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RISPERDAL® (risperidone)

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Adverse Event of RISPERDAL - Sexual Dysfunction

Last Updated: 01/29/2025

Summary

This reply focuses on clinical trials evaluating or reporting antipsychotic-induced sexual dysfunction that included at least one risperidone cohort. For additional information on specific topics related to sexual dysfunction including priapism and ejaculatory dysfunction, please contact Medical Information at 1-800-JANSSEN (1-800-526-7736).
Anorgasmia, ejaculation disorder, erectile dysfunction, libido decreased, retrograde ejaculation and sexual dysfunction have been reported as adverse reactions with RISPERDAL use.¹
A significant positive dose-related trend has been noted for the occurrence of erectile dysfunction, ejaculation disorder and abnormal sexual function (Cochran-Armitage test; P<0.05).¹
In the majority of reported cases, the sexual dysfunction resolved upon dosage reduction or discontinuation of risperidone.
Priapism has been reported during postmarketing surveillance.¹
The long-term effects of RISPERDAL on growth and sexual maturation have not been fully evaluated in children and adolescents.¹

PRODUCT LABELING

Please refer to the following sections of the enclosed Full Prescribing Information that are relevant to your inquiry: WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS.

SEXUAL DYSFUNCTION REPORTED IN CLINICAL TRIALS

Double-Blind Pivotal/Clinical Trials

Double-Blind Pivotal/Clinical Trials - Sexual Dysfunction During Risperidone Treatment

