugs with low liver toxicity (for example, citalopram and escitalopram). 59,60

SIDE EFFECT:

Following adverse effects are reported in patient undergoing (SNRIS) therapy include
nausea, diarrhea, dyspepsia, GI bleeding and abdominal pain61.

 Venlafaxine can cause a clinically significant increase in diastolic blood pressure 62.

 Duloxetine and levomilnacipran may increase both systolic and diastolic blood
pressure.

 Among SNRIS, some studies suggest that venlafaxine may cause orthostatic
hypotension in more than 50% of patients aged over 60 years. It is also reported that
duloxetine can potentially cause orthostatic hypotension. 62

 Mirtazapine may cause orthostatic hypotension in up to 7% of patients. 62

 Mirtazapine and agomelatine have been associated with lower risks of sexual side
effects. 62

 Venlafaxine and mirtazapine also have been associated with an increased risk of
bleeding. 62

 The risk of bleeding appears to be higher with concomitant use of non-steroidal

anti-inflammatory drugs (NSAIDS) including aspirin, preexisting platelet
dysfunction, or a concomitant use of heparin. 61,62

 Venlafaxine trusted Source, may increase suicidal thoughts, particularly in the first
few weeks of treatment. 62

 The SNRIS have not been consistently associated with clinically significant cardiac
conduction defects or arrhythmias. 63

36
CONTRAINDICATION:
A person should avoid taking SNRIS along-side monoamine oxidase inhibitors (MAOIS).
(64)

PREGNANCY AND LACTATION:

SNRIS may cause complications during pregnancy. However, depression in the birthing
parent may also adversely affect the fetus’s development.64 Exposure to SNRIS (e.g.
Duloxetine and venlafaxine) has been associated with an increased risk of postpartum
hemorrhage, and venlafaxine in particular has been associated with an increased risk of
hypertension during pregnancy.64

NOREPINEPHRINE AND DOPAMINE REUPTAKE INHIBITORS (NDRIS):

ATYPICAL ANTIDEPRESSENT (BUPROPION):

Norepinephrine and dopamine reuptake inhibitors (ndris) are antidepressant medications

that block the action of specific transporter proteins, increasing the amount of active
norepinephrine and dopamine neurotransmitters in the brain. Bupropion (Wellbutrin) is the
main drug used to treat depression in the United States.65
In addition to depression NDRIS may also indicated for smoking cessation and seasonal
affective disorder. Additional, off-label indications include bipolar disorder and adult
attention-deficit hyperactivity disorder.65

BUPROPION:

When introduced in the United States in 1989, bupropion was categorized as an

“atypical”antidepressants because their mechanism of action differs from that of the other
known antidepressant classes (e.g., MAOIS, SSRIS, SNRIS) Might affect serotonin or
postsynaptic receptors and therefore is an antidepressant with unique pharmacologic
properties 66 Bupropion, a compound currently available in 3 distinct but bioequivalent
formulations8 (Wellbutrin, Wellbutrin SR [sustained-release], and Wellbutrin XL
[extended release])
Methylphenidate (Ritalin), a stimulant drug used to treat attention-deficit hyperactivity
disorder (ADHD) and narcolepsy, also inhibits the reuptake of dopamine and
37
norepinephrine but is generally not used to treat depression. 65,66

MECHANISM OF ACTION:

NDRIS inhibit the transport of norepinephrine and dopamine back into the brain cells that
released them. In turn, a greater number of active neurotransmitters remains available in the
brain, which may over time lead to changes that help relieve the symptoms of depression. 67

INDICATION:

 Major depressive disorder, particularly in people who do not respond well to|
selective serotonin reuptake inhibitors (ssris) or cannot tolerate SSRI side effects. 67

 Seasonal affective disorder. 67

 Nicotine addiction/smoking cessation. 67

 SSRI-associated sexual dysfunction. 67

 Bipolar depression. 67

 Attention-deficit hyperactivity disorder. 68

It may take 2 to 4 weeks after people start on an NDRI before experiencing an

improvement in their symptoms.68.

ADRs:

 Headache. 69

 Anxiety.69

 Dizziness. 69

 Ringing in the ears. 69

 Sweating. 69

 Dry mouth. 69

 Nausea. 69

 Abdominal pain. 69

 Weight loss. 69
38
 Constipation. 69

 High blood pressure. 69

 Tremors. 69

 Rash. 69

 Higher-than-normal energy levels and mood (hypomania – rare). 69

CONTRAINDICATION:

Bupropion may increase the risk of seizures. There is a greater risk with higher doses. Since
the medication can cause insomnia, it should not be used with people who have severe
insomnia.70

DRUD-DRUG INTERATION:

 Additionally, bupropion may interact with the following drugs:

 Tricyclic antidepressants. 71

 Monoamine oxidase inhibitors potentially cause serotonin syndrome. 72

 Levodopa and amantadine. 72

 Antipsychotics, theophylline, systematic steroids – can increase the risk of seizure.72

 Beta blockers and antiarrhythmics increase blood plasma concentration of drug.72

OVERDOSAGE:

Signs and symptoms of bupropion toxicity include:(71,72,73)

 Hallucinations.71

 Seizures. 71

 Loss of consciousness. 71

 Severe tachycardia/bradycardia. 71

 Cardiac conduction disturbances/arrhythmias. 71

 Cardiac failure. 71
39
Most people recover from an overdose, but deaths have been reported due to catastrophic
cardiac events and repeated, uncontrolled seizure. (73)

WITHHDRAWAL EFFECTS:(74)

 Headaches.74

 Irritability. 74

 Anxiety. 74

 Restlessness. 74

 Dizziness. 74

 Insomnia. 74

 Tiredness. 74

 Flu-like symptoms. 74

 Nausea and vomiting. 74

 Appetite changes. 74

 Aches and pains. 74

 “Electric shock” sensations. 74

 Tingling or prickling sensation in the skin. 74

 Withdrawal symptoms usually develop within 3-5 days of going off the
medication(75)

ABUSIVE DRUG

Bupropion can be used as abusive drug,it reported that this drug is being used for
intoxication provide stimulant effect, Some athletes may abuse bupropion to enhance their
motivation and achieve euphoria following symptoms are reported such as(75):

 Seizures. 75

 Psychotic symptoms. 75

 Cardiotoxicity. 75
40
MOOD STABILIZERS:

LITHIUM CARBONATE: The use of lithium carbonate in mental illness was described by
Cade in 1949. (76)

Lithium is useful as a mood stabiliser in manic depressive psychosis (MDP). As

Compared to chlorpromazine, lithium causes less drowsiness while lowering the
Psychomotor hyper activity in about 75% of the patients. (76)

MECHANISM OF ACTION:

 Its exact mechanism of action is not known. It causes:

 Inhibition of phospholipase C synthesis with subsequent decrease in brain inositol

 Triphosphate and dia-cylglycerol concentration. 77

 Modification of GABA concentration in the brain and modulation of synaptic

 Glutarnateavailability.77

 Decrease in the synthesis of DA and NA in the brain, and enabling neuronal

 Re-uptake. 77

 Decrease in the function of brain protein kinases, leading to modifications in the

release of neurotransmitters and hormones. 77

ABSORPTION, FATE AND EXCRETION:

