An official website of the United States government
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
CADTH Health Technology Review
Authors; Khai Tran, and Jennifer Horton.
A 2015 survey estimated that about 30% of inmates in federal Canadian prisons received prescriptions for psychotropic medications, compared with about 8% in the general population.1 Psychotropic medications, including antipsychotics and antidepressants, may cause sexual dysfunction (SD) in men and women.2 Sexual dysfunction associated with psychotropic medications in women may include low desire, reduced arousal, and pain, while erectile dysfunction, premature or delayed ejaculation, and low desire are the primary problems in men.3
There are 2 types of antipsychotics, typical and atypical antipsychotic drugs.4 Typical antipsychotics are first generation antipsychotic drugs developed in the 1950s, while second generation antipsychotic drugs developed in the 1990s are atypical antipsychotics.4 Typical antipsychotic drugs bind strongly to dopamine type 2 (D2) receptors, while atypical antipsychotic drugs have lower affinity for dopaminergic receptors.5 Both typical and atypical antipsychotics are associated with impairment of sexual functioning.6,7 However, some drugs may affect sexual function more than others.6,7 A systematic review with meta-analysis showed that quetiapine, ziprasidone, perphenazine, and aripiprazole were associated with frequencies of SD ranging from 16% to 27%, while olanzapine, risperidone, haloperidol, clozapine, and thioridazine were associated with higher frequencies of SD (i.e., 40% to 60%).8
Treatment with different antidepressant classes such as tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors can lead to all types of sexual side effects.9 A meta-analysis on treatment-emergent SD related to antidepressants indicated that fluoxetine, paroxetine, citalopram, venlafaxine, and sertraline were associated with highest frequencies of total SD (70% to 80%).10 The frequencies of SD of mirtazapine, fluvoxamine, escitalopram, duloxetine, phenelzine, and imipramine varied from 25% to 45%.10 Other antidepressant drugs that had frequencies of SD comparable to or lower than placebo were moclobemide, agomelatine, amineptine, nefazodone, and bupropion.10
Most antipsychotics and some antidepressants are associated with elevation of plasma prolactin, termed hyperprolactinemia.11,12 Patients with hyperprolactinemia frequently have SD, osteoporosis, and even breast cancer.11 The secretion of prolactin is regulated by the inhibitory action of the D2 receptors in the hypothalamic infundibular system.12 Therefore, the use of psychotropic medications can lead to a decrease in dopamine and consequently an increase in prolactin, resulting in SD.12 Typical antipsychotics are responsible for hyperprolactinemia, termed prolactin-raising drugs, while atypical antipsychotics are unfrequently or transiently associated with increase in prolactin, termed prolactin-sparing drugs.12 Among antidepressant drugs, some tricyclics (e.g., clomipramine, trimipramine), selective serotonin reuptake inhibitors (e.g., sertraline, fluoxetine), and monoamine oxidase inhibitors (e.g., pargyline, clorgyline) can cause hyperprolactinemia.12 There are several guidelines with recommendations for the assessment and management of antipsychotic-induced hyperprolactinemia.13
Table 1 presents information regarding the frequencies of SD of various drug classes of antipsychotics and antidepressants, distinguishing the effect of the drugs on serum prolactin levels and the degree of prolactin elevation.
Sexual dysfunction caused by psychotropic medications is often overlooked in clinical practice.7,14 Given the frequency of psychotropic medication-induced SD, management of this adverse effect is important to prevent long-term nonadherence.7,15 Several strategies for the treatment of medication-associated SD have been proposed in the literature, include waiting for spontaneous remission, dose reduction, drug holiday (i.e., off medication for 2 to 3 days before sexual activity), nonpharmacologic interventions, switching to another medication, and adding a medication to reverse SD.2,15 However, it is unclear if there are any evidence-based guidelines that provide recommendations for treatment strategies for the management of SD induced by psychotropic medications.
