Major Depression and Bipolar
Disorder
dr Silas Henry Ismanto, Sp.KJ
08/02/2016 1
• Depressive disorder and bipolar disorder are
psychiatric ilnesses that are included in the
disoders of mood
• Mood can be defined as pervasive and
sustained emotion or feeling tone that
influences a person’s behavior and colors his
or her perception of being in the world
08/02/2016 2
• Mood can be described as depressed, sad,
empty, melancholic, distressed, irritable,
disconsolate, elated, euphoric, manic,
gleeful, etc
• Unhappy visage, hopelessness
• Labile, fluctuating or alternating rapidily
• Other signs and symptoms of mood: changes in
activity level, cognitive abilities, speech, and
vegetative functions
08/02/2016 3
• Patients with only major depressive episodes
are said to have major depressive disorder or
unipolar depression
• Patients with both manic and depressive
episodes or patients with manic episodes
alone are said to have bipolar disorders
• Three additional categories of mood disorders
are hypomania, cyclothymia, dysthymia
08/02/2016 4
Depression
• A major depressive disorder occurs without a
history of a manic, mixed, or hypomanic episode
• must last at least 2 weeks
• experiences at least 4 symptoms of: 1) changes in
appetite and weight, 2)changes in sleep and
activity, lack of energy, 3)feelings of guilt,
problem thinking and making decisions,
4)recurring thoughts of death or suicide
08/02/2016 5
Mania
• A manic episode is a distinct period of an
abnormally and persistently elevated, expansive,
or irritable mood lasting for at least 1 week or
less if a patient must be hospitalized.
• A hypomanic episode last at least 4 days and is
similar to a manic episode except that it is not
sufficiently severe to cause impairment in social
or occupational functioning, and no psychotic
features are present.
08/02/2016 6
Mania (cont)
• Both mania and hypomania are associated
with inflated self-esteem, a decreased for
sleep, distractibility, great physical and mental
activity, and overinvolvement in pleasurable
behavior.
• Bipolar I disorder is defined as having a clinical
course of one or more manic episodes and,
sometimes, major depressive episodes.
08/02/2016 7
Mania (cont)
• A mixed episode is a period of at least 1 week
in which both a manic episode and a
depressive episode occur daily.
• A variant of bipolar disorder characterized by
episodes of major depression and hypomania
rather than mania is known as bipolar II
disorder.
08/02/2016 8
Dysthymia
• Dysthymic disorder is characterized by at least
2 years of depressed mood that is not
sufficiently severe to fit the diagnosis of major
depressive episode
08/02/2016 9
Cyclothymia
• Cyclothymic disorder is characterized by at
least 2 years of frequently occuring
hypomanic symptoms that cannot fit the
diagnosis of manic episode.
08/02/2016 10
Epidemiologi
Incidence and Prevalence
• Mood disorders are common
• MDD has the highest lifetime prevalence (5-
17% of any psychiatric disorder)
• The annual incidence of bipolar disorder is less
than 1%, but it is difficult to estimate because
milder forms of bipolar disorder are often
missed
08/02/2016 11
Incidence and Prevalence (cont)
Sex
• Twofold greater prevalence of MDD in woman
than man
– Hypothesized to involve hormonal differences,
effect of childbirth, differing psychosocial
stressors for woman and for man, behavioral
models of learned helplessness
• Bipolar I has an equal prevalence among men
and women
08/02/2016 12
Incidence and Prevalence (cont)
• Manic episode are more common in men
• Depressive episode are more common in
woman
• When manic episodes occur in woman, they
are more likely than men to present a mixed
picture
• Woman also have a higher rate of being rapid
cyclers, defind as having 4 or more manic
episodes in 1-year period
08/02/2016 13
Incidence and Prevalence (cont)
Age
• The onset of bipolar I is earlier than MDD; the
age of onset ranges from 5-50 years, with a
mean age of 30 years
• The mean onset of MDD is 40 years, can also
begin in childhood or in old age
• Recent epiddemiological data suggest that the
incidence of MDD may be increasing among
people younger than 20 years of age
08/02/2016 14
Marital Status
