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Lancet (London, England) Jul 2022Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.
METHODS
In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ.
FINDINGS
We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]).
INTERPRETATION
Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice.
FUNDING
UK National Institute for Health Research Oxford Health Biomedical Research Centre.
Topics: Adult; Benzodiazepines; Doxepin; Eszopiclone; Humans; Melatonin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Zolpidem
PubMed: 35843245
DOI: 10.1016/S0140-6736(22)00878-9 -
The Cochrane Database of Systematic... May 2018Insomnia disorder is a subjective condition of unsatisfactory sleep (e.g. sleep onset, maintenance, early waking, impairment of daytime functioning). Insomnia disorder... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Insomnia disorder is a subjective condition of unsatisfactory sleep (e.g. sleep onset, maintenance, early waking, impairment of daytime functioning). Insomnia disorder impairs quality of life and is associated with an increased risk of physical and mental health problems including anxiety, depression, drug and alcohol abuse, and increased health service use. hypnotic medications (e.g. benzodiazepines and 'Z' drugs) are licensed for sleep promotion, but can induce tolerance and dependence, although many people remain on long-term treatment. Antidepressant use for insomnia is widespread, but none is licensed for insomnia and the evidence for their efficacy is unclear. This use of unlicensed medications may be driven by concern over longer-term use of hypnotics and the limited availability of psychological treatments.
OBJECTIVES
To assess the effectiveness, safety and tolerability of antidepressants for insomnia in adults.
SEARCH METHODS
This review incorporated the results of searches to July 2015 conducted on electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 6), MEDLINE (1950 to 2015), Embase (1980 to 2015) and PsycINFO (1806 to 2015). We updated the searches to December 2017, but these results have not yet been incorporated into the review.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of adults (aged 18 years or older) with a primary diagnosis of insomnia and all participant types including people with comorbidities. Any antidepressant as monotherapy at any dose whether compared with placebo, other medications for insomnia (e.g. benzodiazepines and 'Z' drugs), a different antidepressant, waiting list control or treatment as usual.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility and extracted data using a data extraction form. A third review author resolved disagreements on inclusion or data extraction.
MAIN RESULTS
The search identified 23 RCTs (2806 participants).Selective serotonin reuptake inhibitors (SSRIs) compared with placebo: three studies (135 participants) compared SSRIs with placebo. Combining results was not possible. Two paroxetine studies showed significant improvements in subjective sleep measures at six (60 participants, P = 0.03) and 12 weeks (27 participants, P < 0.001). There was no difference in the fluoxetine study (low quality evidence).There were either no adverse events or they were not reported (very low quality evidence).Tricyclic antidepressants (TCA) compared with placebo: six studies (812 participants) compared TCA with placebo; five used doxepin and one used trimipramine. We found no studies of amitriptyline. Four studies (518 participants) could be pooled, showing a moderate improvement in subjective sleep quality over placebo (standardised mean difference (SMD) -0.39, 95% confidence interval (CI) -0.56 to -0.21) (moderate quality evidence). Moderate quality evidence suggested that TCAs possibly improved sleep efficiency (mean difference (MD) 6.29 percentage points, 95% CI 3.17 to 9.41; 4 studies; 510 participants) and increased sleep time (MD 22.88 minutes, 95% CI 13.17 to 32.59; 4 studies; 510 participants). There may have been little or no impact on sleep latency (MD -4.27 minutes, 95% CI -9.01 to 0.48; 4 studies; 510 participants).There may have been little or no difference in adverse events between TCAs and placebo (risk ratio (RR) 1.02, 95% CI 0.86 to 1.21; 6 studies; 812 participants) (low quality evidence).'Other' antidepressants with placebo: eight studies compared other antidepressants with placebo (one used mianserin and seven used trazodone). Three studies (370 participants) of trazodone could be pooled, indicating a moderate improvement in subjective sleep outcomes over placebo (SMD -0.34, 95% CI -0.66 to -0.02). Two studies of trazodone measured polysomnography and found little or no difference in sleep efficiency (MD 1.38 percentage points, 95% CI -2.87 to 5.63; 169 participants) (low quality evidence).There was low quality evidence from two studies of more adverse effects with trazodone than placebo (i.e. morning grogginess, increased dry mouth and thirst).
