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The Cochrane Database of Systematic... Oct 2016This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP.
OBJECTIVES
This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE, and Embase for relevant studies. We ran the searches for the original review in September 2011 and subsequent searches for this update up to April 2016. We sought additional studies from clinical trials databases and reference lists of retrieved papers.
SELECTION CRITERIA
We included randomised and quasi-randomised trials studying the effectiveness of pharmacologic interventions compared with placebo, another active treatment, or no treatment, in established PLP. We considered the following outcomes: change in pain intensity, function, sleep, depression or mood, quality of life, adverse events, treatment satisfaction, and withdrawals from the study.
DATA COLLECTION AND ANALYSIS
We independently assessed issues of study quality and extracted efficacy and adverse event data. Due to the wide variability in the studies, we did not perform a meta-analysis for all the interventions and outcomes, but attempted to pool the results of some studies where possible. We prepared a qualitative description and narrative summary of results. We assessed clinical heterogeneity by making qualitative comparisons of the populations, interventions, outcomes/outcome measures, and methods.
MAIN RESULTS
We added only one new study with 14 participants to this updated review. We included a 14 studies (10 with low risk of bias and 4 with unclear risk of bias overall) with a total of 269 participants. We added another drug class, botulinum neurotoxins (BoNTs), in particular botulinum toxin A (BoNT/A), to the group of medications reviewed previously. Our primary outcome was change in pain intensity. Most studies did not report our secondary outcomes of sleep, depression or mood, quality of life, treatment satisfaction, or withdrawals from the study.BoNT/A did not improve phantom limb pain intensity during the six months of follow-up compared with lidocaine/methylprednisolone.Compared with placebo, morphine (oral and intravenous) was effective in decreasing pain intensity in the short term with reported adverse events being constipation, sedation, tiredness, dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory problems.The N-methyl D-aspartate (NMDA) receptor antagonists ketamine (versus placebo; versus calcitonin) and dextromethorphan (versus placebo), but not memantine, had analgesic effects. The adverse events of ketamine were more serious than placebo and calcitonin and included loss of consciousness, sedation, hallucinations, hearing and position impairment, and insobriety.The results for gabapentin in terms of pain relief were conflicting, but combining the results favoured treatment group (gabapentin) over control group (placebo) (mean difference -1.16, 95% confidence interval -1.94 to -0.38; 2 studies). However, gabapentin did not improve function, depression score, or sleep quality. Adverse events experienced were somnolence, dizziness, headache, and nausea.Compared with an active control benztropine mesylate, amitriptyline was not effective in PLP, with dry mouth and dizziness as the most frequent adverse events based on one study.The findings for calcitonin (versus placebo; versus ketamine) and local anaesthetics (versus placebo) were variable. Adverse events of calcitonin were headache, vertigo, drowsiness, nausea, vomiting, and hot and cold flushes. Most of the studies were limited by their small sample sizes.
AUTHORS' CONCLUSIONS
Since the last version of this review, we identified another study that added another form of medical therapy, BoNTs, specifically BoNT/A, to the list of pharmacologic interventions being reviewed for clinical efficacy in phantom limb pain. However, the results of this study did not substantially change the main conclusions. The short- and long-term effectiveness of BoNT/A, opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and local anaesthetics for clinically relevant outcomes including pain, function, mood, sleep, quality of life, treatment satisfaction, and adverse events remain unclear. Based on a small study, BoNT/A (versus lidocaine/methylprednisolone) does not decrease phantom limb pain. Morphine, gabapentin, and ketamine demonstrate favourable short-term analgesic efficacy compared with placebo. Memantine and amitriptyline may not be effective for PLP. However, results must be interpreted with caution, as they were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long-term efficacy and safety outcomes. The direction of efficacy of calcitonin, local anaesthetics, and dextromethorphan needs further clarification. Overall, the efficacy evidence for the reviewed medications is thus far inconclusive. Larger and more rigorous randomised controlled trials are needed for us to reach more definitive conclusions about which medications would be useful for clinical practice.
