-
The Lancet. Psychiatry Jul 2024Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature.
METHODS
We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables.
FINDINGS
From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial.
INTERPRETATION
Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm.
FUNDING
None.
Topics: Humans; Antidepressive Agents; Incidence; Substance Withdrawal Syndrome; Randomized Controlled Trials as Topic
PubMed: 38851198
DOI: 10.1016/S2215-0366(24)00133-0 -
Basic & Clinical Pharmacology &... Jan 2016Major depressive disorder is common among women in child-bearing age, and medical treatment is subject to substantial discussions and controversies. For Selective... (Review)
Review
Major depressive disorder is common among women in child-bearing age, and medical treatment is subject to substantial discussions and controversies. For Selective Serotonin reuptake inhibitors, SSRIs, a vast amount of data are available. For the newer antidepressant group of serotonin and noradrenaline reuptake inhibitors, SNRIs, significantly less data are available. Following the PRISMA guideline for systematic reviews, we performed a systematic search on the risk of major congenital malformations after first trimester in utero exposure to venlafaxine or duloxetine. We identified eight cohort studies reporting on the outcome upon in utero exposure to venlafaxine or duloxetine during the first trimester. The cumulated data for venlafaxine were 3186 exposed infants and 107 major malformations, resulting in a relative risk estimate and 95% confidence interval of 1.12 (0.92-1.35). The corresponding data for duloxetine were 668 infants and 16 major malformations, resulting in a relative risk estimate and 95% confidence interval of 0.80 (0.46-1.29). First-trimester in utero exposure to venlafaxine is not associated with an increased risk of major congenital malformations. The amount of data for duloxetine are significantly smaller but does not suggest a clinically important increased risk.
Topics: Abnormalities, Drug-Induced; Cohort Studies; Depressive Disorder, Major; Duloxetine Hydrochloride; Female; Humans; Pregnancy; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 26435496
DOI: 10.1111/bcpt.12497 -
Neurology May 2017To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life. (Review)
Review
OBJECTIVE
To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life.
METHODS
We searched PubMed and Cochrane Database of Systematic Reviews for systematic reviews from 2011 to October 12, 2015, and PubMed, Embase, and the Cochrane Central Register of Controlled Trials for primary studies from January 1, 2013, to May 24, 2016. We searched Clinicaltrials.gov on March 9, 2016. Two reviewers independently evaluated studies for eligibility, serially abstracted data, and independently evaluated risk of bias and graded strength of evidence (SOE).
RESULTS
We updated a recently completed systematic review of 57 eligible studies with 24 additional published studies and 25 unpublished studies. For reducing neuropathy-related pain, the serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine (moderate SOE), the anticonvulsants pregabalin and oxcarbazepine (low SOE), the drug classes tricyclic antidepressants (low SOE) and atypical opioids (low SOE), and botulinum toxin (low SOE) were more effective than placebo. We could not draw conclusions about quality of life due to incomplete reporting. All studies were short-term (less than 6 months), and all effective drugs had more than 9% dropouts from adverse effects.
CONCLUSIONS
For reducing pain, duloxetine and venlafaxine, pregabalin and oxcarbazepine, tricyclic antidepressants, atypical opioids, and botulinum toxin were more effective than placebo. However, quality of life was poorly reported, studies were short-term, drugs had substantial dropout rates, and opioids have significant risks. Future studies should evaluate longer-term outcomes, use methods and measures recommended by pain organizations, and assess patients' quality of life.
Topics: Analgesics; Diabetic Neuropathies; Humans; Neuralgia; Pain; Peripheral Nervous System Diseases; Quality of Life
PubMed: 28341643
DOI: 10.1212/WNL.0000000000003882 -
Neuropsychopharmacology Reports Mar 2024To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis... (Meta-Analysis)
Meta-Analysis
AIM
To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD.
METHODS
Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI).
RESULTS
Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation.
CONCLUSIONS
Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.
Topics: Humans; Aged; Depressive Disorder, Major; Japan; Antidepressive Agents; Duloxetine Hydrochloride; Venlafaxine Hydrochloride; Randomized Controlled Trials as Topic
PubMed: 38318955
DOI: 10.1002/npr2.12422 -
Journal of Affective Disorders Mar 2018Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest... (Comparative Study)
Comparative Study Meta-Analysis Review
Efficacy and safety of levomilnacipran, vilazodone and vortioxetine compared with other second-generation antidepressants for major depressive disorder in adults: A systematic review and network meta-analysis.
BACKGROUND
Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants.
METHODS
We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses.
RESULTS
Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low.
LIMITATIONS
Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses.
CONCLUSIONS
Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants.
