Selective Serotonin Reuptake Inhibitor Monotherapy Research Articles

What Is the Added Benefit of Combining Cognitive Behavioral Therapy and Selective Serotonin Reuptake Inhibitors in Youth with Obsessive Compulsive Disorder? A Bayesian Hierarchical Modeling Meta-Analysis.

Background: Treatment of obsessive-compulsive disorder (OCD) in children and adolescents frequently involves cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), or their combination. However, how adding CBT to SSRIs affects the trajectory and magnitude of improvement has not been evaluated meta-analytically. Methods: We performed a meta-analysis using weekly data from prospective randomized parallel group trials of CBT and SSRIs in pediatric patients with OCD. Response was modeled for the change in the Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) using a Bayesian hierarchical model over 12 weeks. Results: Fourteen studies included pharmacotherapy arms, 4 studies included combined pharmacotherapy and psychotherapy, and 10 studies included a placebo or control arm. The studies included 1146 patients (mean age 12.7 ± 1.3 years, mean 42.1% female). In the logarithmic model of response, statistically significant differences in treatment effects for CBT+SSRI and SSRI monotherapy were observed compared with placebo (SSRI β = -3.59, credible interval [95% CrI]: -4.13 to -3.02, p < 0.001; SSRI+CBT β = -4.07, 95% CrI: -5.05 to -3.04, p < 0.001). Adding CBT to an SSRI produced numerically (but not statistically significantly) greater improvement over 12 weeks. Greater improvement was observed in studies with more boys (p < 0.001), younger patients (p < 0.001), and in studies with greater baseline symptom severity (p < 0.001). Conclusions: In children and adolescents with OCD, compared with placebo, both SSRIs and SSRI+CBT produced early and sustained improvement over 12 weeks, although the improvement was also related to sample characteristics. Longer term studies are needed to determine when the additive benefit of CBT emerges relative to SSRI monotherapy.

Head-To-Head Comparison of Vortioxetine Versus Desvenlafaxine in Patients With Major Depressive Disorder With Partial Response to SSRI Therapy: Results of the VIVRE Study.

Objective: To compare the efficacy of vortioxetine and the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine in patients with major depressive disorder (MDD) experiencing partial response to initial treatment with a selective serotonin reuptake inhibitor (SSRI).Methods: This randomized, double-blind, active-controlled, parallel-group, 8-week study of vortioxetine (10 or 20 mg/d; n = 309) versus desvenlafaxine (50 mg/d: n = 293) was conducted from June 2020 to February 2022 in adults with a DSM-5 diagnosis of MDD who experienced partial response to SSRI monotherapy. The primary endpoint was mean change from baseline to week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Differences between groups were analyzed using mixed models for repeated measures.Results: Non-inferiority of vortioxetine versus desvenlafaxine was established in terms of mean change from baseline to week 8 in MADRS total score; however, a numeric advantage was observed in favor of vortioxetine (difference, -0.47 MADRS points [95% CI, -1.61 to 0.67]; P = .420). At week 8, significantly more vortioxetine-treated than desvenlafaxine-treated patients had achieved symptomatic and functional remission (ie, Clinical Global Impressions-Severity of Illness scale [CGI-S] score ≤ 2) (32.5% vs 24.8%, respectively; odds ratio = 1.48 [95% CI, 1.03 to 2.15]; P = .034). Vortioxetine-treated patients also experienced significantly greater improvements in daily and social functioning assessed by the Functioning Assessment Short Test (P = .009 and .045 vs desvenlafaxine, respectively) and reported significantly greater satisfaction with their medication assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire (P = .044). Treatment-emergent adverse events (TEAEs) were reported in 46.1% and 39.6% of patients in the vortioxetine and desvenlafaxine groups, respectively; these were mostly mild or moderate in intensity (> 98% of all TEAEs in each group).Conclusions: Compared with the SNRI desvenlafaxine, vortioxetine was associated with significantly higher rates of CGI-S remission, better daily and social functioning, and greater treatment satisfaction in patients with MDD and partial response to SSRIs. These findings support the use of vortioxetine before SNRIs in the treatment algorithm in patients with MDD.Trial Registration: ClinicalTrials.gov Identifier: NCT04448431.

