MOOD DISORDERS

objectives
• Define emotion
• Assessing mood disorder
• Classifying mood disorders
• Identify sign and symptoms of mood disorders.
• Diagnosing mood disorders
• Managing patients with mood disorder
 Definition of terms
1. Stupor: no psychomotor activity
2. Catalepsy: passive induction of a posture held against gravity.
3. Waxy flexibility: slight, even resistance to positioning by examiner
4. Mutism: no, or very little verbal response.
5. Negativism: opposition or no response to instructions/external stimuli.
6. Mannerism: odd, exaggerated implementation of normal actions
7. Stereotypy: repetitive, abnormally frequent, non-goal-directed movements.
8. Agitation: anxious/ distress
9. Grimacing: ugly facial expression to feel pain
10. Echolalia: mimicking another’s speech
11. Echo-phenomena
– Echolalia – Senseless repetition of another person's utterances
– Echopraxia – Senseless repetition of another person's movements
 What is mood
• Mood is
 Sustained feeling tone that is experienced internally and that
influences a person's behaviour and perception of the world.
• Mood can be normal, elevated, or depressed.
 Mood disorder

• Are a group of clinical conditions characterized by a

Loss of that sense of control and
Subjective experience of great distress.

• The disorder includes physiological and psychological symptoms

• These disorders virtually always result in impaired functioning.
 Concepts of Mood Disorder

 Continuum model

This model argues that there is a continuum among emotional disorders:

 anxiety disorders mild neurotic depression

severe endogenous depression psychotic depression

Bipolarity model:
Unipolar depressive episodes only
Bipolar: depression plus (mania, hypomania, or mixed
episodes)
 Epidemiology
 Most mood disorders are chronically relapsing conditions
 Mood disorders underlie 50-70 % of all suicides
 Sex: Unipolar depression is approximately 2x more common in women
compared to men
 Age - Depressive disorders show much higher lifetime prevalent among people <
45 years
Race and Ethnicity- have no clearly noticeable differences
Marital status: Major depression and bipolar illness are most frequent among
divorced, widowed, separated individuals
The following have some more important role in the development of MDD in
later life
Isolation,
Loss of interpersonal contacts,
Medical disorders, and
Disability
 Etiology of mood disorder
• Biological Factors
The monoamine hypothesis of depression
It suggests that depression is associated with a
– relative depletion of the monoamines, especially NE and 5-HT
 Most of the classic antidepressants target
NE, 5-HT, and to a lesser extent DA
• Many of the newer ones selectively act on serotonin
• Dopamine activity may be
–reduced in depression and
–increased in mania
• Increased 5-HT2 receptors, a factor that was felt to be secondary to
low 5-HT content
Noradrenergic Dysfunction
• NE plays a major role in maintaining arousal and drive.
• There is evidence of noradrenergic dysfunction in depression
• Many antidepressants are potent inhibitors of the reuptake of
noradrenalin
 Classification of mood disorders
Based on DSM-V mood disorders classified as
1. Bipolar I disorder
2. Bipolar II disorder
3. Cyclothymic disorder
 Depressive disorders include
Major depressive disorder MDD
Persistent depressive disorder (dysthymia) - PDD
depressive disorder
• Individual feels no sense of enjoyment in activities that were
previously considered pleasurable.
• There is associated reduction in all drives including
Energy and
Alteration in sleep,
Interest in food, and
Interest in sexual activity.
 Major Depressive Disorder

Diagnostic Criteria
A. >=5 of the following symptoms have been present during the same 2-week
period
 5 of following symptoms, must include one of first two, occurred almost every
day for 2 weeks
1. Depressed mood most of the day, nearly every day, as indicated by either
subjective report (e.g., feels sad, empty, hopeless) or observation made by
others (e.g .appears tearful).
2. Markedly diminished interest or pleasure in all, or almost all, activities most of
the day, nearly every day
3. Significant weight loss when not dieting or weight gain
4. Insomnia or hypersomnia nearly every day.
5. Psychomotor agitation or retardation (feelings of restlessness or being slowed
down).
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness
8. Diminished ability to think or concentrate,
9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation

B. The symptoms cause clinically significant distress or impairment

C. The episode is not due to a substance or to another medical condition.
The symptoms are not better accounted for by bereavement, i.e., after the loss of a
loved one,
 Management of MDD
Desired Outcome
• To reduce the symptoms of acute depression
• To facilitate the patient's return to a level of functioning
• Prevent further episodes of depression.
There are three phases of treatment
1. The acute phase lasting from 6-10 wks
• the goal is remission (i.e., Absence of symptoms).
2. The continuation phase lasting 4-9 months after remission is achieved, the
goal is to eliminate residual symptoms
3. Maintenance phase lasting at least 12 - 36 month,
– the goal is to prevent recurrence.
• The duration of antidepressant therapy depends on the risk of
recurrence.
• Lifelong maintenance therapy for
• Persons < 40 years of age >= 2 prior episodes and
• persons of any age > = 3 prior episodes
Non-pharmacologic therapy
 Psychotherapy whenever the patient is able and willing to participate.
 Psychotherapy alone is not recommended for the acute treatment of patients
with
Severe and/or psychotic MDD
 If the depressive episode is mild to moderate in severity,
Psychotherapy may be the first-line therapy
For patients with partial responses
– Combined treatment may be advantageous
• Sole maintenance psychotherapy is not recommended.
• Often, medication alone may prevent recurrence
 Electroconvulsive therapy
• Patients with depression are candidates for ECT when
 A rapid response is needed
 There is a poor response to antidepressants
 A history of good response to ECT, and
 The patient expresses a preference for ECT.
• Consists of either unilateral or bilateral ECT administered 2-3X/wk for a total of
6-12 treatments.
 Relative contraindications include
– Increased ICP
– Cerebral lesions
– Recent MI
– Recent intracerebral hemorrhage
 Antidepressants
Mechanism of action
 Monoamine oxidase inhibitors (MAOIs) inhibit the enzyme responsible for the
intraneuronal breakdown of 5-HT, NE, and DA.
 Tricyclic antidepressants (TCAs) possess both
 5-HT reuptake inhibition (SRI) and
 NE reuptake inhibition (NRI)
Choice of specific antidepressants
 Serotonin reuptake inhibitors (SSRIs) are classified as such because SRI is the
predominant effect.
 Bupropion is an NE and DA reuptake inhibitor.
 Venlafaxine and duloxetine are 5-HT and NE reuptake inhibitors (SNRIs)
Dosing of antidepressants
Dosing of antidepressants
 Managing Partial Response or Nonresponse

 Initiate either of the antidepressant based on patient safety, as

monotherapy
 If no response, change to another class of antidepressant, not tried
before.
 If no response, Augment with lithium,
 If no response, use combination of antidepressants
 If no response, apply ECT.
 Case 1

Mrs A is 37 years old female came from rural part of Ethiopia. She
came with the C/C of excessive worry and tension for the last two
months.
HPI Starting from 2 months she feels sad and hopeless, she has no
any interest in her daily work. She stays on her bed for long period
of time but she didn’t get sleep. She feels worthless and has history
of suicidal attempt by hanging her self two times. She has suicidal
ideation still now.
She has Hx of early morning awakening. She has history of
decreased appetite and weight loss. She also complains easy
fatigability. She has no any previous episodes
No any sign of manic episode
No any psychotic symptoms
No any substance abuse Hx
Her mom had also similar illness but not treated and died because
of other medical illness before 2 years

• Discuss the signs and symptoms of MDD

• State one regimen in terms of phases
Dysthymic disorder
• Dysthymic disorder is defined by the
–Presence of chronic depressive symptoms most of the day,
for at least 2 years.
DSM –V criteria for DYSTHYMIC DISORDER
A. Depressed mood for most of the day, for more days than not, as indicated either
by subjective account or by observation by others, for at least 2 years
B. Presence, while depressed, of two (or more) of the following:
1. Poor appetite or overeating
2. Insomnia or hypersomnia
3. Low energy or fatigue
4. Poor concentration or difficulty making decisions
5. Low self-esteem
6. Feelings of hopelessness
C. During the 2-year period of the disturbance,
– the person has never been without the symptoms in Criteria A and B
for >2 months at a time.
D. There has never been a manic episode or a hypomanic episode
E. The disturbance is not better explained by psychotic disorder.
F. The symptoms are not attributable to a substance or another medical condition
G. The symptoms cause clinically significant distress or impairment

