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The Cochrane Database of Systematic... Feb 2011Depression is a common problem in patients with multiple sclerosis (MS). It is unclear which pharmacologic treatment is the most effective and the least harmful. (Review)
Review
BACKGROUND
Depression is a common problem in patients with multiple sclerosis (MS). It is unclear which pharmacologic treatment is the most effective and the least harmful.
OBJECTIVES
To investigate the efficacy and tolerability of pharmacologic treatments for depression in patients with MS.
SEARCH STRATEGY
We searched the Cochrane Multiple Sclerosis Group's Trials Register (June 2010), reference lists of relevant articles and conference proceedings. Regulatory agencies were used as additional sources of information on adverse effects.
SELECTION CRITERIA
Adequately and quasi-randomized controlled blinded or unblinded trials in children and adults with MS.
EXPERIMENTAL INTERVENTION
pharmacologic treatments for depression without restrictions regarding dose, route of administration, frequency, or duration. Control intervention: placebo treatment or no treatment.
DATA COLLECTION AND ANALYSIS
Two teams of reviewers independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects from the trials.Information about study population, type of intervention, outcome measures, and study design were extracted from the selected studies. Trial quality was evaluated with the criteria: randomization, allocation concealment, blinding, handling of incomplete outcome data, freedom from selective reporting and freedom from other bias.The impact of missing data on the study results was explored with sensitivity analyses comparing the results from the analyses of study completers with those from best- and worst-case scenarios.
MAIN RESULTS
Two trials (70 participants) were included. One trial (28 participants) compared treatment with desipramine for five weeks to placebo. The other trial (42 participants) compared treatment with paroxetine for twelve weeks to placebo. Both trials had a significant number of patients lost to follow-up or with missing outcome measurements.There was a trend towards efficacy of both treatments compared to placebo, but this difference was not statistically significant except for one outcome. Confidence intervals were wide in all analyses and our sensitivity analysis showed that the missing data may have had an important effect in both trials, with large differences between best-case and worst-case scenarios for all assessed outcomes.Both treatments were associated with adverse effects, with significantly more patients treated with paroxetine suffering from nausea or headache. Given the difference in trial duration and type of drug, we decided not to perform a meta-analysis.
AUTHORS' CONCLUSIONS
Both desipramine and paroxetine show a trend towards efficacy in depression in MS the short term, but both treatments were associated with adverse effects, with significantly more patients treated with paroxetine suffering from nausea or headache. Further clinical research on the treatment of depression in MS is clearly needed. Future trials should address the efficacy and tolerability in the long term and compare antidepressant treatments head-to-head.
Topics: Adult; Antidepressive Agents; Depression; Desipramine; Humans; Multiple Sclerosis; Paroxetine; Randomized Controlled Trials as Topic
PubMed: 21328292
DOI: 10.1002/14651858.CD007295.pub2 -
Frontiers in Pharmacology 2022Post-stroke depression (PSD) is a common mental health problem after cerebrovascular accidents. There are several treatments that have been shown to be effective in...
Post-stroke depression (PSD) is a common mental health problem after cerebrovascular accidents. There are several treatments that have been shown to be effective in treating post-stroke depression. However, it is not clear which treatment is more effective. In this meta-analysis, an appropriate search strategy was used to search eligible randomized controlled trials (RCTs) on different treatments to treat patients with Post-stroke depression published up to December 2021 from the CNKI, PubMed, and Cochrane Library. We assessed the mean difference or odds ratio between each treatment and placebo and summarized them as the average and 95% confidence interval (CI) by conducting Bayesian network meta-analyses. By constructing a Bayesian network meta-analysis, we found that acupuncture combined with fluoxetine (vs placebo MD, -8.9; 95% CI, [-15, -2.9]) or paroxetine (vs placebo MD,-8.5; 95% CI, [-15, -2.5]) was the most effective for change in Hamilton depression scale (HAMD) at the end of the 4th week. For change in Hamilton depression scale at the end of the 8th week, rTMS combined with paroxetine (vs placebo MD, -13; 95% CI, [-17, -7.9]) had the greatest amount of change. The efficacy of medication combined with adjuvant therapy was also superior for the percentage of patients with Hamilton depression scale change over 50%. The combination of antidepressants with adjuvant therapy may enhance the efficacy of antidepressants and achieve better results than antidepressant monotherapy in both Hamilton depression scale changes at the end of week 4 or 8 and 50% Hamilton depression scale improvement rate. Acupuncture combined with fluoxetine treatment was more effective in the treatment of post-stroke depression at week 4, while rTMS combined with paroxetine was more effective at week 8. Further research is needed to determine whether acupuncture combined with fluoxetine is better than rTMS combined with paroxetine for post-stroke depression at week 8.
