Switching antipsychotic medication to reduce sexual dysfunction in people with psychosis: the REMEDY RCT

Abstract

Background Sexual dysfunction is common among people who are prescribed antipsychotic medication for psychosis. Sexual dysfunction can impair quality of life and reduce treatment adherence. Switching antipsychotic medication may help, but the clinical effectiveness and cost-effectiveness of this approach is unclear. Objective To examine whether or not switching antipsychotic medication provides a clinically effective and cost-effective method to reduce sexual dysfunction in people with psychosis. Design A two-arm, researcher-blind, pilot randomised trial with a parallel qualitative study and an internal pilot phase. Study participants were randomised to enhanced standard care plus a switch of antipsychotic medication or enhanced standard care alone in a 1 : 1 ratio. Randomisation was via an independent and remote web-based service using dynamic adaptive allocation, stratified by age, gender, Trust and relationship status. Setting NHS secondary care mental health services in England. Participants Potential participants had to be aged ≥ 18 years, have schizophrenia or related psychoses and experience sexual dysfunction associated with the use of antipsychotic medication. We recruited only people for whom reduction in medication dosage was ineffective or inappropriate. We excluded those who were acutely unwell, had had a change in antipsychotic medication in the last 6 weeks, were currently prescribed clozapine or whose sexual dysfunction was believed to be due to a coexisting physical or mental disorder. Interventions Switching to an equivalent dose of one of three antipsychotic medications that are considered to have a relatively low propensity for sexual side effects (i.e. quetiapine, aripiprazole or olanzapine). All participants were offered brief psychoeducation and support to discuss their sexual health and functioning. Main outcome measures The primary outcome was patient-reported sexual dysfunction, measured using the Arizona Sexual Experience Scale. Secondary outcomes were researcher-rated sexual functioning, mental health, side effects of medication, health-related quality of life and service utilisation. Outcomes were assessed 3 and 6 months after randomisation. Qualitative data were collected from a purposive sample of patients and clinicians to explore barriers to recruitment. Sample size Allowing for a 20% loss to follow-up, we needed to recruit 216 participants to have 90% power to detect a 3-point difference in total Arizona Sexual Experience Scale score (standard deviation 6.0 points) using a 0.05 significance level. Results The internal pilot was discontinued after 12 months because of low recruitment. Ninety-eight patients were referred to the study between 1 July 2018 and 30 June 2019, of whom 10 were randomised. Eight (80%) participants were followed up 3 months later. Barriers to referral and recruitment included staff apprehensions about discussing side effects, reluctance among patients to switch medication and reticence of both staff and patients to talk about sex. Limitations Insufficient numbers of participants were recruited to examine the study hypotheses. Conclusions It may not be possible to conduct a successful randomised trial of switching antipsychotic medication for sexual functioning in people with psychosis in the NHS at this time. Future work Research examining the acceptability and effectiveness of adjuvant phosphodiesterase inhibitors should be considered. Trial registration Current Controlled Trials ISRCTN12307891. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 44. See the NIHR Journals Library website for further project information.

Second-Generation Antipsychotics’ Effectiveness and Tolerability: A Review of Real-World Studies in Patients with Schizophrenia and Related Disorders

“…Therefore, a key component of the long-term management of schizophrenia and related disorders is to select an appropriate antipsychotic treatment for the needs of each individual [ 37 , 38 ]. The efficacy and tolerability of antipsychotic treatment might profoundly affect adherence to therapy and clinical response, with the risk of relapses [ 39 , 40 ].…”

“…Adverse effects are also a frequent cause for discontinued treatment, besides lack of insight, disease severity, and treatment characteristics. In addition, adverse effects may impact environmental factors such as patient’s erroneous belief in the effectiveness of medication, and substance abuse [ 39 ]. For this reason, there is a need for new treatments with improved tolerability and efficacy for negative, affective, and cognitive symptoms.…”

Barriers to the management of sexual dysfunction among people with psychosis: analysis of qualitative data from the REMEDY trial

“…To improve the evidence base on the management of sexual dysfunction associated with the use of antipsychotic medication, the National Institute for Health Research (NIHR) in England, commissioned the REM-EDY trial (Randomised Evaluation of Management of sExual DYsfunction) [22]. The main aim of the trial was to try to find out if switching to an alternative antipsychotic with a lower potential of impacting on sexual functioning, provides a safe and effective strategy for improving sexual functioning among people with psychosis.…”

“…The REM-EDY trial included plans for a nested process evaluation designed to examine the implementation of the trial and the impact of context on study outcomes [23]. However, as the study progressed, we realised how challenging recruitment was and changed the focus of the qualitative component of the study instead to examine barriers to recruitment to the study [22].…”

Management Strategies for Antipsychotic-Related Sexual Dysfunction: A Clinical Approach

“…Most authors agree on aripiprazole as the best option in this case [ 1 , 89 , 119 , 134 , 150 , 157 ], as several studies have proven that it improves SD rates across all sexual dimensions (desire, arousal, and orgasm) and decreases prolactin when switching from previous antipsychotics such as typical ones [ 158 , 159 ], risperidone [ 88 , 154 , 158 , 159 , 160 , 161 ], paliperidone [ 106 ], amisulpride [ 158 , 159 , 160 ], quetiapine [ 159 ], olanzapine [ 158 , 159 ], and clozapine [ 159 ]. The only study assessing the issue of TESD in long-acting intramuscular presentations [ 106 ] corroborates this recommendation when comparing aripiprazole to paliperidone palmitate.…”