– Treatment of DYSTHYMIC disorder

– The treatment in DD are similar to those in MDD.
Bipolar
Disorders
The diagnoses included in this chapter are
 bipolar I disorder
 bipolar II disorder
 Mixed features

o Episodes of bipolar mania, hypomania, and major depression

can be accompanied by symptoms of the opposite polarity, and
are referred to as mood episodes with mixed features.
 (eg, major depression with mixed features or hypomania with mixed
features) .
o Other terms used in the literature include mixed episodes,
mixed states, mixed mania/hypomania, and
dysphoric mania/hypomania.
o Manic or hypomanic episodes with mixed features are
characterized by episodes that meet full criteria for mania or
hypomania , and at least three of the following symptoms
during most days of the episode:
 Depressed mood
 Diminished interest or pleasure in most activities
 Psychomotor retardation
 Low energy
 Excessive guilt or thoughts of worthlessness
 Recurrent thoughts about death or suicide, or suicide attempt
o Major depressive episodes with mixed features are characterized
by episodes that meet full criteria for major depression , and at
least three of the following symptoms during most days of the
episode:
• Elevated or expansive mood
• Inflated self-esteem or grandiosity
• More talkative than usual or pressured speech
• Flight of ideas (abrupt changes from one topic to another that are
based upon understandable associations) or racing thoughts
• Increased energy or goal-directed activity

• Excessive involvement in pleasurable activities that have a high

potential for painful consequences (eg, buying sprees or sexual
indiscretions)
• Decreased need for sleep
o Compared with bipolar patients without mixed features, patients with
mixed features are at greater risk for suicidal ideation and behavior,
and comorbid anxiety disorders and substance use disorders
• Psychosis — Psychotic features such as
– delusions (false, fixed beliefs) and

– hallucinations (false sensory perceptions) can occur during manic, major

depressive, and mixed episodes;
– disorganized thinking and behavior can occur as well.

• Psychotic features may be more common during mania than bipolar

major depression.
• By definition, psychosis does not occur in hypomania.

• Delusions may involve grandiosity, as well as persecutory, sexual,

religious, or political themes; hallucinations are typically auditory in
nature
Frequency of specific symptoms during mania
 Psychiatric disorders
o Most bipolar patients have at least one other psychiatric
disorder.
o Patients with bipolar disorder commonly manifest comorbid
psychiatric disorders, including:
• Anxiety disorders
• Substance use disorders
• Attention deficit hyperactivity disorder (ADHD)
• Eating disorders
• Intermittent explosive disorder
• Personality disorders
• Posttraumatic stress disorder
 Anxiety disorders

o Anxiety disorders that can occur in patients with bipolar

disorder include:
– Agoraphobia
– Generalized anxiety disorder
– Panic attacks and panic disorder
– Specific phobia
– Social anxiety disorder (social phobia)
• Epidemiologic studies show that patients with bipolar disorder
frequently suffer comorbid anxiety disorders
 Manic syndrome
Criteria for manic episode
A. A distinct period of abnormally and persistently elevated,
expansive, irritable mood, lasting at least 1 week or any duration if
hospitalization is necessary.
B. During the period of mood disturbance, 3 (or more) of the
following symptoms have persisted
1. Inflated self-esteem or grandiosity.
2. Decreased need for sleep (e.g., feels rested after only 3 hours of
sleep).
3. More talkative than usual or pressure to keep talking.
4. Flight of ideas or subjective experience that thoughts are racing.
5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant
external stimuli), as reported or observed

6. Increase in goal-directed activity (either socially, at work or school, or sexually)

7. Excessive involvement in activities that have a high potential for painful

consequences (e.g., engaging in unrestrained buying, sexual indiscretions, or
foolish business investments).

C. The mood disturbance is sufficiently severe to cause marked impairment

D. The episode is not attributable to substance

Note: Criteria A-D constitute a manic episode.

 At least 1 lifetime manic episode is required for the diagnosis of bipolar I
disorder.
 Criteria for Hypomanic Episode
A. A distinct period of abnormally and persistently elevated mood lasting at
least 4 consecutive days

B. During the period of mood disturbance and increased energy and activity, 3 (or
more) of the following symptoms have persisted,

1. Inflated self-esteem or grandiosity.

2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).

3. More talkative than usual

4. Flight of ideas or subjective experience that thoughts are racing.

5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant
external stimuli)

6. Increase in goal-directed activity (either socially, at work or school, or sexually)

7. Excessive involvement in activities that have a high potential for painful

consequences

C. The episode is associated with change in functioning that is uncharacteristic of

the individual when not symptomatic.