PubMed: 36601053
DOI: 10.3389/fphar.2022.1035895 -
BMC Urology Jan 2015Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). However, tramadol may cause addiction and difficulty in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). However, tramadol may cause addiction and difficulty in breathing and the beneficial effect of tramadol in PE is yet not supported by a high level of evidence. The purpose of this study was to systematically review the evidence from randomised controlled trials (RCT) for tramadol in the management of PE.
METHODS
We searched bibliographic databases including MEDLINE to August 2014 for RCTs. The primary outcome was intra-vaginal ejaculatory latency time (IELT). Methodological quality of RCTs was assessed. Between-group differences in IELT and other outcomes were pooled across RCTs in a meta-analysis. Statistical and clinical between-trial heterogeneity was assessed.
RESULTS
A total of eight RCTs that evaluated tramadol against a comparator were included. The majority of RCTs were of unclear methodological quality due to limited reporting. Pooled evidence (four RCTs, 721 participants), suggests that tramadol is significantly more effective than placebo at increasing IELT over eight to 12 weeks (p = 0.0007). However, a high level of statistical heterogeneity is evident (I-squared = 74%). Single RCT evidence indicates that tramadol is significantly more effective than paroxetine taken on-demand, sildenafil, lidocaine gel, or behavioural therapy on IELT in men with PE. Tramadol is associated with significantly more adverse events including: erectile dysfunction, constipation, nausea, headache, somnolence, dry mouth, dizziness, pruritus, and vomiting, than placebo or behavioural therapy over eight to 12 weeks of treatment. However, addiction problems or breathing difficulties reported by patients for PE is not assessed in the current evidence base.
CONCLUSIONS
Tramadol appears effective in the treatment of PE. However, these findings should be interpreted with caution given the observed levels of between-trial heterogeneity and the reporting quality of the available evidence. The variability across placebo-controlled trials in terms of the tramadol dose evaluated and the treatment duration does not permit any assessment of a safe and effective minimum daily dose. The long-term effects and side effects, including addiction potential, for men with PE have not been evaluated in the current evidence base.
TRIAL REGISTRATION
The review is registered on PROSPERO 2013: CRD42013005289 .
Topics: Drug Administration Schedule; Evidence-Based Medicine; Humans; Male; Off-Label Use; Orgasm; Patient Satisfaction; Premature Ejaculation; Prevalence; Randomized Controlled Trials as Topic; Tramadol; Treatment Outcome
PubMed: 25636495
DOI: 10.1186/1471-2490-15-6 -
The Cochrane Database of Systematic... Apr 2014Paroxetine is the most potent inhibitor of the reuptake of serotonin of all selective serotonin reuptake inhibitors (SSRIs) and has been studied in many randomised... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paroxetine is the most potent inhibitor of the reuptake of serotonin of all selective serotonin reuptake inhibitors (SSRIs) and has been studied in many randomised controlled trials (RCTs). However, these comparative studies provided contrasting findings and systematic reviews of RCTs have always considered the SSRIs as a group, and evidence applicable to this group of drugs might not be applicable to paroxetine alone. The present systematic review assessed the efficacy and tolerability profile of paroxetine in comparison with tricyclics (TCAs), SSRIs and newer or non-conventional agents.
OBJECTIVES
1. To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of Major Depressive Disorder.2. To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.3. To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents.
SEARCH METHODS
We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialized Register (CCDANCTR, to 30 September 2012), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). Reference lists of relevant papers and previous systematic reviews were handsearched. Pharmaceutical companies marketing paroxetine and experts in this field were contacted for supplemental data.
