This document discusses psychotic disorders and their pharmacotherapy. It defines psychotic disorders as illnesses that make it difficult to think clearly and behave appropriately. It describes several types of psychosis including schizophrenia, schizoaffective disorder, delusional disorder, and dissociative disorders. Symptoms are outlined along with possible causes such as genetics and drug abuse. Diagnosis involves medical history, exams, and scans. Treatment involves antipsychotic drugs which work to reduce disturbed behaviors associated with delusions and hallucinations. Atypical antipsychotics are most commonly used now due to their better efficacy and safety profile.

1. Pharmacotherapy of
Psychotic & Mania
disorders
Late. BRKM GMC
Dimrapal, Jagdalpur

2. Psychotic disorder
• Psychotic disorder are a group of serious
illnesses that affect the mind.
• They make it hard for someone to
• think clearly,
• make good judgments,
• respond emotionally,
• communicate effectively,
• understand reality, and
• behave appropriately.

3. •When symptoms are severe, people
with psychotic disorders have trouble
staying in touch with reality and often
are unable to handle daily life.
•But even severe psychotic disorders
usually can be treated.

4. Types:
Schizophrenia:
• People with this illness have changes in
behavior and other symptoms--such as
delusions and hallucinations -- that last
longer than 6 months.
• It usually affects them at work or school,
as well as their relationships.

5. Demographics
• Onset and Prevalence of Schizophrenia worldwide
• About 1% of the population
• Usually develops in early adulthood, but can emerge at any
time
• Schizophrenia Is Generally Chronic
• Most suffer with moderate-to-severe impairment throughout
their lives
• Life expectancy in persons with schizophrenia is slightly less
than average
• Schizophrenia Affects Males and Females About Equally
• Females tend to have a better long-term prognosis
• Onset of schizophrenia differs between males (earlier) and
females (later)
• Schizophrenia Appears to Have a Strong Genetic
Component

6. A neurobiological illness that
impairs:
• Perceptions
• Thinking
• Language
• Emotions
• Social interactions

7. Positive Symptoms
Type I Schizophrenia
• Hallucinations
• Delusions
• Thought Disorder
• Paranoia
• Ideas of Reference
• Loose Associations
• Thought Broadcasting
• Thought Insertion
• Concrete Thinking
• Odd Speech
• Neologisms
• Word Salad
• Perseveration
• Clang Associations
• Echolalia
• Odd Behavior
• Agitation/Aggression
• Catatonia
• Regression
• Stereotypy

8. Schizophrenia
• Hallucinations
• Auditory
• Visual
• Delusions: Firm, fixed, false belief
• Grandeur
• Persecution
• Ideas of Reference
• Self-accusation
• Infidelity
• Paranoid

9. Meaning of terms
• Neologisms:
• new words or condensations of words used in an attempt to
express a highly complex idea.
• Word Salad:
• an incoherent mixture of words & phrases
• Perseveration:
• pathological repetition of the same response to different
questions.
• Clang Associations:
• using words similar in sound, but not in meaning.
• Echolalia:
• repeating of words or phrases of one person by another.

10. Cont..
• Agitation/Aggression: constant movement,
irritability, confrontation
• Catatonia: motor abnormalities
• Catalepsy: constantly maintained immobile position
• Excited: agitated purposeless motor activity w/o cause
• Stupor: marked slowed activity - immobile - unaware
• Rigidity: rigid posture - resists all attempts to be moved
• Posturing: voluntary assumption of position - long periods
• Cerea flexibilitas: person can be molded into position
• Negativism: motiveless resistance to all attempts to move
• Regression: may assume and maintain fetal position
• Stereotypy: repetitive fixed pattern of physical
action or speech

11. Negative Symptoms
Type II Schizophrenia
• Flat, Blunt, or Restricted Affect: lack vocal inflection,
paucity of expressive gestures, poor eye contact,
decreased movement, or unchanging facial expression.
• Alogia: poverty of speech
• A sociality: lack of social interaction
• Anhedonia: lack of interest in activities that formerly
brought pleasure
• Avolition: lack of goal directed motivation
• Inattention: inwardly focused - not aware of
surroundings or activity

12. Schizoaffective disorder
• Has symptoms of both Schizophrenia and a major
mood disorder at the same time.
• Patients with Schizoaffective Disorder experience a
combination of symptoms associated with both
diseases, but do not meet the full criteria for either.
• Two types of Schizoaffective disorder:
• Bipolar type is where the patient has symptoms of a
Manic or
• Mixed and/or a Depressive episode with his/her
psychotic sx.