Study Design	Summary
*Double-Blind Pivotal Trials – Adult Schizophrenia*
Kelly et al (2006)² conducted a 12-week, double-blind study assessing the effects of risperidone (RIS; mean age: 46.4 years) and quetiapine (QUE; mean age: 42.5 years) compared to fluphenazine (FLU; mean age: 45.1 years) on sexual function and serum prolactin in 27 patients with treatment-resistant schizophrenia. *Fixed Doses* RIS: 4 mg/day QUE: 400 mg/day FLU: 12.5 mg/day The PRAEQ (Prolactin Related Adverse Event Questionnaire) and CSFQ (Changes in Sexual Functioning Scale) were administered as semi-structured interviews at baseline and 12 weeks. The CSFQ is designed to measure illness and medication related changes in sexual function.	*Outcomes*: Of the 38 patients randomized to the trial, twenty-seven patients had baseline and endpoint data for sexual functioning. Patients reporting sexual dysfunction at endpoint included: RIS 5/12 (42%); QUE 3/6 (50%); and FLU 7/9 (78%). Compared to previous treatment, subjects reported a subjective improvement (measured as worsening, no change, or improvement) in sexuality of 13% (1/18) on FLU compared to 55% (6/11) on RIS and 40% (2/5) on QUE (P=NS). QUE treated patients noted improvements regarding orgasm (P=0.033) and arousal (P=0.117) compared to RIS and FLU-treated subjects. Mean prolactin levels were elevated in RIS and FLU treated patients, with RIS patients experiencing the greatest prolactin elevation (P=0.005). Sexual dysfunction did not correlate with prolactin levels (P>0.05). Mean prolactin levels for patients experiencing sexual dysfunction was 29.25±27.44 mg/dL compared to 35.56±441.63 mg/dL in patients not complaining of sexual dysfunction (P=NS). Prolactin-related side effects included: galactorrhea and gynecomastia, gynecomastia and amenorrhea.
Peuskens et al (1995)³ conducted an 8-week, multinational, parallel-group, double-blind study assessing the safety and efficacy of RIS versus haloperidol (HAL) in 1362 patients with DSM-III-R chronic schizophrenia. *Fixed RIS Doses* were 2, 6, 10, 16 mg/day. *Fixed HAL Dose* was 10 mg/day	*Outcomes: RIS patients experienced a dose-proportional increase in serum prolactin concentrations. As per the Udvalg for Kliniske Undersøgelser (UKU) side-effect rating scale: % of patients with increased/decreased sexual desire:* RIS 1 mg (n=226): 7.5/9.3 RIS 4 mg (n=227): 10.6/10.1 RIS 8 mg (n=228): 5.7/10.1 RIS 12 mg (n=225): 8.0/14.2 RIS 16 mg (n=224): 7.1/11.6 HAL 10 mg (n=225): 7.6/11.6
Marder et al (1994)⁴ conducted an 8-week, multicenter, prospective, randomized, double-blind, fixed dose trial assessing the safety, efficacy, and optimal dose of RIS compared to placebo and HAL in 388 DSM-III-R schizophrenic patients. *Fixed RIS Doses* were 2, 6, 10, 16 mg/day. *Fixed HAL Dose* 20 mg/day	*Outcomes*: Of the 4 women receiving 10 mg of RIS, 1 patient spontaneously reported dysmenorrhea. In addition, 1 out of 11 women receiving RIS 16 mg reported vaginitis. The UKU scale items of diminished sexual desire (P<0.05) and erectile dysfunction (ED; P<0.01), elicited from the patients, were positively and significantly related to the dose of RIS.
*Additional Single/Double-Blind Trials*
Kumar et al (2017)⁵ conducted a non-randomized, naturalistic, rater blinded, prospective 8-12-week comparative study between RIS (n=22) and aripiprazole (ARI; n=13) in patients with schizophrenia (mean age: 29 years). Patients were previously being treated with ARI or RIS *Dose*: ARI: 10-30 mg/day; RIS: 3-8 mg/day	Adverse events were assessed by the UKU Scale. Diminished sexual desire (16.7% vs.0%; P=0.02) occurred more frequently in the RIS group than in the ARI group.