Topics: Adult; Antidepressive Agents, Second-Generation; Cyclopropanes; Depressive Disorder, Major; Humans; Milnacipran; Network Meta-Analysis; Piperazines; Sulfides; Vilazodone Hydrochloride; Vortioxetine
PubMed: 29197738
DOI: 10.1016/j.jad.2017.11.056 -
Breast Cancer Research and Treatment Jul 2015Toxicity due to treatment causes a negative impact on quality of life in breast cancer survivors. Hot flash symptoms, described as intense sensations of heat, sweating... (Meta-Analysis)
Meta-Analysis Review
Toxicity due to treatment causes a negative impact on quality of life in breast cancer survivors. Hot flash symptoms, described as intense sensations of heat, sweating and flushing occur in more than 50 % of breast cancer patients taking tamoxifen. We hypothesized that venlafaxine, a selective-norepinephrine reuptake inhibitor drug, was effective for reducing patient-reported hot flash scores among women treated for breast cancer compared to other non-hormonal treatments. We searched Medline, Scopus, and Cochrane Central Register of Controlled Trials from inception till May 2015 for venlafaxine (75 mg once daily or greater) with non-hormonal comparators for the treatment of hot flashes in female breast cancer patients. The primary outcome was hot flash score (derived from patient-reported hot flash severity and frequency) in randomized controlled trials. Standardized mean differences (SMD) were calculated for each study due to variation in the outcome measures. Heterogeneity was determined using I (2) statistics, and publication bias was assessed using a contour funnel plot and Egger's tests. Pooled analyses demonstrated that venlafaxine significantly reduced hot flash scores compared to the trial comparators (overall SMD 2.06; 95% confidence interval (CI) [0.40, 3.72]). There was significant heterogeneity among these studies (I (2) = 98.7%, P < 0.001). Asymmetry in the contour funnel plot suggests the presence of publication bias and a trend towards small study effects (Egger's test, P = 0.096). Venlafaxine is efficacious in managing hot flashes among women with breast cancer. This review highlights methodological issues that arise from eligible trials and recommends a collaborative approach in survivorship studies.
Topics: Breast Neoplasms; Disease Management; Female; Hot Flashes; Humans; Serotonin and Noradrenaline Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 26067931
DOI: 10.1007/s10549-015-3465-5 -
Canadian Journal of Psychiatry. Revue... Aug 2004This review critiques published randomized placebo-controlled trials pertaining to the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and... (Review)
Review
Selective serotonin reuptake inhibitor and venlafaxine use in children and adolescents with major depressive disorder: a systematic review of published randomized controlled trials.
OBJECTIVE
This review critiques published randomized placebo-controlled trials pertaining to the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine in the treatment of major depressive disorder in children and adolescents.
METHOD
Medline was searched for articles meeting defined inclusion criteria. The following key terms were used: depressive disorders, antidepressive agents, fluoxetine, paroxetine, sertraline, citalopram, fluvoxamine, venlafaxine, child, and adolescent.
RESULTS
Six articles met inclusion criteria. Only 2 studies claim efficacy by significant results in primary outcomes; both have since been contested in further analysis. Not one study adequately examines safety, particularly with respect to whether a link exists between antidepressant use and induction of suicidal ideation or attempts.
CONCLUSION
Published studies on SSRI or venlafaxine use in children and adolescents are inconclusive with respect to safety and efficacy, owing to inappropriate claims of efficacy, lack of improvement in global functioning scores, nonstandardized data collection regarding adverse effects, exclusion of suicidal subjects in the recruitment process, grouping of children and adolescents together, small sample sizes, conflict of interest posed by pharmaceutical company sponsorship, and publishing bias. Future investigators should consider these factors when developing study designs.
Topics: Adolescent; Child; Cyclohexanols; Depressive Disorder, Major; Female; Humans; Male; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 15453105
DOI: 10.1177/070674370404900807 -
BMC Psychiatry Jul 2006Data comparing duloxetine with existing antidepressant treatments is limited. A comparison of duloxetine with fluoxetine has been performed but no comparison with... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Data comparing duloxetine with existing antidepressant treatments is limited. A comparison of duloxetine with fluoxetine has been performed but no comparison with venlafaxine, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that duloxetine should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a systematic review of the efficacy of duloxetine, fluoxetine and venlafaxine versus placebo in the treatment of Major Depressive Disorder (MDD), and performed indirect comparisons through meta-regressions.
METHODS
The bibliography of the Agency for Health Care Policy and Research and the CENTRAL, Medline, and Embase databases were interrogated using advanced search strategies based on a combination of text and index terms. The search focused on randomized placebo-controlled clinical trials involving adult patients treated for acute phase Major Depressive Disorder. All outcomes were derived to take account for varying placebo responses throughout studies. Primary outcome was treatment efficacy as measured by Hedge's g effect size. Secondary outcomes were response and dropout rates as measured by log odds ratios. Meta-regressions were run to indirectly compare the drugs. Sensitivity analysis, assessing the influence of individual studies over the results, and the influence of patients' characteristics were run.
RESULTS
22 studies involving fluoxetine, 9 involving duloxetine and 8 involving venlafaxine were selected. Using indirect comparison methodology, estimated effect sizes for efficacy compared with duloxetine were 0.11 [-0.14;0.36] for fluoxetine and 0.22 [0.06;0.38] for venlafaxine. Response log odds ratios were -0.21 [-0.44;0.03], 0.70 [0.26;1.14]. Dropout log odds ratios were -0.02 [-0.33;0.29], 0.21 [-0.13;0.55]. Sensitivity analyses showed that results were consistent.