 Given orally, it is well absorbed and gets distributed all over the body. Being a
metallic ion, it is not processed and protein-bound, excreted

 unchanged in the urine, the renal clearance being proportional to its plasma
concentration. Lithium declines the sodium reabsorption by the renal tubules
leading to sodium depletion. 77,78

41
ADVERSE REACTIONS:

 Lithium toxicity is closely related to its serum level and the therapeutic window is
narrow. Hence, the drug must be administered under supervision. 79

 Blood levels exceeding 2.0 meq/1 are associated with dangerous toxic effects. Salt
depletion from any cause, including a diuretic, increases the renal tubular
reabsorption of lithium and its plasma level, thus advancing toxicity. 79

 Mild toxicity includes GI disturbances, drowsiness, muscular weakness and

alopesia. 80

 It can also cause allergic reactions, blurred vision, glycosuria, polyuria and weight
gain. 80

 Large doses (level >1.5 mol/L) cause sodium depletion, cerebellar ataxia,
tremors. 80

 Cardiac arrythmias seizures, hypotension and coma. 80

 Chronic administration may give rise to goitre formation, hypothyroidism (rare). 80

 ECG changes. The drug should be administered cautiously in the presence of

Cardiovascular, renal or brain damage.79,80

 Embryotoxicity: Lithium is embryotoxic and increases the risk of Ebstein’s

anomaly. 80

THERAPEUTIC INDICATION:

 To prevent the recurrence of mania and of depressive episodes in bipolar disorder.

 Lithium salts are the first choice for long term prevention of MDP. 75,76

 To treat acute episodes of mania when combined with an anti- psychotic like
haloperidol.

 To treat alcohol dependence. 76

ALTERNATIVE METHOD TO CURE DEPRESSION:

42
There is no proof that any elective treatment our domestic remedy is successful in treating
direct to serious misery however a few individual with gentle misery we discover
advantage from domestic cures through expanded relaxation81
Relaxation can give elevation from depression indication it can also offer assistance adapt
with a few of the causes of discouragement such as grief uneasiness changing parts and
indeed physical torment on the off chance that you have sadness and are considering
utilizing an elective shape of therapy it is critical to look for council of the well- being care
provider example of elective treatment in corporate needle therapy,
biofeedback ,chiropractic ,medication, guided imagery ,home grown, cures, trance, rub
treatment, meditation unwinding ,yoga etc81

GENERAL WITHDRAWAL EFFECTS OF ANTIDEPRESSANT:

 55% of people who try to come off or reduce reports some degree of difficulty
doing so. 82

 61% Of people who try to come off or reduce reports some degree of difficulty
doing so 61% report my daughter effects with 44% of these describing the effects as
severe. 82

 40% report addiction with 39% of these describing their addiction as severe. 81,82

 Anxiety panic 66% and irritability 62% are particularly common. 81,82

 less than 1% has been told anything about withdrawal effects or dependence

43
 CHAPTER#2:

LITERATURE REVIEW

44
Literature Review:

The purpose of our literature review was to understand the state of research related to
different parameter on the disease depression. We have collected data through
different research review.
Depression is the leading cause of disability across the world. More than 300 million
people suffer from depression worldwide. According to the National Institute of
Mental Health, approximately 16.1 million people in 2015, and ages 18 and above,
experienced at least one of the major depressive symptoms within the past year.
Especially for college students in the United States, depression is a prevalent issue.
Within the college population, immigrant college students may be more susceptible to
depression According to different research reviews (84).

Literature and folk wisdom have long linked depression and death; however, only
recently have scientific studies examined the relation between them. Beginning in the
1970s, investigators compared mortality among patients treated for major depression
and the general population. Nine of ten studies found an increased mortality from
cardiovascular disease among depressed patients (85). However, such studies confound
the relation between depression and its treatment.
Community surveys circumvent this difficulty, but as these studies began to appear,
other investigations revealed the strong association between depression and cigarette
smoking, which made obvious a need to control for smoking.
The first study to do this appeared in 1993, and not only did a relation between
depression and mortality persist, but a relation between depression and the
development of ischemic disease was revealed (86). In the past 2 years, six more
community surveys have followed populations initially free of disease, and five have
observed an increased risk of ischemic heart disease among depressed persons.
Another research strategy is to start with subjects who have preexisting cardiovascular
disease. Here, too, depression has consistently been associated with a worse outcome.
In one well-designed study, patients with depression in the period immediately after a
myocardial infarction were 3.5 times more likely to die than nondepressed patients.
The basis of this association remains speculative. However, it is likely that the changes
in the autonomic nervous system and platelets that are seen in depression account for a
substantial portion of the association. (Am J Psychiatry 1998; 155:4–11) (87).
45
For centuries poets and folklore have asserted that there is a relation between the mind
and body in general and human moods and the heart in particular. Almost 400 years
ago Shakespeare wrote, “My life. Sinks down to death, oppressed with melancholy”
(Sonnet 45). However, only in the last few years has this conviction been scientifically
tested. Nevertheless, it is now abundantly clear that depression is associated with
ischemic heart disease (87,88). The ‘vascular depression’ hypothesis proposes that
vascular disease predisposes to, precipitates or perpetuates depression, and this
proposal has stimulated further research into the relationship of depression to vascular
disease. Methods: We investigated the nature of the relationship between depression
and vascular diseases by reviewing epidemiological, clinical, neuroimaging and
neuropathology studies which have reported on the relationship of depression to
coronary artery disease, stroke disease, alterations in blood pressure, vascular
dementia, diabetes mellitus and cholesterol levels and by reviewing potential
mechanisms by which depression could be associated with vascular diseases (89).
Results: there is abundant and increasing evidence from these different lines of
research that depression has a bidirectional association with vascular diseases and
plausible mechanisms exist which explain how depression might increase these
vascular diseases and vice versa (89). Limitations: this was not a systematic review and
so not every report of relevance has been included. Conclusions: depression has a
clear bidirectional relationship with vascular diseases. Further study is needed to
clarify the mechanisms involved and to investigate the benefits of conventional and
novel treatments for vascular diseases in depressive illness (87,89)

In 1970 L G Kiloh and I finished recruiting patients for a prospective study of

depression in admissions to a new general hospital psychiatric unit. When we
published the 15 year follow up we discovered that our patients had not done at all.

.1 Only a fifth recovered and remained continuously well, three fifths recovered but had
further episodes, and a fifth either committed suicide or were always incapacitated (90).
An English 15 year follow up study published at the same time showed identical
results.2 The obvious conclusion was that people admitted to hospital in the 1970s
with a depressive illness did not have a good prognosis. In retrospect, I ask why more
of those who relapsed did not return to us for treatment (91). These results are not
atypical. A detailed 12 year follow up in US specialist care showed that patients on
average had symptoms in 59% of weeks and met full criteria for a depressive episode
in 15% of weeks (90,91).
46
Reviews the literature regarding depression in Parkinson's disease and synthesizes the
information into a neurobiological model relating structural and biochemical changes
in this disorder to behavioral manifestations (92). Depression occurs in approximately
40% of patients with Parkinson's disease; depression in Parkinson's disease is
distinguished from other depressive disorders by greater anxiety and less self-punitive
ideation. Lower cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-
HIAA), a past history of depression, and greater functional disability are associated
with a greater risk of depression in Parkinson's disease (93). Female gender, early age at
onset of Parkinson's disease, and greater left brain involvement may also be risk
factors. Approximately half of depressed patients with Parkinson's disease meet
criteria for major depressive episodes; half have dysthymia. (PsycINFO Database
Record (c) 2016 APA, all rights reserved) (94).