Topics: Analgesics, Opioid; Anesthetics; Anticonvulsants; Antidepressive Agents; Botulinum Toxins, Type A; Calcitonin; Humans; Neurotoxins; Phantom Limb; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate
PubMed: 27737513
DOI: 10.1002/14651858.CD006380.pub3 -
Biomedicines Feb 2022(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules.... (Review)
Review
(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules. As current knowledge on the abuse of centrally acting anticholinergics is limited, the aim of the present study is to review the relevant published data, focusing on the following molecules: benztropine, biperiden, scopolamine, orphenadrine, and benzhexol/trihexyphenidyl (THP). (2) Methods: A systematic literature review was carried out using Pubmed, Scopus, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Research methods were registered on PROSPERO (CRD42021257293). (3) Results: A total of 48 articles, including case reports, surveys, and retrospective case series analyses, were included. Most articles focused on benzhexol/THP ( = 25), and benztropine ( = 4). The routes of administration were mostly oral, and macrodoses together concomitant illicit drugs, e.g., cocaine, have been recorded. Toxidromes included both physical (e.g., tachycardia, tachypnoea, dilatated pupils, dry skin, urinary retention, ataxia, etc.) and psychiatric symptoms (e.g., anxiety, agitation, delirium, etc.). Fatal outcomes were very rare but reported. (4) Conclusion: Results from the present study show that anticholinergic misusing issues are both widespread worldwide and popular. Considering the potential adverse effects associated, healthcare professionals should be vigilant and monitor eventual misusing issues.
PubMed: 35203563
DOI: 10.3390/biomedicines10020355 -
Pain Physician Jan 2021Diabetic peripheral neuropathy (DPN) is a most common devitalizing complication of diabetes mellitus, which is primarily characterized by sensory loss, paresthesia,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a most common devitalizing complication of diabetes mellitus, which is primarily characterized by sensory loss, paresthesia, prickling, pain, or allodynia.
OBJECTIVES
To evaluate the relative efficacy and safety of the interventions used in the DPN pain management and rank their order.
STUDY DESIGN
A systematic review and Bayesian network meta-analysis (NMA).
METHODS
Randomized, controlled trials were identified through a comprehensive, systematic literature exploration, primarily utilizing the PubMed, EMBASE, Ovid, and Cochrane Library databases. The efficacy and safety outcomes consist of the proportion of patients reporting either 30% or 50% pain reduction and overall withdrawal or withdrawal due to adverse drug events, respectively. Effect estimates from Bayesian NMA were presented as odds ratio (OR) with 95% credible intervals (CrI). Heterogeneity and convergence were assessed by using I2 and deviation information criteria. The risk of bias was evaluated by using Pedro Scale.
RESULTS
A total of 3,246 potentially relevant trials were identified and screened, finally 43 trials consisting of 7,877 randomized patients met the inclusion criteria. Statistically significant treatment difference for 50% pain reduction was reported for duloxetine vs. placebo (OR: 2.50; CrI: 1.62-3.91), mirogabalin vs. placebo (OR: 3.25; CrI: 1.16-9.35), pregabalin vs. placebo (OR: 2.33; CrI: 1.69-3.27), duloxetine vs. carbamazepine (OR: 3.37; CrI: 1.07-10.90), mirogabalin vs. carbamazepine (OR: 4.39; CrI: 1.01-19.63), mirogabalin vs. lamotrigine (OR: 4.05: CrI: 1.07-15.77), pregabalin vs. lamotrigine (OR: 2.90, CrI: 1.19-7.22) and pregabalin vs. nortriptyline (OR: 4.10, CrI: 1.13-5.28). Nortriptyline reported the highest possibility of achieving 30% and 50% pain reduction. Sodium valproate and benztropine reported the highest probability of total withdrawals and withdrawals due to adverse drug events, respectively.
LIMITATION
The different follow-up time of the included studies can result in the variation of intended results.
CONCLUSION
Nortriptyline reported the advantage relative to other drugs in achieving 30% and 50% pain reduction from the baseline. Gabapentin reported a significance of 50% pain reduction relative to placebo.