13. Cont…
• Depressive type is where the patient has only the
symptoms of a Major Depressive Disorder with
his/her psychotic symptoms.
• Symptoms include:
• auditory/visual hallucinations,
• suspiciousness,
• unusual thought content,
• disorganization,
• emotional withdrawal,
• blunted affect,
• inability to express pleasure, and
• attention difficulties

14. • Schizophreniform disorder:
• This includes symptoms of schizophrenia, but
the symptoms last for a shorter time: between 1
and 6 months.
• Brief psychotic disorder:
• People with this illness have a sudden, short
period of psychotic behavior, often in response
to a very stressful event, such as a death in the
family.
• Recovery is often quick -- usually less than a
month.

15. Delusional disorder
• Delusional disorder :
• The key symptom is having a delusion (a false,
fixed belief).
• Involving a real-life situation that could be true
but isn't, such as being followed, being plotted
against, or having a disease.
• The delusion lasts for at least 1 month.

16. Subtypes:
• Erotomanic: someone of higher status loves me
• Grandiose: inflated self worth, power, knowledge,
identy or special relationship with God or a famous
person.
• Jealous: belief that one’s sexual partner is unfaithful
• Persecutory: belief that you are being wrongly treated
in some way - often take their complaints to legal
authorities
• Somatic: belief that you have some physical defect,
disorder, or disease
• Unspecified: doesn’t fit any of the above

17. • Shared psychotic disorder (also called folie à
deux):
• This illness happens when one person in a
relationship has a delusion and the other person
in the relationship adopts it, too.
• Substance-induced psychotic disorder:
• This condition is caused by the use of or
withdrawal from drugs, such as hallucinogens
and crack cocaine, that cause hallucinations,
delusions, or confused speech.

18. • Psychotic disorder due to another medical
condition:
• Hallucinations, delusions, or other symptoms
may happen because of another illness that
affects brain function, such as a head injury
or brain tumor.
• Paraphrenia:
• This condition has symptoms similar to
schizophrenia.
• It starts late in life, when people are elderly.

19. Dissociative Disorders
• Depersonalization Disorder
• Dissociative Amnesia
• Dissociative Fugue
• Dissociative Identity Disorder (formerly Multiple
Personality Disoder)

20. Depersonalization
• Person feels a change in sense of self - feels
mechanical, dreamy, or detached from their body
• Temporary state
• Usually follows a traumatic event, but is often
present during panic attacks

21. Dissociative Amnesia
• Inability to recall important personal
information
• Information is frequently traumatic in nature
• Sub categories:
• Generalized amnesia
• Localized amnesia
• Selective amnesia

22. Dissociative Fugue
• Sudden, unexpected travel away from usual
surroundings coupled with amnesia of former life
• Usually time-limited
• Person suddenly remembers who they are and
becomes amnesic for the time away
• Also follows traumatic event.

23. Dissociative Identity Disorder
• Splitting of personality into two or more separate
and distinct personalities
• “Primary” personality usually not consciously
aware of others
• “Alternates” may be very ill (suicidal) or extremely
different from the primary
• Caused by extreme trauma in childhood

24. Symptoms
• Hallucinations means seeing, hearing, or
feeling things that don’t exist.
• For instance, someone might see things that
aren't there, hear voices, smell odors, have a
"funny" taste in their mouth, or feel sensations
on their skin even though nothing is touching
their body.

25. • Delusions are false beliefs that don’t go away
after even after they've been shown to be
false.
• For example, a person who is certain his or her
food is poisoned, even if someone has shown
them that the food is fine, has a delusion.