AUTHORS' CONCLUSIONS
We identified relatively few, mostly small studies with short-term follow-up and design limitations. The effects of SSRIs compared with placebo are uncertain with too few studies to draw clear conclusions. There may be a small improvement in sleep quality with short-term use of low-dose doxepin and trazodone compared with placebo. The tolerability and safety of antidepressants for insomnia is uncertain due to limited reporting of adverse events. There was no evidence for amitriptyline (despite common use in clinical practice) or for long-term antidepressant use for insomnia. High-quality trials of antidepressants for insomnia are needed.
Topics: Adult; Antidepressive Agents; Antidepressive Agents, Tricyclic; Fluoxetine; Humans; Mianserin; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sleep Initiation and Maintenance Disorders; Trazodone
PubMed: 29761479
DOI: 10.1002/14651858.CD010753.pub2 -
Health Technology Assessment... 2000Atopic eczema is the commonest inflammatory skin disease of childhood, affecting 15-20% of children in the UK at any one time. Adults make up about one-third of all... (Review)
Review
BACKGROUND
Atopic eczema is the commonest inflammatory skin disease of childhood, affecting 15-20% of children in the UK at any one time. Adults make up about one-third of all community cases. Moderate-to-severe atopic eczema can have a profound effect on the quality of life for both sufferers and their families. In addition to the effects of intractable itching, skin damage, soreness, sleep loss and the social stigma of a visible skin disease, other factors such as frequent visits to doctors, special clothing and¿the need to constantly apply messy topical applications all add to the burden of disease. The cause of atopic eczema is unknown, though a genetic pre-disposition and a combination of allergic and non-allergic factors appear to be important in determining disease expression. Treatment of atopic eczema in the UK is characterised by a profusion of treatments aimed at disease control. The evidential basis of these treatments is often unclear. Most people with atopic eczema are managed in primary care where the least research has been done.
OBJECTIVES
The objectives of this scoping review are two-fold. To produce an up-to-date coverage 'map' of randomised controlled trials (RCTs) of treatments of atopic eczema. To assist in making treatment recommendations by summarising the available RCT evidence using qualitative and quantitative methods.
DATA SOURCES
Data sources included electronic searching of MEDLINE, EMBASE, the Cochrane Controlled Clinical Trials Register, the Cochrane Skin Group specialised register of trials, hand-searching of atopic eczema conference proceedings, follow-up of references in retrieved articles, contact with leading researchers and requests to relevant pharmaceutical companies.
INCLUSION/EXCLUSION CRITERIA
Only RCTs of therapeutic agents used in the prevention and treatment of people with atopic eczema of any age were considered for inclusion. Only studies where a physician diagnosed atopic eczema or atopic dermatitis were included.
DATA EXTRACTION
Data extraction was conducted by two observers onto abstraction forms, with discrepancies resolved by discussion.
QUALITY ASSESSMENT
The quality assessment of retrieved RCTs included an assessment of: a clear description of method and concealment of allocation of randomisation, the degree to which assessors and participants were blinded to the study interventions, and whether all those originally randomised were included in the final main analysis.
DATA SYNTHESIS
Where possible, quantitative pooling of similar RCTs was conducted using the Cochrane Collaboration's methods. Where statistical heterogeneity was found, sources of heterogeneity in terms of study participants, formulation or posology of intervention, and use of co-treatments were explored. Where pooling was not deemed to be appropriate, detailed descriptions of the study characteristics and main reported results were presented along with comments on study quality.
RESULTS
A total of 1165 possible RCTs were retrieved in hard copy form for further scrutiny. Of these, 893 were excluded from further analysis because of lack of appropriate data. The 272 remaining RCTs of atopic eczema covered at least 47 different interventions, which could be broadly categorised into ten main groups. Quality of reporting was generally poor, and limited statistical pooling was possible only for oral cyclosporin, and only then after considerable data transformation. There was reasonable RCT evidence to support the use of oral cyclosporin, topical corticosteroids, psychological approaches and ultraviolet light therapy. There was insufficient evidence to make recommendations on maternal allergen avoidance for disease prevention, oral antihistamines, Chinese herbs, dietary restriction in established atopic eczema, homeopathy, house dust mite reduction, massage therapy, hypnotherapy, evening primrose oil, emollients, topical coal tar and topical doxepin. (ABSTRACT TRUNCATED)
Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Anti-Infective Agents; Clinical Trials as Topic; Complementary Therapies; Dermatitis, Atopic; Desensitization, Immunologic; Diet; Drugs, Chinese Herbal; Eczema; Histamine H1 Antagonists; Humans; Immunosuppressive Agents; Randomized Controlled Trials as Topic; Research Design
PubMed: 11134919
DOI: No ID Found -
Acta Odontologica Latinoamericana : AOL Apr 2023Oral mucositis (OM) is a frequent complication in cancer patients who are undergoing chemotherapy or radiotherapy. It manifests as an inflammation of the oral mucosa,...
