Antipsychotics, Prolactin, and Sexual Side Effects: What the Evidence Shows

Creator: Ryan S. Sultan, MD
Published: 2026-11-12

By Ryan S. Sultan, MD
Psychiatrist · Columbia University Irving Medical Center
Published November 12, 2026 · 6-minute read

Antipsychotics differ widely in how much they raise prolactin, a hormone linked to several of their sexual and reproductive side effects. In a network meta-analysis with prolactin data for 21,569 participants in acute-treatment trials, paliperidone sat at the top of the range, 48.51 ng/mL above placebo.¹

Sexual dysfunction is common and often goes unmentioned. In a cross-sectional study of 243 sexually active patients taking antipsychotics, 46% had sexual dysfunction, and only 37% of those patients reported it spontaneously.² There are options to discuss, and any change is made with the prescriber.

Which antipsychotics raise prolactin

Eight drugs were associated with significantly elevated prolactin in that analysis: olanzapine, asenapine, lurasidone, sertindole, haloperidol, amisulpride, risperidone, and paliperidone, with mean differences from 4.47 to 48.51 ng/mL. Heterogeneity for this outcome was high, and many antipsychotics had no prolactin data.¹

The bottom of the published range is -77.05 ng/mL for clozapine. The authors caution that the apparent reduction with clozapine and zotepine might be a statistical artifact driven by outliers, because only two small trials were available.¹ A 2021 network meta-analysis of 130 trials with 25,610 participants no longer found either drug associated with decreased prolactin, and it found large effects for risperidone, amisulpride, paliperidone, chlorpromazine, haloperidol, and sulpiride.³

What the risperidone and paliperidone labels say

The risperidone label states that the drug elevates prolactin, that the elevation persists during chronic administration, and that risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents.⁴ The label for paliperidone (Invega) describes a prolactin-elevating effect similar to that of risperidone.⁵

Both labels list galactorrhea, amenorrhea, gynecomastia, and impotence as reported with prolactin-elevating compounds. Both state that long-standing hyperprolactinemia, when associated with hypogonadism, may lead to decreased bone density, and that the drug may impair fertility in females, an effect described as reversible.^{4, 5} The risperidone label advises patients to seek medical attention for absent periods or milk discharge in females and for erectile dysfunction or breast enlargement in males.⁴

How common sexual dysfunction is, by drug

A 2011 meta-analysis sorted antipsychotics into two groups. Quetiapine, ziprasidone, perphenazine, and aripiprazole were associated with sexual dysfunction rates of 16% to 27%. Olanzapine, risperidone, haloperidol, clozapine, and thioridazine were associated with rates of 40% to 60%. The authors noted the difficulty of separating dysfunction related to the drugs from dysfunction related to the illness.⁶

In the cross-sectional study, dysfunction affected 50% of the males and 37% of the females, and 32% of affected patients reported tolerating it poorly.² Across 72 studies with 21,076 participants with schizophrenia, the pooled prevalence of sexual dysfunction was 56.4%, and erectile dysfunction was the most frequent form in men, at 44%.⁷

In a 6-week study of 264 patients, around 40% of emerging sexual side effects were attributable to the prolactin-raising properties of the medication.⁸

Breast cancer was associated with 5 or more years of exposure in one study

A Finnish nested case-control study identified 1,069 women with breast cancer among 30,785 women with schizophrenia and compared them with 5,339 matched controls. Compared with less than 1 year of exposure to prolactin-increasing antipsychotics, the association appeared only with long exposure. While 1 to 4 years of exposure was not associated with increased risk, exposure for 5 or more years was, with an adjusted odds ratio of 1.56 (95% CI 1.27 to 1.92). Prolactin-sparing antipsychotics, which the study defined as including clozapine, quetiapine, and aripiprazole, showed no such association.⁹

A Danish case-control study reached a different conclusion. Long-term antipsychotic use (at least 10,000 mg olanzapine equivalents) was associated with breast cancer, with an adjusted odds ratio of 1.18, the odds ratio for drugs that don't induce prolactin was similar at 1.17, and the authors concluded that their results do not suggest a clinically important association.¹⁰ Both labels describe published epidemiologic studies as showing “inconsistent results when exploring the potential association between hyperprolactinemia and breast cancer.”^{4, 5} These studies are observational and can't establish cause.