• MDD occurs most often in persons without
close interpersonal relationships (e.g
divorced, separated)
• Bipolar I is more common in divorced and a
single persons than among married persons
08/02/2016 15
Comorbidity
• Individuals with MDD are at increased risk of
having one or more additional comorbid
disorders, such as are alcohol abuse, panic
disorder, OCD, social anxiety
• Patients who are bipolar more frequently
show comorbidity of substance abuse and
anxiety than do patients with unipolar major
depression
08/02/2016 16
Etiology
Biological Factors
• Biogenic Amines Neurotransmitter
Disturbances
– Norepinephrine
• Down regulaton or decreased sensitivity of beta-
adrenergic receptors
• Activation of presynaptic beta2-receptors
• The clinical effectiveness of antidepressant drugs with
noradrenergic effects (e.g venlafaxine) supports a role
for NE in the pathophysiology of at least some of the
symptoms of depression
08/02/2016 17
Etiology (cont)
– Serotonin
• With the huge effect that SSRIs (e.g fluoxetine) have made
on treatment of depression, serotonin has become the
biogenic amine neurotransmitter most commonly associated
with depression
– Dopamine
• Drugs that reduce dopamine concentration (e.g reserpine)
and disease that reduce dopamine concentrations (e.g
parkinson) are associated with depressive symptoms.
• Drugs that increase dopamin concentrations (tyrosin,
amphetamine, bupropion) reduce the symptoms of
depression
08/02/2016 18
Etiology (cont)
• Other Neurotransmitter Disturbances
– Acethylcholine (Ach). Cholinergic agonists can
produce lethargy, anergy, psychomotor
retardation (can exacerbate symptoms in
depression and reduce symptoms in mania)
– GABA. Reduction of GABA have been observed in
brain GABA levels in depression
08/02/2016 19
Etiology (cont)
• Alteration of Hormonal Regulation
– Recent studies in depressed humans indicate that
a history of early trauma (maternal deprivation) is
associated with increased HPA activity
accompanied by structural changes (atrophy or
decreased volume) in the cerebral cortex
– Protracted stress thus can induce changes in the
functional status of neurons and, eventually, cell
death
08/02/2016 20
Etiology (cont)
– Elevated HPA activity is a hallmark of mamalian
stress responses and one the clearest links
between depression and the biology of chronic
stress
– Hypercortisolemia in depression suggests one or
more of the following central disturbances:
decreased inhibitory serotonin tone, increased
drive from norepinephrine, ACh, or corticotropin-
releasing hormon (CRH); or decreased feedback
inhibition from hippocampus
08/02/2016 21
Etiology (cont)
Genetic Factors
• Family Studies
– If one parent has a mood disorder, a child will have a
risk of between 10 and 25%
– If both parents are`affected, this risk roughly doubles.
– The more members of the family who are affected,
the greater risk is to a child
– The risk is greater if the affected family members are
first degree relatives than more distant relative
08/02/2016 22
Etiology (cont)
• Twin Studies
– Twin data provide evidence that genes explain
only 50-70% of etiology of mood disorders
– Concordance rate for mood disorder in
monozygotic twins of 70 to 90% compared with
dizygotic twins of 16 to 35%.
08/02/2016 23
Etiology (cont)
Psychosocial Factors
• Life Events and Environmental Stress
– Stressful life events more often precede first,
rather than subsequent, episode of mood
disorders (MDD, bipolar I)
– One theory proposed that stress accompanying
the first episode results in long-lasting changes in
the brain’s biology
08/02/2016 24
Etiology (cont)
– The long-lasting changes may alter the functional
states of various neurotransmitter and
intraneuronal signaling systems, changes that may
even include the loss of neurons and an excessive
reduction in synaptic contacts
– As a result, a person has a high risk of undergoing
subsequent episodes of mood disorder, even
without an external stressor
– The life event most often associated with
development of depression is losing a parent
before age 11 years
08/02/2016 25
Etiology (cont)
– The environmental stressor most often associated
with the onset of an episode of depression is the
loss of a spouse.