SELECTION CRITERIA
All randomised controlled trials allocating participants with major depression to paroxetine versus any other antidepressants (ADs), both conventional (such as TCAs, SSRIs) and newer or non-conventional (such as hypericum). For trials which had a cross-over design, only results from the first randomisation period were considered.
DATA COLLECTION AND ANALYSIS
Two review authors independently checked eligibility and extracted data using a standard form. Data were then entered in RevMan 5.2 with a double-entry procedure. Information extracted included study and participant characteristics, intervention details, settings and efficacy, acceptability and tolerability measures.
MAIN RESULTS
A total of 115 randomised controlled trials (26,134 participants) were included. In 54 studies paroxetine was compared with older ADs, in 21 studies with another SSRI, and in 40 studies with a newer or non-conventional antidepressant other than SSRIs. For the primary outcome (patients who responded to treatment), paroxetine was more effective than reboxetine at increasing patients who responded early to treatment (Odds Ratio (OR): 0.66, 95% Confidence Interval (CI) 0.50 to 0.87, number needed to treat to provide benefit (NNTb) = 16, 95% CI 10 to 50, at one to four weeks, 3 RCTs, 1375 participants, moderate quality of evidence), and less effective than mirtazapine (OR: 2.39, 95% CI 1.42 to 4.02, NNTb = 8, 95% CI 5 to 14, at one to four weeks, 3 RCTs, 726 participants, moderate quality of evidence). Paroxetine was less effective than citalopram in improving response to treatment (OR: 1.54, 95% CI 1.04 to 2.28, NNTb = 9, 95% CI 5 to 102, at six to 12 weeks, 1 RCT, 406 participants, moderate quality of evidence). We found no clear evidence that paroxetine was more or less effective compared with other antidepressants at increasing response to treatment at acute (six to 12 weeks), early (one to four weeks), or longer term follow-up (four to six months). Paroxetine was associated with a lower rate of adverse events than amitriptyline, imipramine and older ADs as a class, but was less well tolerated than agomelatine and hypericum. Included studies were generally at unclear or high risk of bias due to poor reporting of allocation concealment and blinding of outcome assessment, and incomplete reporting of outcomes.
AUTHORS' CONCLUSIONS
Some possibly clinically meaningful differences between paroxetine and other ADs exist, but no definitive conclusions can be drawn from these findings. In terms of response, there was a moderate quality of evidence that citalopram was better than paroxetine in the acute phase (six to 12 weeks), although only one study contributed data. In terms of early response to treatment (one to four weeks) there was moderate quality of evidence that mirtazapine was better than paroxetine and that paroxetine was better than reboxetine. However there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any time point. Even if some differences were identified, the findings from this review are better thought as hypothesis forming rather than hypothesis testing and it would be reassuring to see the conclusions replicated in future trials. Finally, most of included studies were at unclear or high risk of bias, and were sponsored by the drug industry. The potential for overestimation of treatment effect due to sponsorship bias should be borne in mind.
Topics: Antidepressive Agents; Depression; Humans; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 24696195
DOI: 10.1002/14651858.CD006531.pub2 -
BMJ (Clinical Research Ed.) Oct 2010To assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the... (Meta-Analysis)
Meta-Analysis Review
Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials.
OBJECTIVES
To assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the impact of potential publication bias in trials of reboxetine.
DESIGN
Systematic review and meta-analysis including unpublished data.
DATA SOURCES
Bibliographic databases (Medline, Embase, PsycINFO, BIOSIS, and Cochrane Library), clinical trial registries, trial results databases, and regulatory authority websites up until February 2009, as well as unpublished data from the manufacturer of reboxetine (Pfizer, Berlin).
ELIGIBILITY CRITERIA
Double blind, randomised, controlled trials of acute treatment (six weeks or more) with reboxetine versus placebo or SSRIs in adults with major depression.
OUTCOME MEASURES
Remission and response rates (benefit outcomes), as well as rates of patients with at least one adverse event and withdrawals owing to adverse events (harm outcomes).
DATA EXTRACTION AND DATA SYNTHESIS
The procedures for data extraction and assessment of risk of bias were always conducted by one person and checked by another. If feasible, data were pooled by meta-analyses (random effects model). Publication bias was measured by comparing results of published and unpublished trials.
