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Frontiers in Pharmacology 2024Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the...
Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the efficacy and safety of alternative treatments. This study uses a Bayesian network meta-analysis to rigorously evaluate the therapeutic potential of Chinese herbal medicines in the treatment of depression, focusing on their comparative efficacy and safety against standard pharmacological interventions. Five databases (PubMed, Wanfang Data, EMBASE, CNKI, and the Cochrane Library) and grey literature were searched from inception to end of July 2023 to identify studies that assessed the efficacy and safety of Chinese herbal medicines in treating depression. The response rate, Hamilton Depression Scale (HAMD) scores, and rates of adverse events were assessed through both direct and indirect comparisons. Data extraction and risk of bias assessment were meticulously performed. Statistical analysis used Markov chain Monte Carlo methods, with effect size estimates provided as odd ratios and their 95% confidence intervals. A total of 198 RCTs involving 8,923 patients were analyzed, assessing 17 Chinese herbal medicines. Surface Under the Cumulative Ranking results indicated that the top three treatments with the best response rate were possibly , , and ; the top three treatments on the reduction of HAMD scores were , , and ; and the top three treatments with the lowest adverse effects rates were , , and . Interestingly, commonly used synthetic drugs such as , , , , , and , not only appeared to be less effective than specific Chinese herbal medicines (, , , , and ), but they were also related to substantially higher risk of adverse events. Our findings elucidate the promising therapeutic potential of Chinese herbal medicines as viable alternatives in the treatment of depression, with certain herbs demonstrating enhanced efficacy and safety profiles. The outcomes of this study advocate for the integration of these alternative modalities into contemporary depression management paradigms. However, it underscores the necessity for larger, methodologically robust trials to further validate and refine these preliminary findings. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023452109.
PubMed: 38633609
DOI: 10.3389/fphar.2024.1295564 -
Pain and Therapy Dec 2022The IASP ICD-11 chronic primary pain (CPP) definition includes 19 different painful conditions. In recent years, interest in the potential role of cannabinoids in the...
INTRODUCTION
The IASP ICD-11 chronic primary pain (CPP) definition includes 19 different painful conditions. In recent years, interest in the potential role of cannabinoids in the management of CPP has increased, since they demonstrated a possible efficacy in treating pain, especially in secondary pain conditions. However, limited evidence is available for patients with CPP. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of cannabinoid administration in CPP.
METHODS
PubMed, EMBASE, and Cochrane Library were searched form the beginning up to 31 October 2021 to retrieve published articles of randomized controlled trials (RCTs) or observational, retrospective or prospective, studies, investigating cannabinoids in CPP. The study screening process was completed during November 2021. The primary outcome was pain reduction by means of the visual analogue scale (VAS). Secondary outcomes were quality of life by means of the fibromyalgia impact questionnaire (FIQ) or other available scales, appetite, anxiety, depression, and sleep by means of any available scales. Safety was assessed with the reporting of serious adverse events (SAE) and discontinuation due to adverse events. Risk of bias was assessed. The weighted generic inverse variance method and Mantel-Haenszel method were used to estimate the mean difference (MD) and odds ratios (OR) with 95% confidence intervals (CI) for continuous and dichotomous outcomes, respectively. For outcome measures reported with different scales (pain, anxiety, depression), we used the standardized MD (SMD) as the effect measure and then converted it into units of the VAS scale for pain, the Beck Anxiety Inventory (BAI) for anxiety, and the Beck Depression Inventory (BDI) for depression. Summary of findings was produced using GRADEproGDT.