D. The disturbance in mood and the change in functioning are observable by others.

E. The episode is not severe enough to cause marked impairment in social or

occupational functioning or to necessitate hospitalization.
F. The episode is not attributable to the physiological effects of a substance

 Note: Criteria A-'F constitute a hypomanie episode.

Bipolar Depression (Depressive Phase)

 Uncomplicated depressive phase of bipolar I disorder is

marked by

1. Psychomotor retardation
2. Insomnia with or without hypersomnia,
3. Often abrupt onset and offset
4. Possible recovery into a free interval
 Bipolar I Disorder

A. Criteria have been met for at least 1 manic episode

(Criteria A-D under “Manic Episode”).
B. The occurrence of the manic and major depressive episode(s) is not better
explained by psychotic disorders
 Rapid-Cycling Bipolar Disorder

 Rapid cycling is defined as

The occurrence of at least 4 episodes—both retarded depression and

hypomania (or mania)—a year
 Bipolar II Disorder

A. Criteria have been met for at least 1 hypomanie episode

(Criteria A-F under “Hypomanic Episode” above) and
at least 1 major depressive episode
(Criteria A-C under “Major Depressive Episode” above).
B. There has never been a manic episode.
C. The occurrence of the hypomanie episode(s) and major depressive
episode(s) is not better explained by schizophrenia spectrum and
other psychotic disorders.
BD in adults: Choosing pharmacotherapy for acute
mania and hypomania

• Despite clinical differences between manic and hypomanic

episodes, for the purpose of treatment they are considered to be
similar and thus treated with the same medications
• Despite clinical differences among manic and hypomanic
episodes (eg, hypomania is less severe than mania), for the
purpose of treatment they are considered to be similar and thus
treated with the same medications
 Pharmacotherapy for manic episodes
• depends upon their severity.
• Although there are no established criteria that demarcate severe
episodes from mild to moderate illness,
• we classify episodes as severe if they include any of the
following:
– Suicidal ideation or behavior
– Homicidal ideation or behavior
– Aggressive behavior
– Psychotic features (ie, delusions or hallucinations)
– Poor judgement that places the patient or others at imminent
risk of being harmed
 Goal

• The goal of treating acute mania and hypomania is remission, which

is defined as
– resolution of the mood symptoms or
– improvement to the point that only one or two symptoms of mild intensity
persist.
• If psychotic features (delusions or hallucinations) are also present,
resolution of the psychosis is required for remission.
• Patients with subsyndromal symptoms of mania are at increased risk
of relapse.
• For patients who do not achieve remission, a reasonable goal is
response, which is defined as stabilization of the patient’s safety and
substantial improvement in the number, intensity, and frequency of
mood (and psychotic) symptoms
 Drug classes
o Based upon randomized trials, drug classes commonly used to treat acute
mania or hypomania include:
• Lithium
• Anticonvulsants
• Antipsychotics
• Benzodiazepines
• The mainstays of treatment are lithium, anticonvulsants, and antipsychotics
used in combination pharmacotherapy
• (eg, lithium plus an antipsychotic) or as monotherapy, depending upon the severity of symptoms.

• Benzodiazepines are primarily used as adjunctive treatment for insomnia,

agitation, or anxiety.
• Duration — Although it is not established how long clinicians
should wait to assess the benefit of a medication regimen, it is
reasonable to allow up to two weeks for a treatment trial.
• However, most randomized trials last three weeks, and the
superior efficacy of active drugs compared with placebo
generally begins to manifest within one week.
 Severe manic episodes

• Severe manic or mixed episodes are characterized by

– suicidal or homicidal ideation or behavior
– Aggressiveness
– psychotic features (ie, delusions or hallucinations), and
– poor judgement that places the patient or others at imminent
risk of being harmed.
• Severely ill patients generally require hospitalization.
 First line medication combinations
Severely ill patients with acute mania typically require treatment
with a medication combination
• Lithium plus an antipsychotic (valproate plus an antipsychotic is a
reasonable alternative)
• Lithium or valproate with aripiprazole, haloperidol (or another
first-generation antipsychotic), olanzapine, quetiapine, or
risperidone.
• No head-to-head trials have compared antipsychotics in
combination with lithium or valproate.
• Thus, the choice between lithium and valproate, and choice of
an antipsychotic is based upon other factors, including
– past response to medications
– side effect profiles
– comorbid general medical conditions
– potential for drug-drug interactions
– drug preparation (eg, intramuscular or oral disintegrating),
– patient preference, and cost
• In addition, we generally avoid using adjunctive ziprasidone

