Treatment-emergent Sexual Dysfunction Research Articles

Treatment-emergent sexual dysfunctions due to antidepressants: A primer on assessment and management strategies

Antidepressants (ADs) are among the most commonly prescribed drugs worldwide. Persons with mental illness taking ADs commonly report sexual dysfunction (SD) related to treatment. A brief discussion on the neurobiology of sexual functioning and mechanism of treatment-emergent SD (TESD) was performed. The incidence of prevalence of TESD in various studies has been reviewed. TESD impacts patients as it frequently leads to nonadherence, while psychiatrists have challenges in proceeding forward with treatment in such patients. Assessment of patients with suspected TESD is described with a focus on practical tips for clinicians. Five strategies (watchful waiting, drug holiday, downward titration, switching, and add-on therapy) to manage TESD have been extensively discussed with evidence in the literature. Each strategy comes with its own bag of advantages and drawbacks, which have been pointed out for simplicity. A detailed discussion on individual pharmacological strategies is given, and options for non-pharmacological management that can be tried are enlisted. Common clinical case scenarios have been discussed to incorporate the implementation of this literature.

Antidepressant use and treatment-emergent sexual dysfunction among patients with major depressive disorder: Results from an internet-based survey study

BackgroundAntidepressants (ADs) are the mainstay of treatment for patients with major depressive disorder (MDD). Insufficient efficacy of ADs and tolerability issues/side effects, such as treatment-emergent sexual dysfunction (TESD), can lead to treatment discontinuation, symptom persistence, and diminished quality of life. MethodsIn this cross-sectional, internet-based survey, patients with MDD (aged 18–64 years) treated with ADs were categorized as continuers, switchers, or discontinuers based on their current oral AD use and any prior oral AD use in the last 12 months. The Carelon Research Healthcare Integrated Research Database was used as a sampling frame to identify survey-eligible adult patients. The survey fielding was conducted from May 29–October 1, 2020. ResultsOverall, 900 patients completed the survey (554 [62%] continuers, 298 [33%] switchers, and 48 [5%] discontinuers). The 852 patients currently using ADs reported current use of 1178 ADs (mean: 1.4 AD per patient), while the 294 respondents who either switched or discontinued ADs reported using a total of 534 ADs in the past 12 months (mean: 1.8 AD per patient). Provider recommendations, treatment efficacy, and medication side effects played an important role in AD continuation, switching, or discontinuation. Furthermore, 19% of respondents (continuers and switchers) with no history of sexual problems reported sexual problems with use of at least one current or prior AD. LimitationsThe discontinuer cohort was small with few respondents; thus, the between-group statistical comparisons were limited. ConclusionsThese findings highlight the importance of patient-physician shared decision-making for MDD management, including minimization of side effects.

Influence of CYP2C19, CYP2D6, and ABCB1 Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study.

Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, CYP2C19 and CYP2D6, and the transmembrane efflux pump, P-glycoprotein (i.e., ABCB1), on treatment-emergent changes in sexual function (SF) and sexual satisfaction (SS) in the Canadian Biomarker Integration Network in Depression 1 (CAN-BIND-1) sample. A total of 178 adults with MDD received treatment with escitalopram (ESC) from weeks 0-8 (Phase I). At week 8, nonresponders were augmented with aripiprazole (ARI) (i.e., ESC + ARI, n = 91), while responders continued ESC (i.e., ESC-Only, n = 80) from weeks 8-16 (Phase II). SF and SS were evaluated using the sex effects (SexFX) scale at weeks 0, 8, and 16. We assessed the primary outcomes, SF and SS change for weeks 0-8 and 8-16, using repeated measures mixed-effects models. In ESC-Only, CYP2C19 intermediate metabolizer (IM) + poor metabolizers (PMs) showed treatment-related improvements in sexual arousal, a subdomain of SF, from weeks 8-16, relative to CYP2C19 normal metabolizers (NMs) who showed a decline, F(2,54) = 8.00, p < 0.001, q = 0.048. Specifically, CYP2C19 IM + PMs reported less difficulty with having and sustaining vaginal lubrication in females and erection in males, compared to NMs. Furthermore, ESC-Only females with higher concentrations of ESC metabolite, S-desmethylcitalopram (S-DCT), and S-DCT/ESC ratio in serum demonstrated more decline in SF (r = -0.42, p = 0.004, q = 0.034) and SS (r = -0.43, p = 0.003, q = 0.034), respectively, which was not observed in males. ESC-Only females also demonstrated a trend for a correlation between S-DCT and sexual arousal change in the same direction (r = -0.39, p = 0.009, q = 0.052). CYP2C19 metabolizer phenotypes may be influencing changes in sexual arousal related to ESC monotherapy. Thus, preemptive genotyping of CYP2C19 may help to guide selection of treatment that circumvents selective serotonin reuptake inhibitor-related sexual dysfunction thereby improving outcomes for patients. Additionally, further research is warranted to clarify the role of S-DCT in the mechanisms underlying ESC-related changes in SF and SS. This CAN-BIND-1 study was registered on clinicaltrials.gov (Identifier: NCT01655706) on 27 July 2012.

