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The Cochrane Database of Systematic... 2001This is one of series of reviews of cervical ripening and labour induction using standardised methodology. Homoeopathy involves the use, in dilution, of substances which... (Review)
Review
BACKGROUND
This is one of series of reviews of cervical ripening and labour induction using standardised methodology. Homoeopathy involves the use, in dilution, of substances which cause symptoms in their undiluted form. A type of herb, 'caulophyllum' is one type of homoeopathic therapy that has been used to induce labour.
OBJECTIVES
To determine the effects of homoeopathy for third trimester cervical ripening or induction of labour.
SEARCH STRATEGY
The Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Last searched: March 2001.
SELECTION CRITERIA
Randomised controlled trials comparing homeopathy used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods.
DATA COLLECTION AND ANALYSIS
A generic strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally.
MAIN RESULTS
One trial involving 40 women was included in the review. This trial was placebo controlled and double blind, but the quality was not high. Insufficient information was available on the method of randomisation and the study lacked clinically meaningful outcomes. This trial demonstrated no differences in any outcome between the treatment and control group.
REVIEWER'S CONCLUSIONS
There is insufficient evidence to recommend the use of caulophyllum as a method of induction. It is likely that the demand for complementary medicine will continue and women will continue to consult a homoeopath during their pregnancy. Although caulophyllum is a commonly used homoeopathic therapy to induce labour, the treatment strategy used in this trial may not reflect routine practice of homoeopathy. It may be more appropriate to undertake further evaluation of individualised homeopathic therapies for induction of labour in future clinical trials.
Topics: Caulophyllum; Cervical Ripening; Female; Homeopathy; Humans; Labor, Induced; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 11687203
DOI: 10.1002/14651858.CD003399 -
The Cochrane Database of Systematic... Oct 2016Opioid drugs, including fentanyl, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids... (Review)
Review
BACKGROUND
Opioid drugs, including fentanyl, 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 fentanyl, at any dose, and by any route of administration. Other opioids are considered in separate reviews.
OBJECTIVES
To assess the analgesic efficacy of fentanyl for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to June 2016, together with the reference lists of retrieved articles, and two online study registries.
SELECTION CRITERIA
We included randomised, double-blind studies of two weeks' duration or longer, comparing fentanyl (in any dose, administered by any route, and in any formulation) 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. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE.
MAIN RESULTS
Only one study met our inclusion criteria. Participants were men and women (mean age 67 years), with postherpetic neuralgia, complex regional pain syndrome, or chronic postoperative pain. They were experiencing inadequate relief from non-opioid analgesics, and had not previously taken opioids for their neuropathic pain. The study used an enriched enrolment randomised withdrawal design. It was adequately blinded, but we judged it at unclear risk of bias for other criteria.Transdermal fentanyl (one-day fentanyl patch) was titrated over 10 to 29 days to establish the maximum tolerated and effective dose (12.5 to 50 µg/h). Participants who achieved a prespecified good level of pain relief with a stable dose of fentanyl, without excessive use of rescue medication or intolerable adverse events ('responders'), were randomised to continue with fentanyl or switch to placebo for 12 weeks, under double-blind conditions. Our prespecified primary outcomes were not appropriate for this study design, but the measures reported do give an indication of the efficacy of fentanyl in this condition.In the titration phase, 1 in 3 participants withdrew because of adverse events or inadequate pain relief, and almost 90% experienced adverse events. Of 258 participants who underwent open-label titration, 163 were 'responders' and entered the randomised withdrawal phase. The number of participants completing the study (and therefore continuing on treatment) without an increase of pain by more than 15/100 was 47/84 (56%) with fentanyl and 28/79 (35%) with placebo. Because only 63% responded sufficiently to enter the randomised withdrawal phase, this implies that only a maximum of 35% of participants entering the study would have had useful pain relief and tolerability with transdermal fentanyl, compared with 22% with placebo. Almost 60% of participants taking fentanyl were 'satisfied' and 'very satisfied' with their treatment at the end of the study, compared with about 40% with placebo. This outcome approximates to our primary outcome of moderate benefit using the Patient Global Impression of Change scale, but the group was enriched for responders and the method of analysis was not clear. The most common adverse events were constipation, nausea, somnolence, and dizziness.There was no information about other types of neuropathic pain, other routes of administration, or comparisons with other treatments.We downgraded the quality of the evidence to very low because there was only one study, with few participants and events, and there was no information about how data from people who withdrew were analysed.