– Another risk factor is unemployment
• Personality Factors
– No single personality trait or type uniquely
predisposes a person to depression
– Person with OCD, histrionic, borderline may be at
greater risk for depression than persons with
antisocial or paranoid personality disorder
08/02/2016 26
Etiology (cont)
– The latter can use projection and other
externalizing defense mechanisms to protect
themselves from their inner rage
08/02/2016 27
Etiology (cont)
• Psychodynamic Factors
– Stressor that the patient experiences as reflecting
negatively on his/her self-esteem are more likely
to produce depression
– What may seem to be relatively mild stressor to
outsiders may be devastating to the patient
because of particular idiosyncratic meanings
attached to the event
08/02/2016 28
Etiology (cont)
– Psychodynamic understanding of depression defined
by Sigmund Freud and expanded by Karl Abraham
1. Disturbances in the infant-mother relationship during oral
phase predispose to subsequent vulnerability to
depression
2. Depression can be linked to real or imagined object loss
3. Introjection of the departed objects is a defense
mechanism invoke to deal with the distress connected
with the object’s loss
4. Because the lost object is regarded with a mixture of love
and hate, feelings of anger are directed inward at the self
08/02/2016 29
Etiology (cont)
– Melanie Klein: depression is expression of
agression toward loved one
– Edward Bibring regarded depression as a
phenomenon that sets in when a person become
aware of discrepancy between extraordinary high
ideals and the ability to meet the goals
– John Bowlby believed that damaged early
attachments and traumatic separation in
childhood predispose to depression
• Adult losses are said to revive the traumatic childhood
loss and so precipitate adult depressive episodes
08/02/2016 30
Etiology (cont)
• Other Formulation of Depression
– Cognitive Theory: depression results from specific
cognitive distortions present in persons
susceptible to depression
– Aaron Beck postulated a cognitive triad of
depression: 1) views about the self—a negative
self-percept 2) about the environment—tendency
to experience the world as hostile and demanding
3) about the future—the expectation of suffering
an failure
08/02/2016 31
Etiology (cont)
– Cognitive distortions
Element Definition
Arbitrare inference Drawing a specific conclusion without sufficient
evidence
Specific abstraction F ocus on single detail while ignoring other,
more important aspects of an experience
Overgeneralization Forming conclusions based on too little and too
narrow experience
Magnification and Over- or undervaluing the significance of a
minimization particular event
Personalization Tendency to self-reference external events
without basis
Absolutist, Tendency to place experience into all-or-none
dichotomous categories
08/02/2016thinking 32
Etiology (cont)
– Learned helplessness
• The learned helplessness theory of depression
connects depressive phenomena to the experience of
uncontrollable events
• The dog exposed to the shocks would not cross a
barrier to stop the flow of electric shock when put in
new learning situation; they remaind passive and did
not move
• Behaviorists who subscribe to theory stress that
improvement of depression is contingent on patient’s
learning a sense of control and mastery of the
environment
08/02/2016 33
Diagnosis
• Major Depressive Disorder
• Major Depressive Disorder, Single Episode
• Major Depressive Disorder, Recurrent
• Bipolar I Disorder
– Bipolar I Disorder, Single Manic Episode
– Bipolar I Disorder, Recurrent
• Bipolar II Disorder
08/02/2016 34
Diagnosis (cont)
• Specifier (Symptom Feature)
– With Psychotic Features
• The presence of psychotic features in MDD reflects
severe disease and is poor prognosis
– With Melancholic Features
• A depression characterized by severe anhedonia, early
morning awakening, weight loss, and profound feelings
of guilt, suicidal ideation
• Melancholia is associated with change in the
autonomic nervous system and endocrine function
• Sometimes reffered to as “endogenous depression”
08/02/2016 35
Diagnosis (cont)
– With Atypical Features
• Depression with characteristics: overeating,
oversleeping
– With Catatonic Features
• Stuporousness, blunted affect, extrem withdrawal,
negativism, marked motor retardation
– Postpartum Onset
• Onset of symptoms is within 4 weeks postpartum
• Postpartum mental disorders commonly include
psychotic symptoms
08/02/2016 36
Diagnosis (cont)
– Rapid Cycling.
• Patients with rapid cycling bipolar are likely to be
female and to have had depressive and hypomanic
episodes.