Phosphodiesterase inhibitor and selective serotonin reuptake inhibitor combination therapy versus monotherapy for the treatment of major depressive disorder: a systematic review and meta-analysis.

Selective serotonin reuptakeinhibitors (SSRIs) are the gold standard treatment for major depressive disorder (MDD). However, the use of phosphodiesterase (PDE) inhibitors in the treatment of MDD remains unclear. Our study aims to compare the effect of PDE inhibitor combination therapy to SSRI monotherapy for the treatment of MDD. We performed a comprehensive literature search using PubMed, EMBASE, and Web of Science databases, for studies that assess the impact of PDE inhibitor therapy on MDD patients. The primary outcome of our study was treatment response rate at the end of study time. Pooled odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. A P -value <0.05 was considered statistically significant. A total of four randomized control trials (RCTs), including 270 patients with MDD, were included in the analysis. Follow-up periods ranged from 6 to 12 weeks. The PDE inhibitor group was associated with a significantly higher treatment response rate (OR, 4.77; 95% CI, 2.05-11.12; P = 0.0003). Our meta-analysis demonstrated that MDD patients receiving PDE inhibitor combination therapy had a higher treatment response rate than MDD patients receiving SSRI monotherapy. Further large-scale RCTs with long-term follow-ups are necessary to validate our findings.

Dose-response effects of selective serotonin reuptake inhibitor monotherapy for the treatment of depression: systematic review of reviews and meta-narrative synthesis

ObjectiveTo assess and clarify the relations between selective serotonin reuptake inhibitor (SSRI) dose efficacy, acceptability (early treatment discontinuation (dropouts)), and tolerability (reported adverse drug effects), and critically evaluate methods previously...

Selective serotonin reuptake inhibitors combined with traditional Chinese medicine for premature ejaculation: A systematic review and meta-analysis.

Premature ejaculation (PE) is still a tough problem in drug treatment. Many clinical trials have proven that traditional Chinese medicine (TCM) has a significant effect in the treatment of PE. This article aims to provide the latest evidence for the efficacy and safety of TCM combined with selective serotonin reuptake inhibitors (SSRIs) in the treatment of PE. We looked for randomized controlled trials (RCTs) from China National Knowledge Infrastructure, Wanfang, VIP Database, MEDLINE, PubMed, Web of Science, EMBASE, and Cochrane Library until June 30, 2022. STATA 15.1 software was used to analyze all data for this article. The quality of the included articles was evaluated using the Cochrane Reviewer's Handbook 5.3. Finally, we selected 16 high-quality RCTs in our meta-analysis, which containing 889 patients. Meta-analysis suggested that, compared with SSRIs alone, combination of TCM with SSRIs increased significantly intravaginal ejaculation latencv time and the scores of ejaculation control ability, sexual life satisfaction, PE-related distress, and communication difficulties between partners related to PE. Also, there was no significant difference in adverse effects between the two groups. In addition, the results of publication bias test showed that no significant bias occurred. The combined use of TCM and SSRIs has significant effect in the treatment of PE compared with SSRIs monotherapy and was generally well tolerated. Due to the small sample size, multicenter and large sample RCT is still needed in the future to further confirm the effectiveness and safety of TCM combined with SSRIs in the treatment of PE.

Sexual Dysfunction in Remitted Female Patients with Depression on SSRIs: Associated Factors and Relation to Marital Satisfaction and Quality of Life.

Background:Sexual dysfunction, a potential side effect of selective serotonin reuptake inhibitors (SSRIs), can lead to marital dissatisfaction in remitted depression patients, affecting their quality of life (QOL), and all of these are risk factors for treatment noncompliance. We aimed to estimate the proportion of female sexual dysfunction and its subtypes compared to the general population and correlate it with various factors, including marital satisfaction and QOL, in remitted depressive patients on SSRI treatment.Methods:This analytical cross-sectional study assessed 116 women, comprising 58 patients aged 18– to 45 years with rsemitted depression on SSRI monotherapy for a minimum of six weeks and their age-matched comparative group. Hamilton Depression Rating Scale was used to assess depression severity and Female Sexual Functional Index, to assess sexual dysfunction. Couple Satisfaction Index and WHOQOL-BREF version were used to assess marital satisfaction and QOL, respectively.Results:In total, 56.89% of the patients had sexual dysfunction, compared to 39.65% in the general population. Exploratory analyses revealed that overall sexual functioning had a significant positive correlation with education (P = .002), marital satisfaction (P < .001), and QOL (P < .01), and a significant negative correlation with the age of onset of depression (P = .004), total marital duration (P = .02), and duration of current treatment (P = .02).Conclusion:Sexual dysfunction is common in remitted female depression patients on SSRI treatment, which may further impair their marital satisfaction and QOL. Hence, routine screening for sexual dysfunction is necessary for them.

