Anti-manic drugs: Lithium and others

This page is a short summary of antimanic drugs. For detailed notes, click here

Summary Points

Anti-manic drugs are a class of medications used to treat manic episodes associated with bipolar disorder.

Lithium

• Lithium is a small monovalent cation that acts as a mood stabilizer.
• It inhibits the regeneration of PIP2 by inhibiting an enzyme inositol monophosphatase, thereby decreasing the activity of neurotransmitters in the brain that are postulated to be markedly increased during a manic episode.
• It also inhibits glycogen synthase kinase 3 (GSK3), an enzyme involved in the degradation of BDNF, which is likely involved in the use of lithium for unipolar depression.
• It has a narrow margin of safety, and therapeutic drug monitoring (TDM) is essential.
• It takes 1-2 weeks to exert its maximum effect.
• It is the drug of choice for the prophylaxis of bipolar disorder and is the only drug used in bipolar disorder that has documented anti-suicide properties.
• It can be used in acute mania, but benzodiazepines like lorazepam must be added (due to the slow action of Li).
• Plasma concentration of lithium should be 0.5-0.8 mEq/L for maintenance therapy of bipolar disorder and 0.8-1.2 mEq/L for acute mania. Toxic symptoms are seen if plasma concentration exceeds 1.5 mEq/L.
• Diuretics (particularly thiazides) decrease the renal excretion of lithium and thus may result in toxicity.
• Adverse effects include acne, weight gain, and benign and reversible elevation of T waves in ECG.

Alternatives to Lithium

• Carbamazepine and valproate are useful in manic depressive psychosis (bipolar disorder) and can be used for acute mania.
• Valproic acid is the drug of choice for the treatment of rapid cyclers (> 4 cycles/year).
• Benzodiazepines like lorazepam are the drugs of choice for acute mania when combined with lithium.
• Olanzapine and other atypical antipsychotics show efficacy in bipolar disorder as well as acute mania.
• Lamotrigine is specifically useful for the depressive phase of bipolar disorder. It is the first agent to be approved by the FDA for bipolar disorder without an indication for acute mania.

Lithium Toxicity 

• Acute intoxication is characterized by vomiting, diarrhea, coarse tremors (fine tremors in mild intoxication), ataxia, coma, and convulsions.
• More serious effects involve mental confusion, hyperreflexia, dysarthria, seizures, and cranial and focal neurological signs progressing to coma and death.
• Other toxic effects are cardiac arrhythmias, hypotension, and albuminuria.
• There is no specific antidote for lithium. Dialysis is the most effective means of removing Li from the body. It is indicated at serum Li levels of > 4 mEq/L in acute overdose or > 1.5 mEq/L in chronic overdose.

Disclaimer: This article is for informational purposes only and should not be taken as medical advice. Always consult with a healthcare professional before making any decisions related to medication or treatment.

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