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The Aging Male : the Official Journal... Dec 2022Postprostatectomy urinary incontinence (PPUI) is a serious complication despite surgical advances. Treatment options for PPUI include conservative care like Pelvic floor... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Postprostatectomy urinary incontinence (PPUI) is a serious complication despite surgical advances. Treatment options for PPUI include conservative care like Pelvic floor muscle exercise (PFME), which is a physiotherapy performed by the patients themselves; Pelvic floor muscle therapy (PFMT), a physiotherapy performed under the guidance of a therapist, and duloxetine treatment; and surgical interventions. In this study, network meta-analysis (NMA) was performed for direct comparison of these treatment options.
MATERIALS AND METHODS
The NMA pooled the odds ratios and 95% credible intervals using the number of patients achieving urinary continence and the total number of patients in an intention-to-treat population. The treatments were ranked based on the surface under the cumulative ranking curve (SUCRA) probabilities and the rankograms.
RESULTS
The pooled overall ORs of patients achieving urinary continence compared with no treatment was 1.73 (95% CrI: 0.657, 4.71) in PFME, 2.62 (95% CrI: 0.553, 13.5) in PFME plus Duloxetine, and 4.05 (95% CrI: 1.70, 10.2) in PFMT. The SUCRA values of ranking probabilities for each treatment showed high rates of continence in the order of PFMT, PFME plus Duloxetine, and PFME.
CONCLUSION
The results suggest that patients with PPUI should undergo PFMT and consider duloxetine as an additional treatment option.
Topics: Duloxetine Hydrochloride; Exercise Therapy; Female; Humans; Male; Network Meta-Analysis; Pelvic Floor; Treatment Outcome; Urinary Incontinence
PubMed: 35535703
DOI: 10.1080/13685538.2022.2069238 -
European Journal of Oncology Nursing :... Jun 2022The aim in this review was to explore recent advances in chemotherapy-induced peripheral neuropathy (CIPN) management interventions and to identify the implications for...
PURPOSE
The aim in this review was to explore recent advances in chemotherapy-induced peripheral neuropathy (CIPN) management interventions and to identify the implications for practice and future research.
METHODS
A comprehensive search through seven electronic databases (AMED, CINAHL, Cochrane Library, EMBASE, PEDro, PubMed, and Web of Science) was conducted for studies published between January 1, 2013 and August 3, 2019. An updated search for subsequently published studies was made through PubMed on February 15, 2022. Randomized controlled trials (RCTs) involving either pharmacological or non-pharmacological interventions were considered eligible. The Cochrane Risk of Bias tool version 2.0 (RoB 2.0) was used to appraise the methodological risk of bias. Data extracted from the included RCTs were synthesized in a narrative approach.
RESULTS
Forty-two RCTs involving a total of 3393 participants were included. Overall, a high risk of bias was found in most of the included RCTs. The results further confirmed the analgesic effect of duloxetine on pain-related to CIPN. Exercise-based interventions, acupuncture, and several non-invasive neuromodulation techniques showed promise for managing CIPN.
CONCLUSIONS
The effects of most pharmacological and non-pharmacological interventions on CIPN are inconclusive due to methodological issues. Duloxetine remains the only pharmacological intervention recommended for managing pain related to CIPN. Although definitive recommendations cannot be made based on current research evidence, non-pharmacological interventions, especially non-invasive neuromodulation techniques, warrant future research.
Topics: Antineoplastic Agents; Duloxetine Hydrochloride; Humans; Pain; Pain Management; Peripheral Nervous System Diseases
PubMed: 35421796
DOI: 10.1016/j.ejon.2022.102134 -
L'Encephale Aug 2022Major depression is a significant public health problem since its lifetime prevalence is estimated at 15-18 %. Its standard treatment is based on the use of...
OBJECTIVE
Major depression is a significant public health problem since its lifetime prevalence is estimated at 15-18 %. Its standard treatment is based on the use of antidepressant medications but their effectiveness is limited. Indeed, only two thirds of patients with a major depressive episode will reach remission after two lines of conventional treatment. In major depression, there are arguments in favour of disturbances in neuronal glutamatergic transmission. Esketamine appears to have an antidepressant action through modulation of the NMDA receptors involved in this glutamatergic neurotransmission. The aim of this review to systematically investigate the efficacy of esketamine combined with an SSRI or SNRI for major depressive disorder resistant to treatment.