Adding aripiprazole lowered prolactin in randomized trials

A 2020 systematic review identified 26 studies of prolactin-lowering strategies and could perform a meta-analysis only for the addition of aripiprazole, which it called the strategy with the best level of evidence. Across five randomized trials, adding aripiprazole reduced prolactin, with a Hedges' g of -1.35.¹¹ An earlier meta-analysis of five placebo-controlled trials with 639 patients reported that adjunctive aripiprazole was associated with a prolactin normalization rate of 79.11% (125 of 158).¹²

One 16-week trial reported symptoms. Among 46 premenopausal women, prolactin normalized in 45% on aripiprazole (9 of 20) and 12% on placebo (2 of 17), galactorrhea resolved in 77% (10 of 13) and 33% (4 of 12), and sexual function normalized in 50% (7 of 14) and 9% (1 of 11).¹³ A 2022 network meta-analysis found no option significantly better than placebo among patients whose prolactin was below 50 ng/mL.¹⁴

Other options have little trial evidence

A PubMed search for this page on November 12, 2026 found no randomized trial of cabergoline for antipsychotic-related high prolactin and none of lowering the antipsychotic dose to treat it. The 2020 review counted three cabergoline studies.¹¹ A case report describes two patients with schizophrenia who had a psychotic exacerbation after starting cabergoline.¹⁵ A 2021 review lists dose reduction, discontinuation, and switching as first-line management and notes that these options carry a risk of relapse.¹⁶ Each is a decision for the prescriber. I've written separately about stopping antipsychotics.

For sexual dysfunction itself, a Cochrane review included four studies with 138 participants and concluded that sildenafil may be useful for men, based on one small short trial.¹⁷ A 2019 systematic review found 6 randomized trials of 6 different interventions and concluded that no clinical recommendations can be made.¹⁸

Limitations of the evidence

This evidence has limitations. First, the prolactin comparisons come from short acute trials, and many antipsychotics had no prolactin data. Second, the breast cancer and sexual dysfunction data are observational, and the add-on trials are small; the one that reported symptoms enrolled 46 women for 16 weeks. Nevertheless, sexual side effects are common, differ by drug, and often go unreported, so they're worth raising with the prescriber, who can review the options.

Frequently asked questions

Which antipsychotics raise prolactin the most?

In a network meta-analysis of acute trials, paliperidone was at the top of the range, 48.51 ng/mL above placebo. Olanzapine, asenapine, lurasidone, sertindole, haloperidol, amisulpride, and risperidone were also associated with significantly elevated prolactin. The risperidone label states that risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents.^{1, 4}

Is there an antipsychotic that doesn't raise prolactin?

A Finnish study classed clozapine, quetiapine, and aripiprazole as prolactin-sparing. A published figure showing clozapine lowering prolactin by 77.05 ng/mL was flagged by its authors as a possible statistical artifact from two small trials, and a 2021 analysis no longer found it. The choice of drug is made with the prescriber.^{9, 1, 3}

Does Abilify lower prolactin?

Added to another antipsychotic, aripiprazole reduced prolactin in five randomized trials. In one meta-analysis of five trials, the prolactin normalization rate with adjunctive aripiprazole was 79.11% (125 of 158). Adding or changing a medication is the prescriber's decision.^{11, 12}

Do antipsychotics cause erectile dysfunction?

Across 72 studies of people with schizophrenia, erectile dysfunction was the most frequent sexual dysfunction in men, at 44%. In a study of 243 sexually active patients taking antipsychotics, 46% had sexual dysfunction and only 37% of them reported it spontaneously. There are options to discuss with the prescriber.^{7, 2}

Do antipsychotics increase breast cancer risk?

A Finnish study found an association only after 5 or more years of exposure to prolactin-increasing antipsychotics, with an adjusted odds ratio of 1.56 compared with less than 1 year of exposure. A Danish study concluded that its results do not suggest a clinically important association, and the risperidone and paliperidone labels describe the epidemiologic results as “inconsistent.”^{9, 10, 4, 5}

In a crisis: call or text 988, or go to the nearest emergency department. A first episode of psychosis belongs in a hospital-based or coordinated specialty care program.

I start and manage clozapine in an outpatient practice in Chelsea, Manhattan. Details are on the schizophrenia care in NYC page. Clozapine should not be stopped, skipped, or restarted without the prescriber. This page is general information and does not replace an evaluation.