• adding ziprasidone to lithium or divalproex is not efficacious

• avoid combining carbamazepine with an antipsychotic, because

no more efficacious than carbamazepine alone
• Carbamazepine induces hepatic enzymes that metabolize
antipsychotics
• When prescribing a medication combination, both drugs are
started and titrated up simultaneously
 Resistant patients

• A severe manic episode that does not respond to one medication

combination should be treated with a 2nd medication combination.
• Generally, lithium is switched to valproate or vice versa.
• As an example, for patients who do not respond to lithium plus
haloperidol within two weeks of reaching target doses,
– we suggest tapering and discontinuing lithium at the same time that
valproate is started and titrated up.
– Lithium is generally tapered over one week by the same amount for each
dose decrease (eg, lithium 1800 mg per day is decreased by 600 mg per
day, every one to two days)
• Conversely, for patients who do not respond to valproate plus
haloperidol within two weeks of reaching target doses,
– we suggest tapering and discontinuing valproate at the same time that
lithium is started and titrated up.
– Valproate is generally tapered over one week by the same amount for
each dose decrease (eg, valproate 2000 mg per day is decreased by
500 mg per day, every one to two days).
• For patients who do not respond to lithium plus an antipsychotic
or to valproate plus the same antipsychotic,
– we suggest starting a third medication combination involving lithium or
valproate plus an antipsychotic.
– The choice between lithium and valproate is based upon efficacy and
tolerability in the two prior trials.
– In addition, the antipsychotic used in the two prior trials is discontinued
and a new one chosen from amongst aripiprazole, haloperidol (or another
first-generation antipsychotic), olanzapine, quetiapine, or risperidone.
• The antipsychotic is generally tapered over one week by the same
amount for each dose decrease (eg, haloperidol 10 mg per day is
decreased by 5 mg per day, every one to two days), and at the
same time, the other antipsychotic is started and titrated up
 Refractory patients
Electroconvulsive therapy —
• Electroconvulsive therapy (ECT) for refractory patients whose
manic episode does not respond to four to six medication
combinations
• Several studies suggest that ECT is effective for mania.
• ECT is generally safe and there are no absolute contraindications,
even in patients whose general medical status is compromised
• However, safety concerns regarding ECT necessitate preprocedure
medical consultation.
• Adverse effects include cardiopulmonary events, aspiration
pneumonia, fractures, dental and tongue injuries, headache, nausea,
and cognitive impairment.
 Other medications
• For patients with refractory mania who

– decline ECT,

– do not remit with it, or

– have no access to it, and

– who do not respond to medication combinations involving lithium or

valproate plus aripiprazole, haloperidol (or another first-generation
antipsychotic), olanzapine, quetiapine, risperidone, or ziprasidone, we
suggest pharmacotherapy with lithium or valproate plus clozapine
• Patients unresponsive to lithium or valproate plus clozapine may possibly
benefit from allopurinol plus lithium, tamoxifen monotherapy, and tamoxifen
plus lithium
• Thus, the choice is based upon other factors, including past
response to medications, side effect profiles, comorbid general
medical conditions, potential for drug-drug interactions, patient
preference, and cost.
Acutely agitated patients
• Hospitalized patients with mania who are acutely agitated may
require
– oral or intramuscular medications
– isolation and physical restraints.
– Severely ill patients generally receive antipsychotics (eg, aripiprazole
, haloperidol, or olanzapine) as part of their daily medication regimen
 Hypomania and mild to moderate mania
• marked by the absence of suicidal or homicidal ideation or
behavior, aggressiveness, psychotic features (ie, delusions or
hallucinations), and poor judgement that places the patient or
others at imminent risk of being harmed.
• Monotherapy is commonly used for initially treating hypomania
and mild to moderate mania
• First line monotherapy — For patients with either hypomanic or
mild to moderate manic episodes, monotherapy with risperidone
or olanzapine, based upon efficacy and tolerability
• However, reasonable alternatives include aripiprazole, asenapine,
carbamazepine, cariprazine, haloperidol, lithium, paliperidone,
quetiapine, valproate, or ziprasidone
 Treatment resistance

