Sex differences in effectiveness and adverse effects of mood stabilizers and antipsychotics: A systematic review.

BACKGROUND: Psychiatric disorders differ in their prevalence, symptom profiles, and disease courses in men and women. However, sex differences in psychiatric disorders have not received enough attention to guide treatment recommendations. This systematic review aims to summarize sex differences in the treatment responses and adverse effects of mood stabilizers and antipsychotics transdiagnostically. METHODS: We conducted a systematic review following the PRISMA 2020 statement (CRD42020212478). A literature search was conducted using MEDLINE, Embase, Cochrane Central, PsycINFO, Web of Science Core Collection, and Scopus databases. Studies comparing mood stabilizer or antipsychotic treatment outcomes in men and women were included. JBI critical appraisal checklists were used to assess bias risk. RESULTS: Out of 4866 records, 129 reports (14 on mood stabilizers, 115 on antipsychotics) with varying designs were included. Sample sizes ranged from 17 to 22,774 participants (median = 147). The most common psychiatric diagnoses were schizophrenia spectrum (n = 109, 84.5 %) and bipolar disorders (n = 38, 29.5 %). Only four studies explored sex differences in mood stabilizer treatment response. In 40 articles on antipsychotic treatment response, 18 indicated no sex difference, while 16 showed females had better outcomes. Women had more adverse effects with both mood stabilizers and antipsychotics. The risk of bias was low in 84 (65.1 %) of studies. LIMITATIONS: Substantial heterogeneity among the studies precluded performing a meta-analysis. CONCLUSION: Number of studies focusing on sex differences in treatment outcomes of mood stabilizers is limited. Women may respond better to antipsychotics than men, but also experience more side effects. The impact of pharmacokinetics on sex differences warrants more attention.

Circulating sex hormones in women with severe anxiety during pregnancy / Hormonas sexuales circulantes en mujeres con ansiedad severa durante el embarazo

Abstract Introduction Anxiety, mood- and stress-related behaviors are regulated by sex hormones in pregnant and non-pregnant women. Very scarce information exists about the role of sex steroids in pregnant women displaying high levels of anxiety. Objective To determine sex hormones serum levels in pregnant women exhibiting high levels of anxiety symptoms. Method The Hamilton Anxiety Rating Scale (HARS/ HAM-A) was used to assess the intensity of anxiety symptoms in third-trimester pregnant women. Two groups were included in the study, pregnant women exhibiting severe anxiety (ANX; HARS scores ≥ 25; n = 101) and healthy control subjects (CTRL; n = 40) displaying lower scores for anxiety (HARS scores ≤ 7). Estradiol (E2), progesterone (P4), and testosterone (T) serum levels were measured using a standard chemiluminescent immunoassay. Bivariate and partial correlations were performed to detect significant associations between groups, clinical measures, biochemical data, and HARS scores. Results The anxiety group (ANX) showed an increase in E2 and T serum levels (p < .001) compared to CTRL. Conversely, significantly lower P4 levels were found in the symptomatic group (p < .001) as compared to the CTRL hormone values. The P4:E2 index was significantly reduced in pregnant women with high levels of anxiety (p < .001). Negative correlations between anxiety (HARS) scores, P4 serum levels (p = .02), and P4:E2 ratio (p = .04) were found in the symptomatic group. Conversely, T serum levels displayed a positive association (p = .001) with high levels of anxiety symptoms in the same group, after adjusting our data by clinical confounders. Discussion and conclusion Serum levels of sex-steroid hormones are altered in pregnant women exhibiting severe anxiety.

Resumen Introducción La ansiedad, el estado de ánimo y el estrés están regulados por diversos esteroides sexuales. Existe poca información sobre el papel que juegan estos esteroides en mujeres embarazadas con niveles elevados de ansiedad. Objetivo Determinar los niveles séricos de hormonas sexuales en mujeres embarazadas con altos índices de síntomas de ansiedad con respecto a mujeres gestantes sanas. Método Determinación de la intensidad de síntomas ansiosos empleando la escala de Hamilton de Ansiedad (HAM-A) en 141 mujeres embarazadas en el tercer trimestre de gestación. Cuantificación de los niveles séricos de estradiol (E2), progesterona (P4) y testosterona (T) por inmunoensayo estándar. Aplicación de las correlaciones de Pearson para detectar asociaciones entre parámetros clínicos y valores hormonales entre los grupos de estudio. Resultados Las mujeres con ansiedad severa (ANX; n = 101; HAM-A ≥ 25) mostraron niveles séricos más altos de E2 y T (p < .001), así como niveles más bajos de P4 (p < .001) en relación con el grupo control (CTRL, n = 40, HAM-A < 7). Se detectó una disminución significativa en el índice P4:E2 en el grupo de ANX (p < .001) y se observaron correlaciones negativas y positivas entre los puntajes elevados de ansiedad con los niveles circulantes de P4 (p = .02), en la taza P4:E2 (p = .04) y en los niveles séricos de T (p = .001) respectivamente, al ajustar nuestros datos con variables confusoras. Discusión y conclusión Los niveles circulantes de los esteroides sexuales se encontraron alterados en mujeres con ansiedad severa.