26. Other possible symptoms:
• Disorganized or incoherent speech
• Confused thinking
• Strange, possibly dangerous behaviour
• Slowed or unusual movements
• Loss of interest in personal hygiene
• Loss of interest in activities
• Problems at school or work and with relationships
• Cold, detached manner with the inability to express
emotion
• Mood swings or other mood symptoms, such as
depression or mania

27. Causes
• Unknown
• Hereditary
• Stress induced
• Drug abuse
• Eventful Life events

28. Schizophrenia
• May associated with involvement of pathology of
some parts of the brain that control thinking,
perception, and motivation.
• It is also believe that; In schizophrenia, nerve cell
receptors that work with a brain chemical called
glutamate may not work properly in specific brain
regions.
• These conditions usually first appear when a
person is in his or her late teens, 20s, or 30s. They
tend to affect men and women about equally.

29. Diagnosis
•By:
• Medical and psychiatric history
• Brief physical exam.
• MRI scans

30. Management
• The antipsychotic drugs are broadly defined as the
drugs, which are used to treat the psychiatric disorders.
• In earlier times, these drugs were also known as major
tranquilizers due to their calming effect; but this term
has been abandoned now.
• These drugs are also called as neuroleptic agents as
they reduce the agitation and disturbed behaviour
associated with delusions and hallucinations in
schizophrenia (antipsychotic effect) as well as produce
a high incidence of extrapyramidal side effects (EPS) at
clinically effective doses.

31. • The probable cause of mental illnesses
involving mania and schizophernia is
dopaminergic overactivity in the limbic
system, whereas, depression involves
monoaminergic (NA, 5-HT) deficiency.
• The “atypical” antipsychotic drugs are most
widely used nowadays due to their better
antipsychotic and minimal extrapyramidal
side effect profile.

32. The antipsychotic or neuroleptic
drugs are classified as:
A. TYPICAL ANTIPSYCHOTIC DRUGS
SN CLASS DRUGS
1 Phenothiazines Chlorpromazine (CPZ), Triflupromazine,
Thioridazine, Trifluoperazine, Fluphenazine
2 Butyrophenones Haloperidol, Trifluperidol, Penfluridol
3 Thioxanthenes Flupenthixol
4 Other
heterocyclics
Pimozide, Loxapine
A. ATYPICAL ANTIPSYCHOTICS
Clozapine, Risperidone, Olanzapine, Quetiapine, Aripiprazole,
Ziprasidone, Amisulpiride, Zotepine

33. MECHANISM OF ACTION OF ANTIPSYCHOTIC DRUGS
• All antipsychotics (except atypical antipsychotics)
have common mechanism of action.
• These drugs have potent dopaminergic D2 receptor
blocking action in the ‘limbic system’ and in
mesocortical region, which is responsible for their
antipsychotic action.
• The atypical antipsychotic drugs block dopaminergic
as well as other monoamine receptors especially
5HT2A.

34. PHARMACOLOGICAL EFFECTS OF CHLORPROMAZINE
(prototype)
SITE EFFECTS
CNS (by blocking Dopaminergic receptors)
a. Limbic system a. Decrease in spontaneous motor activity, induction
of sleep and improvement of cognitive &
intellectual function.
a. Mesocortical area
a. Basal ganglia a. Extrapyramidal symptoms, reduces spasticity.
a. Pituitary a. Prolactin release (gynaecomastia in male;
galactorrhoea in females)
a. CTZ a. Antiemetic effects
CVS (α1 adrenergic
receptor)
• Postural hypotension, tachycardia, palpitations and
Q-Tc prolongation (at higher doses).
Skin (H1 receptor) • Antipruritic effects
GIT (M3 receptor) • Dry mouth, constipation
Eye (M3 receptor) • Blurred vision
Urinary bladder (M3
receptor)
• Urinary retention

35. Pharmacokinetics
• Antipsychotic drugs are erratically absorbed from
the GIT; whereas, intramuscular and intravenous
doses produce consistent effects.
• These drugs are widely distributed in the tissues
and often accumulate after repeated
administrations.
• These drugs crosses BBB and attain higher
concentrations in brain than in plasma.
• These drugs cross placental barrier and also enter
the breast milk.

36. Cont…
• They are metabolized in the liver and excreted
through the bile and urine with an average t1/2 of 18-
30 hours.
• The excretion remains continued for months even
after discontinuation of the drug due to cumulative
effect.
• The dose adjustment of antipsychotic drugs is
advocated according to age as metabolism of these
drugs is faster in children & slow in elderly
individuals.
• The patients should be informed/counseled
regarding long duration of treatment as the clinical
effects of these drugs appear after few weeks only.