Combining selective serotonin reuptake inhibitors and cognitive behavioral therapy in youth with depression and anxiety

BackgroundTreatment studies of children and adolescents with internalizing disorders suggest that the combination of a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy (CBT) consistently produces greater improvement than either treatment alone. We sought to determine how response to combined treatment varies across disorders (anxiety versus depression), and by specific patient characteristics. MethodsThree large National Institutes of Health-funded trials of children and adolescents with major depression (n = 2) and anxiety disorders (n = 1) were evaluated, each comparing CBT + SSRI to SSRI only, Bayesian Hierarchical Models (BHMs) were used, for endpoint response, time course of response and predictors of response in participants who received SSRI or SSRI+CBT. ResultsSSRI+CBT significantly decreased symptoms by week 4 (p<0.001) across disorders. This improvement continued at week 8 and 12 (p<0.001); however, the additive benefit of CBT over SSRI monotherapy was not statistically significant until week 12 (p<0.001). The fastest response to SSRI+CBT was for patients who were younger, with milder baseline anxiety/depression symptoms and depressive disorders. The slowest response for SSRI+CBT was for boys, adolescents, minoritized children, those with severe symptoms and externalizing disorders. LimitationsLimitations included inconsistent moderators, variation in the number of observations over time and a lack of genetic or pharmacokinetic variables related to SSRI exposure across studies. ConclusionsThe superiority of SSRI+CBT for youth with depression and anxiety is further supported. For purposes of rapid and greater relief, combination treatment is the superior approach across anxiety and depression and is robust to a range of participant characteristics. However, the added value of CBT (with an SSRI) occurs late in treatment. These findings represent a step towards understanding heterogeneity of treatment response and raise the possibility that interventions could be better tailored or adapted based on patient characteristics.

Simultaneous Benzodiazepine and SSRI Initiation in Young People With Anxiety Disorders.

Objective: There are potential risks and benefits of combining benzodiazepine (BZD) and selective serotonin reuptake inhibitor (SSRI) therapy at anxiety disorder treatment onset. We investigated how often adolescents and young adults with anxiety disorders simultaneously initiate BZD treatment with SSRI treatment and examined whether SSRI treatment duration varies by simultaneous BZD initiation.Methods: In a United States commercial claims database (January 2008-December 2016), we identified adolescents (10-17 years) and young adults (18-24 years) with ICD-9-CM/ICD-10-CM anxiety disorder diagnoses initiating SSRI treatment, without past-year SSRI and BZD treatment. We defined simultaneous initiation as filling a new BZD prescription on the date of SSRI initiation. We estimated time to SSRI treatment discontinuation and used stabilized inverse probability of treatment weighting for adjusted estimates.Results: The study included 94,399 adolescents and 130,971 young adults initiating SSRI treatment with an anxiety disorder. Four percent of adolescents and 17% of young adults simultaneously initiated BZD treatment, varying by age, anxiety disorder, comorbidities, health care utilization, and provider type. Simultaneous BZD initiation among SSRI initiators declined from 2008 to 2016. SSRI treatment duration was similar in initiators of simultaneous therapy vs SSRI monotherapy: ≥ 6 months in adolescents (55% vs 56%, respectively) and in young adults (39% vs 40%). Nine percent of simultaneous initiators continued BZDs for ≥ 6 months.Conclusions: Simultaneous initiation of BZD and SSRI treatment is relatively common in young adults with anxiety disorders and was not associated with longer SSRI persistence. Given risks of BZD treatment, potential benefits and risks of adding a BZD at SSRI treatment initiation must be carefully weighed.