RESULTS
From 3007 identified records, we included eight articles reporting the results of eight different RCTs (four parallel and four crossover studies; seven compared to placebo and one to amitriptyline), with a total population of 240 patients. VAS pain reduction was non-significant for cannabinoids against placebo (MD = - 0.64; 95% CI - 1.30 to 0.02) or amitriptyline (MD = - 0.19; 95% CI - 0.58 to 0.19). More than 4 weeks cannabinoid treatment significantly reduced pain compared to placebo in parallel studies with more than 4 weeks of treatment duration (MD = - 1.28; 95% CI - 2.33 to - 0.22). Differences for the FIQ (MD = - 21.69; 95% CI - 46.20 to 2.82), BAI (MD = - 2.32; 95% CI - 7.99 to 3.08), and BDI (MD = 2.32; 95% CI - 1.71 to 6.35) were non-significant, likewise for discontinuation due to adverse events (OR = 2.15; 95% CI 0.44-10.65), when comparing cannabinoids to placebo. The quality of the evidence was generally low mainly as a result of imprecision and risk of bias.
CONCLUSION
Cannabinoid treatment in patients with CPP had limited benefit on pain relief; however, it might improve pain with long-term administration.
PubMed: 36129666
DOI: 10.1007/s40122-022-00434-5 -
Annals of Internal Medicine Nov 2014Multiple treatments for painful diabetic peripheral neuropathy are available. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple treatments for painful diabetic peripheral neuropathy are available.
PURPOSE
To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy.
DATA SOURCES
Multiple electronic databases between January 2007 and April 2014, without language restriction.
STUDY SELECTION
Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy.
DATA EXTRACTION
Duplicate extraction of study data and assessment of risk of bias.
DATA SYNTHESIS
65 randomized, controlled trials involving 12 632 patients evaluated 27 pharmacologic interventions. Approximately one half of these studies had high or unclear risk of bias. Nine head-to-head trials showed greater pain reduction associated with serotonin-norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD], -0.34 [95% credible interval {CrI}, -0.63 to -0.05]) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD, -1.36 [CrI, -1.77 to -0.95]), topical capsaicin (SMD, -0.91 [CrI, -1.18 to -0.08]), TCAs (SMD, -0.78 [CrI, -1.24 to -0.33]), and anticonvulsants (SMD, -0.67 [CrI, -0.97 to -0.37]) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD, -1.57 [CrI, -2.83 to -0.31]), venlafaxine (SMD, -1.53 [CrI, -2.41 to -0.65]), duloxetine (SMD, -1.33 [CrI, -1.82 to -0.86]), and amitriptyline (SMD, -0.72 [CrI, -1.35 to -0.08]) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin.
LIMITATION
Confidence in findings was limited because most evidence came from indirect comparisons of trials with short (≤3 months) follow-up and unclear or high risk of bias.
CONCLUSION
Several medications may be effective for short-term management of painful diabetic neuropathy, although their comparative effectiveness is unclear.
PRIMARY FUNDING SOURCE
Mayo Foundation for Medical Education and Research.
Topics: Analgesics, Opioid; Anticonvulsants; Antidepressive Agents, Tricyclic; Bias; Capsaicin; Diabetic Neuropathies; Humans; Pain; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 25364885
DOI: 10.7326/M14-0511 -
Journal of Thoracic Disease Oct 2016There have been several published reports on the use of orally administered, specific centrally acting medicines for the treatment of idiopathic cough; however, there is... (Review)
Review
BACKGROUND
There have been several published reports on the use of orally administered, specific centrally acting medicines for the treatment of idiopathic cough; however, there is no extant systematic review of randomized controlled trials (RCTs) that evaluated their efficacy and safety for the treatment of idiopathic cough in human beings.
METHODS
We conducted a series of definitive systematic reviews and meta-analyses of RCTs. Claims data from the MEDLINE, EMBASE, LILACS, CBM, CNKI, VIP, Wan Fang, and Cochrane Library databases were used. We also reviewed articles and reference lists of relevant articles pertaining to human subjects published prior to March 26, 2016. No language restrictions were imposed. Two authors independently reviewed the titles and abstracts of the retrieved studies, which were matched using Review Manager 5.3 software. Disagreements were resolved by consensus. The outcome data were the number of subjects whose symptoms declined, measured by cough or Leicester Cough Questionnaire (LCQ) score. Random effect meta-analyses were used to pool the findings. Publication bias was assessed using funnel plots.