37. Drug Dose
(mg/day)
Common pharmacological effects Special features
Extrapyramidal Sedative Hypotension
TYPICAL ANTIPSYCHOTICS DRUGS
Triflupromazine 50–200 High High Moderate  More potent than CPZ.
 Used as antiemetic.
 On IV injection, its produces acute
muscle dystonias (especially in children).
Thioridazine 100–400 Very low High High  Has marked central anticholinergic
action.
 Cardio-toxic & causes inhibition of
ejaculation.
 It also damages eye; hence long-term
therapy should be avoided.
Trifluoperazine 2–20 High Low Low  They have minimum autonomic actions.
 The incidence of loss of glycemic
control, hepatotoxicity and
hypersensitivity reactions are little.
Fluphenazine 1–10
Haloperidol 2–20 High Low Low  It is a potent antipsychotic.
 Used in acute schizophrenia,
Huntington’s disease & Gilles de la
Tourette’s syndrome.
 Fewer incidences of seizure, weight gain
and hepatotoxicity.

38. Drug Dose
(mg/day)
Common pharmacological effects Special features
Extrapyramidal Sedative Hypotension
TYPICAL ANTIPSYCHOTICS DRUGS
Flupentixol 3–15 High Low Low  Less sedative than CPZ.
 Used in schizophrenia and other
psychotic disorders such as in
withdrawn and apathetic
patients.
 Rarely used nowadays.
Pimozide 2–6 High Low Low  Selective DA antagonist with
little α-adrenergic or cholinergic
blocking activity.
 Used for the treatment of Gilles
de la Tourett’s syndrome and in
ticks.
 It has long duration of action;
hence, used for maintenance
therapy.
 Causes cardiac arrhythmia as a
side effect.
Loxapine 20–50 Moderate Low Moderate It is shortest and fastest acting
antipsychotic drug.

39. ATYPICAL ANTIPSYCHOTICS DRUGS
(Clozapine, Risperidone, Olanzapine,
Quetiapine, Aripiprazole, Ziprasidone,
Amisulpiride, Zotepine)

40. •These are also called 2nd generation
antipsychotic drugs.
•They differ from typical or classic
antipsychotic drugs as follows:
•They have weak D2 receptor blocking
activity along with potent 5-HT2
antagonistic activity.

41. • The antipsychotic effect is attributed to a
combination of dopaminergic and 5-HT2
receptor blockade.
• They are effective in the patients
refractory to typical antipsychotic drugs.
• The incidence of extrapyramidal side
effects is very low than typical
antipsychotics as their affinity towards D1
and D2 receptors is very low.

42. Clozapine
 It is the first atypical antipsychotic.
 It blocks D1, D4, 5-HT2, α-adrenergic & H1receptor
with relatively weak D2 selectivity.
 Most effective in
 Both positive and negative symptoms of schizophrenia
 Refractory schizophrenia.
 Low sedation and low incidence of EPS is there.
Dose (mg/day) Common side effects
Extra pyramidal Sedation Hypotension
100–300 No High High

43.  The common side effects are
 weight gain,
 hyperlipidemia,
 loss of glycemic control,
 seizure (in high dose),
 tachycardia and
 urinary incontinence.
 It causes agranulocytosis and other blood
dyscrasias:
 hence, weekly monitoring of leucocyte count is
advocated.

44. Risperidone
• D2 + 5-HT2 receptor antagonist with high affinity
for α1, α2 and H1 receptors.
• More potent than clozapine.
• Weight gain & the incidence of diabetes is less
prominent than clozapine.
• It increases the level of prolactin.
• It may produce EPS at high dose.
• Should be avoided in elderly patients with stroke.
Dose Extrapyramidal Sedation Hypotension
2–8 Moderate Moderate Moderate

45. Olanzapine
• Blocks D2, 5-HT2, α1, α2, H1 and muscarinic
receptors.
• Used for both positive and negative symptoms of
schizophrenia and mania.
• The common side effects are
• weight gain,
• loss of diabetic control and
• increase incidence of seizure.
Dose Extrapyramidal Sedation Hypotension
2.5–20 Low Low Moderate