UNLABELLED
Oral mucositis (OM) is a frequent complication in cancer patients who are undergoing chemotherapy or radiotherapy. It manifests as an inflammation of the oral mucosa, sometimes provoking severe consequences such as eating limitations, difficulty in speaking, and possibly superinfection.
AIM
The aim of this review was to update the evidence published during the last five years on the treatment of oral mucositis induced by radiotherapy and/or chemotherapy in patients with cancer.
MATERIALS AND METHOD
A search was conducted in Pubmed, Scielo and Scopus, using the search terms mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, with Mesh terms and free terms, from 2017 to January 2023. The systematic review was conducted in accordance with the PRISMA guidelines.
RESULTS
A total 287 articles were retrieved, of which 86 were selected by title and abstract, and 18 were included after full-text analysis. The most frequently assessed variables were OM severity, pain intensity and healing time. Treatment types were diverse, and included drugs, mouthwashes, medicines based on plant extracts, cryotherapy and low-intensity laser therapies.
CONCLUSION
Dentoxol mouthwashes, Plantago major extract, thyme honey extract, zinc oxide paste, vitamin B complex combined with GeneTime, and the consumption of L-glutamine are effective in diminishing the severity of OM. Pain intensity was lower with doxepin mouthwashes and diphenhydramine-lidocaine-antacid mouthwashes.
Topics: Humans; Mucositis; Radiotherapy
PubMed: 37314054
DOI: 10.54589/aol.36/1/3 -
The Cochrane Database of Systematic... 2000There are two reasons to believe anxiolytics might help in smoking cessation. Anxiety may be a symptom of nicotine withdrawal. Second, smoking appears to be due, in... (Review)
Review
BACKGROUND
There are two reasons to believe anxiolytics might help in smoking cessation. Anxiety may be a symptom of nicotine withdrawal. Second, smoking appears to be due, in part, to deficits in dopamine, serotonin and norepinephrine, all of which are increased by anxiolytics and antidepressants.
OBJECTIVES
The aim of this review is to assess the effectiveness of anxiolytic drugs in aiding long term smoking cessation. The drugs include buspirone; diazepam; doxepin; meprobamate; ondansetron; and the beta-blockers metoprolol, oxprenolol and propanolol.
SEARCH STRATEGY
We searched the Cochrane Tobacco Addiction Group trials register which includes trials indexed in Medline, Embase, SciSearch and PsycLit, and meetings abstracts.
SELECTION CRITERIA
We considered randomized trials comparing anxiolytic drugs to placebo or an alternative therapeutic control for smoking cessation. We excluded trials with less than 6 months follow-up.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate on the type of study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effects model.
MAIN RESULTS
There was one trial each of the anxiolytics diazepam, meprobamate, metoprolol and oxprenolol. There were two trials of the anxiolytic buspirone. None of the trials showed strong evidence of an effect for any of these drugs in helping smokers to quit. However, confidence intervals were wide, and an effect of anxiolytics cannot be ruled out on current evidence.
REVIEWER'S CONCLUSIONS
There is no consistent evidence that anxiolytics aid smoking cessation, but the available evidence does not rule out a possible effect.
Topics: Adrenergic beta-Antagonists; Anti-Anxiety Agents; Humans; Smoking; Smoking Cessation
PubMed: 11034774
DOI: 10.1002/14651858.CD002849 -
The Cochrane Database of Systematic... Jul 2008Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use,... (Review)
Review
BACKGROUND
Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use, hypersalivation, sometimes of a gross and socially unacceptable quantity, is also common (30-80%).
OBJECTIVES
To determine the clinical effects of pharmacological interventions for clozapine-induced hypersalivation.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials.