Topics: Bayes Theorem; Diabetic Neuropathies; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 33400429
DOI: No ID Found -
Movement Disorders Clinical Practice Jul 2022To present a case of refractory medication-induced tremor successfully treated with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) and... (Review)
Review
OBJECTIVE
To present a case of refractory medication-induced tremor successfully treated with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) and to propose a medical and surgical treatment algorithm based on a systematical review of the literature.
METHODS
Patient data were retrospectively collected. A systematic search was performed in PubMed, Embase, and Cochrane Library. Subjective and objective data were pooled for analysis by classifying them into 5 predefined categories(no, minimal, moderate, good, and excellent effects).
RESULTS
The patient presented with lithium-induced bilateral progressive hand tremor lasting 25 years. After DBS, he reported excellent tremor suppression until the last follow-up (36 months after Vim-DBS). For the review, 34 of 140 studies were included and evaluated (178 unique subjects, 31 different treatments). A good-to-excellent tremor suppression (50%-100%) in at least 50% of subjects was achieved using propranolol (12 studies, 50% of 56 subjects), tetrabenazine (5 studies, 51% of 13 subjects), and metoprolol (4 studies, 75% of 8 subjects). The effect of benztropine and diphenhydramine was none or only minimal to moderate (up to 50% improvement; both: 3 studies, 50% of 4 patients). One article reported minimal-to-moderate effectiveness after DBS of the ventral oral posterior nucleus of the thalamus. Methods were highly heterogeneous. All studies scored grade III or IV quality of evidence, which was insufficient for recommendations (level U).
CONCLUSION
Treatment decision making should be performed on a case-by-case basis considering the low level of evidence, and we propose a practically oriented treatment algorithm. Propranolol, tetrabenazine, and metoprolol might be effective. For selected and refractory cases, DBS might be considered.
PubMed: 35844282
DOI: 10.1002/mdc3.13463 -
The Cochrane Database of Systematic... Jan 2018Antipsychotic (neuroleptic) medication is used extensively to treat people with serious mental illnesses. However, it is associated with a wide range of adverse effects,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic (neuroleptic) medication is used extensively to treat people with serious mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders. Because of this, many people treated with antipsychotic medication also receive anticholinergic drugs in order to reduce some of the associated movement side-effects. However, there is also a suggestion from animal experiments that the chronic administration of anticholinergics could cause tardive dyskinesia.
OBJECTIVES
To determine whether the use or the withdrawal of anticholinergic drugs (benzhexol, benztropine, biperiden, orphenadrine, procyclidine, scopolamine, or trihexylphenidyl) are clinically effective for the treatment of people with both antipsychotic-induced tardive dyskinesia and schizophrenia or other chronic mental illnesses.
SEARCH METHODS
We retrieved 712 references from searching the Cochrane Schizophrenia Group's Study-Based Register of Trials including the registries of clinical trials (16 July 2015 and 26 April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We included reports identified in the search if they were controlled trials dealing with people with antipsychotic-induced tardive dyskinesia and schizophrenia or other chronic mental illness who had been randomly allocated to (a) anticholinergic medication versus placebo (or no intervention), (b) anticholinergic medication versus any other intervention for the treatment of tardive dyskinesia, or (c) withdrawal of anticholinergic medication versus continuation of anticholinergic medication.
DATA COLLECTION AND ANALYSIS
We independently extracted data from included trials and we estimated risk ratios (RR) with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The previous version of this review included no trials. We identified two trials that could be included from the 2015 and 2017 searches. They randomised 30 in- and outpatients with schizophrenia in the USA and Germany. Overall, the risk of bias was unclear, mainly due to poor reporting: allocation concealment was not described; generation of the sequence was not explicit; studies were not clearly blinded; and outcome data were not fully reported.Findings were sparse. One study reported on the primary outcomes and found that significantly more participants allocated to procyclidine (anticholinergic) had not improved to a clinically important extent compared with those allocated to isocarboxazid (MAO-inhibitor) after 40 weeks' treatment (1 RCT, n = 20; RR 4.20, 95% CI 1.40 to 12.58; very low quality evidence); that there was no evidence of a difference in the incidence of any adverse effects (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence); or acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence). The other trial compared anticholinergic withdrawal with anticholinergic continuation and found no evidence of a difference in the incidence of acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 10; RR 2.14, 95% CI 0.11 to 42.52; very low quality evidence).No trials reported on social confidence, social inclusion, social networks, or personalised quality of life - outcomes designated important to patients. No studies comparing either i. anticholinergics with placebo or no treatment, or ii. studies of anticholinergic withdrawal, were found that reported on the primary outcome 'no clinically important improvement in TD symptoms and adverse events'.
