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Continuum (Minneapolis, Minn.) Jun 2014Diabetes mellitus has become a modern global epidemic, with steadily increasing prevalence rates related to lifestyle such that 27% of individuals aged 65 years or older... (Review)
Review
PURPOSE OF REVIEW
Diabetes mellitus has become a modern global epidemic, with steadily increasing prevalence rates related to lifestyle such that 27% of individuals aged 65 years or older have diabetes mellitus, 95% of whom have type 2. This article reviews the effects of diabetes mellitus on the neuromuscular system.
RECENT FINDINGS
Diabetes mellitus leads to diverse forms of peripheral neuropathy as the major neuromuscular complication. Both focal and diffuse types of neuropathy can develop, with the most common form being diabetic sensorimotor polyneuropathy. Small fibers are damaged early in the development of diabetic sensorimotor polyneuropathy and are not assessed by nerve conduction studies. Small fiber damage occurs even in the prediabetes stage. No disease-modifying therapy for diabetic sensorimotor polyneuropathy is available at this time, but this complication can be limited in patients who have type 1 diabetes mellitus with strict glycemic control; the same outcome is not clearly observed in patients who have type 2 diabetes mellitus. Recently, the evidence base for symptomatic treatments of painful diabetic sensorimotor polyneuropathy underwent systematic review. Effective evidence-based treatments include some anticonvulsants (eg, pregabalin, gabapentin), antidepressants (eg, amitriptyline, duloxetine), opioids (eg, morphine sulfate, oxycodone), capsaicin cream, and transcutaneous electrical nerve stimulation.
SUMMARY
This article reviews the increasing prevalence of diabetes mellitus and diabetic sensorimotor polyneuropathy and discusses recent consensus opinion on the objective confirmation needed for the diagnosis in the clinical research setting. The evidence from clinical trials shows that intensive glycemic control reduces prevalence of diabetic sensorimotor polyneuropathy in patients with type 1 diabetes mellitus, but variable outcomes are observed in patients with type 2 diabetes mellitus. Finally, despite the lack of disease-modifying treatment, effective evidence-based therapy can control painful symptoms of diabetic sensorimotor polyneuropathy.
Topics: Aged; Diabetic Neuropathies; Humans; Male; Middle Aged
PubMed: 24893232
DOI: 10.1212/01.CON.0000450964.30710.a0 -
The Cochrane Database of Systematic... May 2014Antidepressants are widely used to treat chronic neuropathic pain (pain due to nerve damage), usually in doses below those at which they exert antidepressant effects. An... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antidepressants are widely used to treat chronic neuropathic pain (pain due to nerve damage), usually in doses below those at which they exert antidepressant effects. An earlier review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining individual neuropathic pain conditions.Imipramine is a tricyclic antidepressant that is occasionally used to treat neuropathic pain.
OBJECTIVES
To assess the analgesic efficacy of imipramine for chronic neuropathic pain in adults, and to assess the associated adverse events.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and EMBASE on 18 November 2013, as well as the reference lists of retrieved papers and other reviews. We also used our own handsearched database for older studies, and two clinical trials databases.
SELECTION CRITERIA
We included randomised, double-blind studies of at least two weeks' duration comparing imipramine with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 and over. We included only articles with full journal publication and extended trial abstracts and summaries.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design); second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison; and third tier from data involving small numbers of participants which was considered very likely to be biased or used outcomes of limited clinical utility, or both.
