Over the years there have been multiple reports indicating that women with schizophrenia may experience worsening of their symptoms as they transition into the menopause.  In addition, while schizophrenia typically has its onset in young adulthood, there is a second peak in women around menopause.  Researchers have postulated that falling estrogen levels may modulate dopaminergic and serotonergic neurotransmitter systems and, in this manner, may lead to an increase in schizophrenia symptoms during these hormonal transitions.  

A new report suggests that menopausal women may also become less responsive to antipsychotics over time.  In this relatively small study, including 64 postmenopausal women with schizophrenia or schizoaffective disorder, 42 participants (66%) were found to be antipsychotic responders.  Responsiveness to antipsychotics was associated with shorter time since onset of menopause.  Interestingly, smoking was associated with greater improvement in negative symptoms, depression, and cognition.  

At this point we do not have any treatment guidelines regarding specific interventions for managing postmenopausal worsening of symptoms in women with schizophrenia.  While these data suggest that some women may become less responsive to antipsychotics, it is not clear if merely increasing the dose of antipsychotic medication would resolve the issue.  If it is effective, one must also be vigilant to the possibility of increased side effect burden.  

Other studies have suggested the possibility of using estrogenic compounds to augment antipsychotic medications in both pre- and postmenopausal women.  In one double-blind, placebo-controlled trial, women with schizophrenia received either a 100 mcg estradiol transdermal patch (n=54) or a placebo patch (n=46, no active hormone present), in addition to their regular antipsychotic medications and were followed for 28 days. Patients receiving estrogen showed significant improvement in positive symptoms (hallucinations, delusions), but no difference in negative symptoms (reduction in range of emotional expression, poverty of speech, lack of motivation) was observed.

Another study explored the use of the selective estrogen receptor modulator (SERM), raloxifene, in a group of postmenopausal women.  Unlike estrogen, raloxifene (Evista) does not affect breast or uterine tissue, and thus may be a promising option for older women   The addition of raloxifene (60 mg/day) to regular antipsychotic treatment significantly reduced the negative, positive, and overall symptoms during the 12 week trial, as compared to women receiving placebo.  

The finding that smoking improved certain symptoms, including negative symptoms and cognitive functioning, has been demonstrated in other populations of male and female patients with schizophrenia.  While we obviously would not recommend smoking to manage breakthrough symptoms, there is some interesting research being done on agents that modulate nicotinic receptors and may increase the effectiveness of antipsychotic medications.


Ruta Nonacs, MD PhD


González-Rodríguez A, Catalán R, Penadés R, Ruiz Cortés V, Torra M, Seeman MV, Bernardo M.  Antipsychotic Response Worsens With Postmenopausal Duration in Women With Schizophrenia.  J Clin Psychopharmacol. 2016 Sep 13. [Epub ahead of print]

Kulkarni J, de Castella A, Fitzgerald PB, Gurvich CT, Bailey M, Bartholomeusz C, Burger H. Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry. 2008 Aug;65(8):955-60.

Usall J, Huerta-Ramos, Iniesta R, et al. Raloxifene as Adjunctive Treatment for Postmenopausal Women with Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled trial. J Clin Psychiatry 2011; 72(11):15552-1557.

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