AUTHORS' CONCLUSIONS
Based on currently available evidence, no confident statement can be made about the effectiveness of anticholinergics to treat people with antipsychotic-induced tardive dyskinesia. The same applies for the withdrawal of such medications. Whether the withdrawal of anticholinergics may benefit people with antipsychotic-induced TD should be evaluated in a parallel-group, placebo-controlled randomised trial, with adequate sample size and at least 6 weeks of follow-up.
Topics: Antipsychotic Agents; Biperiden; Cholinergic Antagonists; Dyskinesia, Drug-Induced; Humans; Isocarboxazid; Procyclidine; Randomized Controlled Trials as Topic; Schizophrenia; Withholding Treatment
PubMed: 29341071
DOI: 10.1002/14651858.CD000204.pub2 -
Paediatrics & Child Health May 2022Sialorrhea in children can be associated with adverse physical and social effects. Treatment using anticholinergic medications has been shown to offer symptomatic...
BACKGROUND
Sialorrhea in children can be associated with adverse physical and social effects. Treatment using anticholinergic medications has been shown to offer symptomatic relief, but there is no consensus regarding which treatment is the most efficacious.
OBJECTIVE
To examine the effectiveness of anticholinergic medications for sialorrhea in children.
METHODS
A systematic review was carried out in Medline, EMBASE, Cochrane, Scopus, and the Web of Science from inception until April 29, 2020. Studies reporting original data on the efficacy of anticholinergic medications in the management of sialorrhea in children aged 0 to 17 years of age were included. This review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. Data on study design, setting, population, pharmacologic intervention(s), comparator(s), outcomes, and results were extracted and summarized.
RESULTS
The search strategy identified 2,800 studies of which 27 articles were included in the synthesis, including five randomized controlled trials. Each anticholinergic undergoing experimental study (glycopyrrolate, scopolamine/hyoscine, trihexyphenidyl/benzhexol, benztropine, and atropine) showed evidence of efficacy. Adverse side effects were common. Significant heterogeneity exists in the studies' methodology and the variability of outcome measures used between studies precluded a meta-analysis.
CONCLUSIONS
Glycopyrrolate, scopolamine/hyoscine, trihexyphenidyl/benzhexol, benztropine, and atropine have all shown efficacy in the treatment of sialorrhea in children. The small number of reports and the variability in study design precluded a meta-analysis. More studies are needed with uniformity in outcome measures to help guide evidence-based decision making. A guidance table is presented.
PubMed: 35599670
DOI: 10.1093/pch/pxab051 -
The Cochrane Database of Systematic... Jul 2016This is an update of an earlier review that considered both neuropathic pain and fibromyalgia (Issue 6, 2014), which has now been split into separate reviews for the two... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of an earlier review that considered both neuropathic pain and fibromyalgia (Issue 6, 2014), which has now been split into separate reviews for the two conditions. This review considers neuropathic pain only.Opioid drugs, including oxycodone, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for oxycodone, at any dose, and by any route of administration. Separate reviews consider other opioids.
OBJECTIVES
To assess the analgesic efficacy and adverse events of oxycodone for chronic neuropathic pain in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 6 November 2013 for the original review and from January 2013 to 21 December 2015 for this update. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. This update differs from the earlier review in that we have included studies using oxycodone in combination with naloxone, and oxycodone used as add-on treatment to stable, but inadequate, treatment with another class of drug.