RESULTS
We analysed 13 acute treatment trials that were placebo controlled, SSRI controlled, or both, which included 4098 patients. Data on 74% (3033/4098) of these patients were unpublished. In the reboxetine versus placebo comparison, no significant differences in remission rates were shown (odds ratio 1.17, 95% confidence interval 0.91 to 1.51; P=0.216). Substantial heterogeneity (I(2)=67.3%) was shown in the meta-analysis of the eight trials that investigated response rates for reboxetine versus placebo. A sensitivity analysis that excluded a small inpatient trial showed no significant difference in response rates between patients receiving reboxetine and those receiving placebo (OR 1.24, 95% CI 0.98 to 1.56; P=0.071; I(2)=42.1%). Reboxetine was inferior to SSRIs (fluoxetine, paroxetine, and citalopram) for remission rates (OR 0.80, 95% CI 0.67 to 0.96; P=0.015) and response rates (OR 0.80, 95% CI 0.67 to 0.95; P=0.01). Reboxetine was inferior to placebo for both harm outcomes (P<0.001 for both), and to fluoxetine for withdrawals owing to adverse events (OR 1.79, 95% CI 1.06 to 3.05; P=0.031). Published data overestimated the benefit of reboxetine versus placebo by up to 115% and reboxetine versus SSRIs by up to 23%, and also underestimated harm.
CONCLUSIONS
Reboxetine is, overall, an ineffective and potentially harmful antidepressant. Published evidence is affected by publication bias, underlining the urgent need for mandatory publication of trial data.
Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Humans; Morpholines; Publication Bias; Randomized Controlled Trials as Topic; Reboxetine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 20940209
DOI: 10.1136/bmj.c4737 -
Orphanet Journal of Rare Diseases May 2018Origin of anorectal malformations (ARM) are considered multifactorial. Several genetic and non-genetic risk factors are discussed in literature. Maternal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Origin of anorectal malformations (ARM) are considered multifactorial. Several genetic and non-genetic risk factors are discussed in literature. Maternal periconceptional medical drug use as possible risk factor, however, has not been reviewed systematically.
METHODS
Studies published between 1977 and April 2017 were reviewed through systematic search in PubMed, ISI Web of Knowledge and Scopus databases. Furthermore, related and cross-referencing publications were reviewed. Pooled odds ratios (95% confidence intervals) were determined to quantify associations of maternal periconceptional use of folic acid, multivitamins, anti-asthma medication (separated in any anti-asthma medication, inhaled corticosteroids and salbutamol), thyroid hormone supplements, psychiatric drugs (separated in antidepressants, any selective serotonin reuptake inhibitors [SSRI], sertraline, citalopram, fluoxetine, paroxetine, hypnotics and benzodiazepine) and aspirin with ARM using meta-analyses.
RESULTS
Thirty-seven studies that reported on the association between maternal periconceptional drug intake and infants born with ARM were included in this review. These were conducted in the United States of America (n = 14), Sweden (n = 6), Hungary (n = 5), Germany (n = 3), the Netherlands (n = 3), Denmark (n = 2), France (n = 2), Norway (n = 1) and the UK (n = 1). However, only few of these studies reported on the same risk factors. Studies were heterogeneous with respect to case numbers, period ingestion of medical drug use, control selection and adjustment for covariates. Consistently increased risks were observed for any anti-asthma medication, and hypnotics and benzodiazepine, but not for folic acid, multivitamins, inhaled corticosteroids, salbutamol, thyroid hormone supplements, antidepressants, any SSRI, sertraline, citalopram, fluoxetine, paroxetine and aspirin. In meta-analyses, pooled odds ratios (95% confidence intervals) for any anti-asthma medication, and hypnotics and benzodiazepine were 1.64 (1.22-2.21), and 2.43 (1.03-5.73), respectively.
CONCLUSION
Evidence on maternal drug use before conception and during pregnancy as risk factor for ARM from epidemiological studies is still very limited. Nevertheless, the few available studies indicate any anti-asthma medication, and hypnotics and benzodiazepine to be associated with increased risks. Further, ideally large-scale multicenter and register-based studies are needed to clarify the role of maternal drug intake for the development of ARM.