Depression and cancer commonly co-occur. The prevalence of depression among

cancer patients increases with disease severity and symptoms such as pain and fatigue.
The literature on depression as a predictor of cancer incidence is mixed, although
chronic and severe depression may be associated with elevated cancer risk (95). There is
divided but stronger evidence that depression predicts cancer progression and
mortality, although disentangling the deleterious effects of disease progression on
mood complicates this research, as does the fact that some symptoms of cancer and its
treatment mimic depression. There is evidence that providing psychosocial support
reduces depression, anxiety, and pain, and may increase survival time with cancer,
although studies in this latter area are also divided (96).

Psychophysiological mechanisms linking depression and cancer progression include

dysregulation of the hypothalamic-pituitary-adrenal axis, especially diurnal variation
in cortisol and melatonin. Depression also affects components of immune function that
may affect cancer surveillance. Thus, there is evidence of a bidirectional relationship
between cancer and depression, offering new opportunities for therapeutic
intervention. (95,96) Coronary artery disease (CAD) as well as depression are both highly
prevalent diseases. Both cause a significant decrease in quality of life for the patient
and impose a significant economic burden on society (97). There are several factors that
seem to link depression with the development of CAD and with a worse outcome in
patients with established CAD: worse adherence to prescribed medication and life
style modifications in depressive patients, as well as higher rates in abnormal platelet
47
function, endothelial dysfunction and lowered heart rate variability (98). The evidence is
growing that depression per se is an independent risk factor for cardiac events in a
patient population without known CAD and also in patients with established diagnosis
of CAD, particularly after myocardial infarction. Treatment of depression has been
shown to improve patients' quality of life. However, it did not improve cardiovascular
prognosis in depressed patients even though there is open discussion about the trend to
better outcome in treated patients. Large scale clinical trials are needed to answer this
question (99,100). Selective serotonin reuptake inhibitors seem to be preferable to
tricyclic antidepressants for treatment of depressive patients with comorbid CAD
because of their good tolerability and absence of significant cardiovascular side
effects. Hypericum perforatum (St. John's wort), an increasingly used herbal
antidepressant drug should be used with caution due to severe and possibly dangerous
interaction with cardio active drugs (98,99,100).

Depression is a highly prevalent risk factor for incident coronary heart disease (CHD)
and for cardiovascular morbidity and mortality in patients with established CHD.
Several biological and behavioral mechanisms have been hypothesized to underlie the
relationship between depression and CHD, but none has been shown to account for
more than a small proportion of the risk (101). Only a few clinical trials have examined
whether treating depression decreases the risk of cardiac events in patients with
established CHD (102). None of these trials has shown that treatment results in improved
cardiac outcomes, but the differences in depression outcomes between the intervention
and control groups have been small and not clinically significant (103). Nevertheless,
secondary analyses of these trials suggest that prognosis improves when depression
improves. Concerted efforts to develop more potent interventions for depression,
identification of high-risk subtypes of depression, and further research on the
biobehavioral mechanisms linking depression to CHD are needed to pave the way for
definitive clinical trials (104).

Depressive disorders (DDs) are one of the most widespread forms of psychiatric
pathology. According to the World Health Organization, about 350 million people in
the world are affected by this condition. Family and twin studies have demonstrated
that the contribution of genetic factors to the risk of the onset of DDs is quite large.
Various methodological approaches (analysis of candidate genes, genome-wide

48
association analysis, genome-wide sequencing) have been used, and a large number of
the associations between genes and different clinical DD variants and DD subpheno
types have been published. However, in most cases, these associations have not been
confirmed in replication studies, and only a small number of genes have been proven
to be associated with DD development risk (104,105)

To ascertain the role of genetic factors in DD pathogenesis, further investigations of

the relevant conditions are required. Special consideration should be given to the
polygenic characteristics noted in whole-genome studies of the heritability of the
disorder without a pronounced effect of the major gene. These observations accentuate
the relevance of the analysis of gene-interaction roles in DD development and
progression. It is important that association studies of the inherited variants of the
genome should be supported by analysis of dynamic changes during DD progression
(105)
.

Epigenetic changes that cause modifications of a gene's functional state without

changing its coding sequence are of primary interest. However, the opportunities for
studying changes in the epigenome, transcriptome, and proteome during DD are
limited by the nature of the disease and the need for brain tissue analysis, which is
possible only postmortem (106). Therefore, any association studies between DD
pathogenesis and epigenetic factors must be supplemented through the use of different
animal models of depression. A threefold approach comprising the combination of
gene association studies, assessment of the epigenetic state in DD patients, and
analysis of different “omic” changes in animal depression models will make it
possible to evaluate the contribution of genetic, epigenetic, and environmental factors
to the development of different forms of depression and to help develop ways to
decrease the risk of depression and improve the treatment of DD (106,107).

Depression is highly prevalent in cardiac patients, with 20% to 40% of patients

meeting criteria for major depressive disorder or experiencing an elevation in
depressive symptoms (108). These depressive symptoms are often chronic and
persistent, and they have been associated with the development and progression of
coronary artery disease, worse health-related quality of life, poor physical functioning,
recurrent cardiac events, and a 2- to 2.5-fold increased risk of mortality. Impaired
adherence to health behaviors and adverse physiological effects of depression,
49
including inflammation, endothelial dysfunction, platelet hyperactivity, and autonomic
nervous system abnormalities, may link depression with adverse cardiac outcomes.

Pharmacologic and psychotherapeutic interventions appear to be safe and effective at

reducing depressive symptoms in patients with cardiovascular disease and may impact
cardiac outcomes (109). Unfortunately, depression often is unrecognized and untreated
in this population, despite the availability of brief screening tools that can be used for
this purpose. We recommend the routine screening of cardiac patients for depression
when there are adequate mechanisms for management and referral, such as available
consulting psychiatrists or care management programs that facilitate the delivery of
pharmacologic and psychotherapeutic treatments in this vulnerable population
(108,109,110)
.

The present study examined depressive symptomatology in 440 adults with sickle cell
disease (SCD). Participants completed the Center for Epidemiologic Studies-
Depression scale (CES-D) as part of their yearly routine visits to the Duke University-
University of North Carolina Comprehensive Sickle Cell Center (111). They also
completed questions regarding demographics, disease severity, pain, and health care
use. Data analyses revealed that the percentage of patients with SCD exhibiting
significant depressive symptomatology dropped from 43 to 18% when a more
stringent cutoff was used on the CES-D, suggesting that future studies should
determine the most valid cutoff score for identifying depression in patients with SCD
(112)
.