Personality, symptom, and demographic correlates of perceived efficacy of selective serotonin reuptake inhibitor monotherapy among current users with low mood: A data-driven approach

BackgroundSelective serotonin reuptake inhibitors (SSRIs) are often the first-line treatment option for depressive symptoms, however their efficacy varies across patients. Identifying predictors of response to SSRIs could facilitate personalised treatment of depression and improve treatment outcomes. The aim of this study was to develop a data-driven formulation of demographic, personality, and symptom-level factors associated with subjective response to SSRI treatment. MethodsParticipants were recruited online and data were collected retrospectively through an extensive digital mental health questionnaire. Extreme gradient boosting classification with nested cross-validation was used to identify factors distinguishing between individuals with low (n=37) and high (n=111) perceived benefit from SSRI treatment. ResultsThe algorithm demonstrated a good predictive performance (test AUC=.88±.07). Positive affectivity was the strongest predictor of response to SSRIs and a major confounder of the remaining associations. After controlling for positive affectivity, as well as current wellbeing, severity of current depressive symptoms, and multicollinearity, only low positive affectivity, chronic pain, sleep problems, and unemployment remained significantly associated with diminished subjective response to SSRIs. LimitationsThis was an exploratory analysis of data collected at a single time point, for a study which had a different primary aim. Therefore, the results may not reflect causal relationships, and require validation in future prospective studies. Furthermore, the data were self-reported by internet users, which could affect integrity of the dataset and limit generalisability of the results. ConclusionsOur findings suggest that demographic, personality, and symptom data may offer a potential cost-effective and efficient framework for SSRI treatment outcome prediction.

Side Effect Profiles of Selective Serotonin Reuptake Inhibitors: A Cross-Sectional Study in a Naturalistic Setting.

Background: Side effects of selective serotonin reuptake inhibitors (SSRIs), the most commonly used antidepressants, are usually underreported in clinical trials. Systematic evaluation of side effects associated with SSRIs with structured instruments in a naturalistic setting is an important design to fully understand the side effect profile of various SSRIs. We examined the frequencies of the side effects induced by 3 commonly used SSRIs, sertraline, escitalopram, and fluoxetine, by using a self-rating instrument designed to measure the subjective symptoms of patients in a naturalistic treatment setting.Methods: The subjects were outpatients recruited from the psychiatry department of a tertiary care hospital. The subjects were aged ≥ 18 years; were diagnosed with depression, anxiety spectrum disorders, adjustment disorder, hypochondriasis, or impulse control disorder according to ICD-10 criteria; and were on SSRI monotherapy. The assessment instrument included 42 items and was devised using drug package insert data on the most commonly observed side effects of antidepressants released by the US Food and Drug Administration.Results: A total of 100 patients participated in the study. Among them, 70% were women. The most common diagnosis was depression (49%). Of the patients, 53% were taking sertraline, 38% escitalopram, and 8% fluoxetine. The common side effects reported by patients were flatulence (64%), somnolence (59%), memory impairment (51%), decreased concentration (50%), yawning (47%), fatigue (45%), dry mouth (45%), weight gain (45%), light headedness (43%), and sweating (38%). Patients treated with escitalopram had significantly higher incidence of headache, pruritus, memory impairment, decreased concentration, and dizziness. Patients treated with sertraline had significantly decreased appetite.Conclusions: The study results highlight the prevalence and pattern of side effect profiles of 3 commonly used SSRIs and provide baseline data for comparison with other similar studies.

Pharmacological management of tourette's syndrome comorbid with obsessive-compulsive disorder in adult patients