MAIN RESULTS
Five studies treated 168 participants with painful diabetic neuropathy or polyneuropathy. The mean age in individual studies was between 47 and 56 years. Four studies used a cross-over, and one a parallel group design; 126 participants were randomised to receive imipramine 25 mg to 350 mg daily (most took 100 mg to 150 mg daily). Comparators were placebo (an active placebo in one study), paroxetine, mianserin, venlafaxine, and amitriptyline, and treatment was given for 2 to 12 weeks. All studies had one or more sources of potential major bias.No study provided first or second tier evidence for any outcome. No data were available on the proportion of people with at least 50% or 30% reduction in pain or equivalent, and data were available from only one study for our other primary outcome of Patient Global Impression of Change, reported as patient evaluation of pain relief of complete or good. No pooling of data was possible, but third tier evidence in individual studies indicated some improvement in pain relief with imipramine compared with placebo, although this is was very low quality evidence, derived mainly from group mean data and completer analyses, in small, short duration studies where major bias is possible.Four studies reported some information about adverse events, but reporting was inconsistent and fragmented, and the quality of evidence was very low. Participants taking imipramine generally experienced more adverse events, notably dry mouth, and a higher rate of withdrawal due to adverse events, than did participants taking placebo.
AUTHORS' CONCLUSIONS
This review found little evidence to support the use of imipramine to treat neuropathic pain. There was very low quality evidence of benefit but this came from studies that were methodologically flawed and potentially subject to major bias. Effective medicines with much greater supportive evidence are available.
Topics: Adult; Analgesics; Antidepressive Agents, Tricyclic; Diabetic Neuropathies; Humans; Imipramine; Middle Aged; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 24838845
DOI: 10.1002/14651858.CD010769.pub2 -
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 -
The Cochrane Database of Systematic... Mar 2014Chronic pelvic pain is a common and debilitating condition; its aetiology is multifactorial, involving social, psychological and biological factors. The management of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pelvic pain is a common and debilitating condition; its aetiology is multifactorial, involving social, psychological and biological factors. The management of chronic pelvic pain is challenging, as despite interventions involving surgery, many women remain in pain without a firm gynaecological diagnosis.
OBJECTIVES
To assess the effectiveness and safety of non-surgical interventions for women with chronic pelvic pain.
SEARCH METHODS
We searched the Menstrual Disorders and Subfertility Group Specialised Register. We also searched (from inception to 5 February 2014) AMED, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We handsearched sources such as citation lists, trial registers and conference proceedings.
SELECTION CRITERIA
Randomised controlled trials (RCTs) on non-surgical management of chronic pelvic pain were eligible for inclusion. We included studies of women with a diagnosis of pelvic congestion syndrome or adhesions but excluded those with pain known to be caused by endometriosis, primary dysmenorrhoea (period pain), active chronic pelvic inflammatory disease or irritable bowel syndrome. We considered studies of any non-surgical intervention, including lifestyle, physical, medical and psychological treatments.
DATA COLLECTION AND ANALYSIS
Study selection, quality assessment and data extraction were performed independently by two review authors. Meta-analysis was performed using the Peto odds ratio (Peto OR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). The primary outcome measure was pain relief, and secondary outcome measures were psychological outcomes, quality of life, requirement for analgesia and adverse effects. The quality of the evidence was assessed by using GRADE methods.