46. Quetiapine
• Short-acting atypical antipsychotic.
• It blocks the 5-HT1A, 5-HT2, D2, α1 , α2 and H1
receptors in the brain.
• Used in mania and bipolar depressive disorder as
maintenance therapy.
• Not effective in schizophrenia.
• S/E: Weight gain and loss of diabetic control with
QT prolongation.
Dose Extrapyramidal Sedation Hypotension
50–400 Very low High Moderate

47. Aripiprazole
• It is partial agonist at D2, 5-HT1A with 5-HT2
receptors antagonist.
• Used in schizophrenia, mania and bipolar
disorders.
• The common side effects are
• nausea,
• dyspepsia,
• constipation,
• light-headedness and
• prolongation of Q-Tc (at higher doses).
Dose Extrapyramidal Sedation Hypotension
5–30 Very low Very low Very low

48. Ziprasidone
• It blocks D2 + 5-HT2A/2C+ H1+ α1 for antipsychotic
action.
• It also blocks the 5-HT1D and agonist at 5-HT1A
receptors with inhibition of 5-HT and NA reuptake
resulting its antianxiety & antidepressant actions.
• The common side effects are
• nausea,
• vomiting and
• dose related prolongations of Q-Tc.
Dose Extrapyramidal Sedation Hypotension
40–160 Low Low Low

49. Amisulpiride
• It has high affinity for D2& D3 and has low-affinity for
5-HT2 receptors.
• Used in the treatment for negative symptoms
associated with schizophrenia.
• The common side effects are
• anxiety,
• insomnia,
• agitation,
• Q-Tc (in elderly) and
• hyperprolactinemia.
• It has low incidence of weight gain.
• Dose:
• schizophrenia 50–300 mg/day BD
• acute psychosis 200–400 mg BD.
Extrapyramidal Sedation Hypotension
Low No Low

50. Zotepine
• DOES: 25-100mg TDS
• Blocks D2+D1, 5-HT2, α1, H1 receptors and NA
reuptake.
• Used for positive and negative symptoms of
schizophrenia.
• The common side effects are
• headache,
• postural hypotension,
• weight gain,
• hyperglycaemia and
• dyslipidemia.
Dose Extrapyramidal Sedation Hypotension
25-100mg TDS Low Low Low

51. Lurasidone
 It is a novel 5-HT/DA antagonist.
 It possesses potent activity at 5-HT7 receptor
sites, actions that, based on preclinical and early
clinical studies, may be associated with cognitive
benefits.
 It is devoid of most of the side effects associated
with atypical antipsychotics.

52. COMMON INDICATIONS OF ANTIPSYCHOTIC/
NEUROLEPTIC DRUGS
• Psychiatric illness
• Schizophrenia
• Control of acute mania and also for long term
treatment.
• Organic brain syndromes (dementia and
delirium).
• Anxiety (BZDs preferred).
• Neuro-psychiatric illness
• Alcoholic hallucinations.
• Huntington’s disease.
• Gilles de la Tourette’s.

53. Indications
• Non-psychiatric illness
• As antiemetic (at doses much lower than
needed as antipsychotic).
• Intractable hiccough (parenteral
chlorpromazine is used).
• As preanaesthetic medication (promethazine).

54. COMMON SIDE EFFECTS OF
ANTIPSYCHOTIC/NEUROLEPTIC DRUGS
System Adverse effects
CNS Drowsiness, lethargy, mental confusion and agitation,
extrapyramidal side effects
CVS Postural hypotension, palpitations, Q-Tc prolongation and
cardiac arrhythmias.
Endocrine Hyperprolactinemia.
Amenorrhoea, infertility, galactorrhoea in females and
gynaecomastia in males also occur, but infrequently after
prolonged treatment.
Metabolic Increase in appetite, weight gain, loss of diabetic control
and dyslipidemia.
Eye Blurring of vision
GIT Constipation, dry mouth.
Urinary system Urinary hesitancy in elderly males

55. Extrapyramidal side effects (EPS)
• The extrapyramidal side effects are mostly
seen with potent typical antipsychotic drugs
and rarely with atypical antipsychotics.
• Parkinsonism,
• Acute muscular dystonias,
• Akathisia and
• Malignant neuroleptic syndrome appear early
during the treatment, whereas
• Rabbit syndrome and Tardive dyskinesia appear
nearly a year after initiating the treatment.

