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Pharmacology of
.

Antimanic Agents
(Lithium)

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 Bipolar Disorders
Definition

❑ Bipolar disorder (formally called manic-depression) is a

syndrome in which patients suffer from episodes of mania
and depression

❑ Bipolar disorder is a “cyclic” or “periodic” illness in which

patients mood swings between manic or mixed-manic
episodes and depressive episodes

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 Bipolar Disorders

• Epidemiology
• Bipolar I occurs equally in both men and women
• Bipolar II occurs more commonly in women than men
• Cyclothymia (Bipolar III)
• Average peak of onset is 15-24 years (mean 21 yrs)

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 Bipolar Disorders
Aetiology

❑ Genetic factors (a +ve family history is present in 80-90% of

patients with bipolar disorders)
❑ Imbalance of neurotransmitters (↑se or ↓se)
❑ Dysregulation of neurotransmitters (deficiency of GABA and
excess of glutamate activity)
❑ Others: endocrine, environmental factors, head trauma,
psychosocial factors, etc
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 Diagnosis of Bipolar disorders
Mania:

❑ Mood must be elevated (euphoric or irritable)

❑ Symptoms must be present for at least 1 week or less if
hospitalization is required (4 days in DMS V)
❑ There must be impairment in functioning
❑ ≥3 of the following - elevated self-esteem or grandiosity, reduced
need for sleep, pressured speech, flight of ideas or racing
thoughts, distractibility, psychomotor agitation and excessive
involvement in high risk activities
❑ Symptoms should not be a direct cause of other medical conditions
or substance use
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 Treatment of Bipolar Disorders

Treatment Options
•Pharmacotherapy
•Psychotherapy
•Electroconvulsive Therapy (ECT)
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 Pharmacotherapy of Bipolar Disorders
Drug Classes

❑ Antimanic Agents (or Mood Stabilizers) -

Include Lithium, Valproic acid (VPA), Carbamazepine (CBZ)

❑ Atypical Antipsychotic Drugs (AAPs) -

Include Aripiprazole, Olanzapine, Quetiapine Risperidone
and Ziprasidone

❑ Others
Include BDZ, other antiepileptics and Antidepressants 8
Lithium Carbonate
• An Antimanic agents
• It brings the patient of mania towards normal
• The only agent effective for all three phases of treatment for
both manic and depressive episodes
• Comes in different formulations
• Has delayed onset of therapeutic effect
• Initially the preferred first line agent for mania but now limited
by narrow therapeutic window, drug interactions and
bothersome side effects
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Mechanism of Action
• Exact Mechanism of Action is unknown
• It decreases the neuronal uptake of dopamine and
noradrenaline and their synthesis
• It increases the rate of 5HT synthesis in the brain
• On continuous therapy, cyclic mood changes are prevented

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 • It inhibits ADH action on distal tubules
Other • It has insulin-like action on glucose
Pharmacological metabolism
Actions • It decreases thyroxine synthesis by
interfering with iodination of thyroxine

• Well absorbed after oral administration

• Not bound to plasma protein
Pharmacokinetic • Not metabolised
Profile • Excreted mainly in urine
• Inhibits the reabsorption of sodium in
the renal tubule
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 Adverse Effects
• Nausea, Vomitting, • Acute hypomania,
Epigastric distress,
diarrhoea, dizziness,
ataxia, nystagmus,
hyperreflexia,
arrhythmias, skin rashes,
glycosuria, blurred vision
Indications
recurrent mania,
depression cyclic and
recurring, unipolar
depression, bipolar
depression,
schizoaffective psychosis,
mental depression, cluster
headache, chemotherapy-
induced leucopenia and
agranulocytosis
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