METHOD
A systematic review on the efficacy of esketamine in combination with an SSRI or SNRI for resistant major depressive disorder was performed in July 2021 in the PUBMED database according to the PRISMA criteria. The key words used are: "depressed" [All Fields] OR "depression" [MeSH Terms] OR "depression" [All Fields] OR "depressions" [All Fields] OR "depression s" [All Fields] OR "depressive disorder"[MeSH Terms] OR ("depressive"[All Fields] AND"disorder"[All Fields]) OR"depressive disorder"[All Fields] OR"depressivity"[All Fields] OR"depressive"[All Fields] OR "depressively" [All Fields] OR "depressiveness" [All Fields] OR "depressives" [All Fields]) AND ("esketamine" [Supplementary Concept] OR "esketamine" [All Fields] OR "esketamine" [All Fields]. The inclusion criteria were: efficacy on depressive symptoms of intranasal esketamine combined with an SSRI or an SNRI for major depressive disorder resistant to at least two lines of treatment, RCT and meta-analysis, individual≥18 years, articles in English and French.
RESULTS
Four randomized double-blind studies were selected on the basis of these criteria. The included studies are of grade A and B which leads to a high level of scientific evidence.
CONCLUSIONS
Intranasal esketamine in combination with sertraline, escitalopram, duloxetine or venlafaxine prolonged release is more effective than the monotherapy use of these four molecules for the treatment of resistant depression. It has been shown to be effective for a population aged between 18 and 74 years at doses between 28mg and 84mg. Currently, based on these results, intranasal esketamine should be proposed as a second level of treatment after an unsuccessful trial of two antidepressants. It is nevertheless advisable to be careful in its use in a clinical psychiatric population: exclusion of suicidal ideation or antecedent of suicidal acting, absence of psychotic depression, use exclusively for unipolar major depressive disorder. The different conditions of use are also notified in the product characteristics of the European Medicines Agency. Finally, further comparative studies are needed in the future, in the absence of funding from the pharmaceutical company producing esketamine.
Topics: Adolescent; Adult; Aged; Antidepressive Agents; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Duloxetine Hydrochloride; Humans; Middle Aged; Randomized Controlled Trials as Topic; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride; Young Adult
PubMed: 35221019
DOI: 10.1016/j.encep.2021.12.002 -
Journal of Gynecology Obstetrics and... Mar 2022To evaluate the efficacy and safety of preoperative duloxetine on postoperative pain management after gynecologic laparoscopic surgeries. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and safety of preoperative duloxetine on postoperative pain management after gynecologic laparoscopic surgeries.
METHODS
A systematic search was done in Cochrane Library, PubMed, ISI web of science, and Scopus from inception to September 2021. We selected randomized clinical trials (RCTs) that compared preoperative duloxetine (intervention group) versus placebo (control group) among women undergoing gynecologic laparoscopic surgeries. Our primary outcomes were pain scores evaluated by the Visual Analog Scale (VAS) at 2, 6, 12, and 24 h postoperatively. Our secondary outcomes were the time required for the first analgesic request in minutes, postoperative analgesic consumption in milligrams, length of hospital stay in days, and side effects.
RESULTS
Four RCTs with a total number of 244 patients were included in our systematic review and meta-analysis. We found duloxetine was linked to a significant reduction in VAS pain scores at different time intervals. The first analgesic request was significantly earlier in the placebo group than in the duloxetine group (p = 0.03). In addition, duloxetine significantly reduced the postoperative analgesic consumption compared to placebo (MD= -41.97, 95% CI [-53.23, -30.72], p<0.001). However, both groups did not differ in the length of hospital stay and side effects.
CONCLUSIONS
Duloxetine administration prior to gynecological laparoscopic surgeries is safe and effective in improving postoperative pain and analgesia.
Topics: Duloxetine Hydrochloride; Female; Gynecologic Surgical Procedures; Humans; Laparoscopy; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 34974147
DOI: 10.1016/j.jogoh.2021.102305 -
The Clinical Journal of Pain Nov 2021We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine for the treatment of knee osteoarthritis (OA) pain.
METHODS
A comprehensive literature search used 3 English and 4 Chinese biomedical databases from inception through July 10, 2020. We included randomized controlled trials of duloxetine with intervention duration of 2 weeks or longer for knee OA. The primary outcome was pain intensity measured by Brief Pain Inventory and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcome measurements included 36-Item Short Form Health Survey, Patient's Global Impression of Improvement, Clinical Global Impressions of Severity, and adverse events (AEs). The quality of all included studies was evaluated using the Cochrane risk-of-bias criteria. The review was registered in the PROSPERO (CRD 42020194072).
