Recurrence risk in bipolar manic-depressive disorders after discontinuing lithium maintenance treatment: an overview

Lithium remains unequaled in its research support as a standard maintenance treatment for bipolar manic-depressive disorders. It has important beneficial effects on recurring bipolar depression as well as mania, and in both types I and II bipolar syndromes, with powerful antisuicide effects not demonstrated with alternative mood-stabilisers. Data collected from numerous studies indicate that discontinuing lithium maintenance treatment is followed by sharply increased morbidity and possibly mortality, particularly in the first 6 to 12 months. However, we found that gradual discontinuation markedly reduced, and not merely delayed, recurrences of mania or depression after discontinuing lithium, with an even stronger effect in bipolar type II than type I patients. Secondary long-term retreatment with lithium following discontinuation yielded only minor average losses of benefits. Increased early recurrence risk may also arise after stopping long-term treatment with other neuropsychotropic drugs. Such reactions probably reflect physiological adaptations of the brain to pharmacodynamic effects, and their impact may be limited by slow drug discontinuation. The phenomenon of high early post-treatment discontinuation recurrence risk has clinical and scientific implications for the design, management and interpretation of treatment protocols that involve discontinuing long-term treatments in disorders requiring maintenance pharmacotherapy with centrally neuropharmacologically active drugs.