MAIN RESULTS
Twenty-one RCTs were identified that involved non-surgical management of chronic pelvic pain: 13 trials were included in the review, and eight were excluded. The studies included a total of 750 women-406 women in the intervention groups and 344 in the control groups. Included studies had high attrition rates, and investigators often did not blind adequately or did not clearly describe randomisation procedures. Medical treatment versus placebo Progestogen (medroxyprogesterone acetate (MPA)) was more effective than placebo at the end of treatment in terms of the number of women achieving a greater than 50% reduction in visual analogue scale (VAS) pain score immediately after treatment (Peto OR 3.00, 95% CI 1.70 to 5.31, two studies, n = 204, I(2) = 22%, moderate-quality evidence). Evidence of benefit was maintained up to nine months after treatment (Peto OR 2.09, 95% CI 1.18 to 3.71, two studies, n = 204, I(2) = 0%, moderate-quality evidence). Women treated with progestogen reported more adverse effects (e.g. weight gain, bloatedness) than those given placebo (high-quality evidence). The estimated effect of lofexidine on pain outcomes when compared with placebo was compatible with benefit and harm (Peto OR 0.42, 95% CI 0.11 to 1.61, one study, 39 women, low-quality evidence). Women in the lofexidine group reported more adverse effects (including drowsiness and dry mouth) than women given placebo (moderate-quality evidence). Head-to-head comparisons of medical treatments Head-to-head comparisons showed that women taking goserelin had greater improvement in pelvic pain score (MD 3, 95% CI 2.08 to 3.92, one study, n = 47, moderate-quality evidence) at one year than those taking progestogen. Women taking gabapentin had a lower VAS pain score than those taking amytriptyline (MD -1.50, 95% CI -2.06 to -0.94, n = 40, low-quality evidence). Study authors reported that no statistically significant difference was observed in the rate of adverse effects among women taking gabapentin compared with women given amytriptyline. The study comparing goserelin versus progestogen did not report on adverse effects. Psychological treatment Women who underwent reassurance ultrasound scans and received counselling were more likely to report improved pain than those treated with a standard 'wait and see' policy (Peto OR 6.77, 95% CI 2.83 to 16.19, n = 90, low-quality evidence). Significantly more women who had writing therapy as a disclosure reported improvement in pain than those in the non-disclosure group (Peto OR 4.47, 95% CI 1.41 to 14.13, n = 48, very low-quality evidence). No difference between groups in pain outcomes was noted when other psychological therapies were compared with standard care or placebo (quality of evidence ranged from very low to low). Studies did not report on adverse effects. Complementary therapy Distension of painful pelvic structures was more effective for pain when compared with counselling (MD 35.8, 95% CI 23.08 to 48.52 on a zero to 100 scale, one study, n = 48, moderate-quality evidence). No difference in pain levels was observed when magnetic therapy was compared with use of a control magnet (very low-quality evidence). Studies did not report on adverse effects.The results of studies examining psychological and complementary therapies could not be combined to yield meaningful results.
AUTHORS' CONCLUSIONS
Evidence of moderate quality supports progestogen as an option for chronic pelvic pain, with efficacy reported during treatment. In practice, this option may be most acceptable among women unconcerned about progestogenic adverse effects (e.g. weight gain, bloatedness-the most common adverse effects). Although some evidence suggests possible benefit of goserelin when compared with progestogen, gabapentin as compared with amytriptyline, ultrasound versus 'wait and see' and writing therapy versus non-disclosure, the quality of evidence is generally low, and evidence is drawn from single studies.Given the prevalence and healthcare costs associated with chronic pelvic pain in women, RCTs of other medical, lifestyle and psychological interventions are urgently required.
Topics: Amines; Amitriptyline; Analgesics; Chronic Pain; Clonidine; Contraceptive Agents, Female; Cyclohexanecarboxylic Acids; Female; Gabapentin; Goserelin; Humans; Medroxyprogesterone Acetate; Pain Measurement; Pelvic Pain; Psychotherapy; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid
PubMed: 24595586
DOI: 10.1002/14651858.CD008797.pub2 -
Journal of Managed Care Pharmacy : JMCP Jan 2014Migraine is a common neurological disease affecting 12% of Americans and millions worldwide. Medication adherence has been studied extensively in many chronic... (Review)
Review
BACKGROUND
Migraine is a common neurological disease affecting 12% of Americans and millions worldwide. Medication adherence has been studied extensively in many chronic conditions, with poor adherence adversely affecting treatment outcomes. However, little is known about adherence to oral prophylaxis for migraine.
OBJECTIVE
To examine the literature on assessing oral prophylaxis medication adherence and persistence among migraine patients.
METHODS
A systematic search of the PubMed (1966 to present) and EMBASE (1974 to present) databases was conducted to locate prospective and retrospective observational studies and randomized controlled trials (RCTs) of propranolol, amitriptyline, and topiramate. RCTs were pooled, weighted by sample size, and stratified by drug and length of study. Average persistence rates and reasons for discontinuation cited in RCTs were examined for each medication.