Practical Advice for Primary Care Clinicians on the Safe and Effective Use of Vortioxetine for Patients with Major Depressive Disorder (MDD).

Primary care clinicians have a vital role to play in the diagnosis and management of patients with major depressive disorder (MDD). This includes screening for MDD as well as identifying other possible psychiatric disorders including bipolar disorder and/or other comorbidities. Once MDD is confirmed, partnering with patients in the shared decision-making process while considering different treatment options and best management of MDD over the course of their illness is recommended. Vortioxetine has been approved for the treatment of adults with MDD since 2013, and subsequent US label updates indicate that vortioxetine may be particularly beneficial for specific populations of patients with MDD, including those with treatment-emergent sexual dysfunction and patients experiencing certain cognitive symptoms. Given these recent label updates, this prescribing guide for vortioxetine aims to provide clear and practical guidance for primary care clinicians on the safe and effective use of vortioxetine for the treatment of MDD, including how to identify appropriate patients for treatment.

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

Antipsychotic medication can be often associated with sexual dysfunction (SD). Given its intimate nature, treatment emergent sexual dysfunction (TESD) remains underestimated in clinical practice. However, psychotic patients consider sexual issues as important as first rank psychotic symptoms, and their disenchantment with TESD can lead to important patient distress and treatment drop-out. In this paper, we detail some management strategies for TESD from a clinical perspective, ranging from prevention (carefully choosing an antipsychotic with a low rate of TESD) to possible pharmacological interventions aimed at improving patients’ tolerability when TESD is present. The suggested recommendations include the following: prescribing either aripiprazole or another dopaminergic agonist as a first option antipsychotic or switching to it whenever possible. Whenever this is not possible, adjunctive treatment with aripiprazole seems to also be beneficial for reducing TESD. Some antipsychotics, like olanzapine, quetiapine, or ziprasidone, have less impact on sexual function than others, so they are an optimal second choice. Finally, a variety of useful strategies (such as the addition of sildenafil) are also described where the previous ones cannot be applied, although they may not yield as optimal results.

Development of erectile dysfunction in men treated for major depressive disorder with selective serotonin reuptake inhibitors: a systematic review

Introduction: Sexual dysfunction (SD) is known to be associated with selective serotonin reuptake inhibitors (SSRIs). To determine the effect of different SSRIs on SD development in males, particularly erectile dysfunction (ED), a systematic review was conducted according to PRISMA guidelines.Material and methodsLiterature, in English language, published between January 2009 and September 2019 was searched using two electronic databases, PubMed and EMBASE. Studies were screened according to the predefined inclusion-exclusion criteria. The bibliographies of the included articles were screened to identify any relevant articles.ResultsA total of ten articles were included (8/811 articles searched; two from bibliographies of eight included articles). Treatment-emergent SD, particularly ED was observed in male participants, although the ED incidence was low, less than 2%. SSRIs – fluoxetine, escitalopram, and citalopram – showed a higher risk of ED than other SSRIs.ConclusionsThe findings indicated a positive association between SSRIs and SD. However, evidence supporting a strong link between SSRIs and ED was insufficient.