Safe et al (2008)⁶ conducted a 3-month, double-blind study assessing the metabolic and adverse effects of RIS (n=31) versus olanzapine (OLA; n=32) in 63 patients (mean age: 32.6 years) with delusional disorder, schizophreniform and schizoaffective disorder. *Dose: OLA: 5-10 mg/day x 1 week followed by increase to 15-20 mg/day. RIS*: titrated to 6-12 mg/day	*Outcomes*: Significantly more patients in the RIS group reported impotence versus OLA group; 25.8% versus 0%, respectively (P=0.02).
Akhondzadeh et al (2008)⁷ conducted a prospective, 8-week, double-blind study assessing the effect of ritanserin (RIT), a 5HT2A/2 antagonist, added to RIS as augmentation therapy in patients (n=40) with chronic schizophrenia. RIS 6 mg/day/RIT 12 mg/day: mean age: 32 years (n=13 male; n=7 female) RIS 6 mg/day/Placebo: mean age: 33 years (n=12 male; n=8 female)	*Outcomes*: Sexual dysfunction was reported in 1 patient in the RIS/RIT and 3 patients in the RIS/PLA treatment groups.
Byerly et al (2008)⁸ conducted a double-blind, randomized, 6-week trial evaluating the effect of a switch to quetiapine (QUE) (n=20; mean age: 43.5 years; 6-week mean dose: 290 mg/day) versus RIS continuation (n=22); 6-week mean dose: 4.1 mg/day) in 42 outpatients with schizophrenia or schizoaffective disorder experiencing moderate sexual dysfunction (ASEX [Arizona Sexual Experience Scale] total score ≥15) associated with pre-existing RIS treatment (≤4 mg/day). *Endpoints*: ASEX ratings were obtained at baseline and again at the end of weeks 2, 4, and 6 while PANSS ratings were obtained at baseline and the end of week 6. The primary data analysis was a mixed linear model controlling for gender, baseline ASEX scores and baseline PANSS total scores.	*Outcomes*: During week 1 patients assigned to QUE were titrated to 300 mg/day while RIS was gradually tapered off. Flexible doses, up to 800 mg/day, were prescribed during the final 4 weeks of the study. Patients randomized to RIS continuation for 6 weeks received doses identical to their prestudy regimen. A total of 24 patients were concomitantly receiving antidepressants known to cause sexual dysfunction. No correlation was observed between total ASEX scores at weeks 2, 4 and 6 and the presence or absence of antidepressant treatment. At week 6, PRL levels were significantly lower in patients receiving QUE compared to RIS (9.7 ng/mL versus 44.8 ng/mL, respectively; P=0.001). Overall, the QUE group had slightly lower ASEX total scores at weeks 2 (21.27 versus 22.18, respectively; P=0.63) and 6 (18.51 versus 20.53, respectively; P=0.3). However, there was no significant treatment group effect or treatment group x period interaction for ASEX total and sub-item scores at weeks 2, 4, and 6.
Nakonezny et al (2007)⁹ conducted a 6 week, double-blind, randomized trial assessing the relationship between serum prolactin levels and sexual functioning in 22 RIS-treated male patients switched to QUE (n=10; mean dose: 300 mg/day) or continued on RIS (n=12; mean dose: 4.3 mg/day) for schizophrenia or schizoaffective disorders. Prior to randomization all patients had an ASEX score of ≥15 during treatment with RIS monotherapy. Sexual functioning was assessed with the ASEX scale at baseline and again at week 6 (higher scores reflect greater sexual impairment).	*Prolactin Levels*: Baseline mean prolactin levels for the RIS and QUE groups were 17.3 ng/mL and 21.4 ng/mL, respectively. Week 6 mean prolactin levels were significantly lower in the QUE group compared to the RIS group (P=0.05). At week 6, a significant positive correlation was observed between serum prolactin level and ASEX total (β=0.17; P=0.04), and ASEX subitems: strength of sex drive (β=0.03; P=0.04), sexual arousal (β=0.04; P=0.04), and penile erection (β=0.04; P=0.02) scores for RIS. No significant correlations between prolactin levels and ASEX total or subitem scores were observed for QUE.