RESULTS
Three RCTs, regarding the medicines baclofen, amitriptyline, and gabapentin, were conducted involving 92 persons in total. Our reviews confirmed that baclofen, amitriptyline, and gabapentin show promise in the treatment of cough for select cases of refractory chronic cough. After-treatment relief of cough symptoms was significant (risk ratio =2.41; 95% CI: 1.15-5.04, n=84). Each of the medicines was well tolerated with minimal side effects. Methodological biases in the design and execution of cluster randomized trials might contribute to any selection bias in this review.
CONCLUSIONS
Baclofen, amitriptyline, and gabapentin may be effective 'non-specific' antitussives in clinical settings, although none of them are used in medical assessments or routinely included in the anatomic diagnostic protocol.
PubMed: 27867572
DOI: 10.21037/jtd.2016.10.51 -
Headache Jul 2020Sleep disorders and circadian dysregulation appear to be associated with primary headache disorders. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sleep disorders and circadian dysregulation appear to be associated with primary headache disorders.
OBJECTIVE
The aim of this study was to review the existing evidence for the deployment of melatonin in migraine prophylaxis. Initially, case-control studies investigating nocturnal melatonin and 6-sulphatoxymelatonin (aMT6s, melatonin metabolite discarded by the urine) levels in patients with migraine and healthy controls (HC) would be reviewed and meta-analyzed. Second, results from randomized controlled trials (RCTs) and non-randomized studies evaluating the use of melatonin in migraine would be synthesized.
METHODS
MEDLINE EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar, and OpenGrey were comprehensively searched. The quality of studies was assessed according to the Newcastle-Ottawa Scale (case-control studies) and the Risk-of-Bias Cochrane tool (RCTs). Random-effects (RE) or fixed-effects (FE) model was used based on heterogeneity among studies (homogeneity assumed when PQ > 0.1 and I < 30%). Publication bias was assessed by funnel plots.
RESULTS
Literature search provided 11 case-control studies. Evidence was compatible with lower nocturnal serum [5 of 6 studies were synthesized due to deficient reporting of 1 abstract, migraine n = 197, HC n = 132, RE MD = -12.29 pg/ml, 95%CI = (-21.10, -3.49)] and urinary melatonin [3 studies, migraine n = 30, HC n = 29, RE MD = -0.12 nmol/nocturnal (12 hours) urinary collection, 95%CI = (-0.22, -0.03)], as well as urine aMT6s levels [1 study, migraine n = 146, HC n = 74, MD = -11.90 μg/nocturnal (12 hours) urine collection, 95%CI = (-19.23, -4.57)] in adult migraine patients compared to HC [1 study involving children did not reveal any difference regarding nocturnal urine aMT6s, n = 18 per group, MD = -6.00 μg/nocturnal (12 hours) urine collection, 95%CI = (-21.19, 9.19)]. Regarding the treatment-prevention of migraine, 7 RCTs and 9 non-randomized studies were retrieved. Data synthesis was not feasible for the comparison of melatonin and placebo due to the existing clinical and methodological heterogeneity of the 5 relevant RCTs. Overall, melatonin was more efficacious and equally safe with placebo in the prevention of migraine in adults (3 of 4 RCTs provided superior efficacy results for melatonin, 1 RCT revealed no difference regarding Headache Frequency -HF-), while there are limited data for children (1 RCT revealed no difference against placebo regarding HF). Additionally, no difference was revealed between melatonin and amitriptyline (1 RCT), sodium valproate (1 RCT) or propranolol (1 non-randomized study) with respect to their efficacy in adults with migraine, while melatonin was more effective than pizotifen (1 RCT). In children with migraine, amitriptyline is more efficacious regarding most assessed parameters (2 studies, n = 85 per group, HF: RE MD = 4.03, 95%CI = (2.64, 5.42), Headache Duration: RE MD = 0.72, 95%CI = (0.41, 1.03), Headache Severity: FE MD = 1.57, 95%CI = (1.13, 2.00), Response to Treatment: FE MD = 0.33, 95%CI = (0.16, 0.69), Headache Induced Disability Severity: RE MD = 6.07, 95%CI = (-11.87, 24.01 ), Analgesic Consumption - assessed in 1 study, n = 40 per group - MD = 1.11, 95%CI = (-0.10, 2.32)), although melatonin presents a superior safety profile than amitriptyline both in adults and in children.
