Peri- and Post-Menopausal Women with Schizophrenia and Related Disorders Are a Population with Specific Needs: A Narrative Review of Current Theories

Abstract

Background: While gender differences in antipsychotic response have been recognized, the potential role of menopause in changing drug efficacy and clinical outcome in schizophrenia related disorders has been understudied. We aimed to review the relevant literature to test whether optimizing menopausal and post-menopausal treatment and addressing specific health needs of this stage in life will improve outcome. Methods: Non-systematic narrative review using the PubMed database (1900–July 2021) focusing on randomized controlled trial results addressing our question. Forty-nine studies met our criteria. Results: Premenopausal women show significantly better antipsychotic response than postmenopausal women. Hormone replacement therapies (HRT) should be used in postmenopausal women with schizophrenia with caution. Raloxifene, combined with antipsychotics, is effective for psychotic and cognitive symptoms in postmenopausal women with schizophrenia and related disorders. Medical comorbidities increase after menopause, but the influence of comorbidities on clinical outcomes has been poorly investigated. Preventive strategies include weighing risks and benefits of treatment, preventing medical comorbidities, and enhancing psychosocial support. Ideal treatment settings for this population warrant investigation. Conclusions: Antipsychotic dose adjustment at menopause is recommended for schizophrenia. Raloxifene may play an important role in permitting dose reduction and lessening adverse effects. Prevention of comorbidities will help to reduce the mortality rate.

Antipsychotic Polypharmacy-Related Cardiovascular Morbidity and Mortality: A Comprehensive Review

“…Risperidone has a mean QTc increase of 9.1 ms, and causes QTc prolongation via actions on IKr channels, with a similar potency as haloperidol [ 16 ]. Still, the risk is much lower than haloperidol and thioridazine [ 13 , 18 , 21 ]. Table 1 summarizes the antipsychotics discussed here, the associated cardiac events, and the mechanism by which these events could happen.…”

“…Age and the onset of menopause can lead to an increase in antipsychotic adverse effects. With the onset of menopause, estrogen levels drop, which studies have shown to lead to the worsening of hallucinations and delusions during this time [ 13 ]. This may necessitate the need for increased dosages of antipsychotic doses, which can lead to increased adverse effects.…”

Serious mental illness in women

“…The menopausal transition is marked by the loss of the neuroprotection conferred by estrogens during the reproductive period, leading to psychiatric exac erbations [51]. Antipsychotic doses often need to be adjusted and women show inferior responses to antipsychotics than during premenopause [52 ▪▪ ], which may worsen medical comorbidities. Estrogen receptor modulators, such as raloxifene, have been effectively added to treatment with antipsychotics allowing to decrease their doses, which results in lower risk for metabolic and cardiovascular side effects [39].…”

Application of Antipsychotic Medication: Gender Differences in Tolerance and Medication Response

“…In general, these studies showed that the stages of the positive reaction in female animals and improvement of symptomatic in women were higher [13], though the level of the expression of extrapyramidal symptoms was also higher [22,39]. As some authors say [17,22,27,32,34,35], young women with schizophrenia require less doses of the first-generation antipsychotics than men. Authors think that it can be explained either by a smaller body mass in women (younger than 40 years old), or by the fact that after the menopause women more often require even higher doses of antipsychotics than men.…”