Open-Label Studies (N≥50)

Open-Label Studies (N≥50) - Sexual Dysfunction During Risperidone Treatment

Study Design	Summary
Montejo et al (2010)¹⁰ conducted a multicenter, cross-sectional, naturalistic study examining the frequency of sexual dysfunction and its impact on treatment adherence in 243 patients receiving antipsychotics for a psychotic disorder. *Mean Dose; Mean Duration of Treatment: Risperidone, RIS (n=119): 5.7 mg/day; 9 months Olanzapine, OLA (n=73): 12.8 mg/day; 8.3 months Clozapine, CLOZ (n=7): 160.7 mg/day; 30.3 months Quetiapine, QUE (n=6): 550 mg/day; 3 months Conventionals (n=25)* Conventionals, depot (n=13) Endpoint: Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SalSex)	*Outcomes*: The most frequent diagnosis was schizophrenia (71%). According to the SalSex, 46% of patients exhibited sexual dysfunction however, only 37% spontaneously reported it. Medications associated with the highest rates of sexual dysfunction were RIS (64%), conventionals, depot (54%), and conventionals (52%). Lowest rates were associated with OLA (19%), QUE (17%), and CLOZ (14%). According to univariate logistic regression analysis, utilizing OLA as the reference, a significant increased risk of sexual dysfunction was observed with RIS. RIS-induced sexual dysfunction was dose related. OLA-induced sexual dysfunction was dose related for the occurrence of delayed ejaculation/orgasm and for difficulties with erection/lubrication. With the exception of depot conventionals, severity and tolerance to sexual dysfunction was worse in males compared to females, regardless of antipsychotic studied.
Stroup et al (2009)¹¹ Phase 3 of the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial (n=270; 40.5 years; 70% male) which included patients who had discontinued treatment in DB phases 1 and 2, were eligible to select from 9 antipsychotic treatment regimens, with the help of their study doctor, allowing them to complete the entire 18 months of treatment. *Mean Modal Dose: Aripiprazole* (ARI; n=30): 16.1 mg/day CLOZ (n=32): 317.2 mg/day COMBO (n=40): N/A Fluphenazine Decanoate (FLU-D; n=7): 41.1 mg OLA (n=39): 21.8 mg/day Perphenazine (PER; n=4): 30.0 mg/day QUE (n=33): 500 mg/day RIS (n=32): 3.9 mg/day Ziprasidone (ZIP; n=33): 132.1 mg/day	*Outcomes: Percent of patients reporting sexual dysfunction (sex drive, sexual arousal, sexual orgasm) as moderate or severe AEs by systematic inquiry: ARI* (n=33): 9% CLOZ (n=37): 27% COMBO (n=40): 30% FLU-D (n=9): 11% OLA (n=41): 10% PER (n=4): 25% QUE (n=33): 30% RIS (n=36): 17% ZIP (n=37): 14%
van Bruggen et al (2009)¹² examined the effect of RIS (n=17; mean dose: 3.3 mg/day) and OLA (n=23; mean dose: 13.4 mg/day) on hormonal state and sexual dysfunction using the QSD (Questionnaire for Sexual Dysfunction) in patients with a first episode psychosis was compared to healthy controls (n=34; mean age: 20.8 years). Patients were inpatients who had been treated for at least 6 weeks prior to study entry.	*Outcomes*: In response to the QSD, overall satisfaction with sexuality was less in patients compared to the control group (P<0.01), with no difference between the RIS and OLA groups. A significantly higher frequency of problems with ejaculation existed in the OLA and RIS groups compared to control group (P<0.01). Both the frequency and the amount of suffering from problems with sexual arousal were significantly higher in OLA compared to the RIS groups. Although patients in the RIS group had higher prolactin levels than the OLA group, sexual dysfunction was prevalent in the OLA group with normal prolactin levels. Sexual dysfunction was also prevalent in the healthy control group suggesting that sexual problems may exist in young adults regardless of treatment or illness.