• For hypomanic and mild to moderate manic episodes that do

not respond to three to five monotherapy trials involving
aripiprazole, carbamazepine, haloperidol, lithium, olanzapine,
quetiapine, risperidone, valproate, and ziprasidone,
– we suggest combining lithium or valproate with an antipsychotic.
However, lithium plus valproate is a reasonable alternative
 Benzodiazepines

• Clonazepam for patients who have

– hypomanic or mild to moderate manic or mixed episodes and cannot tolerate
lithium, anticonvulsants, or antipsychotics. However, lorazepam is a
reasonable alternative.

• Benzodiazepine are generally used as adjunctive therapy to treat

– insomnia, agitation, or anxiety in patients with pathologic mood elevated
syndromes.

• Given the high rate of substance use disorders among bipolar patients
and the potential for abusing benzodiazepines, these drugs are
generally limited to acute treatment
• However, maintenance treatment with benzodiazepines is administered to
catatonic patients who remit with benzodiazepines
• Clonazepam is usually started at a dose of 1-3mg/day, taken in two divided
doses.
• The drug is generally titrated up to a target dose ranging from 2-6mg/day,
depending upon efficacy and tolerability, although doses as high as 24 mg per
day have been used
• Side effects include disinhibition, sedation, and respiratory depression.
• Lorazepam is usually started at a dose of 2-4mg/day, taken in three to four
divided doses.
• The drug is generally titrated up to a target dose ranging from 3 to 8 mg per
day, depending upon efficacy and tolerability, although doses as high as
24mg/day have been used
• Side effects include disinhibition, sedation, and respiratory depression
 Management of bipolar dipression

Pharmacologic Therapy

Mood stabilizers
 Mood-stabilizing drugs are the primary treatment for

 Bipolar depression.

 Among antipsychotic drugs,

• Quetiapine as monotherapy

• Olanzapine + fluoxetine are approved for bipolar .

 Antidepressants can be used but along with a mood stabilizing agent to

 Reduce risk of a mood switch to mania

 Lithium

• The first approved mood-stabilizing drug.

• It remains a first-line agent and

• Sets the standard for efficacy

• It has anti-manic efficacy,

• Prevents bipolar disorder relapse

• One of the oldest drugs used for psychiatric illness

• It is most effective for patients with few previous episodes

• However, patients with rapid cycling bipolar disorder are less responsive
 Lithium

• Mechanism of action is not well understood

• 900–2400 mg/day once daily or in 2–4 divided doses, preferably with meals.

• Once-daily dosing improve adherence

• Lithium requires regular monitoring

• Hypothyroidism is not usually an indication to discontinue the drug can be

supplement with levothyroxine
• A severe form of polyuria, when urine volume > 3L/day, is known as lithium-
induced nephrogenic diabetes insipidus.
• It can be treated with HCT or amiloride.

• Benign fine hand tremor can be evident in many patients while a course hand
tremor may be a sign of toxicity
 Strategies to reduce the fine tremor include standard approaches
 switch to long-acting preparation, lower dose if possible) or
 adding a β-adrenergic antagonist (eg, propranolol 20-120 mg/day).
• Lithium can cause many acute and long-term adverse effects.
• The most common acute side effects are nausea, tremor, polyuria
and thirst, weight gain, loose stools, and cognitive impairment.
• Severe or sudden worsening of acute side effects may be a sign of
lithium toxicity.
• Over the long term, lithium can adversely affect the kidneys and
thyroid gland.
• In addition, cardiac rhythm disturbances have been described; these
almost always occur in patients with preexisting cardiac disease.
 Divalproex Sodium and Valproic Acid
• Divalproex sodium is composed of sodium valproate and valproic acid (VPA).
• It is generally equal in efficacy to lithium
• It has particular utility in bipolar disorder with
Rapid cycling
Mixed and
Substance abuse comorbidity.
• DVP can be used as
monotherapy or
combination with lithium or antipsychotic drug.
• It is known to affect ion transport and enhances the activity of
g-aminobutyric acid (GABA).
• DVP is usually initiated at 750–3,000 mg/day (20–60 mg/kg/day) in 2–3 divided
doses.
• Common side effects of valproate include
weight gain, nausea, vomiting, hair loss, easy bruising, and tremor.