Gender and family income were positively and significantly associated with
depressive symptomatology. Also, patients who reported more frequent painful
episodes were more likely to report depressive symptoms. Implications for assessment
and treatment of depression in adults with SCD are discussed (113).

50
CHAPTER # 3: METHODOLOGY

51
METHODOLOGY:

STUDY DESIGN AND PARTICIPANTS

This cross-sectional study included general population under age from 13 or above

Both male female are included

This study was conducted from February 2022 to July 2022
All the general population includes student employed unemployed married single businessman
were took the part in survey

The survey was in the form of online questionnaire and the result was compile with the help of
Microsoft excel

INSTRUMENTS

The online questionnaire over the internet took approximately 20 to 30 minutes to answer and
collected data about:

Demographics: age, ethnicity/race, marital status, employment status, Simultaneous study of

depression included.

PROCEDURES

Data collection duration was 6 months from Feb 2022 to July 2022 and the online questionnaire
was explained the objectives of the study, and asked the public to fill out the questionnaire, and
guaranteed confidentiality of the data they provided.

Data analysis
The data collected were keyed into Excel
Descriptive analysis with measurements of frequency, and percentages was used to express
sociodemographic variables and results from the questionnaires. General population were
compared for demographic, socioeconomic, and health variables using the pie charts

Ethical consideration:
Confidentiality of the participant was preserved by not revealing their names and identity in
the data collection

52
CHAPTER # 4: RESULTS

53
Results:
Demographic Details of Participants:
This survey was conducted on general public with age range starting from under 13 to 65+,
so the survey was conducted over the Internet in which 70% of the response were recorded
from audience aged between 18 to 25, in which 53.9% were female and rest of the 46.1%
were male from which the 70% of them were single and 27.2 were married by marital status.
This response was collected in which 61.7% were student while 18.3% were employed with
interest from both the public and private sectors and 7.2% had their own business while
10.6% were unemployed. A total of 180 responses were recorded. A detailed information
and responses of all the contributors is described in table below.

Demographic Data of Participants:

Age range:
In age range starting from under 13 to 65+, 70% of the response were received from
audience aged between 18 to 25 while 21.7% were received from age ranges in between 26-
30 and remaining 8.3% received from the age of above 35.

Gender:
The response were recorded from which 53.9% were female and rest of the 46.1% were
male.

54
Race/Ethnicity:
In this survey 95.6% of the response were recorded from Asian people while remaining
4.4% were recorded from middle eastern or native Hawaiian.

Marital status:
The 70% of the response were received from single people and 27.2 were received from
married while 2.8% were divorced by marital status.

Employment status:
This response were collected in which 61.7% were student while 18.3% were employed
with interest from both the public and private sectors and 7.2% had their own business while
10.6% were unemployed.

Frequency and Percentage Distribution Tables:

Over the last two weeks, how often have participants been bothered by any of the
following problems that are, Feeling of sadness, worthlessness, emptiness as there is
55
no joy in your life anymore.
From the data collected 25% of the participants feel sadness, worthlessness, emptiness
several days and 12.8% nearly every day over the last two weeks while rest of the 57.8%
do not feel like this at all.

Little interest in doing things that was important to them once upon a time.
From the data collected 38.9% of the participants feel little interest in doing things that
were important to them once upon a time several days and 8.9% nearly every day while
rest of the 46.1% do not feel like this at all.

50.00%
45.00%
40.00%
35.00%
30.00%
25.00%
20.00%
15.00%
10.00%
5.00%
0.00%
Little interest in do-
ing things that were
important to you
Several
once day
upon a Nearly
time every day More than half of the day Not at all

Little interest in talking to family and friends.

From the data collected 25.6% of the participants feel little interest in talking to family
and friends several days and 14.4% nearly every day while rest of the 54.4% do not feel
like this at all.

56
Having trouble in all their relationships (home as well as professional).
From the data collected 25% of the participants had trouble in all their relationships
(home as well as professional) several days and 7.2% nearly every day while rest of the
60% do not had trouble at all.

80%

70%

60%

50%

40%

30%

20%

10%

0%
Having trouble in all your relationships (home as well as professional).

Several days Nearly Every day

More than half of the day Not at all

Facing lack of concentration.

From the data collected 37.2% of the participants faced lack of concentration several days
and 8.3% nearly every day while rest of the 48.3% do not faced lack of concentration at
all.

57
Feeling tired or having little energy.
From the data collected 32.8% of the participants feel tired or having little energy several
days and 15.6% nearly every day while rest of the 43.3% do not faced lack of
concentration at all.

Trouble falling or staying asleep, or sleeping too much.

From the data collected 20% of the participants had trouble falling or staying asleep, or
they may sleeping too much several days and 16.1% nearly every day while rest of the
57.2% do not that trouble at all.

Poor appetite or overeating.

From the data collected 24.4% of the participants had Poor appetite or they may
overeating several days and 7.2% nearly every day while rest of the 62.2% do not had
trouble at all.

58
Feeling very irritated and angry recently.
From the data collected 30.6% of the participants feel very irritated and angry recently
several days and 11.1% nearly every day while rest of the 52.2% do not feel like this at
all.

60.00%

50.00%

40.00%

30.00%

20.00%

10.00%

0.00%
Feeling very irri-
tated and angry
recently

Several days Nearly every day

More than half of the day Not at all

Feeling guilty for everything they do.

From the data collected 30.6% of the participants felt guilty for everything they do several
days and 11.1% nearly every day while the rest of the 52.2% do not feel like this at all.

Moving or speaking so slowly that other people could have noticed Or the opposite -
being so fidgety or restless that they have been moving around a lot more than usual.
59
From the data collected 18.3% of the participants move or speak so slowly that other people
could have noticed Or the opposite - being so fidgety or restless that they had been moving
around a lot more than usual over several days and 6.7% nearly every day while rest of the
71.1% do not had trouble at all.

Thoughts that they would be better off dead or of hurting themselves.

From the data collected 18.9% of the participants had thoughts that they would be better off
dead, or of hurting themselves over several days while 72.8% do not had these thoughts at
all.

80.00%
70.00%
60.00%
50.00%
40.00%
30.00%
20.00%
10.00%
0.00%
Thoughts that you
would be better off
dead, or of hurting
yourself

several days Nearly every day

Not more than half of the day Not at all

Having suicidal thoughts.

From the data collected 85% of the participants had suicidal thoughts over several days
while 12.2% do not had these thoughts at all.

If participants feel depressed, they know whom to approach and where to go.
60
From the data collected 62.2% of the participants knew whom to approach and where to
go while 37.8% do not know whom to approach and where to go.

If they have been diagnosed with any of form of depression in the past.
From the data collected 15% of the participants diagnosed with any form of depression in
the past while 85% do not diagnosed.

Type of depression they were diagnosed with in the past or currently.

From the data collected 63.9% participants were not diagnosed with any type of
depression in the past and 19.3% diagnosed with situational depressive disorder, 10.2%
with bipolar disorder also depression due to illness,6% with seasonal affective disorder
also major depressive disorder while 4.2% with psychotic depression, 3.6% with
posttraumatic stress disorder, 1.8% with postpartum (or perinatal) depression also treatment
resistant depression, 1.2% with premenstrual dysphoric disorder also atypical depression
while 0.6% with attention-deficit/hyperactivity disorder also sub-syndromal depression,
substance-induced mood disorder, mother illness stress, borderline personality disorder,
insomnia.

