Antipsychotics are indispensable in the management of schizophrenia, bipolar disorder, and related psychoses. However, their use is frequently limited by adverse endocrine effects, particularly hyperprolactinemia. First described shortly after the introduction of chlorpromazine, AIH remains clinically relevant with both first-generation and second-generation antipsychotics. Given its impact on quality of life, fertility, treatment adherence, and long-term morbidity, a systematic understanding of AIH is essential for psychiatrists. Elevated prolactin can be asymptomatic early, but sustained elevations are linked to sexual dysfunction, menstrual irregularities, infertility, galactorrhea, gynecomastia, and longer-term hypogonadism with low bone mineral density and fracture risk1. EPIDEMIOLOGY The prolactin-increasing property varies among antipsychotics, is dose-related, and is greater in females. Risk varies markedly by agent and dose. Amisulpride and risperidone (and its metabolite paliperidone) and first generation antipsychotics are most frequently implicated; olanzapine and lurasidone tend to be lower; partial agonists (aripiprazole, brexpiprazole, cariprazine), clozapine, quetiapine, are prolactin sparing prolactin. Recent meta-analytic work confirms a dose–response relationship across multiple agents2.

Blockade of pituitary D₂ receptors disinhibits lactotrophs. Chronic hyperprolactinemia suppresses hypothalamic GnRH → lowers LH/FSH → hypogonadism (amenorrhea/ oligomenorrhea, decreased libido, erectile dysfunction) and bone effects3. CLINICAL CONSEQUENCES Short-term effects are sexual dysfunction, menstrual disturbances, galactorrhea, gynecomastia. Long-term adverse consequences are infertility, decreased bone mineral density/osteoporosis, and possible increase in risk of breast cancer. Risk is cumulative with duration and degree of elevation. Given the negative consequences of hyperprolactinemia, and the possibility for reasonable modifications to antipsychotic regimens, routine monitoring of prolactin in patients who are prescribed antipsychotics is better4. ASSESSMENT AND DIFFERENTIAL DIAGNOSIS 1. History & drug review → recent initiation or dose change of antipsychotics. 2. Serum prolactin level (fasting, morning sample preferable): Normal levels are 0-20 ng/ml in men and 0-25 ng/ml in women 3. Rule out other causes: Antipsychotic exposure is a common secondary cause, but other medication use, renal failure, hypothyroidism, seizures and pituitary and parasellar tumors in patients with symptomatic non-physiological hyperprolactinemia must be excluded5,6. 4. Imaging (MRI sella) if prolactin very high (>118 ng/mL) or if neurological symptoms don’t correlate with drug use7. MANAGEMENT STRATEGIES 1) Dose reduction / discontinuation / switch. First-line where feasible: if symptomatic reduce the dose of the offending antipsychotic, discontinue, or switch to a prolactin-sparing drug(Aripiprazole, cariprazine, clozapine, quetiapine, lumateperone). This is supported across guidelines, with relapse risk considerations. If elevated but asymptomatic discuss clinical consequences with the patient and take decision7. 2) Adjunctive aripiprazole. Robust evidence (RCT meta-analyses) shows adjunctive low-dose aripiprazole normalises prolactin in most patients while maintaining psychiatric control; 5–10 mg/day is often effective. Network meta-analyses place aripiprazole augmentation among the most effective strategies for normalisation and menses restoration8. If successful, guidelines recommend slowly reducing dose of prolactin raising drug and aim for aripiprazole as sole treatment. If this fails, consider long term combined antipsychotics. 3) High dose vitamin B6 seems to be effective in reducing antipsychotic induced hyperprolactinemia and is well tolerated7. 4) Dopamine agonists (cabergoline, bromocriptine). These agents reliably lower prolactin, but can worsen psychosis; consider only after psychiatric risks are carefully weighed and discussed9. 5) A reduction in prolactin levels was also achieved by taking high daily doses (2.5-3 G) of metformin in some studies10.

Antipsychotic induced hyperprolactinemia remains a clinically significant adverse effect of antipsychotic therapy. Awareness of its Prevalence, clinical burden, and management options is critical for optimising patient outcomes. The degree of prolactin elevation is probably dose related, and for most antipsychotic medications the threshold activity for increasing prolactin is very close to that of therapeutic efficacy. Practical approaches include a baseline level pre-treatment and a follow-up after dose stabilization or sooner if symptoms emerge. Prolactin elevating drugs with high risk should be avoided if possible in young women, patients under 25yrs, patients with osteoporosis, and in those with history of hormone dependent breast cancer. Early recognition, proactive monitoring, and individualized management-particularly switching to or augmenting with prolactin-sparing agents—are central to care.

1. Ghahramani A, Bellon A. Monitoring prolactin in patients taking antipsychotics. Front Psychiatry. 2024 Jan 30;15:1333280. doi: 10.3389/fpsyt.2024.1333280. PMID: 38352655; PMCID: PMC10861782. 2. Burback L. (2015). Management of a microprolactinoma with aripiprazole in a woman with cabergoline-induced mania. Endocrinology, diabetes & metabolism case reports, 2015, 150100. https://doi.org/10.1530/EDM-15-0100 3. Lin, X., Siafis, S., Tian, J. et al. Antipsychotic-Related Prolactin Changes: A Systematic Review and Dose–Response Meta-analysis. CNS Drugs (2025). https://doi.org/10.1007/s40263-025-01218-z 4. Ghahramani, A., & Bellon, A. (2024). Monitoring prolactin in patients taking antipsychotics. Frontiers in psychiatry, 15, 1333280. https://doi.org/10.3389/fpsyt.2024.1333280 5. Thapa S, Bhusal K. Hyperprolactinemia [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan– [updated 2023 Jul 24; cited 2025 Sep 5]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537331 6. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JAH. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Feb;96(2):273–88. doi:10.1210/jc.2010-1692. 7. Taylor DM, Barnes TR, Young AH. The Maudsley prescribing guidelines in psychiatry. John Wiley & Sons; 2025 Jun 11 8. Jiang Q, Li T, Zhao L, Sun Y, Mao Z, Xing Y, Wang C, Bo Q. Treatment of antipsychotic-induced hyperprolactinemia: an umbrella review of systematic reviews and meta-analyses. Frontiers in psychiatry. 2024 Mar 5;15:1337274. 9. Gupta S, Lakshmanan DAM, Khastgir U, Nair R. Management of antipsychotic-induced hyperprolactinaemia. BJPsych Advances. 2017;23(4):278–86. doi:10.1192/apt.bp.115.014928. 10. Rusgis MM, Alabbasi AY, Nelson LA. Guidance on the treatment of antipsychotic-induced hyperprolactinemia when switching the antipsychotic is not an option. American Journal of Health-System Pharmacy. 2021 May 15;78(10):862-71.