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Clinical Pharmacology of Mood Stabilizers

Mood stabilizers – Lithium: Low therapeutic index Serum levels: acute phase- 0.8 –1.2 meq/l Stabilization phase: 0.6 - 0.8 meq/L.
Acts by inhibiting Na/K ATPase, adenosine receptors
Behaviorally like Na; no metabolism, excretion via kidney unchanged: no liver toxicity
Side Effects: Fine Tremors (DOC propranolol), hypothyroidism, acne, renal toxicity, leukocytosis
Toxicity of Lithium >1.5meg/L - Coarse Tremors, Nystagmus, Brisk Reflexes, Ataxia, Seizures, Coma, Death.
Treatment of toxicity is Hemodialysis

Table: Various Mood Stabilizers
          Agent and Dosing          Side effects and other effects
1. Lithium
Starting dose: 300 mg
bid or tid            
Therapeutic blood level:
0.8-1.2 meg/L   
2. Valproic acid
Starting dose: 250 mg. tid
Therapeutic blood level:
3. Carbamazepine/oxcarbazepine
Starting dose: 200 mg
bid for carbamazepine,
150 bid for
Therapeutic blood level
1-12 for carbamazepine
Starting dose : 25 mg/d
Common side effect :  Nausea/anorexia/ diarrhea, fine
tremor, thirst, polyuria, fatigue, weight gain, acne,
folliculitis, neutrophilia, hypothyroidism
Blood level is increased by thiazides, tetracyclines, and NSAIDs         
Blood level is decreased by bronchodilators, verapamil, and carbonic anhydrase inhibitors
Rare side effect: Neurotoxicity, renal toxicity, hypercalcemia,
ECG changes  
Common side effects: Nausea/anorexia, weight gain,
sedation, tremor, rash alopecia
Inhibits hepatic metabolism of other medications
Rare side effects: Pancreatitis, hepatotoxicity, Stevens-
Johnson syndrome       
Common side effect: Nausea/anorexia, sedation, rash,
Carbamazepine, but not oxcarbazepine,
induces hepatic metabolism of other medications
Rare side effects: Hyponatermia,
agranulocytosis, Stevens-Johnson syndrome
Common side effects: Rash, dizziness, headache, tremor, sedation, nausea
Rare side efect: Stevens-Johnson syndrome

Consensus Guidelines on the Drug Treatment of Acute Mania And Bipolar Depression
Condition Preferred Agents
1. Mixed/dysphoric mania
2. Mania with psychosis
    or risperidone
3. Hypomania
4. Severe depression with
5. Severe depression without psychosis
6. Mild to moderate depression
Valproic acid
Valproic acid with olanzapine, conventional antipsychotic,
Lithium, lamotrigine, or valproic acid alone
Venlafaxine, bupropion, or paroxetine, plus lithium plus
olanzapine, or risperidone; Consider ECT
Bupropion, paroxetine, sertraline, venlafaxine, or citalopram plus lithium
Lithium or lamotrigine alone; add bupropion if need be.

The Bipolar disorders are now classified into ^6 types of which two are clinically important: BPAD I :Mania and Depression
BPAD II : Recurrent depression with Hypomania..... DOC is Lamotrigine.

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