AimsTourette's Syndrome (TS) is a neurodevelopmental disorder, which often presents in childhood and is hallmarked by motor and vocal tics. Obsessive-Compulsive Disorder (OCD) is a chronic neuropsychiatric condition characterised by intrusive thoughts and time-consuming repetitive behaviours. Research suggests that 15-20% of adult patients with TS will also meet the diagnostic criteria for OCD. Both illnesses appear to have neurobiological similarities but a differing course and clinical response to pharmacological treatments.Despite this, research into optimal management of adults with co-occurring TS or other tic disorders and OCD remains sparse. Comorbidities, are known to be poor predictor of response to selective serotonin reuptake inhibitors (SSRI) monotherapy in OCD and are often associated with treatment-refractory OCD. Similarly SSRI monotherapy in patients with OCD and comorbid TS can sometimes worsen motor tics (1 in 2000) and fail to improve OCD symptoms. In this review, we aim to evaluate evidence on the management of patients with co-occurring TS and OCD and address an important knowledge gap in clinical practice.MethodThis review was conducted in accordance with PRISMA Guidelines. We performed a search using PubMed, Cochrane Library and PsychINFO using the following Boolean Input “Tourettic-OCD” OR “tic-related OCD” OR ((OCD OR “obsessive-compulsive” OR “obsessive compulsive”) AND (Tourette OR “Tourette's” OR Tourettes OR tic))”. The search was conducted until January 2020. We then screened the articles of systematic reviews to extract additional studies from their reference lists.Result1888 studies were identified, of which 15 clinical trials were included in our systematic review. The presence of tics in patients with OCD are a major predictor for treatment-refractory OCD and a lack of improvement following monotherapy with SSRIs. Dual therapy with an SSRI and antipsychotics (particularly risperidone) are associated with improved outcomes in OCD patients with tics and TS patients with obsessive-compulsive symptoms. However, conjoint therapy with neuroleptics and SSRIs was only investigated when OCD burden was unsatisfactory following SSRI monotherapy.ConclusionThere are clinical implications when a patient with OCD also has a chronic tic disorder. The findings indicate the need for further research, particularly in the form of a larger cohort in randomised controlled trials, to determine when it is best to initiate patients with OCD and comorbid tic disorders on a dual antipsychotic-SSRI management strategy. Further evidence should also be done to determine other characteristics that predict an improvement to conjoint SSRI/neuroleptic therapy for effective symptom reduction.

Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy

Intranasal treatment with oxytocin showed beneficial effects in post-traumatic stress disorder and autism spectrum disorders; however, it was not investigated as much in depression. Keeping in mind the favorable effects of oxytocin on animal models of anxiety and depression, we postulated that synergy between prescribed first choice drugs, selective serotonin reuptake inhibitors (SSRIs) and oxytocin could improve the treatment outcome compared with SSRI monotherapy. Our previous in vitro genome-wide transcriptomic study on human lymphoblastoid cell lines exposed to paroxetine resulted in increase of integrin β3 (ITGB3) gene expression, and further, ITGB3/CHL1 expression ratio was hypothesized to influence the sensitivity to SSRIs. The aim of this report was to explore molecular mechanisms behind the antidepressant-like oxytocin effect, alone and in synergy with citalopram, on behavioral and molecular level in corticosterone treated rats, a paradigm used to model anxiety and depression in animals. Oxytocin treatment (1) ameliorated corticosterone-induced reduction of neurogenesis and number of parvalbumin-positive interneurons in the hippocampal CA1 region, (2) enhanced anxiolytic- and antidepressant-like effects of citalopram in the open field test, and (3) the SSRI/oxytocin synergy persisted in reversing the reduction of the Itgb3 gene expression and increased Itgb3/Chl1 ratio in the prefrontal cortices. These results support the existence of synergy between citalopram and oxytocin in reversing the molecular and behavioral changes induced by corticosterone treatment and point to possible molecular mechanisms behind antidepressant-like effect of oxytocin.

Combined Use of Aspirin and Selective Serotonin Reuptake Inhibitors Is Associated With Lower Risk of Colorectal Cancer: A Nested Case-Control Study.