Setting Up Psychosexual Medicine Unit: Insights From a Private University-Based Medical College Hospital

Introduction: Sexual health issues are highly prevalent but are underdiagnosed and underrecognized in day-to-day clinical practice. The lack of awareness of the specific health care needs of the patients with sexual dysfunctions and resource limitations might be certain reasons why many hospitals are not been equipped with the sexual health care units. There is paucity of specialized psychosexual health care services across the country. Trained interdisciplinary team with prepared environment in sexual medicine is the need of the hour. We started this psychosexual medicine unit with an emphasis on sexual wellness to deliver comprehensive sexual health care which will be a primary care linkage to patients presenting with symptoms of sexual disorders, so also treatment emergent sexual dysfunction in psychiatry and other medical and surgical branches.Aim: To portray the methods, opportunities, and challenges that we experienced in establishing a specialty psychosexual medicine facility as a different unit in a private university-based medical college and hospital in Mysuru, India.Methods: This triweekly psychosexual medicine unit is situated in the Outpatient Division of Psychiatry and is staffed with a multidisciplinary group of health care professionals. Structured survey tools and proforma are utilized to assess all patients. Case conclusions are made according to International Classification of Diseases, Tenth Revision, symptomatic/clinical explanations and diagnostic recommendations, and furthermore Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) when required. Patient care included interventions in the form of psychotherapy and pharmacotherapy.Results: It is possible to set up a functional psychosexual medicine facility as a different unit with a trained interdisciplinary group of professionals. Patient-centered approach is vital in our care plan and management. Postgraduate students and internees posted in psychiatry division have been undertaking rotations respectively as per their duty rota. There is also a robust academic program that includes once-weekly seminars pertaining to topics of psychosexual health and monthly journal club gatherings interchanging with seminars on sexual health and well-being appraisal devices.Conclusion: By investing on improving infrastructure and available human resources, the specialty psychosexual medicine unit was established. The psychosexual medicine unit not only gave chances for a more comprehensive assessment of individuals with sexual disorders but also improved training and education for residents with focused interdisciplinary research in the field of sexual medicine. It portrays a versatile model that can be replicated in settings of similar type.

Structured review of the use of the Arizona sexual experiences scale in clinical settings.

Approximately 40% of women and 30% of men describe sexual dysfunction, although recognition in medical settings is suboptimal, due to problems in reporting and eliciting concerns relating to sexual function and satisfaction. Screening questionnaires may help to support this aspect of clinical practice. The Arizona sexual experiences scale (ASEX) includes items that quantify sex drive, arousal, vaginal lubrication or penile erection, ability to reach orgasm, and satisfaction from orgasm. We investigated the validity and other psychometric properties of the ASEX, and the findings from the populations in which it has been employed, by searching MEDLINE, EMBASE, and Google Scholar using the terms, Arizona sexual experiences scale, Arizona Sexual Experience Questionnaire, and ASEX. We eliminated duplications, letters, and papers not available in English, and grouped the remaining papers into the categories of psychometric, epidemiological, and outcome-based studies. After elimination of letters and duplicates, papers not in English, and preclinical and irrelevant studies, 104 papers were analyzed. The ASEX has excellent internal consistency, scale reliability and strong test-retest reliability. Analyses of variance reveal significant differences in total ASEX scores between patients and controls and between females and males. ASEX appears to be useful in a range of clinical situations including patients with primary sexual dysfunction, specific psychiatric disorders, specific physical illnesses, and treatment emergent sexual dysfunction. The ASEX appears to be a reliable instrument for identifying and quantifying sexual dysfunction across a range of populations in various clinical settings. Little is known about its utility in patients with anxiety disorders or relationships between ASEX scores and biological parameters.