61
If they have ever approached to the following
From the data collected 78% of the participants approached none and 5.4% approached
counselor while few participants approached their friends or family members.

If they have ever received treatment/support for your depression.

From the data collected 16.1% of the participants received treatment or support for their
depression while 83.9% never received treatment.

62
If they have any of the following general health conditions.
From the data collected 78.9% not had any of the general health conditions, 11.8% had
blood pressure problem, 3.7% had arthritis or other chronic pain, 6.2% had diabetes and
1.9% had heart diseases while other 0.6% had COPD or other lung condition, Movement
Disorders (involuntary tics, tardive dyskinesia), headache and eye pain, asthma, severe
back pain, TB, acne, migraine.

The thoughts of participants about the main reason contributing to their depression.
From the data collected 21% of the participants might think the main reason contributing
to their depression were relationship problems, 17.8% due to financial problems, 16.7%
due to grief or loss of someone or something, 16.1% due to loneliness or isolation, 11.7%
due to past trauma, 7.2% due to any illness or coronavirus, 2.8% due to current events like
news or politics while 2.2% due to racism.

63
64
CHAPTER # 5: DISCUSSION

65
DISCUSSION:

The total number of responses that were recorded were 180 inclusive of both genders, 53.9% of
females, 46.1% of males among which 70% of were single and 27.2% of were married and the
remaining were divorced. 61.7% were students and 10.6% were unemployed 18.3% were
employed and 7.2% were self-employed. the most targeted age group recorded is 18-25 with
70% of ratio 21.7% were 26-34 years of age. 96% of Asians were recorded.

The recorded audience of clinical depression 12.8% felt symptoms nearly every day 8.9% felt
no interest in everyday activity 14.4% of audience were recorded feeling of isolation nearly
every-day, 7.2% were facing troubling with relationship 15.6% felt tired nearly every day 16.1%
felt insomniac nearly every-day 7.2 were recorded with poor apetite 12.2% felt suicidal for
several days.

62.2% seek help from professionals and among which 155 were previously diagnosed with
depression and 16.1% received treatment and support.

The study was done to get a feel for the percentage of people suffering from clinical depression
and to better serve those suffering from the disorder. Students, the unemployed, the single, and
the married, as well as young people in general, were all included in the survey's target
demographic. Those between the ages of 19 and 25 were the most worried, since they are just
starting out in their jobs and would need a lot of positive energy to make it.

Those between the ages of 30 and 45 were the focus of the second set of concerns because they
are the backbone of society; as parents, they are essential to the development of future
generations. The prevalence of depression was found to be 26.2% across the board in a research
of the same kind conducted in Turkey.

In comparison to our findings [91] is substantially smaller. According to our research, the rate of
depression among college students is much greater among females than among boys, and there
is a large racial/ethnic gap in the rate of depression. This is consistent with data from 1999 [92],
which found that roughly 10% of men and 20% of women experience major depression at some
point in their lives. The Global Burden of Disease research [92] likewise found that the
prevalence of depression was higher in women than in men.

66
Undergraduates have been shown to utilize medication irrationally to modify their mood. for the
purpose of this investigation. Those who had relatively minor difficulties were more likely to
take medication regularly low levels of depression (p 0.002). Most students did not seek medical
counsel for their conditions, and only a small percentage of students with a "normal" level of
depression additionally used medication to modify their mood. Sixty-one percent of the students
reported improvement after taking the medication, but five percent of the slightly depressed
students had the opposite effect (p = 0.02). These findings highlight the need of educating
students about the risks of self-medication and the benefits of responsible drug use.

Regular participation in academic pursuits was considerably with the stress and time
commitments of schoolwork, including studying, writing, and taking tests. Students who did not
suffer from depression were more numerous among those who had enough study time,
suggesting that those students who did not have this luxury were more likely to develop the
condition. Academic stress was also reported to be strongly linked with depression by
MacGeorge et al. and Ang &Haun [93,94]. We hypothesised that students who were struggling to
pay their educational expenses would exhibit signs of despair, but the contrary was true.

Furthermore, the following were the outcomes:

-Of the 180 people who filled out the survey, 53.9% were women and 46.1% were men; of the
women, 70% were single; of the men, 27.2% were married; and the rest were divorced.

Whereas the results of a 2012 research by Zainab Saima and colleagues at AKU were as shown
below:

Approximately 66% of married women from both groups were found to be depressed in
the research.

ladies of different economic backgrounds in Pakistan. This is rather high and consistent with
other research findings [95-98]. Despite the fact that a small number of studies have found a low
prevalence of depression in Pakistan these studies have either included both sexes, reducing the
impact of depression on women, or focused on subsets of the population, such as pregnant
women or women living in rural areas.

Though depressive symptoms were equally common in those of high and low socioeconomic
status, the risk factors for depression varied widely across the two groups. Separate research by
the same team of scholars found that social interactions, as opposed to social situations, were
more significant in bringing about depression among pregnant women [99].
67
However, variables based on socioeconomic status were not determined.
We found a strong correlation between having few friends and feeling depressed among those of
low socioeconomic status. In a married woman's life, her social interactions centre on her
family: her husband, her in-laws, and her offspring [100,101]. Women from lower socioeconomic
backgrounds rely heavily on their social networks since, once married, they often move in with
their husband's extended family. They are mostly concerned with the welfare of their immediate
family. Previous research has also shown that marital dissatisfaction is a significant factor in the
development of mental disorders among married women. Our research confirms the results of a
previous study which found that married women often find it difficult to interact with their
spouse's relatives.

Arguing with the in-laws and Abusive Language.

Three are linked to increased risk of mental illness among married women.
The connection with the spouse has been linked to depression in previous research. Spousal
abuse, whether verbal or physical, has been linked to higher rates of depression among married
women. In our research, we found that this was the case for low-socioeconomic-status women.
When a man is the head of the home in Pakistan, he tends to micromanage everything, including
limiting women's ability to make important life choices and causing marital strife [101].

Marriage stress and marital conflict have both been linked to an increased incidence of
depression in wives. A husband's professional success or the presence of an extramarital affair
may also contribute to marital discord.

Among married women of high socioeconomic status, we found that social circumstances and
housework were more likely to be related with depression than social interactions. Previous
research has linked the following social factors to depression significantly: advanced age,
delayed marriage, low levels of education, homemaking responsibilities, and economic hardship
[102].

High-society women have to keep up their standard of life and social standing. The societal
climate puts continual stress on them. Worry sets in whenever they have trouble making ends
meet and keeping up appearances.

Because most women in this socioeconomic bracket spend time outside the home in pursuit of
education or socialization, they often have to juggle many responsibilities, both those outside
the home and at home. If they don't have enough help with the housework, it might add to their
stress levels, which can worsen their melancholy. They get quickly overwhelmed and exhausted
by any circumstance that requires them to carry out domestic duties. According to the research,
68
domestic stress is a major contributor to depression among women with post-secondary
education. Forced domesticity may bring out the worst in even the most independent person
could add to the risk of mental disorder [103].