SELECTION CRITERIA
We included randomised controlled trials comparing pharmacological interventions, at any dose and by any route of administration, for clozapine-induced hypersalivation.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data (homogenous) we calculated relative risk (RR) with 95% confidence intervals (CI) and numbers needed to treat (NNT) on an intention-to-treat basis. We calculated weighted mean difference (WMD) for continuous data.
MAIN RESULTS
Of the 15 trials identified, 14 were conducted in China and 14 in hospitals. The quality of reporting was poor with no studies clearly describing allocation concealment and much data were missing or unusable. All results are vulnerable to considerable bias. Most frequently the primary outcome was the diameter of the wet patch on the pillow. Antimuscarinics (astemizole, diphenhydramine, propantheline, doxepin) were the most commonly evaluated drugs. For the outcome of 'no clinically important improvement' astemizole and diphenhydramine were more effective than placebo (astemizole: n=97, 2 RCTs, RR 0.61 CI 0.47 to 0.81 NNT 3 CI 2 to 5; diphenhydramine: n=131, 2 RCTs, RR 0.43 CI 0.31 to 0.58, NNT 2 CI 1.5 to 2.5), but the doses of astemizole used were those that can cause toxicity. Data involving propantheline were heterogeneous (I2= 86.6%), but both studies showed benefit over placebo. Adverse effects were poorly recorded. Of the other interventions, oryzanol (rice bran oil and rice embryo oil extract) showed benefit over the antimuscarinic doxepin in terms of 'no clinically important change' (n=104, 1 RCT, RR 0.45 CI 0.27 to 0.75, NNT 4 CI 2 to 7). The Chinese medicine suo quo wan (comprises spicebush root, Chinese yam and bitter cardamom) showed benefit over doxepin (n=70, 1 RCT, RR 'no clinically important change' 0.31 CI 0.16 to 0.59, NNT 3 CI 1.5 to 3.7).
AUTHORS' CONCLUSIONS
There are currently insufficient data to confidently inform clinical practice. The limitations of these studies are plentiful and the risk of bias is high. These trials, however, are invaluable guides for current and future study design. Well conducted randomised trials are possible. Some may be underway. Current practice outside of well designed randomised trials should be clearly justified.
Topics: Antipsychotic Agents; Clozapine; Drugs, Chinese Herbal; Muscarinic Antagonists; Phenylpropionates; Randomized Controlled Trials as Topic; Sialorrhea
PubMed: 18646130
DOI: 10.1002/14651858.CD005579.pub2 -
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 Cochrane Database of Systematic... Oct 2015Factors contributing to subjective fatigue in people with idiopathic Parkinson's disease (PD) are not well known. This makes it difficult to manage fatigue effectively... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Factors contributing to subjective fatigue in people with idiopathic Parkinson's disease (PD) are not well known. This makes it difficult to manage fatigue effectively in PD.
OBJECTIVES
To evaluate the effects of pharmacological and non-pharmacological interventions, compared to an inactive control intervention, on subjective fatigue in people with PD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE (via PubMed); Ovid EMBASE; EBSCO CINAHL; Ovid PsycINFO; PEDro; and the WHO International Clinical Trials Registry Platform Search Portal up to April 2015. References of included studies and identified review articles were screened for additional studies. There were no restrictions based on language, date of publication or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that report on subjective fatigue in people with PD.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data collection and risk of bias assessments.
MAIN RESULTS
Eleven studies were eligible for this systematic review, with a total of 1817 people. Three studies included only people who experienced clinically relevant fatigue (Fatigue Severity Scale score ≥ 4 out of 7 or Multidimensional Fatigue Inventory total score > 48 out of 100), whereas all other studies did not select participants on the basis of experienced fatigue. Nine studies investigated the effects of medication (i.e. levodopa-carbidopa, memantine, rasagiline, caffeine, methylphenidate, modafinil or doxepin) on subjective fatigue. All studies were placebo controlled. There was insufficient evidence to determine the effect of doxepin on the impact of fatigue on activities in daily life (ADL) or fatigue severity (one study, N = 12, standardised mean difference (SMD) = -1.50, 95% confidence interval (CI) -2.84 to -0.15; low quality evidence). We found high quality evidence that rasagiline reduced or slowed down the progression of physical aspects of fatigue (one study, N = 1176, SMD = -0.27, 95% CI -0.39 to -0.16, I(2) = 0%). None of the other pharmacological interventions affected subjective fatigue in PD. With regard to adverse effects, only levodopa-carbidopa showed an increase for the risk of nausea (one study, N = 361, risk ratio (RR) = 1.85, 95% CI 1.05 to 3.27; high quality evidence). Two studies investigated the effect of exercise on fatigue compared with usual care. We found low quality evidence for the effect of exercise on reducing the impact of fatigue on ADL or fatigue severity (two studies, N = 57, SMD = -0.45, 95% CI -1.21 to 0.32, I(2) = 44%).