Management Strategies for Antidepressant-Related Sexual Dysfunction: A Clinical Approach.

Major depressive disorder is a serious mental disorder in which treatment with antidepressant medication is often associated with sexual dysfunction (SD). Given its intimate nature, treatment emergent sexual dysfunction (TESD) has a low rate of spontaneous reports by patients, and this side effect therefore remains underestimated in clinical practice and in technical data sheets for antidepressants. Moreover, the issue of TESD is rarely routinely approached by clinicians in daily praxis. TESD is a determinant for tolerability, since this dysfunction often leads to a state of patient distress (or the distress of their partner) in the sexually active population, which is one of the most frequent reasons for lack of adherence and treatment drop-outs in antidepressant use. There is a delicate balance between prescribing an effective drug that improves depressive symptomatology and also has a minimum impact on sexuality. In this paper, we detail some management strategies for TESD from a clinical perspective, ranging from prevention (carefully choosing an antidepressant with a low rate of TESD) to possible pharmacological interventions aimed at improving patients’ tolerability when TESD is present. The suggested recommendations include the following: for low sexual desire, switching to a non-serotoninergic drug, lowering the dose, or associating bupropion or aripiprazole; for unwanted orgasm delayal or anorgasmia, dose reduction, “weekend holiday”, or switching to a non-serotoninergic drug or fluvoxamine; for erectile dysfunction, switching to a non-serotoninergic drug or the addition of an antidote such as phosphodiesterase 5 inhibitors (PD5-I); and for lubrication difficulties, switching to a non-serotoninergic drug, dose reduction, or using vaginal lubricants. A psychoeducational and psychotherapeutic approach should always be considered in cases with poorly tolerated sexual dysfunction.

Not Into Sex: Women’s Experiences of Treatment-Emergent Sexual Dysfunction

Despite recent studies suggesting that treatment-emergent sexual dysfunction (TESD) in women is much more prevalent than previously thought, it is not often discussed between physicians and female patients prior to prescribing psychotropic medication. Missing from the available quantitative research on TESD are stories from the women themselves, their experiences with disclosure or lack thereof, and the impact TESD has had on their sense of self and in their relationships. Concerned that this could have a significant influence on women’s mental, emotional, and sexual health, we conducted a study where we interviewed 10 women who self-identified as experiencing TESD after taking psychotropic medications for their mental health. Semistructured, in-depth interviews were conducted, informed by critical feminist practice, and grounded in feminist standpoint theory. Transcripts were then analyzed using thematic analysis to demonstrate the impact TESD had on the lives of these women. Six themes emerged from the interviews: (1) inadequate disclosure about TESD from physicians, (2) gender-based difference in how TESD is discussed, (3) the experience of physical side effects, (4) emotional responses to side effects, (5) concerns about how the partners of women living with TESD experience it, and (6) the importance of knowledge sharing. We conclude this article with a discussion of how these stories fit within the larger social context.

Paroxetine, but not Vortioxetine, Impairs Sexual Functioning Compared With Placebo in Healthy Adults: A Randomized, Controlled Trial

