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Antipsychotic Medications: Women and Men Respond Otherwise

Clinically women with psychotic disorders are likely to have higher outcomes than men; women are less more likely to be hospitalized, carry a lower risk for suicide, and usually tend to retain relationships with family and friends. This may increasingly reflect underlying differences within the illness; nevertheless, some speculate that higher outcomes could also be related to a greater response to antipsychotic medications in women versus men. But there are other differences between men and ladies with regards to treatment with antipsychotic medications.



Dosage of Antipsychotic Medications

Typically, psychotic symptoms in women reply to lower doses of antipsychotic medication than in men. Various studies have demonstrated that men require higher doses of medication than women so as to achieve an equivalent reduction in psychotic symptoms. The effectiveness of lower doses of antipsychotic medication in women is most evident for clozapine and olanzapine. This finding likely reflects the ameliorative or potentiating effects of estrogen in women, because it has been observed that girls who’re postmenopausal typically require higher doses of antipsychotic medication than premenopausal women. 

Impact of the Menstrual Cycle on Symptoms

How women reply to antipsychotic medications might also be influenced by changes in hormone levels that occur in the course of the menstrual cycle. Some studies have demonstrated worsening of psychotic symptoms in the course of the premenstrual phase of the cycle, the period during which levels of estrogen are falling. Although this has not been well-studied, it is feasible that girls reply to antipsychotics higher at times when their estrogen levels are higher, in the course of the first a part of the menstrual cycle. Provided that symptoms may vary across the menstrual cycle, it might be helpful to have women use each day rankings of their symptoms to find out if variability is related to their menstrual cycle.

Differing Patterns of Side Effects

Although women’s psychotic symptoms may reply to lower doses of antipsychotic medication than men’s, women are more likely than men to suffer from unwanted side effects, which can complicate dose escalation and will ultimately impact adherence to medication. The unwanted side effects that occur more commonly in women include weight gain, metabolic symptoms, and sexual dysfunction.

Exactly why women are more vulnerable to unwanted side effects shouldn’t be well understood but almost certainly reflect gender-based differences in medication pharmacokinetics and pharmacodynamics. One other possible explanation is that girls are more likely than men to take antipsychotic medications together with other psychotropic medications which can increase side effect burden. 

Women taking antipsychotic medications are also at greater risk than men for cardiac arrhythmias. Within the absence of medication, women are likely to have barely longer average QT intervals on the electrocardiogram than men. Antipsychotics corresponding to haloperidol and ziprasidone are commonly related to QTc prolongation, increasing the danger of doubtless dangerous heart rhythm abnormalities. Other aspects might also play a job, including age, dosage of medication, and underlying genetic vulnerability.

Although older studies suggest that girls are more vulnerable than men to tardive dyskinesia (TD), newer studies show similar prevalence rates of TD and other extrapyramidal symptoms in men and ladies.

Some studies suggest that girls could also be more susceptible to developing allergic reactions in comparison with men, possibly on account of hormonal influences on immune responses. 

Impact on Menstrual Cycles and Reproduction

Antipsychotic medications exert various effects on the menstrual cycle and reproductive health in women in comparison with men. Certain antipsychotics with stronger antagonism of dopamine D2 receptors, including first generation antipsychotics and risperidone, may increase prolactin levels, leading to menstrual irregularities, amenorrhea, and even hyperprolactinemia-induced galactorrhea. 

While the reproductive system in men appears to be less vulnerable, some studies have reported decreased libido and erectile dysfunction in men receiving antipsychotic treatment, particularly with medications that possess strong anticholinergic properties, corresponding to chlorpromazine and olanzapine. 

Summary

In comparison with men, women generally require lower doses of antipsychotic medications to attain symptom reduction, possibly on account of the ameliorative effects of estrogen. Hormonal fluctuations in the course of the menstrual cycle may influence medication response, with some evidence suggesting higher outcomes during phases of upper estrogen levels. Nonetheless, women usually tend to experience unwanted side effects corresponding to weight gain and metabolic symptoms, potentially impacting medication adherence. Moreover, antipsychotic use can affect reproductive health otherwise in men and ladies, with some medications resulting in menstrual irregularities in women and decreased libido in men.

Ruta Nonacs, MD PhD

References

Sáenz-Herrero M, Recio-Barbero M, López-Atanes M, Santorcuato A, Bacigalupe A, Segarra R. Gender differences within the management of acute psychiatric episodes within the emergency department: a cross-sectional evaluation of the 2017-2019 triennium. Arch Womens Ment Health. 2023 Dec;26(6):777-783. 

Seeman MV. Men and ladies respond otherwise to antipsychotic drugs. Neuropharmacology. 2020 Feb; 163:107631. 

Shan Y, Cheung L, Zhou Y, Huang Y, Huang RS. A scientific review on sex differences in opposed drug reactions related to psychotropic, cardiovascular, and analgesic medications. Front Pharmacol. 2023 May 2;14:1096366.

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