SELECTION CRITERIA
We included randomised, double-blind studies of two weeks' duration or longer, comparing any dose or formulation of oxycodone with placebo or another active treatment in chronic neuropathic pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table.
MAIN RESULTS
The updated searches identified one additional published study, and one clinical trial registry report. We included five studies reporting on 687 participants; 637 had painful diabetic neuropathy and 50 had postherpetic neuralgia. Two studies used a cross-over design and three used a parallel group design; all studies used a placebo comparator, although one study used an active placebo (benztropine). Modified-release oxycodone (oxycodone MR) was titrated to effect and tolerability. One study used a fixed dose combination of oxycodone MR and naloxone. Two studies added oxycodone therapy to ongoing, stable treatment with either pregabalin or gabapentin. All studies had one or more sources of potential major bias.No study reported the proportion of participants experiencing 'substantial benefit' (at least 50% pain relief or who were very much improved). Three studies (537 participants) in painful diabetic neuropathy reported outcomes equivalent to 'moderate benefit' (at least 30% pain relief or who were much or very much improved), which was experienced by 44% of participants with oxycodone and 27% with placebo (number needed to treat for one additional beneficial outcome (NNT) 5.7).All studies reported group mean pain scores at the end of treatment. Three studies reported a greater pain intensity reduction and better patient satisfaction with oxycodone MR alone than with placebo. There was a similar result in the study adding oxycodone MR to stable, ongoing gabapentin, but adding oxycodone MR plus naloxone to stable, ongoing pregabalin did not show any additional effect.More participants experienced adverse events with oxycodone MR alone (86%) than with placebo (63%); the number needed to treat for an additional harmful outcome (NNH) was 4.3. Serious adverse events (oxycodone 3.4%, placebo 7.0%) and adverse event withdrawals (oxycodone 11%, placebo 6.4%) were not significantly different between groups. Withdrawals due to lack of efficacy were less frequent with oxycodone MR (1.1%) than placebo (11%), with a number needed to treat to prevent one withdrawal of 10. The add-on studies reported similar results.We downgraded the quality of the evidence to very low for all outcomes, due to limitations in the study methods, heterogeneity in the pain condition and study methods, and sparse data.
AUTHORS' CONCLUSIONS
There was only very low quality evidence that oxycodone (as oxycodone MR) is of value in the treatment of painful diabetic neuropathy or postherpetic neuralgia. There was no evidence for other neuropathic pain conditions. Adverse events typical of opioids appeared to be common.
Topics: Adult; Aged; Analgesics, Opioid; Constipation; Delayed-Action Preparations; Diabetic Neuropathies; Disorders of Excessive Somnolence; Dizziness; Female; Humans; Male; Middle Aged; Nausea; Neuralgia, Postherpetic; Oxycodone; Randomized Controlled Trials as Topic
PubMed: 27465317
DOI: 10.1002/14651858.CD010692.pub3 -
Archives of Disease in Childhood Oct 2003Drooling frequently occurs in children with multiple handicaps; application of anticholinergic drugs is a potential strategy to treat drooling. A computer aided search... (Review)
Review
Drooling frequently occurs in children with multiple handicaps; application of anticholinergic drugs is a potential strategy to treat drooling. A computer aided search of original studies concerning the treatment of drooling was carried out. The methodological and statistical integrity of the identified studies were assessed with previously defined criteria. The articles were weighed for their separate contribution to the evidence. The search resulted in 64 reports, of which seven studies passed the screening and were subjected to further assessment and discussion by three referees. Because of the small number of reports and the methodological restriction within the studies, no meta-analysis could be performed. No general conclusion could be made about the efficacy of anticholinergic drugs in treatment of drooling in children with multiple handicaps. There was some evidence that three anticholinergic drugs (benztropine, glycopyrrolate, and benzhexol hydrochloride) are effective in the treatment of drooling, but it could not be concluded that one drug is preferable.