Konarzewska et al (2009)¹³ conducted an open-label study evaluating the effects of RIS versus OLA on the HPG (hypothalamo-pituitary-gonadal) axis in 89 adult male patients with DSM-IV schizophrenia. *Mean Doses* Week 3 (Initial Evaluation): RIS (n=50): 4.7 mg/day OLA (n=39): 17.4 mg/day Week 8 (Final Evaluation): RIS (n=32): 4.4 mg/day OLA (n=27): 15.7 mg/day Prior to study initiation, patients were free from oral (≥3 weeks) and depot (≥3 months) antipsychotic medications. *Endpoints*: At weeks 3 and 8, following treatment initiation, fasting blood samples were drawn prior to the morning dose of medication for analysis of PRL, FSH (follicle-stimulating hormone), LH (luteinizing hormone), estradiol, testosterone, and inhibin B plasma levels. Secondary assessments included the PANSS total, ASEX and DAI-10 (Drug Attitude Inventory) scores.	*Final Evaluation* (Week 8 Following Drug Initiation) ANCOVA results revealed a statistically significant drug effect on FSH (P=0.01) and PRL (P=0.01). Compared to OLA, mean PRL levels were significantly higher in RIS patients whereas FSH levels were lower. PRL levels were slightly affected by the dose of OLA but not RIS (Multiple regression analyses with dose, body mass and age as independent variables, P=0.04) Inhibin B levels<80 pg/mL were detected in 1 RIS patient and 3 OLA patients, indicating Sertoli's cell dysfunction. Testosterone levels were below the lower limit of normal (<241 ng/mL) in 2 out of 32 RIS patients, reflecting Leydig's cell impairment. The prevalence of hyperprolactinemia (mean PRL >17.7 ng/mL) was 78% for RIS patients (n=25/32) and 25.9% for patients receiving OLA (n=7/27). In all cases, mean LH, FSH, testosterone and estradiol levels were with the normal reference range. *Correlations* Inhibin B levels were negatively correlated with FSH in all investigated groups with the exception of the RIS hyperprolactinemic group. *ASEX and DAI-10* Significantly higher ASEX total scores were observed in patients receiving RIS, compared to OLA, at both the initial 22.3 (n=43) versus 17.3 (n=27), respectively; (P=0.04) and final (21 (n=30) versus 14.7 (n=16), respectively; P=0.01) evaluations. Total ASEX scores were positively correlated with negative symptom severity only. In addition, at the final evaluation, higher DAI-10 scores were observed in patients receiving OLA compared to RIS (6.5 versus 3.2; P=0.03). Neither ASEX or DAI-10 scores were affected by PRL or gonadal hormone levels.
Hanssens et al (2008)¹⁴ conducted a post-hoc analysis of a European, multicentre, randomized, naturalistic, 26-week, open-label study comparing the effects of ARI (aripiprazole) to SOC (Standard Of Care = OLA, QUE, and RIS) on PRL levels and sexual functioning in 555 patients (mean age: 38.5 years) with a diagnosis of schizophrenia (DSM-IV-TR). *Mean Doses at Endpoint: ARI* (n=284): 18.7 mg/day OLA (n=75): 12.5 mg/day QUE (n=110): 386.8 mg/day RIS (n=81): 4.6 mg/day Concomitant medications included as needed benzodiazepines and anticholinergics in addition to prestudy antidepressants and mood stabilizers. ASEX scores were obtained at baseline and at weeks 8, 18, and final assessment (week 26 or at time of premature discontinuation).	*ASEX Outcomes* While both treatment groups exhibited a decrease in ASEX scores during the trial, a significantly greater improvement was observed in ARI patients compared to the SOC group from week 8 onwards. From baseline to week 26, ARI patients experienced a 1.88-point drop in the mean ASEX total score compared to a drop of 0.92 within the SOC group (P=0.032, observed cases). When adjusted for CGI-I, this significant difference between treatment groups was still observed. A greater improvement in ASEX total scores was observed in QUE patients compared to OLA or RIS patients. Compared to female patients, male patients experienced a greater mean decrease in ASEX total scores (-0.71 versus -1.53, respectively; ARI and SOC groups combined). No correlation was observed between baseline changes in ASEX total scores and PRL levels.