Chemoprevention against colorectal cancer (CRC) is greatly needed. As the development of CRC involves multiple dysfunctional pathways, it is thus reasonable to combine some agents that address several pathways to achieve better chemoprotection. We aimed to explore whether the use of aspirin and selective serotonin reuptake inhibitors (SSRIs)-either as monotherapy or combined-can have a clinical benefit against CRC. We performed a nested case-control study using nationwide Swedish registers. We recruited 24,786 CRC cases and randomly matched to 74,358 controls conditional on birth year and sex using incidence-density sampling. The conditional logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, and multiplicative interaction was calculated by including a product term in the regression model. Both aspirin and SSRIs monotherapy were negatively associated with CRC risk, but the combined use of aspirin and SSRIs was associated with an even lower CRC risk (adjusted OR, 0.77, 95% CI, 0.67-0.89) than aspirin monotherapy (adjusted OR, 0.91, 95% CI, 0.87-0.97) or SSRI monotherapy (adjusted OR, 0.93, 95% CI, 0.86-1.00). A significant interaction was observed at the additive scale with a relative excess risk for interaction of -0.07 (P < 0.001), whereas no interaction was noted on the interactive scale. The inverse associations of CRC with aspirin and SSRIs showed a dose-dependent pattern. This study suggests that the use of aspirin and SSRIs-either as monotherapy or combined-was associated with a reduced risk of CRC. The stronger chemoprevention of combined use of aspirin and SSRIs is innovative and calls for further studies to confirm the underlying mechanisms and the plausibility of clinical recommendation.

Major Depresif Bozukluk Tanılı 350 Ergen Olgunun Klinik Özellikleri, Hastalık Şiddeti ve Tedavi Seçeneklerinin Değerlendirilmesi: Retrospektif Kesitsel Bir Çalışma

Objective: Major Depressive Disorder (MDD) is an important mental health disorder that is common in adolescence. In our study, it was aimed to evaluate depression severity, treatment methods and clinical features of adolescents who were followed up and treated with MDD diagnosis. Methods: Between January and December 2015, 350 adolescent patients between 12-18 years of age who consulted with child and adolescent psychiatry clinic and diagnosed by unipolar MDD according to DSM-5 was reviewed. The sociodemographic and clinical features of these cases were evaluated. SPSS 17.0 was used for statistical evaluation. Results: MDD was diagnosed in 350 (7.5%) of 4,646 adolescents who applied to the outpatient clinic during the 1-year period. Girls were 75.4% of the sample. When the cases were classified in terms of severity of depression, it was found that 45.7% of the whole sample was mild, 44.3% was middle and 10% was severe MDD and the girls were higher in all groups. Pharmacotherapy was applied in 81.7% of the sample, 15.1% of psychotherapies, 3.1% of the combination of pharmacotherapy and psychotherapy. Selective serotonin reuptake inhibitors (SSRIs) alone were preferred in 87.4% of the cases. Somatoform disorder (dissociative and conversion disorder) and bereavement reaction were significant for the combined use of pharmacotherapy and psychotherapy. At least one adverse event was detected in 8.8% of the cases. Discussion: Compatibly the literature, in adolescence MDD diagnosis was significantly more common in females in all severity groups. SSRIs monotherapy is mostly used as the first option in treatment. Our study will contribute to the related literature in terms of involving wide sampling, treatment and severity evaluation in adolescents with MDD; but generalization may not be appropriate because of the the study’s cross-sectional and situation determination nature

Selective Serotonin Reuptake Inhibitor Monotherapy for Anxiety Disorders in Children and Adolescents with Autism Spectrum Disorder: A Chart Review.

Objective: Anxiety disorders are one of the most commonly co-occurring psychiatric diagnoses in youth with autism spectrum disorder (ASD), with a frequency ranging from 22% to 84%. Methods: We conducted a chart review of 29 children and adolescents with ASD who had been treated with selective serotonin reuptake inhibitor (SSRI) monotherapy for an anxiety disorder for at least 2 months. Subsequent chart reviews were conducted for the first follow-up visit within 2-6 months (M = 4.2 months) and the visit closest to 9 months posttreatment (ranging from 7 to 12 months; M = 10.5 months). The presence of adverse events (AEs) was examined, and a consensus Clinical Global Impressions Improvement (CGI-I) score was determined. Results: Fifty-five percent of patients were given a CGI-I of "improved" or "very much improved" at the 9-month follow-up. Four patients discontinued treatment owing to AEs. Other reported AEs not leading to discontinuation included vivid dreaming, increased emotional lability, and irritability. Responders included a number of patients who had failed previous SSRI trials. Conclusions: This study suggests that SSRI treatment should be considered for individuals with ASD and anxiety disorders, even if prior SSRI trials have been unsuccessful.