Topics: Child; Cholinergic Antagonists; Disabled Children; Humans; Randomized Controlled Trials as Topic; Research Design; Sialorrhea; Treatment Outcome
PubMed: 14500313
DOI: 10.1136/adc.88.10.911 -
The Cochrane Database of Systematic... 2003Anticholinergics were the first drugs available for the symptomatic treatment of Parkinson's disease and they are still widely used today, both as monotherapy and as... (Review)
Review
BACKGROUND
Anticholinergics were the first drugs available for the symptomatic treatment of Parkinson's disease and they are still widely used today, both as monotherapy and as part of combination regimes. They are commonly believed to be associated with a less favourable side effect profile than other antiparkinsonian drugs, in particular with respect to neuropsychiatric and cognitive adverse events. They have been claimed to exert a better effect on tremor than on other parkinsonian features.
OBJECTIVES
To determine the efficacy and tolerability of anticholinergics in the symptomatic treatment of Parkinson's disease compared to placebo or no treatment.
SEARCH STRATEGY
The literature search included electronic searches of the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1966 to 2001), Old Medline (1960-1965), Index Medicus (1927 - 1959), as well as handsearching the neurology literature including the reference lists of identified articles, other reviews and book chapters.
SELECTION CRITERIA
Randomised controlled trials of anticholinergic drugs versus placebo or no treatment in de-novo or advanced Parkinson's disease, either as monotherapy or as an add-on to other antiparkinsonian drugs were included. Trials of anticholinergic drugs that were never in general clinical use were excluded.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by two authors. Differences were settled by discussion among all authors. Data collected included patient characteristics, disease duration and severity, concomitant medication, interventions including duration and dose of anticholinergic treatment, outcome measures, rates of and reasons for withdrawals, and neuropsychiatric and cognitive adverse events.
MAIN RESULTS
The initial search yielded 14 potentially eligible studies, five of which were subsequently excluded. In three cases this was because they dealt with substances that had never been marketed or had not been licensed for as far as could be traced back. One trial had been published twice in different languages. One study was excluded based on the assessment of its methodological quality. The remaining nine studies were all of double-blind cross-over design and included 221 patients. Trial duration was between five and 20 weeks and drugs investigated were benzhexol (mean doses: 8 to 20 mg/d), orphenadrine (mean dose not reported), benztropine (mean dose not reported), bornaprine (8 to 8.25 mg/d), benapryzine (200 mg/d), and methixine (45 mg/d). Only one study involved two anticholinergic drugs. Outcome measures varied widely across studies and in many cases, the scales applied were the authors' own and were not defined in detail. Incomplete reporting of methodology and results was frequent. The heterogeneous study designs as well as incomplete reporting precluded combined statistical analysis. Five studies used both tremor and other parkinsonian features as outcome measures. Outcome measures in these five studies were too different for a combined analysis and results varied widely, from a significant improvement in tremor only to significant improvement in other features but not in tremor. All studies except one (dealing with methixine) found a significant improvement from baseline on the anticholinergic drug in at least one outcome measure. The difference between placebo and active drug was reported in four studies and was found to be significant in all cases. No study failed to show superiority of the anticholinergic over placebo. The occurrence of neuropsychiatric and cognitive adverse events was reported in all but three studies (in 35 patients on active drug versus 13 on placebo). The most frequently reported reason for drop-outs from studies was in patients on placebo due to withdrawal from pre-trial anticholinergic treatment.
REVIEWER'S CONCLUSIONS
As monotherapy or as an adjunct to other antiparkinsonian drugs, anticholinergics are more effective than placebo in improving motor function in Parkinson's disease. Neuropsychiatric and cognitive adverse events occur more frequently on anticholinergics than on placebo and are a more common reason for withdrawal than lack of efficacy. Results regarding a potentially better effect of the anticholinergic drug on tremor than on other outcome measures are conflicting and data do not strongly support a differential clinical effect on individual parkinsonian features. Data is insufficient to allow comparisons in efficacy or tolerability between individual anticholinergic drugs.
Topics: Cholinergic Antagonists; Humans; Muscarinic Antagonists; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 12804486
DOI: 10.1002/14651858.CD003735