AUTHORS' CONCLUSIONS
Based on the current evidence, no clear recommendations for the treatment of subjective fatigue in PD can be provided. Doxepin may reduce the impact of fatigue on ADL and fatigue severity; however, this finding has to be confirmed in high quality studies. Rasagiline may be effective in reducing levels of physical fatigue in PD. No evidence was found for the effectiveness of levodopa-carbidopa, memantine, caffeine, methylphenidate, modafinil or exercise. Studies are needed to investigate the effect of exercise intensity on exercise capacity and subjective fatigue. Future studies should focus on interventions that address the maladaptive behavioural or cognitive aspects of fatigue in people with PD. Characteristics, such as severity and nature of perceived fatigue and underlying mood disorders should be considered to identify responders and non-responders when studying interventions for fatigue. The development of a core-set of self-report fatigue questionnaires with established responsiveness and known minimal important difference values will facilitate the interpretation of change in fatigue scores.
Topics: Central Nervous System Stimulants; Dopamine Agents; Exercise; Fatigue; Humans; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 26447539
DOI: 10.1002/14651858.CD010925.pub2 -
Anais Brasileiros de Dermatologia 2016Among the wide range of symptoms neglected or resistant to conventional treatments in clinical practice, itch is emerging gradually as a theme to be studied. Itch... (Review)
Review
Among the wide range of symptoms neglected or resistant to conventional treatments in clinical practice, itch is emerging gradually as a theme to be studied. Itch complaints and the negative effects in the quality of life are observed in several medical fields. Although the partially obscure pathophysiology, some researchers decided to check and test the use of psychotropic drugs in resistant itch to conventional topical treatments and antihistamines. The objective of this study was to evaluate scientific evidence in psychotropic use in the treatment of itch of various causes. This is a systematic review of scientific literature. The following databases were used: PubMed, Web of Science, Scopus and Scielo. Randomized controlled trials that should focus on treatment with psychotropic drugs of pruritus of various causes were the inclusion criteria. All articles were analyzed by the authors, and the consensus was reached in cases of disagreement. Fifteen articles were included after analysis and selection in databases, with the majority of clinical trials focusing on psychopharmacological treatment of itch on account of chronic kidney disease. Clinical trials with psychotropic drugs mostly indicated significant improvement in the itching. In most trials of chronic kidney disease as basal disease for itch, greater effectiveness was observed with the use of psychotropic drugs compared with placebo or other antipruritic. However, the small amount of controlled trials conducted precludes the generalization that psychiatric drugs are effective for itch of various causes.
Topics: Amines; Antipruritics; Cyclohexanecarboxylic Acids; Doxepin; Gabapentin; Humans; Kidney Diseases; Pruritus; Psychotropic Drugs; Randomized Controlled Trials as Topic; Reproducibility of Results; Treatment Outcome; gamma-Aminobutyric Acid
PubMed: 28099602
DOI: 10.1590/abd1806-4841.20164878 -
The Cochrane Database of Systematic... Apr 2018Alcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The co-occurrence of major depression in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The co-occurrence of major depression in people entering treatment for alcohol dependence is common, and represents a risk factor for morbidity and mortality, which negatively influences treatment outcomes.
OBJECTIVES
To assess the benefits and risks of antidepressants for the treatment of people with co-occurring depression and alcohol dependence.
SEARCH METHODS
We searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2017. We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/).All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies.
SELECTION CRITERIA
Randomized controlled trials and controlled clinical trials comparing antidepressants alone or in association with other drugs or psychosocial interventions (or both) versus placebo, no treatment, and other pharmacological or psychosocial interventions.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane.