• External factors such as stress or drug treatment may
be involved in the pathogenesis of rapid cycling rather
than familial factors
• The DSM-5 criteria specify that the patient must have
at least four epsisode within 12-month periode
08/02/2016 37
Clinical Features
• Basic symptom patterns of mood disorders
are depression and mania
• Depressive episodes can occur in both major
depressive disorder and bipolar I disorder
• To differentiate between bipolar I disorder
depressive episodes and episodes of major
depressive disorder are elusive
08/02/2016 38
Clinical Features (cont)
Depressive Episodes
• A depressed mood, loss of interest or pleasure are the
key symptoms
• Patients may say that they feel blue, hopeless, in the
dumps, or worthless
• About two-third of all depressed patients contemplate
suicide, and 10-15% commit suicide
• Some depressed patients seem unaware of their
depression and do not complain of a mood disturbance
even though they exhibit withdrawal from family,
friends and activities that previously interested them
08/02/2016 39
Clinical Features (cont)
• Almost all depressed patients (97%) complain
about reduced energy; they have difficulty in
finishing tasks, are impaired at school and
work, have less motivation to undertake new
project
• About 80% of patients complain of trouble
sleeping, especially early morning awakening
(terminal insomnia), multiple awakenings at
night
08/02/2016 40
Clinical Features (cont)
• Many patients have decreased appetite and
weigh loss, but others increased appetite and
weight gain and sleep longer than usual
(classified as atypical features)
• Anxiety is a common symptom of depression
• The various change in food intake and rest can
aggravate coexisting medical illnesses such as
DM, hypertension, COPD, hearth disease
08/02/2016 41
Clinical Features (cont)
• Other vegetative symptoms include abnormal
menses, decrease interest and performance in
sexual activities.
• Anxiety (including panic attack), alcohol abuse,
somatic complaints (constipation and headache)
often occure.
• About 50% of all patients describe a diurnal
variation in their symptoms, with increased
severity in the morning and lessening of
symptoms by evening
08/02/2016 42
Clinical Features (cont)
• Cognitive symptoms include subjective
reports of an inability to concentrate (84%)
and impairment of thinking (67%)
08/02/2016 43
Clinical Features (cont)
Manic Episodes
• An elevated (euphoric) , expansive, or irritable
mood is the hallmark of a manic episode
• Manic patients often drink alcohol excessively,
perhaps an attempt to self-medicate.
• Their disinhibited nature is reflected in
excessive use of the telephone, especially in
making long-distance calls during the early
morning hours.
08/02/2016 44
Clinical Features (cont)
• Pathological gambling, a tendency to disrobe
in public places, wearing clothing and jewelry
of bright colors in unusual or outladish
combinations, and inattention to small details
(forgetting to hang up the telephone) are also
symptomatic of the disorder.
• Patient act impulsively and at the same time
with a sense of conviction and purpose.
08/02/2016 45
Clinical Features (cont)
• They are often preoccupied by relegious,
political, financial, sexual, or persecutory ideas
that can evolve into complex delusional
systems.
• Occasionally manic patients become
regressed and play with their urine and feces.
08/02/2016 46
Clinical Features (cont)
Bipolar II Disorder
• The clinical feature of bipolar II disorderare
those of major depressive disorder combined
with those of a hypomanic episode.
08/02/2016 47
Course and Prognosis
• Studies of course and prognosis of mood
disorders have generally cocluded that mood
disorders tend to have long courses and that
patients tend to have relapses.
Major Depressive Disorder
• Course
– Onset. The first depressive episode occures before
age 40 years in about 50% of patients
08/02/2016 48
Course and Prognosis (cont)
– Duration.
• An untreated depressive episode last 6 to 13 months;
most treated episode last about 3 months.
• The withdrawal of antidepressants before 3 months
has elapsed almost always result in return of symptoms
08/02/2016 49
Course and Prognosis (cont)
– Duration. An untreated depressive episode last 6 to
13 months. The withdrawal of antidepressants before
3 months has elapsed almost always result in the
return of symptoms.
• Prognosis.