A Case Report of Serotonin Syndrome in a Patient on Selective Serotonin Reuptake Inhibitor (SSRI) Monotherapy

Introduction: Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with several indications, one of which is for depression. We present a case of probable paroxetine-induced serotonin syndrome. Case Summary: A 21-year-old female with a history of generalized anxiety disorder and major depression presented with increased depressive symptoms over several months while taking fluoxetine 20 mg daily. Fluoxetine was discontinued without taper and replaced with paroxetine 10 mg daily, along with hydroxyzine 50 mg twice daily as needed for anxiety. Within a week of starting the paroxetine, the patient reported increased anxiety, insomnia, and constant shaking. The paroxetine continued to be uptitrated over a 3-week period to a dose 30 mg due to unremitting depressive symptoms. One month later, the patient presented with tachycardia, generalized body aches, extreme fatigue, weakness, uncontrollable twitching, tremor, and hyperreflexia. A widespread burning sensation accompanied by random hot flashes without diaphoresis was also noted. Serotonin syndrome was diagnosed using the Hunters criteria. Paroxetine was discontinued, and the patient’s physical symptoms resolved within a week. Discussion: To date, only 5 cases of serotonin syndrome have been reported in patients receiving SSRI monotherapy at recommended therapeutic doses.

Early symptom non-improvement and aggravation are associated with the treatment response to SSRIs in MDD: a real-world study.

PurposeEarly improvement in major depressive disorder is defined as a reduction of ≥20% in the 17-item Hamilton Depression Rating Scale (HAM-D-17) score at the second week after initiation of treatment, predicting long-term treatment response. However, there remains no effective strategy for switching medications when a patient fails to reach early improvement at the second week. This study focused on the predictive value of early symptom changes in each item of the HAM-D-17 scale for treatment response to selective serotonin reuptake inhibitor (SSRI) monotherapy and to provide a reference for switching antidepressants to enhance early treatment efficacy.Patients and methodsOur study was an observational, real-world study that enrolled 90 treatment-naïve patients experiencing their first episode of major depressive disorder in the outpatient department of Huashan Hospital. Patients who did not achieve the threshold of early improvement in the second week after starting treatment were switched to alternative SSRI monotherapy. Patient follow-up occurred at 2, 4, 8, and 12 weeks after the initiation of treatment. We analyzed the relationship between the change in each symptom on the HAM-D-17 scale and treatment efficacy.ResultsEarly improvement predicted the treatment response at 12 weeks (χ2=19.249, P<0.001), whereas early non-improvement in insomnia and anxiety was associated with a poor response (OR =9.487, 95% CI: 1.312–68.588 and OR =12.947, 95% CI: 1.99–82.246, respectively). At week 2, general somatic symptom aggravation was associated with a poorer response (OR =73.337, 95% CI: 2.232->999.999); treatment-emergent headache and tremor were associated with treatment efficacy (t=−9.521, P<0.001 and t=3.660, P=0.001, respectively). In addition, the increase in suicidal thoughts, once treatment began, had no relationship with the treatment response (OR =0.821, P=0.872).ConclusionThis study suggested that patients with early non-improvement in insomnia and anxiety were not suitable for switches in SSRI monotherapy. Patients with treatment-emergent symptoms, especially headaches and tremors, were not suitable for switching from monotherapy to another SSRI.

Treatment effects on residual cognitive symptoms among partially or fully remitted patients with major depressive disorder: A randomized, double-blinded, exploratory study with vortioxetine