 Divalproex is a formulation of valproate that can minimize

gastrointestinal distress.
 In addition, valproate is rarely associated with hepatic failure
and thrombocytopenia.
 liver function tests and platelets should thus be monitored at 6
to 12 month intervals in all patients taking the drug
• Anticonvulsants — Anticonvulsants that are efficacious for
acute mania and hypomania include valproate and CMZ.
• Suicidality — Bipolar disorder is associated with an increased
risk of suicide deaths, and all patients should be monitored for
emergence or worsening of suicidal thoughts and behavior.
• Although some observational studies suggest that anticonvulsants
may increase the risk of suicidal ideation or behavior, these drugs
are generally safe to use when patients are regularly monitored.
●For patients treated with antiepileptic drugs, the rate of suicide
attempts was greater before treatment than after treatment
●Patients receiving antiepileptic drug monotherapy (and no
concomitant antidepressant or antipsychotic) had fewer suicide
attempts compared to patients receiving no pharmacotherapy
 Carbamazepine
• It is sometimes reserved for patients who fail to
Respond to lithium or
For patients with rapid cycling
• Used as monotherapy or in combination
• The dosage can be increased by 200- 400 mg/day Q2-4 days
• Start at 100–200 mg bid; increase by 200 mg every 3–4 days to 200–1,800
mg/day in 2–4 divided doses.
• The most common adverse effects are
– Drowsiness, dizziness, lethargy, and confusion
– It also causes diplopia and dysarthria.
• Carbamazepine has an antidiuretic effect and it is auto-inducer
• The dosage may require an increase after 1 month or so of therapy because of this
effect.
• The major systemic side effects of carbamazepine are nausea,
vomiting, diarrhea, hyponatremia, rash, pruritus, leukopenia,
and fluid retention.
• In addition, the drug is associated with life-threatening rashes
(Stevens-Johnson syndrome and toxic epidermal necrolysis),
particularly during the first eight weeks of therapy.
• This reaction is significantly more common in patients with the
HLA-B*1502 allele (estimated incidence of 5 percent), which
occurs almost exclusively in patients of Asian ancestry,
including South Asian Indians
 Lamotrigine
• Lamotrigine is effective for the
maintenance treatment of bipolar disorder.
• It is more effective for
 depression relapse prevention than for mania relapse prevention.
• Usually initiated at 25 mg/day for the first 1-2 wks, then increasing in a dose-
doubling fashion every 1-2 wks to a target dosage of 200 to 400 mg/day.
• If lamotrigine is added to DVP, the starting dosage is 25 mg every other day
• If DVP is added to lamotrigine, the lamotrigine dosage should be reduced by
50%
• routine monitoring is not required
• The lamotrigine adverse effect of greatest significance is
– Maculopapular rash
 Antipsychotic Drugs

• FGAs, chlorpromazine and haloperidol are used in the

– Treatment of acute mania.

