Female Sexual Dysfunction Induced by Second-Generation Antipsychotic Drugs — A Disproportionality Analysis Based on the FAERS Database

Aripiprazole flagged for compulsive sexual behavior (ROR: 296.23); risperidone and paliperidone linked to decreased libido and anorgasmia — signals vary sharply by drug

Journal: Schizophrenia Bulletin | Published: 2026-03-07 | Type: Pharmacovigilance / Disproportionality Analysis | PMID: 41863367 Authors: Wang Dongdong (Ningbo MingZhou East Rehabilitation Hospital), Cao Yu (Shanghai Baoshan District Mental Health Center), Wu Linman (Nanchong Mental Health Center, Sichuan), Jin Liuyin (Second People's Hospital of Lishui) — all Chinese institutional affiliations Funding/COI: Funding not disclosed. Authors declare no conflicts of interest.

Summary

Using two decades of FDA adverse event reports, Wang et al., 2026 identified 11,786 cases of female sexual dysfunction attributed to nine second-generation antipsychotics (SGAs). The headline finding is a striking drug-specific divergence: aripiprazole generates a massive disproportionality signal for hypersexuality and compulsive sexual behavior, while prolactin-elevating drugs like risperidone and paliperidone are associated with the opposite — decreased libido and anorgasmia. The study is hypothesis-generating at best; FAERS data cannot establish causation and is riddled with reporting biases, but the signal magnitudes here are large enough to take seriously.

Claims

• 11,786 reports of female sexual dysfunction linked to SGAs identified in FAERS from Q1 2004 to Q4 2023; reports peaked in 2017
• Women aged 19–41 were the largest subgroup (n = 4,787, 40.6%)
• Antipsychotics occupied 9 of the top 50 drugs associated with sexual dysfunction in the database
• Aripiprazole showed an extraordinary disproportionality signal for compulsive sexual behavior: Reporting Odds Ratio (ROR) = 296.23
• Aripiprazole and brexpiprazole (both partial dopamine agonists) dominated the hypersexuality signal; the mechanism is attributed to dopaminergic agonism in reward pathways
• Risperidone and paliperidone (prolactin-elevating drugs) were associated with decreased libido and anorgasmia
• Prolactin-elevating SGAs were associated with older patient age, intramuscular formulation use, and more serious reported outcomes
• All four disproportionality methods (ROR, PRR, BCPNN, MGPS) produced convergent signals for aripiprazole

Study Quality

This is a pharmacovigilance disproportionality analysis — a method designed to detect safety signals in spontaneous reporting databases, not to prove causation. The authors used four complementary statistical approaches (two frequentist, two Bayesian), which is methodologically sound and increases confidence that the large signals aren't artifacts of a single method. Stratification by prolactin-related mechanism adds interpretive value and distinguishes the biological plausibility of divergent symptom profiles.

That said, FAERS is a voluntary reporting system with well-documented flaws: massive underreporting, no denominator (we don't know how many women took each drug without incident), no dose or duration data, and no control for confounders. Critically, psychiatric disorders themselves impair sexual function, and polypharmacy is nearly universal in this population — the paper does not appear to address co-prescribed antidepressants, mood stabilizers, or other agents known to cause sexual dysfunction. The aripiprazole compulsive sexual behavior signal may also be inflated by notoriety bias: clinicians who are aware of this association are more likely to report it, and it has received substantial attention in the literature since early impulse-control disorder reports.

Red Flags

• No causation possible: FAERS disproportionality signals indicate reporting associations, not pharmacological causation
• No denominator: Cannot calculate true incidence rates — only relative reporting patterns
• Confounding unaddressed: Polypharmacy, psychiatric diagnosis severity, and disease-related sexual dysfunction are not controlled
• Notoriety/Weber effect: Aripiprazole's impulse-control disorder reputation likely inflates its compulsive sexual behavior signal via selective reporting
• Funding undisclosed: Not necessarily a red flag, but the omission is noted
• Conclusion overreaches: The abstract tells clinicians to "consider sexual side effects in treatment decisions and monitor patients accordingly" — that's clinical guidance extrapolated from a signal-detection dataset
• Chinese institutional context: All four authors are from Chinese psychiatric institutions; it's unclear whether reporting patterns in a US database (FAERS) are being interpreted through a generalizable lens or with awareness of demographic/prescription differences

Strengths

• 20-year dataset (2004–2023) provides longitudinal breadth
• 11,786 reports is a large case set for this specific adverse event category
• Four-method disproportionality approach (convergent validity strengthens signal confidence)
• Stratification by prolactin mechanism is biologically grounded and clinically useful
• Addresses an understudied population — female sexual side effects of antipsychotics are systematically underreported in clinical trials
• Drug-specific differentiation (hypersexuality vs. hyposexuality) is a genuinely informative finding that contradicts simplistic "antipsychotics cause sexual dysfunction" framing

Verdict

The aripiprazole compulsive sexual behavior signal (ROR 296.23) is striking and biologically plausible given the drug's partial dopamine agonism, but FAERS disproportionality analyses are the epidemiological equivalent of a smoke detector — they tell you something might be on fire, not that the building is burning. The prolactin-mechanism stratification is the paper's strongest contribution: it gives a mechanistic framework for why risperidone causes anorgasmia while aripiprazole causes hypersexuality. Worth reading for the signal hypothesis; not worth citing as evidence of causation.