CONCLUSIONS
Melatonin may be of potential benefit in the treatment-prevention of migraine in adults, but complementary evidence from high-quality RCTs is required.
Topics: Adult; Child; Humans; Melatonin; Migraine Disorders
PubMed: 32352572
DOI: 10.1111/head.13828 -
The Cochrane Database of Systematic... May 2023Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low- and middle-income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services.
OBJECTIVES
To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs.
SEARCH METHODS
We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies.
SELECTION CRITERIA
All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 66 RCTs with 17,626 participants. Sixty-two of these trials contributed to the meta-analysis. Sixty-three studies were conducted in middle-income countries (MICs), and the remaining three studies were conducted in low-income countries (LICs). Twenty-five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder. Fifty-two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive-behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty). Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive-behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=-0.43, 95% confidence interval (CI): -0.61 to -0.24; 475 participants; 4 trials; low certainty). Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use. Thirty-one trials reported rates of retention in the intervention. Meta-analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron. Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition.
AUTHORS' CONCLUSIONS
In LMICs there is low-certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta-analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.
Topics: Humans; Male; Acamprosate; Alcoholism; Amitriptyline; Developing Countries; Disulfiram; Mirtazapine; Naltrexone; Ondansetron; Topiramate
PubMed: 37158538
DOI: 10.1002/14651858.CD013350.pub2 -
The Laryngoscope Jun 2021To evaluate the effectiveness of neuromodulating agents for the management of atypical facial pain and primary facial neuralgias. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness of neuromodulating agents for the management of atypical facial pain and primary facial neuralgias.
METHODS
We searched MEDLINE, Embase, CINAHL, and ClinicalTrials.gov databases for original research articles that examine the effectiveness and adverse reactions of pharmacologic therapy for the treatment of trigeminal neuralgia and atypical facial pain. Studies that included surgical interventions for atypical facial pain or facial pain secondary to other causes were excluded. Meta-analysis was conducted for reductions in symptom scores and adverse effects.
RESULTS
Of 3,409 articles screened, 73 full-text articles were included, consisting of 45 observational studies and 29 randomized controlled trials. Twenty-four different pharmacological agents were assessed; carbamazepine was the most frequently studied while botulinum toxin A demonstrated the highest consistency in reduction of symptom scores. Pooled estimate of three randomized controlled trials revealed that patients with trigeminal neuralgia who received botulinum toxin A had higher odds (odds ratio 7.46; 95% CI 3.53-15.78) of achieving a ≥50% reduction in visual analogue scale scores compared to controls. Pooled estimate of 15 observational studies showed that three-fourths of patients with trigeminal neuralgia who received carbamazepine experienced clinically significant pain reduction (prevalence proportion 0.75; 95% CI 0.66-0.83).
CONCLUSIONS
Patients receiving botulinum toxin A for trigeminal neuralgia had higher odds of achieving ≥50% reduction in pain scores. A significant proportion of patients with trigeminal neuralgia experienced positive response to carbamazepine. There was moderate evidence for amitriptyline in patients with atypical facial pain. Standardization of outcome reporting would facilitate future quantitative comparisons of therapeutic effectiveness. Laryngoscope, 131:1235-1253, 2021.