69
CHAPTER # 6: CONCLUSION

70
CONCLUSION:

We conclude in this study that a big number of people are diagnosed and affected with depression
usually from the young adult and are facing difficulties in their daily routine and work schedules
By analyzing the results a big number of students were found to be affected showing that the
educational sectors are influencing the mental health of the students directly causing them to feel
worthless and hard to carry their daily life , with respect to this survey it is the responsibility of
higher authorities to take measures for prevention of depression in students and provide them
proper psychological assessment and counselling with in the institution so that they can get along
with life with motivation to do something good with their life ahead as they’re the future pillar of
our economy and society .

71
REFERENCES

72
REFRENCES:

1. Blair-West G.W., Mellsop G.W. and Eyeson-Annan M.L., Down-rating lifetime

suicide risk in major depression, Acta PsychiatrScand, 95, 259-263 (2010)

2. Borowsky S.J., Rubenstein L.V., Meredith L.S., Camp P., Jackson-Triche M. and
Wells K.B., Who is at risk of nondetection of mental health problems in primary
care, J Gen Intern Med,. 15, 381-388 (2000)

3. Carvalho A, F, Sharma M, S, Brunoni A, R, Vieta E, Fava G, A: The Safety,

Tolerability and Risks Associated with the Use of Newer Generation Antidepressant
Drugs: A Critical Review of the Literature. Psychother-Psychosom 2016;85:270
288. doi: 10.1159/000447034

4. Consensus Development Panel, NIMH/NIH Consensus Development Conference

statement Mood disorders: pharmacologic prevention of recurrences, Am J
Psychiatry, 142, 469-476 (2003)

5. Cooper-Patrick L., Crum R.M., Ford D.E., Characteristics of patients with major
depression who received care in general medical and specialty mental health
settings, Med Care, 32, 15-24 (2009)
6. Davis, L., Uezato, A., Newell, J. M., & Frazier, E. (2008). Major depression and
comorbid substance use disorders. Current opinion in psychiatry, 21(1), 14–18.
https://doi.org/10.1097/YCO.0b013e3282f32408
7. Depression Guideline Panel. Depression in Primary Care: Volume 1.
Detection and Diagnosis Clinical Practice Guideline, Number 5. Rockville,
Maryland: U.S Department of Health and Human Services; AHCPR No 0493- 0550 (2001)
8. Gerber P.D., Barrett J., Barrett J., Manheimer E., Whiting R. and Smith R.,
Recognition of depression by internists in primary care, a comparison of internist
and gold standard psychiatric assessments, J Gen Intern Med,. 4, 7- 13 (2003)
9. Greenberg P.E., Stiglin L.E., Finkelstein S.N. and Berndt E.R., The economic
burden
of depression in 1990, J Clan Psychiatry, 54, 405-418 (2009)
10. Harris E.C., Barraclough B., Suicide as an outcome formental disorders, A meta-
73
 analysis Br J Psychiatry, 170, 205-228. (2001)
11. Howland R., General health, health care utilization, and medical comorbidity in
dysthymia, Int J Psychiatry Med 23, 211-238 (2005)
https://www.aafp.org/pubs/afp/issues/2006/0801/p449.html
12. Katon W. The epidemiology of depression in medical care, Int J Psychiatry Med,
17,
93-112 (2006)
13. Kessler R.C., Nelson C.B., McGongale K.A., Liu J., Swartz M. and Blazer
DG., Comorbidity of DSMIIIR major depressive disorder in the general
population, Results from the US National Comorbidity Survey, Br J Psychiatry,
168, 17-30 (2006)
14. Kessler R.C., Nelson C.B., McGongale K.A., Liu J., Swartz M. and Blazer DG.,
Comorbidity of DSMIIIR major depressive disorder in the general population,
Results from the US National Comorbidity Survey, Br J Psychiatry, 168, 17-30
(2006)

15. Klinkman M.S., Competing demands in psychosocial care, A model for the
identification and treatment of depressive
disorders in primary care, Gen Hospital
Psychiatry, 19, 98-111 (2001)
16. Murray L., Stanley C., Hooper R., King F., Fiori-Cowley A, The role of infant
factors in postnatal depression and mother-infant interactions, Dev Med Child
Neurol, 38, 109 ,119 (2000)
17. Murray L., Stanley C., Hooper R., King F., Fiori-Cowley A, The role of infant
factors in postnatal depression and mother-infant interactions, Dev Med Child
Neurol, 38, 109,119 (2000)
18. Musselman D., Evans D. and Nemeroff C., The relationship of depression to
cardiovascular disease, ArchGen Psychiatry, 55, 580-592 (2002)
19. Nefs, G., Pouwer, F., Denollet, J., & Pop, V. (2012). The course of depressive
symptoms in primary care patients with type 2 diabetes: results from the Diabetes,
Depression, Type D Personality Zuidoost-Brabant (DiaDDZoB) Study.
Diabetologia, 55(3), 608-616.
20. Nefs, Giesje, et al. "The course of depressive symptoms in primary care patients
with type 2 diabetes: results from the Diabetes, Depression, Type D Personality
Zuidoost-Brabant (DiaDDZoB) Study." Diabetologia 55.3 (2012): 608-616.
74
21. Patel, K., Allen, S., Haque, M. N., Angelescu, I., Baumeister, D., & Tracy, D.
K. (2016). Bupropion: a systematic review and meta-analysis of effectiveness as an
antidepressant. Therapeutic advances in psychopharmacology, 6(2), 99– 144.
https://doi.org/10.1177/2045125316629071
22. Paykel E. and Priest R., Recognition and management of depression in general
practice, consensus statement, BMJ 305, 1198-1202 (2002)

23. Pennix B.W., Guralnik J.M., Ferrucci L., Simonsick E.M., Deeg D.J., Wallace
R.B., Depressive symptoms and physical decline in community-dwelling older
persons JAMA, 276, 1720-1726 (2007) American Psychiatric Association,
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Washington,
DC: American Psychiatric Association (2000)
24. Pincus H.A., Tanielian T.L. and Marcus S.C., et al., Prescribing trends in
psychotropic medications, primary care, psychiatry and other medical specialities,
JAMA, 279, 526-531 (2007)
25. Regier D.A., Narrow W.E., Rae D.S., Manderscheid R.W., Locke B.Z. and
Goodwin F.K., The de facto US mental and addictive disorders service system,
Epidemiologic catchment area prospective 1-year prevalence rates of disorders and
services, Arch Gen Psychiatry, 50, 85-94 (2005)
26. Robins L., Regier D., Psychiatric Disorders in America, New York: Free Press
(2004)
27. SatoskerR.S ,BandarkarR.D,Rege N.N, (2015). Pharmacology and Therapeutics
(24
ed). Indiapvt.ltd.ReedElsevier.ThomsonPress.chap( 13,14),346-370.
https://pborhome.files.wordpress.com/2019/09/pharmacology
pharmacotherapeutics-by-r.-s.satoskar.
pdf#%5B%7B%22num%22%3A356%2C%22gen%22%3A0%7D%2
C%7B%22name%22%3A%22XYZ%22%7D%2C5%2C554%2Cnull%5D
28. Simon G.E. and Von Korff M., Recognition, management, and outcomes of
depression in primary care,Arch Fam Med., 4, 99-105 (2007)

