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Does long-term medication with lithium, clozapine or antidepressants prevent or attenuate dementia in bipolar and depressed patients?

Background. Recent preclinical research suggests that lithium, clozapine, and possibly even antidepressants, have neurotrophic and neuroprotective properties. However, it remains unclear whether their long-term use can prevent the development of dementia or attenuate its severity in patients with major mood disorders. Method. Subjects included patients with bipolar disorder (N=220) and major depressive disorder (N=186) admitted between 1959 and 1963 and followed from 1965 to 1985. The presence of dementia was assessed clinically using ICD-9 criteria, and functioning was determined with the Global Assessment Schedule (GAS). Long-term medication with lithium, clozapine and antidepressants was documented. Results. In the total sample, the occurrence of dementia correlated only with age. In a restricted analysis of the 88 patients with dementia, age became non-significant and lithium showed a trend to an inverse correlation with the severity of dementia. In the subgroup of bipolar demented patients, both lithium and clozapine medication were inversely related to the severity of dementia. Conclusions. The results are consistent with an attenuating effect of lithium and possibly clozapine on the development of severe dementia. Limitations. The sample of patients with dementia was small and the results are based on a naturalistic study. Dementia was only assessed once, without the use of cognitive measures.