IntroductionSexual dysfunction is prevalent among patients with depression, but assessment of treatment-emergent sexual dysfunction (TESD), a common side effect of antidepressants, can be confounded by the treatment of depressive symptoms in some patients. AimTo evaluate sexual functioning in healthy volunteers administered vortioxetine compared with paroxetine, an antidepressant known to cause sexual dysfunction, and placebo. MethodsThis phase 4, multicenter, randomized, double-blind, placebo-controlled, 4-arm, fixed-dose, head-to-head study compared sexual functioning in healthy volunteers administered vortioxetine (10 and 20 mg once daily [QD]), paroxetine (20 mg QD), or placebo for 5 weeks. Approximately equal numbers of men and women ages 18–40 years with normal sexual functioning (self-reported Changes in Sexual Functioning Questionnaire Short-Form [CSFQ-14] score > 47 for men; > 41 for women) were enrolled. Two modified full analysis sets adjusting for treatment non-compliance were prespecified. Main Outcome MeasureThe primary endpoint was change in CSFQ-14 total score for vortioxetine (10 and 20 mg) vs paroxetine after 5 weeks. Additional endpoints included CSFQ-14 change scores vs placebo, CSFQ-14 subscales, and patient global impression. ResultsOf the 361 subjects enrolled (mean age, 28.4 years), approximately 57% were white, 34% black/African American, and 4% Asian. Vortioxetine 10 mg was associated with significantly less TESD than paroxetine (mean difference, +2.74 points; P = .009). Although vortioxetine 20 mg was associated with numerically less TESD than paroxetine (mean difference, +1.05 points), this difference did not reach statistical significance. Non-compliance appeared to influence results, particularly the paroxetine and vortioxetine 20 mg arms. Paroxetine, but not vortioxetine, was associated with statistically significantly more TESD vs placebo. Vortioxetine also had better outcomes than paroxetine in the 3 phases and 5 dimensions of sexual functioning measured by CSFQ-14. Clinical ImplicationsThese data establish that vortioxetine is associated with less TESD than paroxetine in healthy individuals, suggesting that vortioxetine may be a drug of choice in managing depressive disorders when sexual functioning is a concern. Strengths & LimitationsConducting the study in healthy adults mitigated the risk of an underlying condition (eg, depression) confounding the results. Assay sensitivity was demonstrated by statistically significant TESD with paroxetine vs placebo. The single comparator, paroxetine, and short study duration limit the generalizability of these results. ConclusionVortioxetine is associated with less TESD than paroxetine in healthy adults across all phases and dimensions of the sexual response cycle. Vortioxetine was not significantly different from placebo on sexual functioning; however, the difference was significant between paroxetine and placebo, validating study results.Jacobsen P, Zhong W, Nomikos G, et al. Paroxetine, but not Vortioxetine, Impairs Sexual Functioning Compared With Placebo in Healthy Adults: A Randomized, Controlled Trial. J Sex Med 2019; 16:1638–1649.

Acute kidney failure in congenital toxoplasmosis: A case report

Sexual dysfunction is common with serotonergic antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), and does not resolve in most patients. Vortioxetine, an antidepressant with a multimodal mechanism of action, has shown low rates of sexual dysfunction in previous major depressive disorder (MDD) trials.This study compared the effects of vortioxetine and escitalopram on sexual functioning in adults with well-treated MDD experiencing treatment-emergent sexual dysfunction (TESD).Participants treated with, and responding to, citalopram, paroxetine, or sertraline were randomized to switch to either vortioxetine (10/20 mg; n = 225) or escitalopram (10/20 mg; n = 222) for 8 weeks. Sexual function was assessed using the Changes in Sexual Functioning Questionnaire Short Form (CSFQ-14), and antidepressant efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI) scale, and Profile of Mood States brief form (POMS-brief). Safety and tolerability were also assessed.The primary endpoint was change from baseline in the CSFQ-14 total score after 8 weeks of treatment. The MADRS, CGI, and POMS-brief were used to assess antidepressant efficacy. Safety was assessed via adverse events, vital signs, electrocardiograms, laboratory values, weight, and physical examination findings.Vortioxetine showed significantly greater improvements in CSFQ-14 total score (8.8 ± 0.64, mean ± standard error) vs. escitalopram (6.6 ± 0.64; P = 0.013). Benefits vs. escitalopram were significant on four of five dimensions and all three phases of sexual functioning assessed by the CSFQ-14 (P < 0.05). Antidepressant efficacy continued in both groups, with similar, but slight, improvements in MADRS and CGI scores. Vortioxetine and escitalopram had similar clinical efficacy profiles in this study, with safety profiles similar to previous trials. Nausea (n = 9, 4.0%) was the most common treatment-emergent adverse event leading to discontinuation of vortioxetine.Switching antidepressant therapy to vortioxetine may be beneficial for patients experiencing sexual dysfunction during antidepressant therapy with SSRIs. Jacobsen PL, Mahableshwarkar AR, Chen Y, Chrones L, and Clayton AH. Effect of vortioxetine vs. escitalopram on sexual functioning in adults with well-treated major depressive disorder experiencing SSRI-induced sexual dysfunction.

