"Lithium has been used in the treatment of acute bipolar mania for over 50 years, and has demonstrated superiority over placebo in several controlled clinical trials.16 In these studies, the percentage of patients showing at least moderate improvement after 2 to 3 weeks of treatment ranged from 40% to 80%. Lithium appears to be most, effective in patients with classic (euphoric) mania, while response rates are relatively poor in mixed states or rapid cycling.17
"Drawbacks of lithium therapy include its narrow therapeutic index (recommended plasma level 0.8 to 1.2 mmol/L), poor tolerability, especially at higher doses, and risk of “rebound mania” on withdrawal.18 Common side effects of lithium are tremor, polydipsia, polyuria, and, in the long term, hypothyroidism. Despite these shortcomings, lithium retains a role as a first-line treatment and is widely seen as the gold-standard comparator for newer agents, not to say that it may have antisuicidal effects.19,20 Lithium also been evaluated in relation to other antimanic agents. Head-to-head comparisons with antipsychotic drugs (usually chlorpromazine) have generally found lithium to be superior in terms of overall improvement in symptoms, mood, and ideation, but worse with respect to motor hyperactivity and onset of action. Lithium was as efficacious as quetiapine in a 12-week, randomized, double-blind trial21 In a three-arm randomized study comparing placebo, lithium, and valproate, lithium and valproate were similarly effective in improving manic symptoms.22"