AUTHORS' CONCLUSIONS
There is insufficient evidence to support or refute the suggestion that fentanyl works in any neuropathic pain condition.
Topics: Aged; Analgesics, Opioid; Female; Fentanyl; Humans; Male; Neuralgia; Pain Measurement; Randomized Controlled Trials as Topic
PubMed: 27727431
DOI: 10.1002/14651858.CD011605.pub2 -
The Cochrane Database of Systematic... Dec 2021Epilepsy is one of the most common neurological disorders. Many people with epilepsy are drug-resistant and require add-on therapy, meaning that they concomitantly take... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy is one of the most common neurological disorders. Many people with epilepsy are drug-resistant and require add-on therapy, meaning that they concomitantly take multiple antiepileptic drugs. Carisbamate is a drug which is taken orally and inhibits voltage-gated sodium channels. Carisbamate may be useful for drug-resistant focal epilepsy.
OBJECTIVES
To evaluate the efficacy and tolerability of carisbamate when used as an add-on therapy for drug-resistant focal epilepsy.
SEARCH METHODS
We searched the following databases on 8 April 2021: Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) 1946 to April 07, 2021. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, WHO ICTRP, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane review groups including Epilepsy. We also searched ongoing trials registers, checked reference lists, and contacted authors of the included trials.
SELECTION CRITERIA
Double-blind randomised controlled trials (RCTs) comparing carisbamate versus placebo or another antiepileptic drug, as add-on therapy for drug-resistant focal epilepsy. Trials could have a parallel-group or cross-over design.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the trials for inclusion, assessed trial quality, and extracted data. The primary outcome was 50% or greater reduction in seizure frequency (responder rate). The secondary outcomes were: seizure freedom, treatment withdrawal (for any reason and due to adverse events); adverse events, and quality of life. We analysed data using the Mantel-Haenszel statistical method and according to the intention-to-treat population. We presented results as risk ratios (RRs) with 95% confidence intervals (CIs).
MAIN RESULTS
We included four RCTs involving a total of 2211 participants. All four trials compared carisbamate with placebo for drug-resistant focal epilepsy. Participants in all trials were over 16 years of age and received at least one other antiepileptic drug concomitantly. We detected substantial risk of bias across the included trials. All four trials were at high risk of attrition bias due to the incomplete reporting of attrition and the high treatment withdrawal rates noted, especially with higher doses. All four trials also had unclear risk of detection bias, as they did not specify whether outcome assessors were blinded. Meta-analysis suggested that carisbamate produced a higher responder rate compared to placebo (RR 1.36, 95% CI 1.14 to 1.62; 4 studies; moderate-certainty evidence). More participants in the carsibamate group achieved seizure freedom (RR 2.43, 95% CI 0.84 to 7.03; 1 study); withdrew from treatment for any reason (RR 1.32, 95% CI 0.82 to 2.12; 4 studies); and withdrew from treatment due to adverse events (RR 1.80, 95% CI 0.78 to 4.17; 4 studies) than in the placebo group. However, the evidence for the three outcomes was very low-certainty. There was no difference between treatment groups for the proportion of participants experiencing at least one adverse event (RR 1.10, 95% CI 0.93 to 1.30; 2 studies; low-certainty evidence). More participants in the carisbamate group than in the placebo group developed dizziness (RR 2.06, 95% CI 1.23 to 3.44; 4 studies; very low-certainty evidence) and somnolence (RR 1.82, 95% CI 1.28 to 2.58; 4 studies; low-certainty evidence), but not fatigue (RR 1.11, 95% CI 0.73 to 1.68; 3 studies); headache (RR 1.13, 95% CI 0.92 to 1.38; 4 studies); or nausea (RR 1.19, 95% CI 0.81 to 1.75; 3 studies). None of the included trials reported quality of life.
AUTHORS' CONCLUSIONS
The results suggest that carisbamate may demonstrate efficacy and tolerability as an add-on therapy for drug-resistant focal epilepsy. Importantly, the evidence for all outcomes except responder rate was of low to very low certainty, therefore we are uncertain of the accuracy of the reported effects. The certainty of the evidence is limited by the significant risk of bias associated with the included studies, as well as the statistical heterogeneity detected for some outcomes. Consequently, it is difficult for these findings to inform clinical practice. The studies were all of short duration and only included adult study populations. There is a need for further RCTs with more clear methodology, long-term follow-up, more clinical outcomes, more seizure types, and a broader range of participants.