The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management.

Sexual dysfunction often accompanies severe psychiatric illness and can be due to both the mental disorder itself and the use of psychotropic treatments. Many sexual symptoms resolve as the mental state improves, but treatment-related sexual adverse events tend to persist over time, and are unfortunately under-recognized by clinicians and scarcely investigated in clinical trials. Treatment-emergent sexual dysfunction adversely affects quality of life and may contribute to reduce treatment adherence. There are important differences between the various compounds in the incidence of adverse sexual effects, associated with differences in mechanisms of action. Antidepressants with a predominantly serotonergic activity, antipsychotics likely to induce hyperprolactinaemia, and mood stabilizers with hormonal effects are often linked to moderate or severe sexual dysfunction, including decreased libido, delayed orgasm, anorgasmia, and sexual arousal difficulties. Severe mental disorders can interfere with sexual function and satisfaction, while patients wish to preserve a previously satisfactory sexual activity. In many patients, a lack of intimate relationships and chronic deterioration in mental and physical health can be accompanied by either a poor sexual life or a more frequent risky sexual behaviour than in the general population. Here we describe the influence of psychosis and antipsychotic medications, of depression and antidepressant drugs, and of bipolar disorder and mood stabilizers on sexual health, and the optimal management of patients with severe psychiatric illness and sexual dysfunction.

Assessment and management of sexual dysfunction in the context of depression.

Sexual dysfunction (SD) is pervasive and underreported, and its effects on quality of life are underestimated. Due in part to its bidirectional relationship with depression, SD can be difficult to diagnose; it is also a common side effect of many antidepressants, leading to treatment noncompliance. While physicians often count on patients to spontaneously report SD, treatment is optimized when the clinician instead performs a thorough assessment of sexual functioning before and during drug therapy using a standardized questionnaire such as the Arizona Sexual Experiences Scale (ASEX). Separating the effects of the disorder from those of medications is challenging; we present a concise, evidence-based schematic to assist physicians in minimizing treatment-emergent sexual dysfunction (TESD) while treating depression. Vascular, hormonal, neurogenic, and pharmacological factors should be considered when a patient presents with SD. We also recommend that physicians obtain patient information about baseline and historical sexual functioning before prescribing a drug that may lead to SD and follow up accordingly. When the goal is to treat depression while attenuating the risk of sexual symptoms, physicians may wish to consider agomelatine, bupropion, desvenlafaxine, moclobemide, trazodone, vilazodone, and vortioxetine.

Comparative evaluation of vortioxetine as a switch therapy in patients with major depressive disorder

Switching antidepressant therapy is a recommended strategy for depressed patients who neither respond to nor tolerate an initial pharmacotherapy course. This paper reviews the efficacy and tolerability of switching to vortioxetine. All three published studies of patients with major depressive disorder (MDD) switched from SSRI/SNRI therapy to vortioxetine due to lack of efficacy or tolerability were selected. Vortioxetine was evaluated versus agomelatine directly (REVIVE) and versus sertraline, venlafaxine, bupropion, and citalopram in an indirect treatment comparison (ITC) from switch studies retrieved in a literature review. Vortioxetine׳s impact on SSRI-induced treatment-emergent sexual dysfunction (TESD) was assessed directly versus escitalopram (NCT01364649) in stable patients with MDD. Vortioxetine׳s tolerability in the switch population was compared to the overall MDD population. Vortioxetine showed significant benefits over agomelatine on efficacy, functioning, and quality-of-life outcomes, with fewer withdrawals due to adverse events (AEs) (REVIVE). Vortioxetine had numerically higher remission rates versus all therapies included (ITC). Withdrawal rates due to AEs were significantly lower for vortioxetine versus sertraline, venlafaxine, and bupropion, and numerically lower versus citalopram. Switching to vortioxetine was statistically superior to escitalopram in improving TESD (NCT01364649). Tolerability was similar in the switch and overall MDD populations. These findings suggest that vortioxetine is an effective switch therapy for patients with MDD whose response to SSRI/SNRI therapy is inadequate. Vortioxetine was well tolerated and, for patients with a history of TESD, showed significant advantages versus escitalopram. Vortioxetine appears to be a valid option for patients with MDD who have not been effectively treated with first-line pharmacotherapies.

Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis

Antidepressants are frequently associated with treatment-emergent sexual dysfunction (TESD). Vortioxetine, which was approved for patients with major depressive disorder (MDD), has a receptor profile that suggests limited impact on sexual functioning. Arizona Sexual Experiences Scale (ASEX) patient-level data were pooled from 7 short-term vortioxetine trials (6 in MDD, 1 in generalized anxiety disorder) and analyzed for incidence of TESD at any post-baseline visit in patients without sexual dysfunction at baseline (defined as ASEX total score ≥19; individual ASEX item score ≥5; or a score ≥4 on any 3 ASEX items). The primary objective was to confirm the non-inferiority of vortioxetine 5-20 mg/day to placebo on the incidence of TESD. Comparisons were based on the common risk difference (95% confidence interval). Additional analyses compared vortioxetine to duloxetine and duloxetine to placebo. A sensitivity analysis, defined as TESD at 2 consecutive post-baseline visits, was conducted. TESD incidence, relative to placebo, generally increased with vortioxetine dose with vortioxetine 5 mg non-inferior to placebo. Vortioxetine 10, 15, and 20 mg did not meet the non-inferiority criterion, but no dose had a significantly higher risk of developing TESD versus placebo. Changes in ASEX individual item scores supported the similarity of vortioxetine doses to placebo. Significantly higher TESD risk occurred with duloxetine 60 mg/day versus placebo and versus vortioxetine 5 or 10 mg. The sensitivity analysis was generally consistent with the primary analysis. Rates of spontaneously reported sexual adverse events were low. Vortioxetine was associated with rates of TESD that were not significantly different from placebo in short-term clinical trials.

Sexual Dysfunction Related to Drugs: a Critical Review. Part V: α-Blocker and 5-ARI Drugs.

Sexual dysfunction is a potential side effect of BPH (benign prostatic hyperplasia) and LUTS (lower urinary tract symptoms) drugs: this article is a critical review of the current literature. Many studies have been published on this topic. Methodological flaws limit the conclusions of these studies, mainly because of the lack of diagnostic criteria for ejaculatory and sexual desire dysfunction. Few of these studies are RCTs. The α-blocker (also called α1-adrenergic antagonist, alpha-adrenoceptor antagonist, alpha-blocker or AB) and 5-ARI (also called 5α-reductase inhibitor or testosterone-5-alpha reductase inhibitor) drugs can in particular cause erectile dysfunction, ejaculatory disorders and reduction of sexual desire. The sexual side effect profile of these drugs is different. Among the α-blockers, silodosin appears have the highest incidence of ejaculatory disorders. Persistent sexual side effects after discontinuation of finasteride has recently been reported, however further studies are needed to clarify the true incidence and the significance of this finding. It is desirable that future studies include validated tools to assess and diagnose sexual dysfunction induced by these medications, especially for ejaculation and sexual desire disorders. Only a small amount of research has intentionally set out to investigate sexual dysfunction caused by α-blocker and 5-ARI drugs: studies to specifically assess sexual dysfunction induced by these drugs are needed. Further studies are also needed to assess in the long term the role of combined therapy of phosphodiesterase type 5 inhibitors and α-blockers or 5-ARIs in treating LUTS/BPH. This study was conducted in 2014 using the paper and electronic resources of the library of the "Azienda Provinciale per i Servizi Sanitari (APSS)" in Trento, Italy (http://atoz.ebsco.com/Titles/2793). The library has access to a wide range of databases including DYNAMED, MEDLINE Full Text, CINAHL Plus Full Text, The Cochrane Library, Micromedex healthcare series, BMJ Clinical Evidence. The full list of available journals can be viewed at http://atoz.ebsco.com/Titles/2793, or at the APSS web site (http://www.apss.tn.it). In completing this review, a literature search was conducted using the key words "benign prostatic hyperplasia drugs", "lower urinary tract symptoms drugs", "α-blockers", "5-ARIs", "sexual dysfunction", "sexual side effects", "treatment-emergent sexual dysfunction", "phosphodiesterase type 5 (PDE5) inhibitors". All resulting listed articles were reviewed. Studies published between 2002 and December 2014 were included in the review. We included all studies that explicitly reported data on sexual dysfunction during treatment with α-blockers and 5-ARIs. We also reviewed studies that have evaluated the use of phosphodiesterase type 5 (PDE5) inhibitors in combination with these drugs. The purpose was to identify possible intervention strategies for sexual dysfunction related to these drugs.