Topics: Adult; Amitriptyline; Botulinum Toxins, Type A; Carbamazepine; Facial Nerve; Facial Pain; Female; Humans; Male; Middle Aged; Neuralgia; Neurotransmitter Agents; Observational Studies as Topic; Odds Ratio; Pain Management; Pain Measurement; Randomized Controlled Trials as Topic; Treatment Outcome; Trigeminal Neuralgia
PubMed: 33037835
DOI: 10.1002/lary.29162 -
Headache Mar 2017Migraine headaches are common in children and adolescents. Current pharmacologic treatment options are limited despite the prevalence and debilitating effects of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Migraine headaches are common in children and adolescents. Current pharmacologic treatment options are limited despite the prevalence and debilitating effects of pediatric migraine. Cognitive behavioral therapy (CBT) is an evidence-based practice that focuses on the development of coping strategies and cognitive restructuring to alter the pain experience. Till date, no meta-analysis has been done to examine the use of CBT in pediatric migraine.
METHODS
Using the keywords (cognitive behavioral therapy OR cognitive behavior therapy OR cognitive behavioral therapy OR cognitive behavior therapy OR CBT) AND (headache OR migraine), a preliminary search on the PubMed and Ovid database yielded 3841 articles published in English between 1 Jan 1980 and 1 May 2016. Full articles were also reviewed for references of interest. After data extraction, 14 studies were included in the meta-analysis.
RESULTS
The results of the meta-analysis well-support the clinical role of CBT in the management of pediatric migraine. The pooled odds ratios of clinically significant improvement, that is, 50% or greater headache activity reduction post-treatment and at follow-up (3 months or later) were OR 9.11 (95% CI: 5.01 to 16.58, P < .001) and OR 9.18 (95% CI: 5.69 to 14.81, P < .001) respectively, demonstrating significant clinical improvement with CBT as compared with wait-list control, placebo, or standard medication. Furthermore, the clinical improvement was stable, even at a 1-year follow-up as evident in some of the studies.
CONCLUSION
There is good evidence that CBT is beneficial to children suffering from migraine, and may also augment the efficacy of standard medications such as amitriptyline.
Topics: Adolescent; Child; Cognitive Behavioral Therapy; Humans; Longitudinal Studies; Migraine Disorders; Pediatrics; Retrospective Studies
PubMed: 28028812
DOI: 10.1111/head.13016 -
Clinical Therapeutics Apr 2017A network meta-analysis (NMA) was performed, aiming to assess the relative efficacy and tolerability of the capsaicin 179-mg (8% weight for weight) cutaneous patch... (Meta-Analysis)
Meta-Analysis Review
Capsaicin 8% Patch Versus Oral Neuropathic Pain Medications for the Treatment of Painful Diabetic Peripheral Neuropathy: A Systematic Literature Review and Network Meta-analysis.
PURPOSE
A network meta-analysis (NMA) was performed, aiming to assess the relative efficacy and tolerability of the capsaicin 179-mg (8% weight for weight) cutaneous patch (capsaicin 8% patch) compared with oral, centrally acting agents (ie, pregabalin, gabapentin, duloxetine, amitriptyline) in patients with painful diabetic peripheral neuropathy (PDPN).
METHODS
A systematic search of EMBASE/MEDLINE, Cochrane Library, and the National Health Service Centre for Reviews and Dissemination Database of Abstracts of Reviews of Effects was conducted to identify all randomized controlled trials. Data from eligible studies according to predefined inclusion and exclusion criteria were extracted, and analyses were based on aggregate-level data. Efficacy outcomes were the proportions of patients with ≥30% and ≥50% reductions in pain, and tolerability outcomes were somnolence, dizziness, nausea, diarrhea, constipation, headache, fatigue, insomnia, and rate of discontinuation due to adverse events (AEs). Data were analyzed by using a Bayesian NMA. Fixed and random effects models were estimated. Relative treatment effect was presented as odds ratios (ORs) with 95% CIs. Sources of heterogeneity were assessed.