This report aims to summarize the recommendations from evidence-based guidelines regarding the management of SD associated with psychotropic medications.
Frequencies of Sexual Dysfunction Associated with Psychotropic Medications.
What are the evidence-based guidelines regarding the management of sexual dysfunction associated with psychotropic medications?
A limited literature search was conducted by an information specialist on key resources including MEDLINE, Embase, PsycINFO, the Cochrane Database of Systematic Reviews, the International HTA Database, and the websites of Canadian and major international health technology agencies, as well as a focused internet search. The search strategy comprised both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were psychotropics, antidepressants, antipsychotics, and sexual dysfunction. CADTH-developed search filters were applied to limit retrieval to guidelines. Where possible, retrieval was limited to the human population. The search was completed on August 23, 2022, and limited to English-language documents published since January 1, 2012.
One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 2.
Selection Criteria.
Articles were excluded if they did not meet the selection criteria outlined in Table 2, or were published before 2012.
The included publications were critically appraised by 1 reviewer using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument30 for guidelines. Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included publication were described narratively.
A total of 454 citations were identified in the literature search. Following screening of titles and abstracts, 451 citations were excluded and 3 potentially relevant reports from the electronic search were retrieved for full-text review. No potentially relevant publications were retrieved from the grey literature search for full-text review. All 3 potentially relevant articles (i.e., guidelines) met the inclusion criteria and were included in this report. Appendix 1 presents the PRISMA31 flow chart of the study selection.
Additional references of potential interest are provided in Appendix 5.
Additional details regarding the characteristics of included guidelines (Table 3) are provided in Appendix 2.
The 2021 and 2019 guidelines by Montejo et al.7,14 provide clinical recommendations for management strategies of antipsychotic-related SD7 and antidepressant-related SD14 for clinicians prescribing antipsychotics and antidepressants, respectively. Both guidelines7,14 involved literature searches from 2 databases, and the evidence was summarized narratively. The major outcome considered in both guidelines was improvement in SD associated with antipsychotics7 or antidepressants.14 The level of evidence assigned to each recommendation was based on the Scottish Intercollegiate Guidelines Network Grading Review Group. Neither guideline7,14 reported on the process of developing the recommendations or the evaluation and guideline validation.
The 2016 guideline by Galletly et al.32 provides recommendations for the clinical management of schizophrenia and related disorders for all health professionals, including policy-makers, working in Australia and New Zealand. The working group planned the scope, and individual members drafted sections according to their areas of interest and expertise. The working group reviewed the manuscript, and discussion occurred via a series of teleconferences. When there was disagreement, the issue was discussed until consensus was reached. The level of evidence was assigned according to the Australian National Health and Medical Research Council criteria. Recommendations were considered as either evidence-based (when there was sufficient evidence on the topic) or consensus-based (when evidence was weak or lacking).
Both guidelines by Montejo et al.7,14 were conducted by authors from Spain.
The guideline by Galletly et al.32 was conducted by authors from Australia.
The target population in the 2021 guideline by Montejo et al. was patients with psychoses,7 and the target population in the 2019 guideline by Montejo et al. was patients with depression.14
The target population in the guideline by Galletly et al.32 was patients with schizophrenia and related disorders, including schizoaffective disorder, schizotypal disorder, schizophreniform disorder, and acute transient psychotic disorder with symptoms of schizophrenia.
The 2 guidelines by Montejo et al.7,14 provide management strategies for treatment-emergent SD in patients taking antipsychotics7 or antidepressants.14
The interventions and practices considered in the guideline by Galletly et al.32 include treatment and management of ultra-high-risk syndromes, first-episode psychoses, and prolonged psychoses, including psychoses associated with substance use.
The outcome in the 2 guidelines by Montejo et al.7,14 was improvement of SD associated with antipsychotics7 or antidepressants.14
The guideline by Galletly et al.32 considered all clinical outcomes related to early intervention, physical health, psychosocial treatments, cultural considerations, and improving vocation.