RESULTS
Six studies totaling 2059 patients met the eligibility criteria. Duloxetine had significant reductions in Brief Pain Inventory 24 hours average pain (mean difference [MD]=-0.74; 95% confidence interval [CI], -0.92 to -0.57; P<0.00001; I2=13%; 5 trials; 1695 patients); patient general activity (MD=-0.76; 95% CI, -0.96 to -0.56; P<0.00001; I2=0%; 5 trials; 1694 patients) WOMAC physical function subscale (MD=-4.22; 95% CI, -5.14 to -3.30; P<0.00001; I2=26%; 5 trials; 1986 patients); Patient's Global Impression of Improvement (MD=-0.48; 95% CI, -0.58 to -0.37; P<0.00001; I2=29%; 5 trials; 1741 patients); and Clinical Global Impressions of Severity (MD=-0.34; 95% CI, -0.44 to -0.24; P<0.00001; I2=0%; 4 trials; 1178 patients) compared with placebo control. However, no difference on WOMAC pain subscale (standard mean difference=-1.68; 95% CI, -3.45 to 0.08; P=0.06; I2=100%; 3 trials; 1104 patients) and in serious AEs (risk ratio=0.92; 95% CI, 0.40-2.11; P=0.84; I2=0%; 5 trials; 1762 patients) between duloxetine and placebo. Furthermore, duloxetine failed to show superior effects for improving the life quality and demonstrated more treatment-emergent AEs.
CONCLUSION
Duloxetine may be an effective treatment option for knee OA patients but further rigorously designed and well-controlled randomized trials are warranted.
Topics: Duloxetine Hydrochloride; Humans; Knee Joint; Osteoarthritis, Knee; Pain; Pain Measurement
PubMed: 34483232
DOI: 10.1097/AJP.0000000000000975 -
Journal of Clinical Anesthesia Dec 2021Selective-serotonin-noradrenaline-reuptake inhibitors (SSNRI) might be an interesting option for postoperative pain treatment. Objective was to investigate postoperative... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVE
Selective-serotonin-noradrenaline-reuptake inhibitors (SSNRI) might be an interesting option for postoperative pain treatment. Objective was to investigate postoperative pain outcomes of perioperative SSNRI compared to placebo or other additives in adults undergoing surgery.
DESIGN
Systematic review of randomised controlled trials (RCT) with meta-analysis and GRADE assessment.
SETTING
Acute and chronic postoperative pain treatment.
PATIENTS
Adult patients undergoing surgery.
INTERVENTIONS
Perioperative administration of SSNRI.
MEASUREMENTS
Primary outcomes were postoperative acute pain at rest/during movement (measured on a scale from 0 to 10), number of patients with chronic postsurgical pain (CPSP) and with SSNRI-related adverse events.
MAIN RESULTS
Fourteen RCTs (908 patients) were included. We have high-quality evidence that duloxetine has no effect on pain at rest at 2 h (MD: -0.02; 95% confidence interval (CI) -0.51 to 0.47), but probably reduces it at 48 h (MD: -1.16; 95%CI -1.78 to -0.54). There is low- and moderate-quality evidence that duloxetine has no effects on pain during movement at 2 h (MD: -0.42; 95%CI -1.53 to 0.69) and 48 h (MD: -0.91; 95% CI -2.08 to 0.26), respectively. We have very low-quality evidence that duloxetine might reduce pain at rest (MD: -0.45; 95%CI -0.74 to -0.15) and movement (MD: -1.19; 95%CI -2.32 to -0.06) after 24 h. We have low-quality evidence that duloxetine may reduce the risk of CPSP at 6 months (RR:0.35; 95%CI 0.14 to 0.90). There is moderate-quality evidence that duloxetine increases the risk of dizziness (RR:1.72; 95%CI 1.26 to 2.34).
CONCLUSION
At the expense of a higher risk for dizziness, SSNRI may be effective in reducing postoperative pain between 24 and 48 h after surgery. However, the results of the meta-analyses are mostly imprecise and duloxetine might only be used in individual cases. Protocol registration: CRD42018094699.
Topics: Adult; Duloxetine Hydrochloride; Humans; Norepinephrine; Pain, Postoperative; Serotonin; Selective Serotonin Reuptake Inhibitors
PubMed: 34311244
DOI: 10.1016/j.jclinane.2021.110451 -
International Journal of Clinical... Nov 2021In patients with diabetes mellitus, painful diabetic peripheral neuropathy (PDPN) is a frequent complication and can cause poor quality of life. We compared the efficacy... (Meta-Analysis)
Meta-Analysis
Comparison of efficacy and safety of gabapentin and duloxetine in painful diabetic peripheral neuropathy: A systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
In patients with diabetes mellitus, painful diabetic peripheral neuropathy (PDPN) is a frequent complication and can cause poor quality of life. We compared the efficacy and safety of duloxetine with those of gabapentin in patients with PDPN through a systematic review and meta-analysis of randomised controlled trials.
