Clinically, women with psychotic disorders tend to have better outcomes than men; women are less likely to be hospitalized, are less likely to commit suicide, and are more likely to maintain relationships with friends and family. This may reflect underlying differences in the disease; However, some speculate that better outcomes may be related to better response to antipsychotic medications in women versus men. But there are even more differences between men and women when it comes to treatment with antipsychotic medications.
Dosage of antipsychotic medications
In general, psychotic symptoms in women respond to lower doses of antipsychotic medications than in men. Several studies have shown that men require higher doses of medications than women to achieve an equivalent reduction in psychotic symptoms. The effectiveness of lower doses of antipsychotics in women is most evident with clozapine and olanzapine. This finding likely reflects the ameliorative or enhancing effects of estrogen in women, as it has been observed that postmenopausal women typically require higher doses of antipsychotic medications than premenopausal women.
Impact of the menstrual cycle on symptoms
The way women respond to antipsychotic medications may also be affected by changes in hormone levels that occur during the menstrual cycle. Some studies have shown a worsening of psychotic symptoms during the premenstrual phase of the cycle, the period when estrogen levels drop. Although not yet well studied, it is possible that women respond better to antipsychotics when their estrogen levels are higher, during the early part of the menstrual cycle. Since symptoms can vary throughout the menstrual cycle, it may be helpful to have women use daily assessments of their symptoms to determine if variability is related to their menstrual cycle.
Different patterns of side effects
Although women’s psychotic symptoms may respond to lower doses of antipsychotic medications than men’s, women are more likely than men to experience side effects, which can complicate dose escalation and ultimately impact treatment compliance. The side effects that are more common in women include weight gain, metabolic symptoms and sexual dysfunction.
It is not yet well understood why exactly women are more vulnerable to side effects, but most likely reflects gender-based differences in the pharmacokinetics and pharmacodynamics of drugs. Another possible explanation is that women are more likely than men to use antipsychotic medications in combination with other psychotropic medications, which may increase side effects.
Women taking antipsychotic medications are also at greater risk for cardiac arrhythmias than men. In the absence of medication, women tend to have slightly longer mean QT intervals on the electrocardiogram than men. Antipsychotics such as haloperidol and ziprasidone are often associated with QTc prolongation, increasing the risk of potentially dangerous cardiac arrhythmias. Other factors may also play a role, including age, medication dosage and underlying genetic vulnerability.
Although older studies suggest that women are more vulnerable than men to tardive dyskinesia (TD), more recent studies show similar prevalence rates of TD and other extrapyramidal symptoms in men and women.
Some research suggests that women may be more susceptible to developing allergic reactions than men, possibly due to hormonal influences on immune responses.
Impact on menstrual cycles and reproduction
Antipsychotic medications have different effects on the menstrual cycle and reproductive health in women than in men. Certain antipsychotics with more potent antagonism of dopamine D2 receptors, including first-generation antipsychotics and risperidone, may increase prolactin levels, resulting in menstrual irregularities, amenorrhea, or even hyperprolactinemia-induced galactorrhea.
Although the reproductive system appears to be less vulnerable in men, some studies have reported decreased libido and erectile dysfunction in men receiving antipsychotic treatment, especially with medications that possess strong anticholinergic properties, such as chlorpromazine and olanzapine.
Resume
Compared to men, women generally require lower doses of antipsychotic medications to achieve symptom reduction, possibly due to the ameliorative effects of estrogen. Hormonal fluctuations during the menstrual cycle can influence medication response, with some evidence suggesting better results during phases of higher estrogen levels. However, women are more likely to experience side effects such as weight gain and metabolic symptoms, which may impact treatment compliance. Additionally, antipsychotic drug use can affect reproductive health differently in men and women, with some medications leading to irregular periods in women and decreased libido in men.
Ruta Nonacs, MD PhD
References
Sáenz-Herrero M, Recio-Barbero M, Lopez-Atanes M, Santorcuato A, Bacigalupe A, Segarra R. Gender differences in the management of acute psychiatric episodes in the emergency department: a cross-sectional analysis of the triennium 2017-2019. Arch women’s mental health. 2023 Dec;26(6):777-783.
Seeman MV. Men and women respond differently to antipsychotics. Neuropharmacology. February 2020; 163:107631.
Shan Y, Cheung L, Zhou Y, Huang Y, Huang RS. A systematic review on gender differences in side effects related to psychotropic, cardiovascular and analgesic medications. Front Pharmacol. May 2, 2023;14:1096366.