FINDINGS
The NMA included 25 randomized controlled trials. For ≥30% pain reduction, the capsaicin 8% patch was significantly more effective than placebo (OR, 2.28 [95% CI, 1.19-4.03]), exhibited a numerical advantage compared with pregabalin (OR, 1.83 [95% CI, 0.91-3.34]) and gabapentin (OR, 1.66 [95% CI, 0.74-3.23]), and had similar efficacy compared with duloxetine (OR, 0.99 [95% CI, 0.5-1.79]). The evidence available was not sufficient to assess the relative efficacy of amitriptyline. In the NMA for tolerability, the capsaicin 8% patch was only included for headache because the incidence was 0% for the other outcomes. Oral, centrally acting agents had a significantly elevated risk compared with placebo for somnolence (pregabalin, gabapentin, duloxetine, and amitriptyline), dizziness (pregabalin, gabapentin, duloxetine, and amitriptyline), nausea (duloxetine), diarrhea (duloxetine), fatigue (duloxetine), and discontinuation because of AEs (pregabalin, gabapentin, and duloxetine). Compared with pregabalin and gabapentin, duloxetine had a significantly lower risk of dizziness but a significantly higher risk of nausea.
IMPLICATIONS
This NMA suggests that the efficacy observed with the capsaicin 8% patch is similar to that observed with oral agents (ie, pregabalin, duloxetine, gabapentin) in patients with PDPN. The oral agents were associated with a significantly elevated risk of somnolence, dizziness, fatigue, and discontinuation because of AEs compared with placebo. The capsaicin 8% patch was as effective as oral centrally acting agents in these patients with PDPN but offers systemic tolerability benefits.
Topics: Administration, Oral; Analgesics; Capsaicin; Diabetic Neuropathies; Humans; Neuralgia; Transdermal Patch
PubMed: 28365034
DOI: 10.1016/j.clinthera.2017.02.010 -
The Journal of Headache and Pain Dec 2023Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication is the most effective. We present a network meta-analysis to determine the effectiveness and rank of preventive drugs for chronic migraine in adults.
METHODS
We identified, reviewed, and extracted data from randomised controlled trials (RCTs) of preventive drugs for chronic migraine with at least 200 participants. Data were analysed using network meta-analysis.
FINDINGS
We included 12 RCTs of six medications (Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Onabotulinumtoxin A, and Topiramate) compared to placebo or each other. All drugs effectively reduced monthly headache and migraine days compared with placebo. The most effective drug for monthly headache days was Eptinezumab 300mg, with a mean difference of -2.46 days, 95% Credible Interval (CrI): -3.23 to -1.69. On the Surface Under the Cumulative Ranking Area (SUCRA) analysis, the probability that Eptinezumab 300mg was ranked highest was 0.82. For monthly migraine days, the most effective medication was Fremanezumab-monthly, with a mean difference: -2.77 days, 95% CrI: -3.36 to -2.17, and 0.98 probability of being ranked the highest. All included drugs, except Topiramate, improved headache-related quality of life. No eligible studies were identified for the other common preventive oral medications such as Amitriptyline, Candesartan, and Propranolol. The main reasons were that the studies did not define chronic migraine, were undertaken before the definition of chronic migraine, or were too small.
INTERPRETATION
All six medications were more effective than the placebo on monthly headache and migraine days. The absolute differences in the number of headache/migraine days are, at best, modest. No evidence was found to determine the relative effectiveness of the six included drugs with other oral preventive medications.
REGISTRATION
PROSPERO (number CRD42021265990).
Topics: Adult; Humans; Topiramate; Network Meta-Analysis; Migraine Disorders; Treatment Outcome; Headache; Double-Blind Method
PubMed: 38057728
DOI: 10.1186/s10194-023-01696-w