– Patients who have been hospitalized for first episode
of MDD have about a 50% chance of recovering in the
first year
– The percentage of patients recovering after repeated
hospitalization decreases with passing time.
08/02/2016 50
Course and Prognosis (cont)
– Many unrecovered patients remain affected with
dysthymic disorder.
– About 25% of patents experience a recurrence of
MDD in the first 6 months after release from
hospital, about 30-50% in the following 2 years,
and about 50-75% in 5 years
– The incidence of relapse is lower than these
figures in patients who continue prophylactic
psychopharmacological treatment and in patients
who have had only one or two depressive episode
08/02/2016 51
Course and Prognosis (cont)
• Prognostic indicators
– Mild episodes, the absence of psychotic
symptoms, and a short hospital stay are good
prognostic indicators.
– Psychosocial indicators of good course include a
history of solid friendships during adolescence,
stable family functioning, and social functioning
for the 5 years preceding the illness.
08/02/2016 52
Course and Prognosis (cont)
– Additional good prognostic signs are the absence
of a comorbid psychiatric disorder and a
personality disorder, no more than one previous
hospitalization for major depressive disorder, and
an advanced age onset.
– The possibility poor prognosis is increased by
coexisting dysthymic disorder, drug and alcohol
abuse, anxiety disorder symptoms, and more than
one previous depressive epsode.
– Men are more likely than women to experience a
chronically impaired course.
08/02/2016 53
Course and Prognosis (cont)
Bipolar I Disorder
• Course
– Bipolar I disorder most often starts with
depression and is recurring disorder
– Most patients experience both depressive and
manic episodes, although 10-20% experience only
manic episodes
– An untreated manic episodes lasts about 3
months; therefore, clinicians should not
discontinue giving drugs before that time
08/02/2016 54
Course and Prognosis (cont)
– Of persons who have a single manic episodes, 90%
are likely to have another
– As the disorder progresses, the time between
episodes often decreases
– After about five episodes, however, the
interepisode interval often stabilizes at 6 to 9
months
– Of persons with bipolar disorder, 5 to 15% have
four or more episodes per year and can be
classified as rapid cycler
08/02/2016 55
Course and Prognosis (cont)
• Prognosis
– Patient with bipolar I disorder have a poorer
prognosis than do patients with MDD
– Although lithium prophylaxis improves the course and
prognosis of bipolar I disorder, only 50-60% of
patients achieve significant control of their symptoms
with lithium
– One 4-year follow up study of patients with bipolar I
disorder found that a poor occupational status,
alcohol dependence, psychotic features, depressive
features, male gender were all factors that
contributed a poor prognosis.
08/02/2016 56
Course and Prognosis (cont)
– Short duration of manic episodes, advanced age of onset,
few suicidal thoughts, and few coexisting psychiatric or
medical problems predict a better outcome
Bipolar II Disorder
• The course and prognosis of bipolar II disorder indicate
that the diagnosis is stable because there is high
likelihood that patients with bipolar II disorder will
have the same diagnosis up to 5 years
• Bipolar II disorder is a chronic disease that warrants
long-term strategies
08/02/2016 57
Treatment
Hospitalization
• The first and most critical decision a physician
must make is whether to hospitalize a patient or
attempt outpatient treatment
• Clear indication for hospitalization are the risk of
suicide or homicide, a patient’s grossly reduced
ability to get food and shelter, the need for
diagnostic procedure, a history of rapidly
progressing symptoms and the rupture of a
patient’s usual support system
08/02/2016 58
Treatment (cont)
Psychosocial Therapy
• Cognitive Therapy
– Aaron Beck focuses on the cognitive distortions
postulated to be present in MDD
– Such distortions include selective attention to
negative aspects of circumstances and
unrealistically morbid inferences about
consequences. For example, apathy and low
energy result from a patient’s expectation of
failure in all areas
08/02/2016 59
Treatment (cont)
– The goal of cognitive therapy is to alleviate
depressive episodes and prevent their reccurence
by helping patients identify and test negative
cognition; develop alternative, flexible, and
possitive ways of thinking; and rehearse new
cognitive and behavioral responses
– Cognitive therapy is effective in the treatment of
MDD
08/02/2016 60
Treatment (cont)
• Interpersonal Therapy
– Interpersonal therapy, developed by Gerald
Klerman, focuses on one or two of a patient’s
current interpersonal problems
– This therapy is based on two assumptions:
1. Current interpersonal problems are likely to have
their roots in early dysfunctional relationships
2. Current interpersonal problems are likely to be
involved in precipitating or perpetuating the current
depressive symptoms
08/02/2016 61
Treatment (cont)
• Behavior Therapy
– Behavior therapy is based on the hypothesis that
maladaptive behavioral patterns result in person’s
receiving little positive feedback and perhaps
outright rejection from society
– By addresing maladaptive behaviors in therapy,
patients learn to function in the world in such a
away that they receive possitive reinforcement
08/02/2016 62
Treatment (cont)
Pharmacotherapy
• Major Depressive Disorder
– SSRI
• Most clinician begin treatment with a selective
serotonin reuptake inhibitor (SSRI).
