Sex differences in antipsychotic efficacy and side effects in schizophrenia spectrum disorder: results from the BeSt InTro study

Abstract

Current guidelines for patients with schizophrenia spectrum disease do not take sex differences into account, which may result in inappropriate sex-specific treatment. In the BeSt InTro study, a total of 144 patients (93 men and 51 women) with a schizophrenia spectrum diagnosis and ongoing psychosis were included and randomized to amisulpride, aripiprazole, or olanzapine in flexible dose. This trial is registered with ClinicalTrials.gov (NCT01446328). Primary outcomes were sex differences in dose, dose-corrected serum levels, efficacy, and tolerability. Dosing was higher for men than for women in the aripiprazole group (p = 0.025) and, at trend level, in the olanzapine group (p = 0.056). Dose-corrected serum levels were 71.9% higher in women than in men for amisulpride (p = 0.019) and 55.8% higher in women than in men for aripiprazole (p = 0.049). In the amisulpride group, men had a faster decrease in psychotic symptoms than women (p = 0.003). Moreover, amisulpride was more effective than the other medications in men but not in women. Prolactin levels were higher in women than in men, especially for amisulpride (p < 0.001). Also, women had higher BMI increase on amisulpride compared to the two other antipsychotics (p < 0.001). We conclude that clinicians should be aware of the risks of overdosing in women, especially for amisulpride and aripiprazole. Amisulpride is highly effective in men, but in women, amisulpride showed more severe side effects and may thus not be the drug of first choice. Our study shows that sex differences should be taken into account in future studies on antipsychotics. Future research is warranted to evaluate these preliminary results.

Olanzapine‐associated dose‐dependent alterations for weight and metabolic parameters in a prospective cohort

“…In line with its efficacy, olanzapine is among the most frequently prescribed antipsychotics, 25 so there is an urgent need to profoundly understand aspects of the consistently reported olanzapine‐induced weight gain and metabolic abnormalities. Apart from the well‐known metabolic effects, treatment with olanzapine has been also linked with less frequent side effects including prolactin elevation and more rarely parasomnias 26,27 . However, it is the major impact of the metabolic effects for olanzapine that does not only raise concerns for the physical health of the patients but also affects efficacy outcomes 28 .…”

Antipsychotic medication for women with schizophrenia spectrum disorders

“…After adjusting for body size, GFR is 10–25% lower in females (Whitley & Lindsey, 2009). These differences in renal clearance are particularly relevant for amisulpride, sulpiride and paliperidone, which are cleared mainly by the kidney, leading to much higher plasma levels of these drugs in female patients of all ages (Hoekstra et al, 2021; Li, Li, Shang, Wen, & Ning, 2020).…”

Stratification by Sex and Hormone Level When Contrasting Men and Women in Schizophrenia Trials Will Improve Personalized Treatment

“…The conclusion was that the influence of sex differs with the drug used, but the study included only 51 women with an average age of 33.8 and a range of 14.4 years. Many would have been postmenopausal [ 73 ], making it impossible to interpret the results.…”