The first clinical practice guideline dedicated to the choice of first antipsychotic medicine for women and girls experiencing first-episode psychosis has been published in the March 2026 issue of Schizophrenia Bulletin. Developed by an international team of clinicians, researchers and experts-by-experience from Europe, North America and Australia, the guideline marks a major step towards truly sex-sensitive care in early psychosis.  

Current guidelines

Current international guidelines are based almost entirely on studies conducted in predominantly male populations and offer no female-specific recommendations. Yet females experience distinct vulnerabilities. For females, prolactin elevation leads to amenorrhea, galactorrhea, sexual dysfunction and infertility which are among the most distressing antipsychotic side-effects and are associated with loss of the feeling of femininity and lower quality of life. Longer-term consequences of prolactin-elevating antipsychotic medicines include impaired bone mineral density, increased fracture risk and elevated breast cancer odds. Cardiometabolic side-effects, particularly weight gain, are also more subjectively burdensome for women, undermining body image and self-esteem. Because peak onset of psychosis in females overlaps with peak reproductive years, these risks have lifelong implications that existing guidelines do not address. Up to 80 per cent of those with first-episode psychosis respond to their first antipsychotic medicine, making the first choice a particularly important decision. Additionally, as early treatment experiences shape long-term adherence and outcomes, getting the first medicine right is a vital part of psychosis care.  

Sex-sensitive prescribing

By focusing on the side-effects that matter most to females, this guideline enables sex-sensitive and more personalised prescribing. The guideline development group, using the GRADE-ADOLOPMENT methodology and AGREE II framework, prioritised hyperprolactinemia and cardiometabolic risks. The result is clear, actionable recommendations that support better tolerability and fewer long-term physical health complications and facilitate shared decision-making. First-episode psychosis prescribing is a crucial time to offer the safest and best tolerated antipsychotic medicine. By prioritising outcomes that matter to women and girls — particularly hormonal and cardiometabolic effects — this guideline helps clinicians offer options with a lower long-term burden and supports females to keep taking medicines that are both effective and acceptable. The guideline strongly recommends against first-generation antipsychotics, olanzapine, quetiapine, risperidone, paliperidone and amisulpride as first-line options in females. Aripiprazole is recommended as the preferred first-choice for both adults and adolescents because it carries the lowest risk for both prolactin elevation and cardiometabolic side-effects. Suitable alternatives for adults are brexpiprazole, cariprazine, lurasidone, asenapine and ziprasidone; for adolescents (13–17 years), brexpiprazole and lurasidone are also recommended. Females exhibit sex-specific pharmacokinetic differences, including a larger volume of distribution due to higher body fat percentage, smaller organ size, and lower blood volume compared with males which may result in higher serum concentrations at equivalent doses. Although antipsychotic medicine manufacturers do not differentiate dosing by sex, the guideline development group recommends a lower starting dose of aripiprazole (5 mg daily for adult females) to account for these differences.

Reproductive health

Given that peak incidence of first-episode psychosis occurs during peak reproductive years, the guideline also includes practical guidance on contraception, pregnancy and breastfeeding. Most recommended agents, including aripiprazole and the listed alternatives, have no clinically significant interactions with hormonal contraceptives. Safety data during pregnancy and lactation (drawn from observational studies, pregnancy registries, and post-marketing surveillance) are summarised to support individualised risk–benefit discussions. The guideline includes a practical, female-specific algorithm detailing lower starting doses (for example, aripiprazole 5 mg), titration schedules, common side-effects, pregnancy and breastfeeding considerations and contraceptive advice. QR codes link directly to short, co-designed information videos for adults and adolescents — created with experts-by-experience and young people — to support shared decision-making.  

Guideline algorithm

Professor Brian O’Donoghue, Director of the UCD Centre of Psychosis Research and lead of the PROGRESS group, said: “Response rates to antipsychotic medications are high and therefore the choice of first antipsychotic medication needs to be based on the expected side-effects and tolerability. There is a very real differences in side-effect vulnerability for females and therefore, these sex specific guidelines should result in females being prescribed lower risk medications from the outset and will have longer term benefits for physical health. This guideline brings together international evidence and expert consensus to support safer first-choice antipsychotic medicine, better shared decision-making, and more equitable care from day one.” The guideline algorithm also includes tailored monitoring schedules for weight, metabolic parameters, prolactin (where relevant) and subjective side-effects. Pharmacists are well positioned to lead on side-effect monitoring, and to support early interventions such as metformin to prevent weight gain. Field-tested by Irish psychiatrists and specialist pharmacists, the guideline has received positive feedback for its user-friendly design and support for patient engagement. The guideline development group is now engaging with policymakers to improve access to recommended agents in Ireland — specifically brexpiprazole and lurasidone — which are the only two antipsychotic medicines licensed in Ireland for psychosis from age 13 but having not been marketed here, are not reimbursable under the community drugs schemes.  

Conclusion

This guideline is the first in a planned series of female-specific recommendations. Future work will focus on implementation, a parallel male guideline and second-line antipsychotic options. The full guideline, algorithm and videos are freely available at progressresearch.org. The open-access paper is published in Schizophrenia Bulletin (doi:10.1093/schbul/sbag023). Pharmacists in community and hospital settings are encouraged to familiarise themselves with the new recommendations, which have the potential to significantly improve outcomes for females presenting with first-episode psychosis in Ireland.