The Effect of Menopause on Antipsychotic Response

Background: It has been hypothesized that, whenever estrogen levels decline, psychosis symptoms in women increase. At menopause, this can happen in two main ways: (a) the loss of estrogen (mainly estradiol) can directly affect central neurotransmission, leading to increase in schizophrenia-related symptoms, and (b) the loss of estrogen can decrease the synthesis of enzymes that metabolize antipsychotic drugs, thus weakening their efficacy. Aims and Methods: The aim of this narrative review was to investigate the second possibility by searching PubMed and ClinicalTrials.gov for studies over the last two decades that investigated the metabolism of antipsychotics and their efficacy before and after menopause in women or that studied systemic and local estrogen level effects on the pharmacokinetics and pharmacodynamics of individual antipsychotic drugs. Results: The evidence suggests that symptom level in women with schizophrenia rises after menopause for many reasons beyond hormones but, importantly, there is an estrogen-dependent loss of efficacy related to antipsychotic treatment. Conclusion: Effective clinical intervention is challenging; nevertheless, several promising routes forward are suggested.