Antipsychotic medication for women with schizophrenia spectrum disorders

Abstract

There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life.

Serious mental illness in women

“…It is important to highlight that menopausal women, because of the decline of sex hormones, are at higher risk for developing QTc prolongation and torsades de pointes when prescribed antipsy-chotics and clinicians should be cautious about this risk, particularly in those with a history of cardio vascular disease [9].…”

“…Although it has been historically proposed that schizophrenia spectrum disorders (SSD) had a more benign course in women than in men, recent studies suggest that this concept should be revisited [9], with female patients having similar number of hos-pitalizations and comparable functional outcomes [10]. Schizophrenia is a SMI with a lifetime prevalence of around 1% and is slightly more prevalent in men than women [11].…”

“…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]. Given the protective effects of estrogens on the course of SSD, estrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy [9].…”

Editorial: Precision psychiatry and the clinical care for people with schizophrenia: sex, race and ethnicity in relation to social determinants of mental health

“…Antipsychotics also need dosing by sex, with lower dose for most drugs for premenopausal women [7]. Antipsychotic drugs (such as amisulpr-ide) that show excellent efficacy-tolerability for men may not be efficacious for women [8].…”

“…Oestrogens protect women from severe negative symptoms and also from cardiovascular comorbidity, but only until menopause. Oestrogens also modulate the CYP1A2 enzyme, which metabolizes most anti-psychotics and (except for quetiapine and lurasi-done) dose adjustment is needed for these medications after menopause [7]. Further, hormonal replacement treatment, or raloxifene aug-mentation in some studies result in improvement in negative symptoms and cognition in postmeno-pausal women [12], yet hormonal replacement therapy is rarely part of clinical care.…”