Antipsychotic medication, mortality and neurodegeneration: The need for more selective use and lower doses

Abstract

Introduction: Although a range of adverse effects of antipsychotic medication are well documented, less attention has been paid to the issue of reduced life expectancy.

Method: The medical literature was searched to identify studies assessing severe somatic side‐effects of long‐term antipsychotic treatment with a possible impact on mortality, and studies evaluating antipsychotic‐associated brain structure changes.

Results: Short‐term cardiac and long‐term metabolic side effects increasing cardiovascular risk exert a negative influence on mortality in people diagnosed with schizophrenia. Three out of five studies examining antipsychotic dosage and higher mortality showed a significant association for one or more antipsychotics. Two out of four found negative effects of antipsychotic polypharmacy on life‐expectancy. One large historical cohort study found an association between longer duration of cumulative use and lower mortality, whereas other prospective studies found no effect. There is evidence for frontal grey matter reduction which seems to be accelerated by antipsychotic treatment, and may depend on cumulative doses. The amount of brain volume changes varies between individuals and with type and duration of antipsychotic treatment.

Conclusion: Antipsychotics should be used more selectively, for shorter durations and with lowest possible effective dose. Greater use of psychosocial interventions that have been proven effective should be an integral part of facilitating reductions in frequency, dosage and duration of antipsycotics.

Keywords:

• mortality
• neurodegeneration
• schizophrenia
• psychosis
• antipsychotics