Lithium Withdrawal in Bipolar Disorder: Implications for Clinical Practice and Experimental Therapeutics Research

Recent clinical research strongly suggests that there is a period of elevated risk of morbidity in the several months following abrupt discontinuation or reduction of doses in maintenance treatments commonly used in the contemporary management of chronic or recurring major psychiatric disorders. This risk is best quantified for the discontinuation of lithium therapy in bipolar disorders, in which risk of mania, depression, and suicidal behavior may rise. Similar symptomatic risks are well known after stopping antianxiety agents, and probably also follow rapid removal of oral neuroleptics in schizophenia and antidepressants in major depression. Morbid risk probably can be limited by slowing the rate of removal of medication. Such responses probably reflect interactions of individual illness diatheses with physiological adaptations to long-term drug treatments. The findings appear to have broad scientific, clinical, and ethical implications for clinical pharmacology in psychiatry as well as in general medicine.