Topics: Anorectal Malformations; Anti-Asthmatic Agents; Anus, Imperforate; Benzodiazepines; Congenital Abnormalities; Female; Humans; Hypnotics and Sedatives; Pregnancy; Risk Factors
PubMed: 29747656
DOI: 10.1186/s13023-018-0789-3 -
The Cochrane Database of Systematic... 2003Tricyclic antidepressants are still extensively prescribed worldwide. Evidence for the recommended dosage of tricyclics, however, is poor. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tricyclic antidepressants are still extensively prescribed worldwide. Evidence for the recommended dosage of tricyclics, however, is poor.
OBJECTIVES
To compare the effects and side effects of low dosage tricyclic antidepressants with placebo and with standard dosage tricyclics in acute phase treatment of depression.
SEARCH STRATEGY
Electronic search of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), incorporating results of group searches of MEDLINE (1966-), EMBASE (1980-), CINAHL (1982-), PsycLIT (1974-), PSYNDEX (1977-) and LILACS (1982-1999) and hand searches of major psychiatric and medical journals. Reference search and SciSearch of the identified studies. Personal contact with authors of significant papers.
SELECTION CRITERIA
All randomised controlled trials 1) comparing low dosage TCA (=< 100 mg/d on average at the end of trial) with placebo or 2) comparing low and standard dosages of the same TCA, in acute phase treatment of depressive disorder
DATA COLLECTION AND ANALYSIS
Two independent reviewers examined eligibility of the identified studies, and extracted data for outcomes at 1 week, 2 weeks, 4 weeks, 6-8 weeks and later. Main outcome measures were relative risk of response in depression (random effects model), according to the original authors' definition but usually defined as 50% or greater reduction in severity of depression according to the last-observation-carried-forward intention-to-treat method, and relative risks of overall dropouts and dropouts due to side effects. Other outcome measures included worst-case-scenario intention-to-treat analysis of response as defined above (in which dropouts were considered non-responders in the active treatment group and as responders in the comparison group), and standardised weighted mean scores of continuous depression severity scales (usually calculated by last-observation-carried-forward method).
MAIN RESULTS
35 studies (2013 participants) compared low dosage tricyclics with placebo, and six studies (551 participants) compared low dosage tricyclics with standard dosage tricyclics. Low dosage tricyclics, mostly between 75 and 100 mg/day, were 1.65 (95% confidence interval 1.36 to 2.0) and 1.47 (1.12 to 1.94) times more likely than placebo to bring about response at 4 weeks and 6-8 weeks, respectively. Standard dosage tricyclics failed, however, to bring about more response but produced more dropouts due to side effects than low dosage tricyclics.
REVIEWER'S CONCLUSIONS
Treatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of varying dosages.
Topics: Antidepressive Agents, Tricyclic; Depression; Humans; Randomized Controlled Trials as Topic
PubMed: 12917952
DOI: 10.1002/14651858.CD003197 -
Journal of General Internal Medicine Apr 2002This review synthesizes available evidence for managing clinically significant dysphoric symptoms encountered in primary care, when formal criteria for major depression... (Review)
Review
OBJECTIVE
This review synthesizes available evidence for managing clinically significant dysphoric symptoms encountered in primary care, when formal criteria for major depression or dysthymia are not met. Discussion is focused on premenstrual dysphoric disorder (PMDD) and minor depression because of their significant prevalence in the primary care setting and the lack of clear practice guidelines for addressing each illness.
DESIGN
English language literature from prior systematic reviews was supplemented by searching medline, embase, the Cochrane Controlled Trials Registry, the Agency for Healthcare Research and Quality National Guideline Clearinghouse, and bibliographies of selected papers. Studies addressing the natural history or treatment of minor depression or PMDD were selected for review. Data were abstracted by 1 of 2 independent reviewers and studies were synthesized qualitatively.