RESULTS
A total of 788 unique articles were identified using the search criteria, 33 of which were included in the final review. Observational studies (n = 14) showed adherence ranges of 41% to 95% at 2 months, 21% to 80% at 6 months, and 35% to 56% at 12 months and persistence ranges of 41% to 88% at 2 months, 19% to 79% at 6 months, and 7% to 55% at 12 months. Pooled persistence from RCTs on propranolol, amitriptyline, and topiramate (n = 19) showed rates of 77%, 55%, and 57%, respectively, at 16-26 weeks. Adverse events were the most common reason for discontinuation cited (24% for topiramate and 17% for amitriptyline).
CONCLUSION
Observational studies and pooled data from RCTs demonstrate poor adherence and persistence to oral migraine prophylaxis.
Topics: Animals; Humans; Medication Adherence; Migraine Disorders; Neuroprotective Agents; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 24372457
DOI: 10.18553/jmcp.2014.20.1.22 -
The Cochrane Database of Systematic... Dec 2013Work-related upper limb disorder (WRULD), repetitive strain injury (RSI), occupational overuse syndrome (OOS) and work-related complaints of the arm, neck or shoulder... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Work-related upper limb disorder (WRULD), repetitive strain injury (RSI), occupational overuse syndrome (OOS) and work-related complaints of the arm, neck or shoulder (CANS) are the most frequently used umbrella terms for disorders that develop as a result of repetitive movements, awkward postures and impact of external forces such as those associated with operating vibrating tools. Work-related CANS, which is the term we use in this review, severely hampers the working population.
OBJECTIVES
To assess the effects of conservative interventions for work-related complaints of the arm, neck or shoulder (CANS) in adults on pain, function and work-related outcomes.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, 31 May 2013), MEDLINE (1950 to 31 May 2013), EMBASE (1988 to 31 May 2013), CINAHL (1982 to 31 May 2013), AMED (1985 to 31 May 2013), PsycINFO (1806 to 31 May 2013), the Physiotherapy Evidence Database (PEDro; inception to 31 May 2013) and the Occupational Therapy Systematic Evaluation of Evidence Database (OTseeker; inception to 31 May 2013). We did not apply any language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-randomised controlled trials evaluating conservative interventions for work-related complaints of the arm, neck or shoulder in adults. We excluded trials undertaken to test injections and surgery. We included studies that evaluated effects on pain, functional status or work ability.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias of the included studies. When studies were sufficiently similar, we performed statistical pooling of reported results.
MAIN RESULTS
We included 44 studies (62 publications) with 6,580 participants that evaluated 25 different interventions. We categorised these interventions according to their working mechanisms into exercises, ergonomics, behavioural and other interventions.Overall, we judged 35 studies as having a high risk of bias mainly because of an unknown randomisation procedure, lack of a concealed allocation procedure, unblinded trial participants or lack of an intention-to-treat analysis.We found very low-quality evidence showing that exercises did not improve pain in comparison with no treatment (five studies, standardised mean difference (SMD) -0.52, 95% confidence interval (CI) -1.08 to 0.03), or minor intervention controls (three studies, SMD -0.25, 95% CI -0.87 to 0.37) or when provided as additional treatment (two studies, inconsistent results) at short-term follow-up or at long-term follow-up. Results were similar for recovery, disability and sick leave. Specific exercises led to increased pain at short-term follow-up when compared with general exercises (four studies, SMD 0.45, 95% CI 0.14 to 0.75)We found very low-quality evidence indicating that ergonomic interventions did not lead to a decrease in pain when compared with no intervention at short-term follow-up (three studies, SMD -0.07, 95% CI -0.36 to 0.22) but did decrease pain at long-term follow-up (four studies, SMD -0.76, 95% CI -1.35 to -0.16). There was no effect on disability but sick leave decreased in two studies (risk ratio (RR) 0.48, 95% CI 0.32 to 0.76). None of the ergonomic interventions was more beneficial for any outcome measures when compared with another treatment or with no treatment or with placebo.Behavioural interventions had inconsistent effects on pain and disability, with some subgroups showing benefit and others showing no significant improvement when compared with no treatment, minor intervention controls or other behavioural interventions.In the eight studies that evaluated various other interventions, there was no evidence of a clear beneficial effect of any of the interventions provided.