MATERIALS AND METHODS
PubMed, Embase and the Cochrane Library were searched for eligible studies published from database inception to January 2021. Visual Analogue Scale (VAS), sleep interference score, Clinical Global Impression of Change (CGIC), Patient Global Impression of Change (PGIC), Diabetic Neuropathy Symptom (DNS) score, Diabetic Neuropathic Examination (DNE) score, Neuropathic Disability Score (NDS) and side effects were used to compare duloxetine and gabapentin in patients with PDPN.
RESULTS
Three eligible randomised controlled trials involving 290 patients were included. No significant differences were observed between patients receiving duloxetine and gabapentin with respect to VAS (mean change difference = -1.23, 95% CI, -6.09 to 3.62; P = .62), sleep interference score (mean change difference = 0.42, 95% CI, -0.15 to 1.00; P = .15), CGIC (mean difference = 0.04, 95% CI, -0.11 to 0.20; P = .60), PGIC (mean difference= 0.24, 95% CI, -0.13 to 0.60; P = .21), DNS (mean change difference = 0.14, 95% CI, -0.35 to 0.63; P = .58), DNE (mean change difference = 0.26, 95% CI, -0.35 to 0.86; P = .41) and NDS (mean change difference = 0.30, 95% CI, -0.02 to 0.63; P = .07).
CONCLUSIONS
No significant differences were observed in the efficacy of duloxetine and gabapentin when treating patients with PDPN.
Topics: Analgesics; Diabetes Mellitus; Diabetic Neuropathies; Duloxetine Hydrochloride; Gabapentin; Humans; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 34171158
DOI: 10.1111/ijcp.14576 -
The Cochrane Database of Systematic... May 2021Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well-being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications.
OBJECTIVES
To investigate, via network meta-analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide-related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician-rated depression (CDRS-R) and suicide-related outcomes.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020.
SELECTION CRITERIA
Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs).
DATA COLLECTION AND ANALYSIS
Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self-rated), functioning, suicide related outcomes and overall adverse outcomes. Random-effects network meta-analyses were conducted in a frequentist framework using multivariate meta-analysis. Certainty of evidence was assessed using Confidence in Network Meta-analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results.
MAIN RESULTS
Twenty-six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS-R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD -1.43, 95% CI -3.90, 1.04; vilazodone: MD -0.84, 95% CI -3.03, 1.35; desvenlafaxine MD -0.07, 95% CI -3.51, 3.36; moderate certainty evidence: sertraline: MD -3.51, 95% CI -6.99, -0.04; fluoxetine: MD -2.84, 95% CI -4.12, -1.56; escitalopram: MD -2.62, 95% CI -5.29, 0.04; low certainty evidence: duloxetine: MD -2.70, 95% CI -5.03, -0.37; vortioxetine: MD 0.60, 95% CI -2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high- or moderate-certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self-harm or suicide was an exclusion criterion for the study. Proportions of suicide-related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide-related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide-related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide-related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide-related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants.
AUTHORS' CONCLUSIONS
Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first-line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide-related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.
Topics: Adolescent; Antidepressive Agents; Bias; Child; Citalopram; Depressive Disorder, Major; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Female; Fluoxetine; Humans; Male; Mirtazapine; Network Meta-Analysis; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Suicidal Ideation; Venlafaxine Hydrochloride; Vilazodone Hydrochloride; Vortioxetine
PubMed: 34029378
DOI: 10.1002/14651858.CD013674.pub2 -
The Cochrane Database of Systematic... Mar 2021Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light therapy, or psychotherapy.
OBJECTIVES
To assess the efficacy and safety of second-generation antidepressants (SGAs) for the treatment of seasonal affective disorder (SAD) in adults in comparison with placebo, light therapy, other SGAs, or psychotherapy.
SEARCH METHODS
This is an update of an earlier review first published in 2011. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1) in the Cochrane Library (all years), Ovid MEDLINE, Embase, and PsycINFO (2011 to January 2020), together with the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all available years), for reports of randomised controlled trials (RCTs). We hand searched the reference lists of all included studies and other systematic reviews. We searched ClinicalTrials.gov for unpublished/ongoing trials. We ran a separate update search for reports of adverse events in the Ovid databases. SELECTION CRITERIA: For efficacy we included RCTs of SGAs compared with other SGAs, placebo, light therapy, or psychotherapy in adult participants with SAD. For adverse events we also included non-randomised studies.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened abstracts and full-text publications against the inclusion criteria. Data extraction and 'Risk of bias' assessment were conducted individually. We pooled data for meta-analysis where the participant groups were similar, and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment.