• Early transient side effects include anxiety,
gastrointestinal upset, and headache.
• Educating patients about the self-limited nature of
these effect can enhance compliance.
• Sexual dysfunction is often a persistent, common side
effect that may respond to a change in drug or dosage
08/02/2016 63
Treatment (cont)
– Buproprion
• Buproprion is noradrenergic drug with stimulanlike
properties.
• It is useful for depression marked by anergy and
paychomotor retardation
• It is also devoid of sexual side effects
• It may exacerbate anxiety and agitation
• Its dopaminergic properties have the potential to
exacerbate psychosis
• The average dose is 150 to 300 mg/day
08/02/2016 64
Treatment (cont)
– Venlafaxine and duloxetine
• Velafaxine and duloxetine are serotonin-norepinephrine
reuptake inhibitors that may be effective in severe or
refractory cases of depression
• Side effects are similar to those of SSRIs
• The average dose of venlafaxine is 75 to 375 mg/day and of
duloxetine 20 to 60 mg/day
– Nefazodone
• Nefazodone is a drug with serotonergic properties
• Its main mechanism of action is postsynaptic 5-HT blockade;
as a result, it produces beneficial effects on sleep and has a
low rate of sexual side effects.
• The average dose is 300 to 600 mg/day
08/02/2016 65
Treatment (cont)
– Mirtazapine
• Mirtazapine has antihistamine, noradrenergic, and
serotonergic actions
• It specifically blocks 5-HT2 and 5-HT3 receptors, so that the
anxiogenic, sexual, and gastrointestinal side effects of
serotoinergic drugs are avoided
• Average dose is 15 to 30 mg/day
– The tricyclics
• The tricyclics are highly effective but require dose titration
• Side effects include anticholinergic effects in addition to
potential cardiac conduction delay and orthostasis
• Lethality in overdose remains a concern
08/02/2016 66
Treatment (cont)
– MAOI
• An MAOI is safe with reasonable dietary restriction of
tyramine-containing substances
• Major depressive episode that have atypical features or
psychotic features or that related to bipolar I disorder
may preferentially respond to MAOI
– All currently available antidepressants may take
up to 3 to 4 weeks to exert significant therapeutic
effects
08/02/2016 67
Treatment (cont)
– Maintenance treatment for at least 5 months with
antidepressants helps to prevent relapse
– Long-term treatment may be indicated in patients
with recurrent major depressive disorder
– The antidepressant dosage required to achieve
remission should be continued during maintenance
treatment
– ECT is useful in refractory major depressive disorder
and major depressive episodes with psychotic
features; ECT also is indicated when rapid therapeutic
response is desired or when side effects of
antidepressants medications mus be avoided
08/02/2016 68
Treatment (cont)
• Bipolar Disorders
– Mood stabilizer such as lithium and divalproex are
the first choice of drugs used for bipolar disorder
– Second generation antipsychotics such as
olanzapine are also used
– Carbamazepine is also a well-established
treatment
– Lamotrigine is used in the maintenance phase of
bipolar disorder
08/02/2016 69
– Topiramate is another anticonvulsant used in
bipolar patients
– ECT is highly effective in all phases of bipolar
disorder
08/02/2016 70
08/02/2016 71