Knegtering et al (2008)¹⁵ assessed 264 in-and outpatients (mean age: male 28 years; female 26 years) for changes in sexual performance using the ASFQ (Antipsychotic and Sexual Functioning Questionnaire) after 6 weeks of treatment with prolactin-raising or prolactin-sparing antipsychotics. *Prolactin-Raising Antipsychotics: RIS* (risperidone n=114; mean dose: 3.8 mg/day) Others: bromperidol, haloperidol, perphenazine, penfluridol, pimozide, sulpiride, zuclopentixol *Prolactin-Sparing Antipsychotics*: clozapine, olanzapine, quetiapine, sertindole	*Outcomes*: Emergence of LIBORG (lack of libdo or orgasmic dysfunction) and EDOD (erectile or ejaculatory dysfunction in men) were strongly associated with prolactin-raising medications and with serum prolactin. The number of patients reporting sexual dysfunctions during the 6 week evaluation period was highest in the patients receiving RIS (39%-49%) compared with patients receiving the other antipsychotics (2.6%-35.7%). Mean serum prolactin levels were higher in patients receiving RIS (1101 ME/L) compared with patients receiving the other antipsychotics (223-738 ME/L).
Westheide et al (2008)¹⁶ conducted an open-label, 4-week, study assessing sexual functioning, subjective well-being and prolactin concentrations in patients (n=102) with schizophrenia treated with RIS (n=38; mean age: 34.1 years; median dose: 4 mg/day) or QUE (n=64; mean age: 37.3 years; median dose: 600 mg/day) for at least a 1 week period prior to enrollment.	*Outcomes*: RIS was associated with a higher level of sexual impairment compared with QUE both at baseline and week 4 including impaired libido (P≤ 0.014) and impaired arousal (P≤0.05). At week 4 this extended to impaired orgasm (p≤ 0.003). There was an increase in plasma prolactin levels in male (P<0.001) patients receiving RIS compared with QUE. In male and female patients, prolactin did not correlate with sexual dysfunction (after 4 weeks).
Ucok et al (2007)¹⁷ conducted a multicenter, noninterventional, cross-sectional observational study in which ASEX and UKU Side Effects Rating Scale were administered to 827 patients (mean age: 33.1 years) to assess incidence and possible predictors of sexual dysfunction.-Adequate doses of the same antipsychotic were given for at least 3 months.	ASEX scores were significantly lower in patients taking QUE versus RIS (P=0.001). ASEX scores were not significantly different in women taking atypical antipsychotics (P=0.2) *Mean ASEX scores:* RIS (n=233): men: 17.1; women: 19.4 OLA (n=187): men: 15.5; women: 19 CLOZ (n=135): men: 15.9; women: 19.3 QUE (n=125): men: 14.2; women: 18.2
Byerly et al (2006)¹⁸ evaluated the sexual dysfunction associated with the use of OLA (n=94), QUE (n=57), or RIS (n=87) in 238 outpatients diagnosed with schizophrenia or schizoaffective disorder. *Endpoints*: A one-time rating of the ASEX was utilized to assess the severity of sexual dysfunction (higher scores reflect a greater severity of sexual dysfunction).	*Outcomes*: After controlling for age, gender, and the presence or absence of antidepressants known to cause sexual dysfunction, mean ASEX total scores were lower for the QUE group (17.8) compared to the RIS (19.69) and OLA (20.34) groups. This difference was significant between OLA and QUE (P=0.04) but not for RIS versus QUE (P=0.17) or OLA versus RIS (P=0.76).
Dossenbach et al (2006)¹⁹ evaluated sexual function at baseline and 3, 6, and 12 months in a subset of outpatients with schizophrenia. This group participated in the IC-SOHO (Intercontinental Schizophrenia Outpatient-Health Outcomes study) prospective naturalistic observational study and maintained their baseline monotherapy prescription for at least 3 months. Patients included in this analysis received: OLA (n=2638), RIS (n=860), QUE (n=142), or HAL (n=188). *Mean Baseline, 3-,6-, and 12-Month Doses (mg/day): OLA: 9.8* (n=2555); 10.7 (n=2536); 10.8 (n=2233); 10.8 (n=1919) *RIS: 3.5* (n=854); 3.9 (n=834); 4 (n=689); 4 (n=549) *QUE: 241(n=139); 337.3* (n=136); 332.2 (n=103); 334.1 (n=76) *HAL: 11.4* (n=169); 11.4 (n=150); 12.2 (n=115); 11.8 (n=92) *Endpoints*: Sexual functioning was examined through patient reports and psychiatrist perception from consultations at 3, 6, and 12 months using a modified UKU Side Effect Rating Scale which referred only to items related to sexual functioning.	