Antipsychotic Response in Schizophrenia Worsens With Menopause

By Will Boggs MD

NEW YORK - The response to antipsychotic medication diminishes during menopause in women with schizophrenia, researchers report.

"It is a well established fact that schizophrenic women experience a worsening of psychotic symptoms at the menopause, and they also need higher doses of antipsychotics, as this period of the reproductive life-span has been considered of high vulnerability for these women," Dr. Alexandre Gonzalez-Rodriguez from Hospital Clinic of Barcelona, University of Barcelona, Spain told Reuters Health by email.

Dr. Gonzalez-Rodriguez and colleagues investigated whether response to antipsychotic drugs in postmenopausal women with schizophrenia differed according to the influence of cumulative estrogen exposure and other potentially confounding factors.
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Among 60 postmenopausal women with schizophrenia and four postmenopausal women with schizoaffective disorder, 42 responded to antipsychotic treatment and 22 were nonresponders, according to the September 13th Journal of Clinical Psychopharmacology online report.

Responders did not differ from nonresponders in age at menarche, age at menopause, cumulative estrogen exposure, or anthropometric measures, but responders were significantly closer to the time of menopause onset than nonresponders were.

In binary logistic regression analysis, time since menopause, a significant predictor of antipsychotic response, explained 42% of the variance of the model.

"This suggests that postmenopausal schizophrenic women may experience a progressive decline of antipsychotic response that is potentially explained by both menopause and its sequelae and adrenopause and its sequelae," the researchers say.

The required antipsychotic dose explained 11% of the variance in positive symptom changes, whereas smoking and cumulative estrogen exposure explained 27% of the variance in negative symptom changes.

Excitement symptoms were significantly associated with time since menopause and smoking, which together explained almost 36% of the variance from the model.

"The main clinical implication is that women at the time of the menopause may be stratified according to the time of menopause," Dr. Gonzalez-Rodriguez said. "That means, women with a shorter time since menopause would have higher response rates than women who present a longer time since menopause, (suggesting) that adrenopause, as well as menopause may influence antipsychotic response."

"I would emphasize that future studies should address the neurobiological basis of these differences according to the time since menopause," Dr. Gonzalez-Rodriguez added. "The hypothalamic-pituitary-adrenal system should be integrated in the potential explanation for this decline of response in postmenopausal women. A role for adrenal system, genetics, and other biological systems should be further investigated, as many of the psychotic populations should be treated as they age."

Dr. Michael C. Craig from Institute of Psychiatry, London, UK told Reuters Health by email, "The study highlights the more general need for clinicians, particularly psychiatrists, to have a far greater awareness of the potential interaction between sex hormones, such as estrogen, and neurotransmitters involved in mental health, such as dopamine and serotonin."

"However," he added, "it is equally important for physicians to be mindful of this interaction at other stages of women's reproductive cycle - not just post menopause."

"Sex hormones can, for example, have a profound effect on mental health premenstrually and postnatally," he explained. "Our awareness of this link, and the absence of multiprofessional services that attempt to translate this into clinical practice, led to us setting up the National Female Hormone Clinic (https://bit.ly/2djYrfs) at the Maudsley Hospital in London."

"In many ways the findings from this study are not surprising and support previous research studies carried out at the Institute of Psychiatry, where we have shown that women with postnatal psychosis who were prescribed higher doses of estradiol required less antipsychotic medication and were discharged sooner than women prescribed lower doses," Dr. Craig said. "There is increased dopaminergic responsivity in postmenopausal women taking long-term estrogen replacement therapy."

"There is a need for greater liaison between gynecologists and psychiatrists to facilitate this type of research being translated into clinical practice," he added.

SOURCE: bit.ly/2cRcBUh

J Clin Psychopharmacol 2016.

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