AUTHORS' CONCLUSIONS
We found very low-quality evidence indicating that pain, recovery, disability and sick leave are similar after exercises when compared with no treatment, with minor intervention controls or with exercises provided as additional treatment to people with work-related complaints of the arm, neck or shoulder. Low-quality evidence also showed that ergonomic interventions did not decrease pain at short-term follow-up but did decrease pain at long-term follow-up. There was no evidence of an effect on other outcomes. For behavioural and other interventions, there was no evidence of a consistent effect on any of the outcomes.Studies are needed that include more participants, that are clear about the diagnosis of work-relatedness and that report findings according to current guidelines.
Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Arm; Behavior Therapy; Cumulative Trauma Disorders; Ergonomics; Humans; Massage; Neck; Occupational Diseases; Physical Therapy Modalities; Randomized Controlled Trials as Topic; Shoulder; Sick Leave
PubMed: 24338903
DOI: 10.1002/14651858.CD008742.pub2 -
Journal of Pain Research 2013Management of neuropathic pain (NeP) associated with spinal cord injury (SCI) is difficult. This report presents a systematic literature review and comparison of the...
BACKGROUND
Management of neuropathic pain (NeP) associated with spinal cord injury (SCI) is difficult. This report presents a systematic literature review and comparison of the efficacy and safety of pharmacologic therapies for treating SCI-associated NeP.
METHODS
Medline, Embase, Cochrane, and Database of Abstracts of Reviews of Effects were searched through December 2011 for randomized, blinded, and controlled clinical trials of SCI-associated NeP meeting predefined inclusion criteria. Efficacy outcomes of interest were pain reduction on the 11-point numeric rating scale (NRS) or 100 mm visual analog scale and proportion of patients achieving ≥30% or ≥50% pain reduction. Discontinuations and adverse events (AEs) were also assessed, for which Bayesian meta-analytic indirect comparisons were performed.
RESULTS
Of the nine studies included in the analysis, samples were <100 patients, except for one pregabalin study (n = 136). Standard errors for the NRS outcome were often not reported, precluding quantitative comparisons across treatments. Estimated 11-point NRS pain reduction relative to placebo was -1.72 for pregabalin, -1.65 for amitriptyline, -1.0 for duloxetine, -1 (median) for levetiracetam, -0.27 for gabapentin, 1 (median) for lamotrigine, and 2 for dronabinol. Risk ratios relative to placebo for 30% improvement were 0.71 for levetiracetam and 2.56 for pregabalin, and 0.94 and 2.91, respectively, for 50% improvement. Meta-analytic comparisons showed significantly more AEs with pregabalin and tramadol compared with placebo, and no differences between placebo and any treatment for discontinuations.
CONCLUSIONS
Studies of SCI-associated NeP were few, small, and reported insufficient data for quantitative comparisons of efficacy. However, available data suggested pregabalin was associated with more favorable efficacy for all outcome measures examined, and that the risks of AEs and discontinuations were found to be similar among the therapies.
PubMed: 23874121
DOI: 10.2147/JPR.S45966 -
The Cochrane Database of Systematic... Jun 2013Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs in the central nervous system. The present review is part of an update of a Cochrane review first published in 2004, and previously updated (conclusions not changed) in 2007.
OBJECTIVES
To describe and assess the evidence from controlled trials on the efficacy and tolerability of topiramate for preventing migraine attacks in adult patients with episodic migraine.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2012, Issue 12), PubMed/MEDLINE (1966 to 15 January 2013), MEDLINE In-Process (current week, 15 January 2013), and EMBASE (1974 to 15 January 2013) and handsearched Headache and Cephalalgia through January 2013.