*Outcomes*: At baseline, QUE treated patients had more impotence/sexual dysfunction compared to OLA and RIS and more amenorrhea/menstrual disturbances compared to RIS or HAL treated patients (P<0.001) Patient-reported sexual dysfunction at 12 months was highest for HAL (71.1%), followed by RIS (67.8%), QUE (60.2%), and OLA (55.7%). Psychiatrist-assessed loss of libido and impotence/sexual dysfunction was lowest in the OLA group (loss of libido: 46.4%, impotence/sexual dysfunction: 32%), followed by QUE (54.6%, 43%), RIS (60%, 46%), and HAL (68.1%, 52.3%). Psychiatrist-assessed amenorrhea/menstrual disturbances emergent during the 12 months was highest for HAL (38.2%), followed by RIS (27.5%), OLA (15.3%), and QUE (13.0%). At the 12-month assessment, 40% (729/1843) of patients reporting sexual problems were assessed by the treating psychiatrist as not experiencing impotence/sexual dysfunction (P<0.001). Results from a similar subanalysis of the IC-SOHO trial by Bitter et al, 2005 are summarized below²⁰ and an efficacy and safety subanalysis is referenced.²¹
Bitter et al (2005)²⁰ examined sexual function at baseline and again 3 and 6 months following the initiation of antipsychotic medication in 570 first-time treated DSM-IV or ICD-10 schizophrenic patients who participated in the IC-SOHO prospective naturalistic observational study. Patients were broken into 3 subgroups for analysis: OLA (n=362), RIS (n=140), or typical antipsychotics (n=68) [haloperidol (n=27), flupentixol (n=7), trifluoperazine (n=8), zuclopenthixol (n=5), perphenazine (n=2), thioridazine (n=5), chlorpromazine (n=3), sulpiride (n=6), pimozide (n=1), levomepromazine (n=1), fluphenazine (n=1), pimozide oxyprothepin (n=1) and perazine (n=1)]. *Mean Baseline Doses: OLA: 9.44 mg/day RIS: 2.98 mg/day 3- and 6-month Mean Dose Increases from Baseline: OLA: 0.78 mg and 0.4 mg, respectively RIS: 0.56 mg and 0.61 mg, respectively Endpoints*: Sexual functioning was examined through patient ratings at baseline and 3 and 6 months plus investigator assessment of antipsychotic-related loss of libido or sexual dysfunction at 3 and 6 months.	*Outcomes: When assessing sexual performance at baseline there was no significant difference between treatment groups. Overrall, 20.2% of patients (n=107/529) reported the inability to perform sexually, while 16.8% (n=89/529) had some problems and 62.9% (n=333/529) reported no problems prior to starting antipsychotic treatment. Patient-related sexual dysfunction (∆ Baseline to 3 months and Baseline to 6 months): OLA: -0.17 (n=268) and -0.29 (n=219), respectively RIS: 0.06 (n=97) and -0.15 (n=71), respectively Typical: 0.05 (n=43) and -0.07 (n=29), respectively Clinician-rated antipsychotic-related loss of libido (3 and 6 months)* *OLA: 28.4%(n=78/275) and 17.8% (n=41/231), respectively RIS: 36.7% (n=36/98) and 35.5% (n=27/76), respectively Typical: 43% (n=18/42) and 38.7% (n=12/31), respectively Clinician-rated antipsychotic-related sexual dysfunction: OLA: 18.7% (n=47/251) and 10.4% (n=22/212), respectively RIS: 28.6% (n=26/91) and 17.6% (n=12/68), respectively Typical*: 28.6% (n=10/35) and 16.7% (n=4/24), respectively
Knegtering et al (2004)²² conducted a 6-week, prospective, randomized, open-label study assessing the effects of RIS (n=26; mean age: 25.2 years; mean dose: 3.2 mg/day) versus QUE (n=25; mean age: 26.5 years; mean dose: 580 mg/day) on sexual dysfunction and serum prolactin levels in 51 patients with schizophrenia or related psychotic disorders. The ASFQ (Antipsychotics and Sexual Functioning Questionnaire), a semistructured interview based upon the items of the UKU, was administered at 6 weeks to assess sexual dysfunction.	*Outcomes*: In response to the ASFQ, 50% (12/24) of RIS patients compared to 16% (4/25) of QUE patients reported sexual dysfunction (libido and/or orgasm; P=0.01). In contrast, sexual dysfunction was only spontaneously reported in 4 RIS patients and 2 QUE patients. Prolactin levels at week 6 were significantly higher in patients receiving RIS compared to patients receiving QUE (57.9±39.7 ng/mL vs. 13.6±17.9 ng/mL, respectively; P=0.000). Severity scores for the group as a whole, in addition to male and female subgroups, showed that patients receiving RIS experienced more serious problems related to sexual dysfunction compared to patients receiving QUE.