MAIN RESULTS
We included 33 studies in the review (2242 participants). Antidepressants were compared to placebo (22 studies), psychotherapy (two studies), other medications (four studies), or other antidepressants (five studies). The mean duration of the trials was 9.9 weeks (range 3 to 26 weeks). Eighteen studies took place in the USA, 12 in Europe, two in Turkey, and one in Australia. The antidepressant included in most of the trials was sertraline; other medications were amitriptyline, citalopram, desipramine, doxepin, escitalopram, fluoxetine, fluvoxamine, imipramine, mianserin, mirtazepine, nefazodone, paroxetine, tianeptine, venlafaxine, and viloxazine. Eighteen studies were conducted in an outpatient setting, nine in an inpatient setting, and six in both settings. Psychosocial treatment was provided in 18 studies. There was high heterogeneity in the selection of outcomes and the rating systems used for diagnosis and outcome assessment.Comparing antidepressants to placebo, low-quality evidence suggested that antidepressants reduced the severity of depression evaluated with interviewer-rated scales at the end of trial (14 studies, 1074 participants, standardized mean difference (SMD) -0.27, 95% confidence interval (CI) -0.49 to -0.04). However, the difference became non-significant after the exclusion of studies with a high risk of bias (SMD -0.17, 95% CI -0.39 to 0.04). In addition, very low-quality evidence supported the efficacy of antidepressants in increasing the response to the treatment (10 studies, 805 participants, risk ratio (RR) 1.40, 95% Cl 1.08 to 1.82). This result became non-significant after the exclusion of studies at high risk of bias (RR 1.27, 95% CI 0.96 to 1.68). There was no difference for other relevant outcomes such as the difference between baseline and final score, evaluated using interviewer-rated scales (5 studies, 447 participants, SMD 0.15, 95% CI -0.12 to 0.42).Moderate-quality evidence found that antidepressants increased the number of participants abstinent from alcohol during the trial (7 studies, 424 participants, RR 1.71, 95% Cl 1.22 to 2.39) and reduced the number of drinks per drinking days (7 studies, 451 participants, mean difference (MD) -1.13 drinks per drinking days, 95% Cl -1.79 to -0.46). After the exclusion of studies with high risk of bias, the number of abstinent remained higher (RR 1.69, 95% CI 1.18 to 2.43) and the number of drinks per drinking days lower (MD -1.21 number of drinks per drinking days, 95% CI -1.91 to -0.51) among participants who received antidepressants compared to those who received placebo. However, other outcomes such as the rate of abstinent days did not differ between antidepressants and placebo (9 studies, 821 participants, MD 1.34, 95% Cl -1.66 to 4.34; low-quality evidence).Low-quality evidence suggested no differences between antidepressants and placebo in the number of dropouts (17 studies, 1159 participants, RR 0.98, 95% Cl 0.79 to 1.22) and adverse events as withdrawal for medical reasons (10 studies, 947 participants, RR 1.15, 95% Cl 0.65 to 2.04).There were few studies comparing one antidepressant versus another antidepressant or antidepressants versus other interventions, and these had a small sample size and were heterogeneous in terms of the types of interventions that were compared, yielding results that were not informative.
AUTHORS' CONCLUSIONS
We found low-quality evidence supporting the clinical use of antidepressants in the treatment of people with co-occurring depression and alcohol dependence. Antidepressants had positive effects on certain relevant outcomes related to depression and alcohol use but not on other relevant outcomes. Moreover, most of these positive effects were no longer significant when studies with high risk of bias were excluded. Results were limited by the large number of studies showing high or unclear risk of bias and the low number of studies comparing one antidepressant to another or antidepressants to other medication. In people with co-occurring depression and alcohol dependence, the risk of developing adverse effects appeared to be minimal, especially for the newer classes of antidepressants (such as selective serotonin reuptake inhibitors). According to these results, in people with co-occurring depression and alcohol dependence, antidepressants may be useful for the treatment of depression, alcohol dependence, or both, although the clinical relevance may be modest.
Topics: Adult; Alcohol Abstinence; Alcohol Drinking; Alcoholism; Antidepressive Agents; Depressive Disorder, Major; Diagnosis, Dual (Psychiatry); Female; Humans; Male; Placebos; Psychotherapy; Randomized Controlled Trials as Topic
PubMed: 29688573
DOI: 10.1002/14651858.CD008581.pub2