• SGA drugs, including aripiprazole, asenapine, olanzapine, quetiapine,

risperidone, and ziprasidone, are approved
for the treatment of bipolar mania

• The combination of olanzapine+fluoxetine is approved for treatment of

acute bipolar depression.
• Quetiapine is approved as monotherapy for acute bipolar depression
• First- and second-generation antipsychotics are efficacious for
treating both psychotic and nonpsychotic manic and hypomanic
episodes
• First-generation — Among first-generation antipsychotics, we
prefer haloperidol for treating manic episodes because it has been
widely studied and generally causes less orthostatic hypotension and
sedation than chlorpromazine, which is also efficacious.
• Other first-generation antipsychotics such as fluphenazine, loxapine,
perphenazine, thiothixene, and trifluoperazine are effective as well.
• We suggest patients initially receive haloperidol at a dose of 5 to 15
mg per day, depending upon the severity of symptoms, the patient’s
body mass index, and adverse effects that emerge.
• The drug is taken either once per day or in two divided doses,
depending upon tolerability and the patient’s ability to adhere
to treatment with divided doses.
• One useful guide is to prescribe 0.2 mg per kg per day.
• In a meta-analysis of 15 randomized trials (2022 acutely ill
patients with pure mania or mania with mixed features), which
found that haloperidol was comparable to carbamazepine,
olanzapine, risperidone, and valproate,
• the dose of haloperidol ranged from 2 to 85 mg per day.
• Conventional antipsychotics are associated with extrapyramidal symptoms,
and includes
– Extrapyramidal symptoms are usually managed by lowering the dose of the
antipsychotic or by adding an anticholinergic drug, either benztropine 1 to 2 mg two to
four times daily or trihexyphenidyl 2 to 5 mg two to four times daily.
• First line medications — For manic and hypomanic pregnant patients, we
suggest first-generation antipsychotics, which have been widely used during
pregnancy.
• We prefer haloperidol, based upon its demonstrated efficacy in randomized
trials (which excluded pregnant patients) , and other studies that suggest
haloperidol is not associated with an increased risk of congenital anomalies.
• Other first-generation antipsychotics that are reasonable alternatives to
haloperidol include chlorpromazine, fluphenazine, perphenazine, thiothixene,
and trifluoperazine.
• Clinicians can expect that response to a first-generation antipsychotic will
occur in approximately 50 percent of patients, based upon trials in nonpregnant
patients
• Resistant patients — In our clinical experience, pregnant patients with manic
and hypomanic episodes often do not respond to or tolerate haloperidol.
• For these resistant patients, we suggest in order of preference risperidone,
quetiapine, or olanzapine, based upon their efficacy and side effects in
randomized trials (that excluded pregnant patients), as well as study findings
that suggest these drugs are not associated with an increased risk of major
malformations.
• Using second-generation antipsychotics during pregnancy is consistent with
the practice of many perinatal psychiatrists.
• Up to 50 to 60 percent of patients may respond, based upon trials in
nonpregnant patients.
• The efficacy of risperidone and olanzapine appears to be superior to
quetiapine and lithium;
• quetiapine appears to be better tolerated than olanzapine; and although the
efficacy of quetiapine and lithium appear comparable, quetiapine may be
better tolerated.
• In addition, study findings suggest that second-generation antipsychotics are not
associated with an increased risk of major malformations ,whereas lithium is
generally regarded as teratogenic.
• The preference for treating pregnant bipolar patients with risperidone, quetiapine,
or olanzapine rather than lithium is consistent with practice guidelines from the
United Kingdom National Institute for Health and Clinical Excellence
• Aripiprazole: 10–30 mg/day once daily
• Asenapine: 5–20 mg/day in two divided doses.
• Olanzapine: 5–20 mg/day in 1 or 2 doses
• Quetiapine:50–800 mg/day in divided doses or once daily when stabilized
• Risperidone: 0.5 – 6 mg/day in 1 or 2 doses
 Case 3

Ms X is 21 years old female university student

who was relatively healthy and functional with
mood stabilizer since two weeks back at which
time she starts to have behavioural changes like
talking and laughing alone she use excessive
make up she didn’t want to sleep the whole
night and she cleans her dormitory during the
night. She went to church many times a day she
thinks that she is very beautiful and also she
has special relationship with God. Her friends
told that
She cries without any reason. She feels sadness. Her mood
fluctuates many times a day. Has no any history of psychotic
symptoms. No substance abuse history.
List signs and symptoms for Bipolar disorder.
Suggestive findings for bipolar disorder
Pharmacotherapeutic plan
Counseling
 Case 4

Mr A is 30years old privet worker brought by

his wife because he starts to be suspicious of
his neighbours that they want to harm him. He
also hear voice that told him he is worthless
and he shouldn’t be alive. He loss his interest
in his work and stay in his home he withdraw
from people. He feels hopeless and has history
of suicidal attempt before 02 days. He
complains sleep difficulty he has difficulty to
concentrate on his work. He starts to talk and
laugh alone. He told that he has no any bright
future.
The symptoms started before 1 year but the
symptoms relived with out treatment after few
months but before 1 and half months the
symptoms started again. He has history of
khat chewing for the last 6 months the amount
increased through time. He also started to
drink alcohol.
Has no any manic symptoms
No family history of mental illness.
Case 5
Mr X is 25 yrs old male came with c/c of I don’t know
why I am coming . From his family members he has
symptoms like believed to be followed by some one,
he also said that he is special one and selected by
God to be a leader of the people. He went to church
many times a day. And he has also hx of crying and
sadness and feeling happy and sad fluctuate many
times a day has no substance abuse histor. No any
other psychotic symptoms