Additional details regarding the strengths and limitations of the included guidelines (Table 4) are provided in Appendix 3.
All 3 guidelines7,14,32 were explicit in terms of scope and purpose (i.e., objectives, health questions, and populations), and had clear presentation (i.e., specific, unambiguous, and easy-to-find key recommendations, with options for managing the different conditions or health issues). In terms of stakeholder involvement, the guideline by Galletly et al.32 clearly defined target users, the development groups, and public consultation groups, while both guidelines by Montejo et al.7,14 did not report the guideline development groups and the views and preferences of the target population. In both guidelines by Montejo et al.,7,14 literature was searched from 2 databases, the evidence was summarized narratively, and the level of evidence assigned to each recommendation was based on the Scottish Intercollegiate Guidelines Network Grading Review Group. The guideline by Galletly et al.32 did not report on the evidence collection, selection, and synthesis, but it provided the criteria for rating the levels of evidence for intervention studies. The recommendations in the guideline by Galletly et al.32 were not graded, but they were classified as evidence-based recommendations or consensus-based recommendations, depending on the availability and strength of the evidence. The strengths and limitations of the body of evidence, and methods of formulating the recommendations, were clearly described in the guideline by Galletly et al.,32 but not in both guidelines by Montejo et al.7,14 All 3 guidelines7,14,32 considered health benefits and risks of side effects in formulating the recommendations. None of the included guidelines7,14,32 provided a procedure for updating the guidelines. For applicability, the guideline by Galletly et al.,32 but not the guidelines by Montejo et al.,7,14 was explicit in terms of facilitators and barriers to application, advice and/or tools on how the recommendations can be put into practice, resource implications, and monitoring or auditing criteria. For editorial independence, all 3 guidelines7,14,32 reported competing interests of the authors or guideline development group members. Overall, the 2 guidelines by Montejo et al.7,14 were of low methodological quality, while the guideline by Galletly et al.32 was of moderate methodological quality.
Appendix 4 presents the summary of guideline recommendations (Table 5).
Two guidelines7,32 provided some management strategies for antipsychotic-related SD.
The guideline by Montejo et al.7 recommends switching to aripiprazole (Evidence Level A), or switching to a non-hyperprolactinemic antipsychotic drug such as quetiapine or ziprasidone (Evidence Level B), as the first option for all sexual dimensions including low sexual desire, orgasm retardation, anorgasmia, erectile dysfunction, and poor vaginal lubrication. Alternatively, the guideline7 recommends adding aripiprazole for low sexual desire, orgasm retardation, and anorgasmia (Evidence Level B), adding phosphodiesterase type 5 (PDE-5) inhibitors for erectile dysfunction (Evidence Level B), and using vaginal lubricants for poor vaginal lubrication (Evidence Level B). Other options are switching to olanzapine below 15 mg/day (Evidence Level B) or lowering the dose of the current antipsychotics (Evidence Level C) for all sexual dimensions.
The guideline by Galletly et al.32 recommends adding estrogen or testosterone treatment to the antipsychotic medication to address SD including lowered libido, poor vaginal lubrication, and anorgasmia in women with psychoses (evidence-based recommendation). In addition, although they are not evidence-based recommendations, the guideline32 provides management strategies for the side effects of antipsychotic drugs, including SD associated with hyperprolactinemia, in a table form. The guideline32 suggests that prolactin level should be evaluated, testing should be conducted to exclude pituitary tumour, and medication should be switched to a prolactin-sparing drug if symptoms of sexual and menstrual dysfunction exist.