56. Parkinsonism
• Features;
• Presents as rigidity, tremors, hypokinesia, mask like
facies, shuffling gait.
• Appears between 1–4 weeks of therapy and persists
unless dose is reduced.
• Perioral tremors ‘rabbit syndrome’ seen after a few
years of therapy.
• Management:
• Changing from typical to atypical antipsychotic reduces
these symptoms.
• Central anticholinergic drugs are used treat Perioral
tremors.

57. Acute muscular dystonias
• Features
• Presents as muscle spasms with involvement of
linguo-facial muscles (tongue thrusting,
torticollis, locked jaw are seen).
• It occurs within a few hours of a single dose or
within first week of therapy.
• Most common seen in children ≤10 years and in
girls, particularly after parenteral
administration.
• Management:
• Central anticholinergics, promethazine or
hydroxyzine injected IM, provide relief within
10–15 min.

58. Akathisia
• Features:
• It is the most common extrapyramidal side effects of
antipsychotic medications.
• Patient presents as feeling of discomfort, restlessness
and agitation
• It occurs between 1–8 weeks of therapy.
• Management:
• Changing of antipsychotic from typical to atypical
reduces these symptoms.
• Benzodiazepine like clonazepam or diazepam is used as
first choice of treatment.
• In non-responsive individuals, propranolol is used.

59. Malignant neuroleptic syndrome
• Features:
• It is rare condition and seen at higher dose of potent
typical antipsychotics.
• It presents as marked rigidity, immobility, tremor,
hyperthermia, semi-consciousness, fluctuating BP and
heart rate.
• It is a fatal condition; death occurs due to cardio-
pulmonary collapse.
• Management:
• Symptomatic management is advocated first.
• Intravenous dantrolene may benefit.
• Bromocriptine in large doses has been found useful

60. Tardive dyskinesia
• Features:
• It presents as purposeless involuntary facial and
limb movements such as chewing, puffing of
cheeks and choreoathetoid movements.
• It is more common in elderly women
• Management:
• Changing of antipsychotic from typical to
atypical ones may reduce these symptoms.

61. Comparative adverse effects profile of
atypical antipsychotic drugs
Drugs Weight
Gain
Hyper-
lipidemia
New-Onset
Diabetes
Mellitus
QTc
Prolongation
Clozapine High High High Negligible
Risperidone Moderate Moderate Moderate Low
Olanzapine High High High Negligible
Quetiapine Moderate Moderate Moderate High
Aripiprazole Negligible No No Moderate
Ziprasidone Negligible No No High
Lurasidone No No No No

62. Schizophrenia related
symptoms
Drug therapy
Agitated, combative and
violent
Haloperidol, Quetiapine, CPZ, Thioridazine.
Withdrawn and apathetic Trifluoperazine, Fluphenazine, Aripiprazole,
Ziprasidone.
Patient with mainly
negative symptoms and
resistant cases
Clozapine Is The Most Effective;
Alternatives Are: Olanzapine, Risperidone,
Aripiprazole, Ziprasidone.
Patient with mood
elevation, hypomania
Haloperidol, Fluphenazine, Quetiapine,
Olanzapine.
If extrapyramidal side
effects must be avoided
Thioridazine, Clozapine Or Any Other Atypical
Antipsychotic.
Elderly patients who are
more prone to sedation,
mental confusion and
hypotension
Phenothiazine, Haloperidol Or Aripiprazole.

63. Mania

64. • Bipolar disorder is a complex disorder that likely
stems from a combination of genetic and non-
genetic factors.
• The mood episodes associated with it
involve clinical depression or mania (extreme
elation and high energy) with periods of normal
mood and energy in between episodes.
• The severity of mood episodes can range from very
mild to extreme, and they can happen gradually or
suddenly within a timeframe of days to weeks.

65. • When discrete mood episodes happen four or more
times per year, the process is called rapid cycling.
• Rapid cycling should not be confused with very
frequent moment-to-moment changes in mood,
which can sometimes occur in people with bipolar
disorder or other conditions such as borderline
personality disorder.