MAIN RESULTS
In this update we identified no new RCT on the effectiveness of SGAs in SAD patients. We included 2 additional single-arm observational studies that reported on adverse events of SGAs. For efficacy we included three RCTs of between five and eight weeks' duration with a total of 204 participants. For adverse events we included two RCTs and five observational (non-randomised) studies of five to eight weeks' duration with a total of 249 participants. All participants met the DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for SAD. The average age ranged from 34 to 42 years, and the majority of participants were female (66% to 100%). Results from one trial with 68 participants showed that fluoxetine (20/36) was numerically superior to placebo (11/32) in achieving clinical response; however, the confidence interval (CI) included both a potential benefit as well as no benefit of fluoxetine (risk ratio (RR) 1.62, 95% CI 0.92 to 2.83, very low-certainty evidence). The number of adverse events was similar in both groups (very low-certainty evidence). Two trials involving a total of 136 participants compared fluoxetine versus light therapy. Meta-analysis showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24, low-certainty evidence), RR of remission 0.81 (95% CI 0.39 to 1.71, very low-certainty evidence). The number of adverse events was similar in both groups (low-certainty evidence). We did not identify any eligible study comparing SGA with another SGA or with psychotherapy. Two RCTs and five non-randomised studies reported adverse event data on a total of 249 participants who received bupropion, fluoxetine, escitalopram, duloxetine, nefazodone, reboxetine, light therapy, or placebo. We were only able to obtain crude rates of adverse events, therefore caution is advised regarding interpretation of this information. Between 0% and 100% of participants who received an SGA suffered an adverse event, and between 0% and 25% of participants withdrew from the study due to adverse events.
AUTHORS' CONCLUSIONS
Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo showing a non-significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy suggesting equivalence between the two interventions. The lack of available evidence precluded us from drawing any overall conclusions on the use of SGAs for SAD. Further, larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs. Data on adverse events were sparse, and a comparative analysis was not possible. The data we obtained on adverse events is therefore not robust, and our confidence in the data is limited. Overall, up to 25% of participants treated with SGAs for SAD withdrew from the study early due to adverse events.
Topics: Adult; Antidepressive Agents, Second-Generation; Bias; Citalopram; Duloxetine Hydrochloride; Female; Fluoxetine; Humans; Male; Morpholines; Observational Studies as Topic; Phototherapy; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Reboxetine; Seasonal Affective Disorder; Thiophenes; Treatment Outcome
PubMed: 33661528
DOI: 10.1002/14651858.CD008591.pub3 -
Acta Psychiatrica Scandinavica Aug 2021Evidence of larger drug effects in highly standardized studies (efficacy) compared to clinical routine (effectiveness) is discussed as efficacy-effectiveness gap. This... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Evidence of larger drug effects in highly standardized studies (efficacy) compared to clinical routine (effectiveness) is discussed as efficacy-effectiveness gap. This study aimed to quantify effect size differences of RCTs and non-RCTs in the treatment of depression with venlafaxine and duloxetine and to identify effect modifying predictors.
METHODS
A comprehensive systematic review and meta-analysis was conducted, including all prospective trials, which evaluated the treatment effects of duloxetine or venlafaxine in patients with depression. The primary outcome was the pre-post effect size after acute therapy, which were compared between RCTs and non-RCTs. Moreover, an exploratory analysis of predictors in a mixed meta-regression model within an information-theoretic approach was performed.
RESULTS
171 RCTs and 74 non-RCTs were included. The pre-post effect size differed significantly between RCTs and non-RCTs (-3.04 vs. -2.62, Δ = 0.41, p = 0.012, high heterogeneity). Study characteristics were very similar between RCTs and non-RCTs. Most important variables to predict effect sizes were 'depression severity', 'dose' and 'number of participants'.
CONCLUSION
Despite differences in effect sizes between RCTs and non-RCTs, study design is not clearly an important predictor for the effect sizes. Our results question the common assumption that non-RCTs are generally better suited to describe a drug's effectiveness in clinical practice than RCTs. Future studies and their reporting should put more emphasis on the description of external validity, in order to allow better assessments of clinical relevance.
Topics: Antidepressive Agents; Depression; Duloxetine Hydrochloride; Humans; Prospective Studies; Venlafaxine Hydrochloride
PubMed: 33661520
DOI: 10.1111/acps.13293