Time-to-onset and -resolution of adverse events before/after atomoxetine discontinuation in adult patients with ADHD

Background. Adults with attention-deficit/hyperactivity disorder treated with atomoxetine were examined for time-to-onset and -resolution of common treatment-emergent adverse events (TEAEs) and male sexual dysfunction, and for changes in blood pressure (BP) and heart rate (HR) upon atomoxetine discontinuation. Methods. 12-week open-label atomoxetine (40–100 mg/day) was followed by 12-week double-blind maintenance treatment (atomoxetine 80 or 100 mg/day). Responders were then randomized to atomoxetine (n = 266) or placebo (n = 258) for 25-week randomized withdrawal. Examined were (1) median time-to-onset and -resolution of TEAEs during atomoxetine treatment, and (2) within group, visitwise mean changes for sitting HR, systolic BP, and diastolic BP for the postrandomization placebo group. Results. Common adverse events (AEs) appeared early, within week 1 of atomoxetine treatment. Some AEs resolve relatively rapidly, whereas others have a more lingering course of resolution (including male sexual side effects); median resolution times were 3 – 53 days. BP and HR increases during atomoxetine treatment returned to baseline upon atomoxetine discontinuation. Conclusion. Atomoxetine is associated with common AEs, with 3- to 53-day median resolution times. Trial registration: ClincialTrials.gov – NCT00700427.

Vortioxetine in the treatment of major depressive disorder

ABSTRACT Vortioxetine is a novel psychotropic drug, with evidence of efficacy in acute treatment of major depressive episodes and in prevention of relapse in major depressive disorder. It has been described as having a ‘multimodal’ serotonergic mechanism of action, involving reuptake inhibition and a range of effects on presynaptic and postsynaptic receptors. It also has important effects on other neurotransmitters thought to be important in the neurobiology of depression and response to antidepressant treatment. It is efficacious in reducing anxiety symptom severity in depressed patients. The tolerability profile of vortioxetine appears predictable from its pharmacological properties. It may have beneficial effects in improving ‘cognition’ in depression, and a lower incidence of treatment-emergent sexual dysfunction, but these potential benefits require further investigation.

Lithium and sexual dysfunction: an under-researched area.

Lithium treatment remains an important part of the management of many patients with bipolar disorder, but the incidence of treatment-emergent sexual dysfunction with lithium is uncertain, and little is known about how it might be managed. Systematic computerised literature search of preclinical and clinical studies. Thirteen relevant papers were identified. Preclinical studies suggest lithium can reduce testosterone levels and impair nitric oxide mediated relaxation of cavernosal tissue. Clinical reports suggest lithium may reduce sexual thoughts and desire, worsen erectile function and reduce sexual satisfaction. Concomitant benzodiazepine prescription with lithium is associated with an increased risk of sexual dysfunction. Sexual dysfunction during lithium treatment appears significantly associated with a lower level of overall functioning and may reduce compliance. The findings of this systematic review reveal the paucity of information about the incidence, associated factors and management of sexual dysfunction with lithium treatment and highlight the need for well-designed studies in this area.