67. • Bipolar disorder usually appears between
ages 15 and 24 and persists through a
lifetime.
• It's rare that newly diagnosed mania is seen
in young children or in adults over age 65.
• It is marked by relapses and remissions,
bipolar disorder has a high rate of recurrence
if untreated.

68. • Patients with severe mania usually require
hospitalization to keep them from risky
behaviors.
• Those who are severely depressed also might
need hospitalization to keep them from
acting on
• suicidal thoughts or
• psychotic symptoms (delusions, hallucinations,
disorganized thinking).

69. Symptoms of Bipolar Disorder
• Decreased appetite/ weight loss, or overeating/
weight gain
• Difficulty concentrating, remembering, and making
decisions
• Feelings of guilt,
• Insomnia
• Lack of interest
• Persistently sad, anxious, or "empty" moods
• Restlessness, irritability
• Suicide attempts

70. Signs of Mania
• Disconnected and very fast (racing) thoughts
• Grandiose beliefs
• Inappropriate elation or euphoria
• Inappropriate irritability
• Inappropriate social behaviour
• Increased sexual desire
• Increased talking speed or volume
• Markedly increased energy
• Poor judgment
• A decreased need for sleep due to high energy

71. Diagnosis
• Clinically
• Mania
• Hypomania
• Depression
• Dysthymia

72. Management

73. MOOD STABILIZERS
• Mood stabilizers are the drugs that are used to
control the mood swings.
• Mood swings are oftenly seen in bipolar mood
disorder.
• These drugs are also known as anti-manic drugs.
• Bipolar disorder is a psychiatric illness, which is
characterized by a period of depression followed by
a period of mania.

74. • The cause of mania is not understood, but it
is thought to be due to overstimulation of
certain neurons in the brain that manifests
as hyperactivity, agitation, uncontrolled
thought and speech disorder etc.
• The mainstay for treatment of mania has
always been lithium.

75. •Nowadays, many other drugs are also
used for the treatment of bipolar
disorders, which includes
• Antipsychotic drugs such as:
• Aripiprazole,
• Olanzapine,
• Quetiapine,
• Ziprasidone
• Antiepileptic drugs such as
• lamotrigine

76. Lithium
• Lithium was first used in patients with gout
in 19th century.
• In 1949, Cade discovered that lithium was an
effective treatment for bipolar disorders.
• It reduces episodes and phases of manic-
depressive disorder by reduction of mood
swings, motor activity of brain, euphoria and
insomnia.

77. Mechanism of action
• The exact mechanism is still unknown.
• It is a monovalent cation which mimics the role of
sodium ions at many sites.
• The proposed hypothesis is as follows:
• Lithium competes and replaces sodium at many sites
including neurons. It alters sodium transport in nerve and
muscle cells and results in mood stabilizing effects.
• It also inhibits the release of norepinephrine and dopamine,
but not serotonin, from stimulated neurons.
• It increases the intraneuronal stores of norepinephrine and
dopamine slightly; and decreases intraneuronal content of
second messengers.
• It selectively modulates the responsiveness of hyperactive
neurons that might contribute to the manic state.

79. Pharmacokinetics
• The oral absorption of lithium is virtually complete
within 6–8 hours.
• It is not metabolized in the body and handled by the
kidneys in the same way as sodium ions.
• Lithium is excreted from the kidneys within 10-12
hours, although about 80% is reabsorbed.
• The plasma t ½ is 20 hours.

80. PK
• It slowly crosses the blood–brain barrier.
• It also crosses the placenta & enters breast milk;
hence contraindicated in pregnancy and lactation.
• Sodium depletion reduces the rate excretion of
lithium, thus increases the lithium toxicity.
Therefore, patients must be encouraged to
maintain hydration while taking this drug.
• It has low therapeutic index; therefore, continuous
monitoring (by salivary concentration of lithium) is
required for optimal therapy.

81. Dose
• Initial dose: 600 mg/day followed by 600–1200
mg/day till the optimal therapeutic concentration
achieved.
• The therapeutically effective serum level is 0.6 to
1.2 mEq/L (0.5-1.5 mmol/L).