RESULTS
Five individual studies that compared antidepressant or psychological treatments to placebo in patients with minor depression suggest short-term improvements in depressive symptoms with paroxetine, problem-solving therapy, and cognitive behavioral therapy, but not with amitryptiline. Modest benefits on mental health function were reported with paroxetine and with problem-solving therapy, but only in patients with severe functional impairment at baseline. Twenty-four controlled trials were identified that compared antidepressant or psychological treatments to placebo in patients with premenstrual dysphoric disorder. Pooled results from a recent systematic review of 15 randomized controlled trials and one additional trial abstract provide strong evidence for a significantly greater improvement in physical and psychological symptoms with serotonin-selective reuptake inhibitor medications when compared with placebo. Individual trials also suggest significantly greater improvements in symptom scores with venlafaxine, but not with tricyclic antidepressants.
CONCLUSIONS
The limited evidence base for minor depression provides only mixed support for a small to moderate benefit for few antidepressant medications and psychological treatments tested. For the treatment of severe psychological or physical symptoms causing functional impairment in patients with PMDD, sertraline and fluoxetine are clearly beneficial in carefully selected patients.
Topics: Antidepressive Agents; Combined Modality Therapy; Complementary Therapies; Depressive Disorder; Female; Humans; Male; Prognosis; Psychotherapy; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 11972726
DOI: 10.1046/j.1525-1497.2002.10350.x -
The Cochrane Database of Systematic... Jan 2014There are at least three reasons to believe antidepressants might help in smoking cessation. Firstly, nicotine withdrawal may produce depressive symptoms or precipitate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are at least three reasons to believe antidepressants might help in smoking cessation. Firstly, nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Secondly, nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Finally, some antidepressants may have a specific effect on neural pathways (e.g. inhibiting monoamine oxidase) or receptors (e.g. blockade of nicotinic-cholinergic receptors) underlying nicotine addiction.
OBJECTIVES
The aim of this review is to assess the effect and safety of antidepressant medications to aid long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; lazabemide; moclobemide; nortriptyline; paroxetine; S-Adenosyl-L-Methionine (SAMe); selegiline; sertraline; St. John's wort; tryptophan; venlafaxine; and zimeledine.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialised Register which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, and other reviews and meeting abstracts, in July 2013.
SELECTION CRITERIA
We considered randomized trials comparing antidepressant medications to placebo or an alternative pharmacotherapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation or to help smokers reduce cigarette consumption. We excluded trials with less than six months follow-up.
DATA COLLECTION AND ANALYSIS
We extracted data and assessed risk of bias using standard methodological procedures expected by the Cochrane Collaboration.The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline, expressed as a risk ratio (RR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model.
MAIN RESULTS
Twenty-four new trials were identified since the 2009 update, bringing the total number of included trials to 90. There were 65 trials of bupropion and ten trials of nortriptyline, with the majority at low or unclear risk of bias. There was high quality evidence that, when used as the sole pharmacotherapy, bupropion significantly increased long-term cessation (44 trials, N = 13,728, risk ratio [RR] 1.62, 95% confidence interval [CI] 1.49 to 1.76). There was moderate quality evidence, limited by a relatively small number of trials and participants, that nortriptyline also significantly increased long-term cessation when used as the sole pharmacotherapy (six trials, N = 975, RR 2.03, 95% CI 1.48 to 2.78). There is insufficient evidence that adding bupropion (12 trials, N = 3487, RR 1.9, 95% CI 0.94 to 1.51) or nortriptyline (4 trials, N = 1644, RR 1.21, 95% CI 0.94 to 1.55) to nicotine replacement therapy (NRT) provides an additional long-term benefit. Based on a limited amount of data from direct comparisons, bupropion and nortriptyline appear to be equally effective and of similar efficacy to NRT (bupropion versus nortriptyline 3 trials, N = 417, RR 1.30, 95% CI 0.93 to 1.82; bupropion versus NRT 8 trials, N = 4096, RR 0.96, 95% CI 0.85 to 1.09; no direct comparisons between nortriptyline and NRT). Pooled results from four trials comparing bupropion to varenicline showed significantly lower quitting with bupropion than with varenicline (N = 1810, RR 0.68, 95% CI 0.56 to 0.83). Meta-analyses did not detect a significant increase in the rate of serious adverse events amongst participants taking bupropion, though the confidence interval only narrowly missed statistical significance (33 trials, N = 9631, RR 1.30, 95% CI 1.00 to 1.69). There is a risk of about 1 in 1000 of seizures associated with bupropion use. Bupropion has been associated with suicide risk, but whether this is causal is unclear. Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation.There was no evidence of a significant effect for selective serotonin reuptake inhibitors on their own (RR 0.93, 95% CI 0.71 to 1.22, N = 1594; 2 trials fluoxetine, 1 paroxetine, 1 sertraline) or as an adjunct to NRT (3 trials of fluoxetine, N = 466, RR 0.70, 95% CI 0.64 to 1.82). Significant effects were also not detected for monoamine oxidase inhibitors (RR 1.29, 95% CI 0.93 to 1.79, N = 827; 1 trial moclobemide, 5 selegiline), the atypical antidepressant venlafaxine (1 trial, N = 147, RR 1.22, 95% CI 0.64 to 2.32), the herbal therapy St John's wort (hypericum) (2 trials, N = 261, RR 0.81, 95% CI 0.26 to 2.53), or the dietary supplement SAMe (1 trial, N = 120, RR 0.70, 95% CI 0.24 to 2.07).