BackgroundResidual cognitive symptoms in major depressive disorder (MDD) are common, yet poorly investigated. We explored the effectiveness of vortioxetine as adjunctive treatment to selective serotonin reuptake inhibitors (SSRI) and as monotherapy versus continued SSRI, in patients with MDD who achieved full or partial remission with SSRI, but report residual cognitive symptoms. MethodsPatients (18–65 years old, N =151) diagnosed with MDD, with a Hamilton Depression Rating Scale 17-items total score ≤10 and a Perceived Deficits Questionnaire–Depression total score >25, were randomized 1:1:1 to 8 weeks of double-blind treatment with current SSRI + placebo, SSRI + vortioxetine (10–20 mg/day), or vortioxetine (10–20 mg/day) + placebo. The primary efficacy measure was the Digit Symbol Substitution Test (DSST), analyzed using a mixed model for repeated measurements. Secondary outcomes comprised cognitive functioning, subjectively-rated cognitive symptoms, patient functioning, and mood symptoms. ResultsFrom baseline to week 8, all treatment groups improved DSST performance, with statistically nonsignificant treatment differences. Similar results were seen for secondary endpoints. Improvement in cognitive performance tended to be numerically larger with vortioxetine monotherapy than with SSRI monotherapy, while vortioxetine as adjunctive treatment tended to perform numerically better in further improving depressive symptoms. Most adverse events were mild or moderate. Nausea was the most common adverse event for vortioxetine. LimitationsSmall sample sizes limited statistical power. ConclusionIn this explorative study, remitted patients with MDD improved their cognitive performance with no treatment differences. Secondary results indicate numerical benefits for cognitive performance with vortioxetine monotherapy, and for depressive symptoms with vortioxetine augmentation.

Optimal treatment for obsessive compulsive disorder: a randomized controlled feasibility study of the clinical-effectiveness and cost-effectiveness of cognitive-behavioural therapy, selective serotonin reuptake inhibitors and their combination in the management of obsessive compulsive disorder.

Established treatments for obsessive compulsive disorder (OCD) include cognitive behaviour therapy (CBT) and selective serotonin reuptake inhibitor (SSRI) medication. Combined treatment may outperform monotherapy, but few studies have investigated this. A total of 49 community-based adults with OCD were randomly assigned to CBT, SSRI, or SSRI+CBT. Sertraline (50–200 mg/day) was given as the SSRI for 52 weeks. A 16-h-manualized individual CBT was delivered over 8 weeks with four follow-up sessions. Assessors were ‘blinded’ to treatment allocation. A preliminary health economic evaluation was conducted. At week 16, combined treatment (n=13) was associated with the largest improvement, sertraline (n=7) the next largest and CBT (n=9) the smallest on the observed case analysis. The effect size (Cohen’s d) comparing the improvement in Yale Brown Obsessive Compulsive Scale on CBT versus combined treatment was −0.39 and versus sertraline was −0.27. Between 16 and 52 weeks, the greatest clinical improvement was seen with sertraline, but participant discontinuation prevented reliable analysis. Compared with sertraline, the mean costs were higher for CBT and for combined treatment. The mean Quality Adjusted Life Year scores for sertraline were 0.1823 (95% confidence interval: 0.0447–0.3199) greater than for CBT and 0.1135 (95% confidence interval: ‑0.0290–0.2560), greater than for combined treatment. Combined treatment appeared the most clinically effective option, especially over CBT, but the advantages over SSRI monotherapy were not sustained beyond 16 weeks. SSRI monotherapy was the most cost-effective. A definitive study can and should be conducted.

Pharmacotherapy of premature ejaculation: a systematic review and network meta-analysis.

The purpose of the study was to conduct a systematic evaluation of the different general prescribed drugs for premature ejaculation (PE). A systematic literature search of MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for Systematic Reviews was performed on 1 March 2018. Intravaginal ejaculation latency time (IELT) was the main outcome. Analysis was performed under multivariate random-effects network model and efficacies of drugs were ranked with surface under the cumulative ranking (SUCRA) probabilities. A total of 48 studies were reviewed and 40 of them were further enrolled into network meta-analysis. The majority of RCTs were of unclear methodological quality. Pooled evidence suggested that topical anaesthetic creams (TAs), tramadol, selective serotonin reuptake inhibitors (SSRIs), and phosphodiesterase type 5 inhibitors (PDE5is) are more effective at prolonging IELT comparing with placebo. TAs (90%) on demand (OD) and PDE5is plus SSRI (89.8%) had the highest SUCRA, which meant the most probable to be the most effective intervention. We recommend the initial use of dapoxetine 30mg OD for PE because it has been tested in largest and better designed clinical trials rather than it is more effective than the other drugs studied. TAs and tramadol 50mg OD can be used as a viable alternative to oral treatment with SSRIs. PDE5is combined with SSRIs are more effective than SSRIs monotherapy but are also associated with more side effects. PDE5is OD can be recommended to PE patients with ED.