29. Simon G.E., Von Korff M. and Durham M.L., Predictors of outpatient mental
health utilization by primary care patients in a health maintenance organization,
Am J Psychiatry, 151, 908-913 (2004)
30. Song F., Freemantle N. and Sheldon T.A., et al., Selective serotonin reuptake
inhibitors: meta-analysis of efficacy and acceptability, BMJ, 306, 683-687 (2006)
75
31. Tabák, A. G., Akbaraly, T. N., Batty, G. D., &Kivimäki, M. (2014).
Depression and type 2 diabetes: a causal association? The lancet Diabetes &
endocrinology, 2(3), 236-245.
32. Talbot, F., & Nouwen, A. (2000). A review of the relationship between depression
and diabetes in adults: Diabetes care, 23(10), 1556-1562.
33. Valkovic, P., Minar, M., Singliarova, H., Harsany, J., Hanakova, M., Martinkova,
J., & Benetin, J. (2015). Pain in Parkinson´ s disease: a cross- sectional study of its
prevalence, types, and relationship to depression and quality of life. PLoS One,
10(8), e0136541.
34. Wagner R., Burns B.J., Yarnall K., Sigmon A., Walker R. and Gaynes B.N., Minor
depression in family practice: functional morbidity, comorbidity, service
utilization and outcomes, Psychol Med., 30(6), 1377-1390 (2000)
35. Warner, C. H., Bobo, W., Warner, C., Reid, S., & Rachal, J. (2006).
Antidepressant discontinuation syndrome. American family physician, 74(3), 449
456.
36. Wells K.B., Burnam M.A., Rogers W., Hays R., Camp P., The course of
depression in adult outpatients Results from the Medical Outcomes Study, Arch
Gen Psychiatry, 49, 788-794 (2002)

37. Wells K.B., Stewart A., Hays R.D. et al., The functioning and well-being of
depressed patients Results from the Medical Outcomes Study, JAMA, 262, 914|
919 (2002)
38. Williams J.W. Jr, Kerber C.A., Mulrow C.D., Medina A. and Aguilar C.,
Depressive disorders in primary care: prevalence, functional disability and
identification, J Gen Intern Med., 10, 7-12 (2008)
39. Glassman, A. H., & Shapiro, P. A. (1998). Depression and the course of coronary
artery disease. American Journal of Psychiatry, 155(1), 4-11.
40. Thomas, A. J., Kalaria, R. N., & T O’Brien, J. (2004). Depression and vascular
disease: what is the relationship? Journal of affective disorders, 79(1- 3), 81-95.
41. Andrews, G. (2001). Should depression be managed as a chronic disease?.Bmj,
322(7283), 419-421.
42. Cummings, J. L. (1992). Depression and Parkinson's disease: a review. The
American journal of psychiatry.
43. Spiegel, D., & Giese-Davis, J. (2003). Depression and cancer: mechanisms and
disease progression. Biological psychiatry, 54(3), 269-282.
76
44. Zellweger, M. J., Osterwalder, R. H., Langewitz, W., &Pfisterer, M. E. (2004).
Coronary artery disease and depression. European heart journal, 25(1), 3-9.
45. Carney, R. M., & Freedland, K. E. (2017). Depression and coronary heart disease.
Nature Reviews Cardiology, 14(3), 145-155.
46. Shadrina, M., Bondarenko, E. A., &Slominsky, P. A. (2018). Genetics factors in|
major depression disease. Frontiers in psychiatry, 9, 334.
47. Celano, C. M., & Huffman, J. C. (2011). Depression and cardiac disease: a review.
Cardiology in review, 19(3), 130-142.

48. Wilson Schaeffer, J. J., Gil, K. M., Burchinal, M., Kramer, K. D., Nash, K. B.,
Orringer, E., & Strayhorn, D. (1999). Depression, disease severity, and sickle cell
disease. Journal of Behavioral Medicine, 22(2), 115-126.
49. Thomas, A. J., Kalaria, R. N., & T O’Brien, J. (2004). Depression and vascular
disease: what is the relationship? Journal of affective disorders, 79(1-3), 81- 95.
50. Celano, C. M., & Huffman, J. C. (2011). Depression and cardiac disease: a review.
Cardiology in review, 19(3), 130-142
51. Wilson Schaeffer, J. J., Gil, K. M., Burchinal, M., Kramer, K. D., Nash, K. B.,
Orringer, E., & Strayhorn, D. (1999). Depression, disease severity, and sickle cell
disease. Journal of Behavioral Medicine, 22(2), 115-126.
52. Shadrina, M., Bondarenko, E. A., &Slominsky, P. A. (2018). Genetics factors in
major depression disease. Frontiers in psychiatry, 9, 334.
53. Cummings, J. L. (1992). Depression and Parkinson's disease: a review. The
American journal of psychiatry
54. Spiegel, D., & Giese-Davis, J. (2003). Depression and cancer: mechanisms and
disease progression. Biological psychiatry, 54(3), 269-282
55. Zellweger, M. J., Osterwalder, R. H., Langewitz, W., &Pfisterer, M. E. (2004).
Coronary artery disease and depression. European heart journal, 25(1), 3-9.
56. Carney, R. M., & Freedland, K. E. (2017). Depression and coronary heart disease.
Nature Reviews Cardiology, 14(3), 145-155

57. Glassman, A. H., & Shapiro, P. A. (1998). Depression and the course of coronary
artery disease. American Journal of Psychiatry, 155(1), 4-11.

58. Andrews, G. (2001). Should depression be managed as a chronic disease? Bmj,

322(7283), 419-421.
59. Spiegel, D., & Giese-Davis, J. (2003). Depression and cancer: mechanisms and

77
 disease progression. Biological psychiatry, 54(3), 269-282
60. Glassman, A. H., & Shapiro, P. A. (1998). Depression and the course of coronary
artery disease. American Journal of Psychiatry, 155(1), 4-11
61. Cummings, J. L. (1992). Depression and Parkinson's disease: a review. The
American journal of psychiatry.
62. Carney, R. M., & Freedland, K. E. (2017). Depression and coronary heart disease.
Nature Reviews Cardiology, 14(3), 145-155.
63. Andrews, G. (2001). Should depression be managed as a chronic disease? Bmj,
322(7283), 419-421
64. Shadrina, M., Bondarenko, E. A., &Slominsky, P. A. (2018). Genetics factors in
major depression disease. Frontiers in psychiatry, 9, 334.
65. Thomas, A. J., Kalaria, R. N., & T O’Brien, J. (2004). Depression and vascular
disease: what is the relationship? Journal of affective disorders, 79(1-3), 81- 95.
66. Zellweger, M. J., Osterwalder, R. H., Langewitz, W., &Pfisterer, M. E. (2004).
Coronary artery disease and depression. European heart journal, 25(1), 3-9
67. Celano, C. M., & Huffman, J. C. (2011). Depression and cardiac disease: a review.
Cardiology in review, 19(3), 130-142
68. Wilson Schaeffer, J. J., Gil, K. M., Burchinal, M., Kramer, K. D., Nash, K. B.,
Orringer, E., & Strayhorn, D. (1999). Depression, disease severity, and sickle cell
disease. Journal of Behavioral Medicine, 22(2), 115-126.