SELECTION CRITERIA
Studies were required to be prospective, controlled trials of topiramate taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data. For headache frequency data, we calculated mean differences (MDs) between topiramate and comparator (placebo, active control, or topiramate in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with ≥ 50% reduction in headache frequency), we calculated odds ratios (ORs) and, in select cases, risk ratios (RRs); we also calculated numbers needed to treat (NNTs). We calculated MDs for selected quality of life instruments. Finally, we summarised data on adverse events from placebo-controlled trials and calculated risk differences (RDs) and numbers needed to harm (NNHs).
MAIN RESULTS
Twenty papers describing 17 unique trials met the inclusion criteria. Analysis of data from nine trials (1737 participants) showed that topiramate reduced headache frequency by about 1.2 attacks per 28 days as compared to placebo (MD -1.20; 95% confidence interval (CI) -1.59 to -0.80). Data from nine trials (1190 participants) show that topiramate approximately doubled the proportion of responders relative to placebo (RR 2.02; 95% CI 1.57 to 2.60; NNT 4; 95% CI 3 to 6). Separate analysis of different topiramate doses produced similar MDs versus placebo at 50 mg (-0.95; 95% CI -1.95 to 0.04; three studies; 520 participants), 100 mg (-1.15; 95% CI -1.58 to -0.71; six studies; 1620 participants), and 200 mg (-0.94; 95% CI -1.53 to -0.36; five studies; 804 participants). All three doses significantly increased the proportion of responders relative to placebo; ORs were as follows: for 50 mg, 2.35 (95% CI 1.60 to 3.44; three studies; 519 participants); for 100 mg, 3.49 (95% CI 2.23 to 5.45; five studies; 852 participants); and for 200 mg, 2.49 (95% CI 1.61 to 3.87; six studies; 1025 participants). All three doses also significantly improved three or more domains of quality of life as compared to placebo. Meta-analysis of the three studies that included more than one dose of topiramate suggests that 200 mg is no more effective than 100 mg. With regard to mean headache frequency and/or responder rate, seven trials using active comparators found (a) no significant difference between topiramate and amitriptyline (one study, 330 participants); (b) no significant difference between topiramate and flunarizine (one study, 83 participants); (c) no significant difference between topiramate and propranolol (two studies, 342 participants); (d) no significant difference between topiramate and relaxation (one study, 61 participants); but (e) a slight significant advantage of topiramate over valproate (two studies, 120 participants). Relaxation improved migraine-specific quality of life significantly more than topiramate. In trials of topiramate against placebo, seven adverse events (AEs) were reported by at least three studies. These were usually mild and of a non-serious nature. Except for taste disturbance and weight loss, there were no significant differences in the frequency of AEs in general, or of the seven specific AEs, between placebo and topiramate 50 mg. AEs in general and all of the specific AEs except nausea were significantly more common on topiramate 100 mg than on placebo, with NNHs varying from 3 to 25, and the RDs versus placebo were even higher for topiramate 200 mg, with NNHs varying from 2 to 17.
AUTHORS' CONCLUSIONS
Meta-analysis demonstrates that topiramate in a 100 mg/day dosage is effective in reducing headache frequency and reasonably well-tolerated in adult patients with episodic migraine. This provides good evidence to support its use in routine clinical management. More studies designed specifically to compare the efficacy or safety of topiramate versus other interventions with proven efficacy in the prophylaxis of migraine are needed.
Topics: Adult; Anticonvulsants; Fructose; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate
PubMed: 23797676
DOI: 10.1002/14651858.CD010610 -
Otolaryngology--head and Neck Surgery :... Mar 2013The goal of this systematic review was to examine the evidence for the use of the neuromodulating agents, amitriptyline, gabapentin, pregabalin, and baclofen, in the... (Review)
Review
OBJECTIVE
The goal of this systematic review was to examine the evidence for the use of the neuromodulating agents, amitriptyline, gabapentin, pregabalin, and baclofen, in the management of chronic, idiopathic cough patients.
