ANTI-MANIC DRUGS

1. Treatment of Bipolar
disorder

2. Drugs for bipolar disorder
 Lithium
 Valproate
 Lamotrigine
 Carbamazepine
 Chlorpromazine
 Olanzapine

3. Lithium
 Used for gout in 19th century .
 Sedative and anticonvulsant.
 Used for mania first in late 1940s.

4. Lithium - mechanism of action
 IP3 and DAG - second messengers for both
adrenergic and muscarinic transmission.
 Lithium inhibits several important enzymes in the
normal recycling of membrane phosphoinositides,
including conversion of IP2 to IP1 (inositol
monophosphate) and the conversion of IP1 to inositol
 This block leads to a depletion of
phosphatidylinositol-4,5-bisphosphate (PIP2), the
membrane precursor of IP3 and DAG.

6. Indications
 Treatment of acute mania – seldom used alone
 Prophylaxis of bipolar disorder.
 Endogenous depression
 Treatment resistant schizophrenia
 SIADH
 Hyperthyroidism

7.  Lithium – reduced risk of suicide in major
depressive disorders
 Control acute mania with BZD/antipsychotics
before starting lithium.
 Lithium – best established treatment to prevent
recurrences of mania and bipolar depression.

8. Use lithium only in ….
 Cooperative patients with normal sodium
intake
 Patients with normal cardiac and renal function
 acute mania

9. Adverse effects
 Neurologic
 Tremors, ataxia, dysarthria, chorea and athetosis
 Hypothyroidism
 Nephrogenic diabetes inspidus
 Sick sinus syndrome
 Worsening of acne
 Worsening of psoriasis

10.  Lithium in pregnancy - neonatal goiter, CNS
depression, hypotonia ("floppy baby"
syndrome),
 Ebstein's malformation
Adverse effects

11.  Sodium valproate and carbamazepine –
employed prophylactically in bipolar disorder
 Evidence is limited

12.  Valproate is FDA approved for mania
 Off label use for prophylactic treatment of
bipolar disorder

13. Pharmacokinetics
 Well absorbed orally.
 Steady state concentrations in 5 days.
 Therapeutic drug monitoring is essential

14.  Why should TDM be done in
lithium treatment?

15.  Large inter individual variability
 Narrow therapeutic index
 a direct relationship exists between Li
concentration in plasma and its
pharmacological and toxic effects