69. 1. Ustun TB, Ayuso-Mateos JL, Chatterji S, Mathers C,Murray CJL. Global
burden of depressive disorders inthe year 2000. Br J Psychiatry 2004; 184: 386
392.
70. WHO. The World Health Report 2000 – health systems: improving performance.
Geneva, World Health Organization, 2000.
71. Ustun TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. Global burden
of depressive disorders in the year 2000. Br J Psychiatry 2004; 184: 386-392.
72. World Health Organization, World Suicide Prevention Day 2012.
73. Kim YS, Koh YJ, Leventhal B. School bullying and suicidal risk in Korean
middle school students. Pediatrics 2005; 115: 357-363.
74. Klomek AB, Marrocco F, Kleinman M, Schonfeld IS, Gould MS. Peer
victimization, depression and suicidiality in adolescents. Suicide Life Threat
Behav 2008; 38: 166-180.
75. Adlaf EM, Gliksman L, Demers A, Newton-Taylor B. The prevalence of elevated
78
 psychological distress among Canadian undergraduates: Findings from the 1998
Canadian campus survey. J Am Coll Health 2001; 50: 67-72.
76. Korten A, Henderson S. The Australian National Survey of Mental Health and
Well- Being. Br J Psychiatry 2000; 177: 325-330.
77. Jones NP, Papadakis AA, Hogan CM, Strauman TJ. Over and over again:
Rumination, reflection, and promotion goal failure and their interactive effects on
depressive symptoms. Behaviour Research & Therapy 2009; 47: 254-259.

78. Papadakis AA, Prince RP, Jones NP, Strauman TJ. Selfregulation, rumination,
and vulnerability to depression in adolescent girls. Dev Psychopathol 2006; 18:
815-829.
79. Ang RP, Haun VS. Relationship between academic stress and suicidal ideation:
Testing for depression as a mediator using multiple regressions. Child Psychiatry
Hum Dev 2006; 37: 133-143.
80. Zung WWK. A self-rating depression scale. Archives of General Psychiatry 1965;
12: 63-70.
81. Fountoulakis KN, Iacovides A, Samolis S, Kleanthous S, Kaprinis SG, Karinis
SG, Bech P. Reliability, Validity and Psychometric Properties of the Greek
Translation of the Zung Depression Rating Scale. BMC Psychiatry 2001; 1: 6.
82. Fountoulakis KN, Iacovides A, Samolis S, Kleanthous S, Kaprinis SG, Karinis
SG, Bech P. Reliability, Validity and Psychometric Properties of the Greek
Translation of the Zung Depression Rating Scale. BMC Psychiatry 2001; 1: 6.
83. Weining C Chang, Jessie Bee Kim Koh. A Measure of Depression in a Modern
Asian Community: Singapore. Depression Research and Treatment 2012; 8 pages.
84. Bostanci M, Ozdel O, Oguzhanoglu NK, Ozdel L, Ergin A, Ergin N, Atesci F,
Karadag F. Depressive Symptomatology among University Students in Denizli,
Turkey: Prevalence and Sociodemographic Correlates. Croat Med J 2005; 46: 96
100.
85. Beers M, Berkow R. Merck Manual - 17th Ed. Centennial Edition.
[Database/electronic text on the Internet]. West Point, PA: Merck & Co., Inc.,
2005. 1999. [Cited 6.6.2006] Available from: http://online.statref.com/document.
aspx?fxid=37&docid=284.
86. MacGeorge E, Samter W, Gillihan S. Academic stress, supportive
communication, and health. Commun Educ 2005; 54: 365-372.

87. Ali BS, Amanullah S. Prevalence of anxiety and depression in an urban squatter
79
 settlement of Karachi. J Coll Physicians Surg Pak 2000; 10: 4-6.
88. Husain N, Gater R, Tomenson B, Creed F. Social factors associated with chronic
depression among a population-based sample of women in rural Pakistan. Soc
Psychiatr Epidemiol 2004; 39: 618-24.
89. Husain N, Creed F, Tomenson B. Depression and social stress in Pakistan.
Psychol Med 2000; 30: 395-402.
90. Mumford DB, Saeed K, Ahmad I, Latif S, Mubbashar MH. Stress and psychiatric
disorder in rural Punjab. A community survey. Br J Psychiatry 1997; 170: 473-8.
91. Gadit AA. Economic burden of Depression in Pakistan. J Pak Med Assoc 2004;
54: 43-4.
92. Kazi A, Fatmi Z, Hatcher J. Social environment and depression among pregnant
women in urban areas of Pakistan: Importance of social relations. Social Sci Med
2006; 63: 1466-76.
93. Fu CM, Parahoo K. Causes of depression: perceptions among people recovering
from depression. J Adv Nurs 2009; 65: 101-9.
94. Patel MJ, Shahid M, Riaz M. Drug overdose: a wakeup call! Experience at a
tertiary care centre in Karachi, Pakistan. J Pak Med Assoc 2008; 58: 298-301.
95. Deyessa N, Berhane Y, Alem A. Intimate partner violence and depression among
women in rural Ethiopia: a cross-sectional study. Clin Pract Epidemol Ment Health
2009; 5: 8-12.
96. Mirza I, Jenkins R. Risk factors, prevalence and treatment of anxiety and
depressive disorders in Pakistan: systematic review. BMJ 2004; 328: 794.

97. Hussain N, Gater R, Tomenson B. Social factors associated with chronic

depression among a population-based sample of women in rural Pakistan. Soc
Psychiatric Epidemiol 2004; 3: 618-24.
98. Mumford DB, Minhas FA, Akhtar I, Akhter S, Mubbashar MH. Stress and
psychiatric disorder in urban Rawalpindi. Br J Psychiat 2000; 177: 557-62.
99. Luni FK, Ansari B, Jawad A, Dawson A, Baig SM. Prevalence of depression and
anxiety in a village in Sindh. J Ayub Med Coll Abbottabad 2009; 21: 68- 72.
100. Mumford DB, Nazir M, Jilani FU, Baig IY. Stress and psychiatric disorder in
Hindu Kush: a community survey of mountain villages in Chitral, Pakistan. Br J
Psychiatric 1996; 168: 299-307.
101. Nisar N, Billoo N, Gadit AA. Prevalence of depression and the associated risk
factors among adult women in a fishing community. J Pak Med Assoc 2004; 54:
80
 519-25.
102. Ian McDowell. Measuring Health: A Guide to Rating Scales and Questionnaires.
3rd ed. New York: Oxford University Press, 2006.
103. Lorant V, Deliege D, Eaton W. Socioeconomic Inequalities in Depression: A
Meta-Analysis. Am J Epidemiol 2003; 157: 98-112.
104. Husain N, Chaudhry IB, Afridi MA, Tomenson B, Creed F. Life stress and
depression in a tribal area of Pakistan. Br J Psychiat 2007; 190: 36-41.

81
82