The guideline by Montejo et al.14 provides some management strategies for antidepressant-related SD. As the first option, the guideline recommends switching to agomelatine (Evidence Level A), switching to non-serotonergic drugs such as bupropion or mirtazapine (Evidence Level B) for all sexual dimensions, or adding bupropion for low sexual desire (Evidence level B). Alternatively, the guideline14 recommends switching to desvenlafaxine (50 mg/day) or vortioxetine (< 15 mg/day) for all sexual dimensions (Evidence Level B). Other options are dose reduction in association with aripiprazole for low sexual desire, dose reduction for orgasm retardation, dose reduction or “weekend holiday” protocol for anorgasmia, adding PDE-5 inhibitors for erectile dysfunction, and dose reduction in addition with using vaginal lubricants for poor vaginal lubrication (Evidence Level C).
The authors of both guidelines by Montejo et al.7,14 recognized that information on the best method of treatment for SD associated with psychotropic medications was scarce. For some strategies, such as waiting for spontaneous SD remission, dosage reduction, and add-on treatment, the evidence is not strong, as there is a lack of controlled studies to support these strategies.
The guideline by Galletly et al.32 has an evidence-based recommendation for the management of SD associated with antipsychotic medication in women with psychoses, but not men. The recommendation only suggests the use of antidotes or adjunctive treatment to improve SD in women, without examining other strategies.
This report identified 2 Spanish guidelines7,14 and 1 Australian guideline32 with low to moderate methodological quality.
For antipsychotic-related SD, the guideline by Montejo et al.7 recommends switching to aripiprazole or another non-hyperprolactinemic antipsychotic as the first option. If this is not possible, the guideline recommends adjunctive treatment with aripiprazole, switching to antipsychotics that have less impact on sexual function, or dose reduction. The guideline by Galletly et al.32 recommends adding estrogen or testosterone treatment to the antipsychotic medication to assist SD in women. This guideline also provides some management strategies for SD associated with hyperprolactinemia induced by antipsychotics.
For antidepressant-related SD, the guideline by Montejo et al.14 recommends switching to agomelatine or to a non-serotonergic drug (e.g., bupropion or mirtazapine) or fluvoxamine as first option. If this is not possible, the guideline recommends switching to a partially non-serotonergic antidepressant (e.g., desvenlafaxine or vortioxetine), adding antidotes such as PDE-5 inhibitors, using vaginal lubricants, or dose reduction.
Given that psychotropic medications can be often associated with SD, a delicate balance between prescribing an effective drug that improves psychotropic symptomatology and minimizing its impact on sexual function is important to improve patients’ quality of life and prevent treatment nonadherence. The identified guidelines provide some strategies for the management of antipsychotic- and antidepressant-related SD, emphasizing switching to drugs that have low impact on SD or using adjunctive treatment. While dose reduction was suggested as an alternative in 2 guidelines,7,14 this approach was neither recommended nor advisable. The recommendations of the included guidelines may be applicable to the Canadian context, provided that the recommended drugs are available and approved for use in Canada. Given the lack of strong evidence, more research is needed to obtain better evidence-based recommendations.
phosphodiesterase type 5
randomized controlled trial
sexual dysfunction
Note that this appendix has not been copy-edited.
Selection of Included Studies.
Characteristics of Included Guidelines.
Note that this appendix has not been copy-edited.
Strengths and Limitations of Guideline Using AGREE II.
Note that this appendix has not been copy-edited.
Summary of Recommendations in Included Guideline.
Note that this appendix has not been copy-edited.
Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.
While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up to date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH.
CADTH is not responsible for any errors, omissions, injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the contents of this document or any of the source materials.
This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners’ own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites.
Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada’s federal, provincial, or territorial governments or any third-party supplier of information.
This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user’s own risk.
This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.
The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors.
About CADTH: CADTH is an independent, not-for-profit organization responsible for providing Canada’s health care decision-makers with objective evidence to help make informed decisions about the optimal use of drugs, medical devices, diagnostics, and procedures in our health care system.
Funding: CADTH receives funding from Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
Questions or requests for information about this report can be directed to Requests@CADTH.ca
Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence (CC BY-NC-ND), a copy of which is available at http://creativecommons.org/licenses/by-nc-nd/4.0/
Your browsing activity is empty.
Activity recording is turned off.
See more...