82. Indications
• Prophylaxis for bipolar disorder.
• Acute mania.
• Chemotherapy induced leucopenia.
• Syndrome of inappropriate anti-diuretic hormone
(SIADH).
• Cluster headache.

83. Adverse Effects
• The side effects of lithium are directly associated
with the serum levels of drug.
• Serum levels of <1.5 mEq/L:
• CNS problems, including lethargy, slurred speech,
muscle weakness, and fine tremor;
• polyuria, which relates to renal toxicity;
• beginning of gastric toxicity, with nausea, vomiting, and
diarrhea.
• Serum levels of 1.5 to 2 mEq/L:
• Intensification of all of the foregoing reactions, with ECG
changes.

84. Cont…
• Serum levels of 2 to 2.5 mEq/L:
• Possible progression of CNS effects to ataxia, clonic
movements, hyperreflexia, and seizures;
• possible CV effects such as severe ECG changes and
hypotension;
• large output of dilute urine secondary to renal toxicity;
• fatalities secondary to pulmonary toxicity.
• Serum levels >2.5 mEq/L:
• Complex multi-organ toxicity, with a significant risk of death.
• Other side effects include hypothyroidism, weight gain,
and diabetes insipidus.

85. Management of lithium overdose
• Lithium should be stopped immediately.
• The serum level of lithium should be monitored
regularly.
• IV administration of normal saline restores sodium
levels and promotes lithium excretion.
• IV infusion of mannitol increases lithium excretion.
• If serum level is > 4 mEq/L; haemodialysis is required.
• Other diuretics, which increase sodium loss can cause
the reabsorption of lithium from the kidney tubules
and enhance the toxicity; hence, contraindicated.

86. Problem with lithium
• It inhibits the action of ADH on distal tubules in the
kidney leads to diabetes insipidus.
• Leukocyte count is increased by lithium therapy.
• Lithium inhibits release of thyroid hormones
resulting in feedback stimulation of thyroid through
pituitary leads to hypothyroid.
• Tremors
• Teratogenicity (Ebstein’s anomaly)
• Polyuria

87. Alternative to lithium

88. Sodium valproate
• It reduces the manic relapses in bipolar disorder.
• It is now a first line treatment of acute mania in
which high dose valproate acts faster than lithium
and is an alternative to antipsychotic ±
benzodiazepine.
• It can be useful in those not responding to lithium
or not tolerating it.
• Patients with rapid cycling pattern may particularly
benefit from valproate therapy.

89. Sodium valproate
• Combination of lithium and valproate useful in
resistant cases.
• It is also used as prophylaxis in bipolar disorder.
• Combination of valproate with an atypical
antipsychotic has high efficacy in acute mania.
• Divalproex, a compound of valproate, is more
commonly used due to better gastric tolerance.

90. Carbamazepine
• Carbamazepine (CBZ) was found to prolong
remission in bipolar disorder.
• Carbamazepine is less effective than lithium
or valproate in acute mania.
• High dose require for controlling rapid cycle.
• Produces in long term therapy- neurotoxicity
and increases suicides tendency

91. Lamotrigine
• It is a newer anticonvulsant for prophylaxis
of depression in bipolar disorder.
• Lamotrigine is not effective for treatment as
well as prevention of mania.
• It is used for maintenance therapy of type II
bipolar disorder because it reduces the risk
of mania.
• Lamotrigine can be combined with lithium to
improve its efficacy.

92. Atypical antipsychotics
Olanzapine, risperidone, aripiprazole,
quetiapine, with or without a BZD.
• These are the first line drugs for control of acute
mania.
• But in severe cases, requiring urgent parenteral
therapy, for which the older neuroleptics are still
the most effective.

93. • Aripiprazole
• Used for the treatment of mania in bipolar I
disorder, both as monotherapy as well as
adjuvant to lithium or valproate.
• Maintenance therapy with aripiprazole prevents
mania, but not depressive episodes.
• Olanzapine
• Used for maintenance therapy of bipolar
disorder.
• It improves both manic and depressive phases.
• Not used as long-term therapy due to higher risk
of weight gain, hyperglycaemia.

94. • Quetiapine
• Used with combination of an atypical
antipsychotic with valproate or lithium.
• Mainly indicated in maintenance therapy of
bipolar disorder.