DATA SOURCES
Online databases, including PubMed, Embase, Cochrane Review, and Web of Science, and publications cited in bibliographies were used.
REVIEW METHODS
Literature was searched by the 2 authors with a priori criteria for study selection.
RESULTS
Eight relevant articles were identified, including 2 randomized controlled trials, 2 prospective cohort or case-series designs with consecutive patients, 1 retrospective case series of consecutive patients, 1 retrospective case series whose consecutive status was not known, and 2 case reports of 6 and 2 patients, respectively. Improvements in cough-specific quality of life were noted in the randomized controlled trials. Cough severity was reduced in studies that measured this outcome measure. In the remaining studies, cough symptoms were less after neuromodulator treatment.
CONCLUSION
Benefit from neuromodulator treatment with amitriptyline, gabapentin, pregabalin, and baclofen in chronic, idiopathic cough patients was demonstrated. Further investigations using objective and subjective outcome measures are needed as well as studies exploring optimal dose, length of treatment, and relapse rates posttreatment.
Topics: Amines; Amitriptyline; Baclofen; Chronic Disease; Cough; Cyclohexanecarboxylic Acids; Gabapentin; Humans; Neurotransmitter Agents; Pregabalin; Quality of Life; gamma-Aminobutyric Acid
PubMed: 23300226
DOI: 10.1177/0194599812471817 -
The Cochrane Database of Systematic... Sep 2012This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2006 and previously updated in 2009.Tinnitus is described as the perception of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2006 and previously updated in 2009.Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. It has been compared with chronic pain, and may be associated with depression or depressive symptoms which can affect quality of life and the ability to work. Antidepressant drugs have been used to treat tinnitus in patients with and without depressive symptoms.
OBJECTIVES
To assess the effectiveness of antidepressants in the treatment of tinnitus and to ascertain whether any benefit is due to a direct tinnitus effect or a secondary effect due to treatment of concomitant depressive states.
SEARCH METHODS
We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; PsycINFO; CINAHL; Web of Science; BIOSIS; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 5 January 2012.
SELECTION CRITERIA
Randomised controlled clinical studies of antidepressant drugs versus placebo in patients with tinnitus.
DATA COLLECTION AND ANALYSIS
Two authors critically appraised the retrieved studies and extracted data independently. Where necessary we contacted study authors for further information.
MAIN RESULTS
Six trials involving 610 patients were included. Trial quality was generally low. Four of the trials looked at the effect of tricyclic antidepressants on tinnitus, investigating 405 patients. One trial investigated the effect of a selective serotonin reuptake inhibitor (SSRI) in a group of 120 patients. One study investigated trazodone, an atypical antidepressant, versus placebo. Only the trial using the SSRI drug reached the highest quality standard. None of the other included trials met the highest quality standard, due to use of inadequate outcome measures, large drop-out rates or failure to separate the effects on tinnitus from the effects on symptoms of anxiety and depression. All the trials assessing tricyclic antidepressants suggested that there was a slight improvement in tinnitus but these effects may have been attributable to methodological bias. The trial that investigated the SSRI drug found no overall improvement in any of the validated outcome measures that were used in the study although there was possible benefit for a subgroup that received higher doses of the drug. This observation merits further investigation. In the trial investigating trazodone, the results showed an improvement in tinnitus intensity and in quality of life after treatment, but in neither case reached statistical significance. Reports of side effects including sedation, sexual dysfunction and dry mouth were common.
AUTHORS' CONCLUSIONS
There is as yet insufficient evidence to say that antidepressant drug therapy improves tinnitus.
Topics: Amitriptyline; Antidepressive Agents; Depression; Humans; Nortriptyline; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Tinnitus; Trazodone; Trimipramine
PubMed: 22972065
DOI: 10.1002/14651858.CD003853.pub3