AUTHORS' CONCLUSIONS
The antidepressants bupropion and nortriptyline aid long-term smoking cessation. Adverse events with either medication appear to rarely be serious or lead to stopping medication. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement. Evidence also suggests that bupropion is less effective than varenicline, but further research is needed to confirm this finding. Evidence suggests that neither selective serotonin reuptake inhibitors (e.g. fluoxetine) nor monoamine oxidase inhibitors aid cessation.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Bupropion; Humans; Nortriptyline; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Smoking; Smoking Cessation; Tobacco Use Cessation Devices
PubMed: 24402784
DOI: 10.1002/14651858.CD000031.pub4 -
The Journal of Clinical Psychiatry Apr 2013Depression is often not optimally treated during pregnancy, partially because of conflicting data regarding antidepressant medication risk. This meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Depression is often not optimally treated during pregnancy, partially because of conflicting data regarding antidepressant medication risk. This meta-analysis was conducted to determine whether antenatal antidepressant exposure is associated with congenital malformations and to assess the effect of known methodological limitations.
DATA SOURCES
EMBASE, CINAHL, PsycINFO, and MEDLINE were searched from their start dates to June 2010. Keywords of various combinations were used, including, but not limited to depressive/mood disorder, pregnancy, antidepressant drug/agent, congenital malformation, and cardiac malformation.
STUDY SELECTION
English language studies reporting congenital malformations associated with antidepressants were included. Of 3,074 abstracts reviewed, 735 studies were retrieved and 27 studies were included.
DATA EXTRACTION
Two reviewers working independently assessed article quality. Data on use of any antidepressant, including fluoxetine and paroxetine specifically, were extracted. Outcomes included congenital malformations, major congenital malformations, cardiovascular defects, septal heart defects (ventral septal defects and atrial septal defects), and ventral septal defects only.
RESULTS
Nineteen studies were above quality threshold and make up the primary meta-analyses. Pooled relative risks (RRs) were derived by using random-effects methods. Antidepressant exposure was not associated with congenital malformations (RR = 0.93; 95% CI, 0.85-1.02; P = .113) or major malformations (RR = 1.07; 95% CI, 0.99-1.17; P = .095). However, increased risk for cardiovascular malformations (RR = 1.36; 95% CI, 1.08-1.71; P = .008) and septal heart defects (RR = 1.40; 95% CI, 1.10-1.77; P = .005) were found; the RR for ventral septal defects was similar to septal defects, although not significant (RR = 1.54; 95% CI, 0.71-3.33; P = .274). Pooled effects were significant for paroxetine and cardiovascular malformations (RR = 1.43; 95% CI, 1.08-1.88; P = .012). These results are contrasted with those addressing methodological limitations but are typically consistent.
CONCLUSIONS
Overall, antidepressants do not appear to be associated with an increased risk of congenital malformations, but statistical significance was found for cardiovascular malformations. Results were robust in several sensitivity analyses. Given that the RRs are marginal, they may be the result of uncontrolled confounders. Although the RRs were statistically significant, none reached clinically significant levels.
Topics: Abnormalities, Drug-Induced; Adult; Antidepressive Agents; Evidence-Based Medicine; Female; Heart Defects, Congenital; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 23656855
DOI: 10.4088/JCP.12r07966