Bobes et al (2003)²³ conducted a naturalistic study assessing the frequency of sexual dysfunction and reproductive side effects in 636 DSM-IV outpatients with schizophrenia prescribed RIS, OLA, QUE, or HAL monotherapy for ≥4 weeks. *Mean Age; Mean Dose: RIS: 36.1 years (n=232); 5.3 mg/day (n=234) OLA: 35.7 years (n=228); 13.5 mg/day (n=228) QUE: 32.2 years (n=43); 360.5 mg/day (n=43) HAL: 41.2 years (n=130); 10.6 mg/day (n=131) Concomitant medications included anti-parkinsonian medications, anti- depressants and nonpsychotropes (RIS n=5; OLA n=2). Endpoints*: Sexual and reproductive side effects were assessed via a modified UKU scale. In addition, the causal relationship of side effect to antipsychotic was judged.	*Outcomes: Sexual dysfunction was present in 38.1% of the entire study population. A significantly (P<0.05) lower percentage of patients receiving QUE (18.2%; n=6/33) experienced sexual dysfunction compared to patients receiving HAL (38.1%; n=37/97) or RIS (43.2%; n=76/176). While the percentage of QUE patients suffering from sexual side effects was also lower than patients receiving OLA (35.3%; 59/167), the difference was not significant (P=0.55). Decreased sexual desire was the most common (27.8%) sexual dysfunction for the entire study population (male: 30.8%; women: 23.8%). The frequency of additionally assessed sexual side effects per antipsychotic treatment is found below: Erectile Dysfunction (male); Ejaculatory Dysfunction (male)* HAL: 30.8% (n=20/65); 27.7% (n=18/65) OLA: 26.3% (n=31/118); 20.3% (n=24/118) QUE: 16.7% (n=3/18); 11.1% (n=2/18) RIS: 32.1% (n=42/131); 32.6% (n=42/129) Orgasmic Dysfunction (female); Vaginal Dryness (female) HAL: 9.4% (n=3/32); 8.1% (n=3/37) OLA: 16.4% (n=10/61); 10.8% (n=7/65) QUE: 0%; 0% RIS: 19% (n=11/58); 15% (n=9/60) For RIS and OLA, a higher frequency of sexual and reproductive side effects occurred at higher doses (P<0.05) whereas the frequency of sexual side effects were unrelated to dose for patients receiving QUE.
Berry et al (2001)²⁴ conducted a post-hoc analyses of Conley trial (2001); 8-wk, randomized, double-blind, trial in schizophrenia or schizoaffective disorder (N=377 pts; RIS patients (n=188): mean age 41 years). *Mean modal RIS dose: 4.8 mg/day Mean modal OLA dose*: 12.4 mg/day	*Outcomes*: Endpoint PRL levels did not differ significantly between male patients reporting sexual dysfunction (22.1 ng/mL) and those who did not (24.1 ng/mL).
Kleinberg et al (1999)²⁵ letter to the editor, Denisov (2002)²⁶ follow-up letter to the editor (Davis and Brecher, 2002)²⁷ Retrospective analysis of 4 randomized double-blind trials to determine the relationship between RIS, serum PRL levels and possible clinical implications in patients with schizophrenia. PRL levels available for n=841 (259F:582M) and adverse event data available for n=1884 patients (554F:1330M).	*Males*: Dose-related increases in PRL with both RIS and HAL. PRL levels were significantly higher at RIS doses greater than 6 mg/day than in males receiving HAL. The frequency of ejaculatory and erectile dysfunction between placebo and RIS 1-2 mg/day, 4-6 mg/day, or 8-10 mg/day groups was not significant. The frequency of ejaculatory and erectile dysfunction for RIS 12-16 mg/day versus placebo was significant, though the frequency was similar for RIS versus HAL.

OTHER RELEVANT LITERATURE

Additional citations identified during a literature search are included in the References section for your review.²⁸^-⁴⁰

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 14 January 2025.

References

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