Antipsychotic-Related Prolactin Levels and Sexual Dysfunction in Mentally Ill Youth: A 3-Month Cohort Study

• Published in: Journal of the American Academy of Child and Adolescent Psychiatry Vol. 62; no. 9; pp. 1021 - 1050
• Main Authors: Koch, Marie T., Carlson, Harold E., Kazimi, Milad M., Correll, Christoph U.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2023
• Subjects: Adolescent; adolescents; Antipsychotic Agents - adverse effects; antipsychotics; Aripiprazole - adverse effects; Benzodiazepines - adverse effects; children; Cohort Studies; Erectile Dysfunction - chemically induced; Erectile Dysfunction - drug therapy; Female; Galactorrhea - chemically induced; Galactorrhea - drug therapy; Humans; Hyperprolactinemia - chemically induced; Hyperprolactinemia - drug therapy; Male; Mentally Ill Persons; Olanzapine - adverse effects; Pregnancy; Prolactin; Prospective Studies; Quetiapine Fumarate - adverse effects; Risperidone - adverse effects; sexual side effect; antipsychotics; sexual side effect; prolactin; children; adolescents
• ISSN: 0890-8567; 1527-5418; 1527-5418
• DOI: 10.1016/j.jaac.2023.03.007

Although these agents are used frequently, prospective data comparing serotonin/dopamine antagonists/partial agonists (SDAs) in youth regarding prolactin levels and sexual adverse effects (SeAEs) are scarce.
Youth aged 4 to 17 years, SDA-naive (≤1 week exposure) or SDA-free for ≥4 weeks were followed for ≤12 weeks on clinician’s-choice aripiprazole, olanzapine, quetiapine, or risperidone. Serum prolactin levels, SDA plasma levels, and rating scale−based SeAEs were assessed monthly.
Altogether, 396 youth (aged 14.0 ± 3.1 years, male participants = 55.1%, mood spectrum disorders = 56.3%, schizophrenia spectrum disorders = 24.0%, aggressive-behavior disorders = 19.7%; SDA-naive = 77.8%) were followed for 10.6 ± 3.5 weeks. Peak prolactin levels/any hyperprolactinemia/triple-upper-limit-of-normal-prolactin level were highest with risperidone (median = 56.1 ng/mL/incidence = 93.5%/44.5%), followed by olanzapine (median = 31.4 ng/mL/incidence = 42.7/76.4%/7.3%), quetiapine (median = 19.5 ng/mL/incidence = 39.7%/2.5%) and aripiprazole (median = 7.1 ng/mL/incidence = 5.8%/0.0%) (all p < .0001), with peak levels at 4 to 5 weeks for risperidone and olanzapine. Altogether, 26.8% had ≥1 newly incident SeAEs (risperidone = 29.4%, quetiapine = 29.0%, olanzapine = 25.5%, aripiprazole = 22.1%, p = .59). The most common SeAEs were menstrual disturbance = 28.0% (risperidone = 35.4%, olanzapine = 26.7%, quetiapine = 24.4% aripiprazole = 23.9%, p = .58), decreased erections = 14.8% (olanzapine = 18.5%, risperidone = 16.1%, quetiapine = 13.6%, aripiprazole = 10.8%, p = .91) and decreased libido = 8.6% (risperidone = 12.5%, olanzapine = 11.9%, quetiapine = 7.9%, aripiprazole = 2.4%, p = .082), with the least frequent being gynecomastia = 7.8% (quetiapine = 9.7%, risperidone = 9.2%, aripiprazole = 7.8%, olanzapine = 2.6%, p = 0.61), galactorrhea = 6.7% (risperidone = 18.8%, quetiapine = 2.4%, olanzapine = 0.0%, aripiprazole = 0.0%, p = .0008), and mastalgia = 5.8% (olanzapine = 7.3%, risperidone = 6.4%, aripiprazole = 5.7%, quetiapine = 3.9%, p = .84). Postpubertal status and female sex were significantly associated with prolactin levels and SeAEs. Serum prolactin levels were rarely associated with SeAEs (16.7% of all analyzed associations), except for the relationship between severe hyperprolactinemia and decreased libido (p = .013) and erectile dysfunction (p = .037) at week 4, and with galactorrhea at week 4 (p = .0040), week 12 (p = .013), and last visit (p < .001).
Risperidone, followed by olanzapine, was associated with the largest prolactin elevations, with little prolactin-elevating effects of quetiapine and, especially, aripiprazole. Except for risperidone-related galactorrhea, SeAEs did not differ significantly across SDAs, and only galactorrhea, decreased libido, and erectile dysfunction were associated with prolactin levels. In youth, SeAEs are not sensitive markers for significantly elevated prolactin levels.