CONCLUSION
Fluoxetine was not statistically different in either tolerability or efficacy when compared with duloxetine. Venlafaxine was significantly superior to duloxetine in all analyses except dropout rate. In the absence of relevant data from head-to-head comparison trials, results suggest that venlafaxine is superior compared with duloxetine and that duloxetine does not differentiate from fluoxetine.
Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Cyclohexanols; Depressive Disorder, Major; Duloxetine Hydrochloride; Fluoxetine; Humans; Randomized Controlled Trials as Topic; Regression Analysis; Thiophenes; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 16867188
DOI: 10.1186/1471-244X-6-30 -
Clinical Therapeutics Jun 2009The objectives of this article were to systematically review, summarize the results of, and assess the quality of economic evaluations and humanistic studies related to... (Comparative Study)
Comparative Study Review
BACKGROUND
The objectives of this article were to systematically review, summarize the results of, and assess the quality of economic evaluations and humanistic studies related to patients with generalized anxiety disorder (GAD).
METHODS
EMBASE, EBM Reviews, MEDLINE, and HealthSTAR databases were searched (from the time of inception through April 2008). Full-text publications describing full economic evaluations (cost-benefit, cost-minimization, cost-effectiveness, and cost-utility analyses), partial economic evaluations (cost, burden-of-illness, and resource-utilization analyses), and humanistic outcomes (utilities, preferences, and willingness-to-pay analyses) were included. GAD diagnoses per official publications (eg, Diagnostic and Statistical Manual of Mental Disorders) and associated comorbid conditions were included; anxiety-related symptoms without a diagnosis of GAD were excluded. Study quality was assessed with a 38-point checklist of criteria previously developed by the Panel on Cost-Effectiveness in Health and Medicine.
RESULTS
Thirty-six articles were included. Full economic evaluations (n = 5) were based on conventional decision-making modeling or population-summary data, using time horizons < or =12 months. Cognitive-behavioral therapy by a public-salaried psychologist and evidence-based care generated savings compared with current care. Pharmacotherapy with extended-release venlafaxine treatment was cost-effective compared with diazepam; escitalopram was cost-effective compared with paroxetine because of productivity gains. Full economic evaluations addressed 55.3% to 68.4% of the 38 items on the quality-assessment checklist. Partial evaluations were reported; GAD incurred larger mean marginal health care costs compared with other anxiety disorders (a difference of US $2138 in year-1999 values). GAD patients with severe pain interference incurred significantly higher costs than did patients with pain but no GAD. Furthermore, GAD patients used more services from a primary care provider or specialist than did patients with other psychiatric disorders. Comorbidities were associated with greater absenteeism than was having a diagnosis of GAD alone. Mean (SE) utility scores for quality-of-life assessments among patients with GAD (15D, 0.783 [0.019]; EuroQoL EQ-5D, 0.589 [0.038]) were similar to those for patients who were 20 years older and reported somatic conditions such as Parkinson's disease or heart failure.
CONCLUSIONS
Current evidence suggests that GAD is associated with substantial economic and humanistic impact on patients and health care systems. Future research should address economic evaluations from the private-payer perspective, studies related to the cost of underdiagnosed or untreated GAD, and full economic evaluations that incorporate longer clinical courses of the disorder.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Cognitive Behavioral Therapy; Cost of Illness; Cost-Benefit Analysis; Evidence-Based Medicine; Health Care Costs; Humans; Quality of Life
PubMed: 19695395
DOI: 10.1016/j.clinthera.2009.06.004 -
Journal of Clinical PsychopharmacologyThis systematic review aimed to investigate the clinical manifestations and characteristics of venlafaxine-associated rhabdomyolysis.
PURPOSE
This systematic review aimed to investigate the clinical manifestations and characteristics of venlafaxine-associated rhabdomyolysis.
METHODS
A systematic search was conducted in PubMed, Elsevier, Science Direct, Embase, Springer Link, Wiley Online Library, CNKI, and Wanfang databases from the date of database inception to January 2023. Previously reported cases of venlafaxine-associated rhabdomyolysis were identified, and relevant data from these cases were collected for descriptive statistical analysis. Cases that met the inclusion criteria were evaluated to determine the correlation between adverse reactions and venlafaxine.
RESULTS
A total of 12 patients with venlafaxine-associated rhabdomyolysis were included. None of these patients had a history of muscle pain or discomfort. Of the 12 patients, 5 patients received venlafaxine at doses of ≤225 mg/d, whereas the remaining 7 patients received doses exceeding 225 mg/d. The main clinical symptoms included myalgia, muscle weakness, and renal injury. All 12 patients discontinued venlafaxine and received symptomatic care.
CONCLUSIONS
Venlafaxine, used either as a monotherapy or in combination with other drugs, may be associated with rhabdomyolysis. Creatine kinase levels may normalize or significantly decrease after discontinuation of venlafaxine and symptomatic treatment.
Topics: Rhabdomyolysis; Venlafaxine Hydrochloride; Humans; Male; Adult; Female; Middle Aged; Creatine Kinase; Myalgia
PubMed: 38506608
DOI: 10.1097/JCP.0000000000001838