Topics: Adult; Anticonvulsants; Carbamates; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Humans; Pharmaceutical Preparations; Randomized Controlled Trials as Topic
PubMed: 34870321
DOI: 10.1002/14651858.CD012121.pub2 -
Neuropsychopharmacology : Official... Mar 2013Clinical trials on low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the right dorsolateral prefrontal cortex have yielded conflicting evidence... (Meta-Analysis)
Meta-Analysis Review
Clinically meaningful efficacy and acceptability of low-frequency repetitive transcranial magnetic stimulation (rTMS) for treating primary major depression: a meta-analysis of randomized, double-blind and sham-controlled trials.
Clinical trials on low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the right dorsolateral prefrontal cortex have yielded conflicting evidence concerning its overall efficacy for treating major depression (MD). As this may have been the result of limited statistical power of individual trials, we have carried the present systematic review and meta-analysis to examine this issue. We searched the literature for English language randomized, double-blind and sham-controlled trials (RCTs) on LF-rTMS for treating MD from 1995 through July 2012 using EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses, and from October 2008 until July 2012 using MEDLINE. The main outcome measures were response and remission rates as well as overall dropout rates at study end. We used a random-effects model, odds ratios (ORs) and number needed to treat (NNT). Data were obtained from eight RCTs, totaling 263 subjects with MD. After an average of 12.6±3.9 rTMS sessions, 38.2% (50/131) and 15.1% (20/132) of subjects receiving active LF-rTMS and sham rTMS were classified as responders (OR=3.35; 95% CI=1.4-8.02; p=0.007). Also, 34.6% (35/101) and 9.7% (10/103) of subjects receiving active LF-rTMS and sham rTMS were classified as remitters (OR=4.76; 95% CI=2.13-10.64; p<0.0001). The associated NNT for both response and remission rates was 5. Sensitivity analyses have shown that protocols delivering >1200 magnetic pulses in total as well as those offering rTMS as a monotherapy for MD were associated with higher rates of response to treatment. No differences on mean baseline depression scores and dropout rates for active and sham rTMS groups were found. Finally, the risk of publication bias was low. In conclusion, LF-rTMS is a promising treatment for MD, as it provides clinically meaningful benefits that are comparable to those of standard antidepressants and high-frequency rTMS. Furthermore, LF-rTMS seems to be an acceptable intervention for depressed subjects.
Topics: Depressive Disorder, Major; Double-Blind Method; Humans; Patient Acceptance of Health Care; Randomized Controlled Trials as Topic; Transcranial Magnetic Stimulation; Treatment Outcome
PubMed: 23249815
DOI: 10.1038/npp.2012.237 -
The Cochrane Database of Systematic... May 2012A number of preclinical studies in both in vitro and in vivo models of Parkinson's disease have demonstrated that coenzyme Q10 can protect the nigrostriatal dopaminergic... (Review)
Review
BACKGROUND
A number of preclinical studies in both in vitro and in vivo models of Parkinson's disease have demonstrated that coenzyme Q10 can protect the nigrostriatal dopaminergic system. Some clinical trials have looked at the neuroprotective effects of coenzyme Q10 in patients with early and midstage Parkinson's disease.
OBJECTIVES
To assess the evidence from randomized controlled trials on the efficacy and safety of treatment with coenzyme Q10 compared to placebo in patients with early and midstage Parkinson's disease.
SEARCH METHODS
We searched the Cochrane Movment Disorders Group Trials Register, CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (January 1966 to March 2011), and EMBASE (January 1985 to March 2011). We handsearched the references quoted in the identified trials, congress reports from the most important neurological association and movement disorder societies in Europe and America (March 2011), checked reference lists of relevant studies and contacted other researchers.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared coenzyme Q10 to placebo for patients who suffered early and midstage primary Parkinson's disease. Studies in which the method of randomization or concealment were unknown were included. Cross-over studies were excluded.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. All disagreements were resolved by consensus between authors and were explained. We attempted to contact the authors of studies for further details if any data were missing and to establish the characteristics of unpublished trials through correspondence with the trial coordinator or principal investigator. Adverse effects information was collected from the trials.
MAIN RESULTS
Four randomized, double-blind, placebo-controlled trials with a total of 452 patients met the inclusion criteria and were included in the review. In overall, there were improvements in activities of daily living (ADL) UPDRS (WMD -3.12, 95% CI -5.88 to -0.36) and Schwab and England (WMD 4.43, 95% CI 0.05 to 8.81) for coenzyme Q10 at 1200 mg/d for 16 months versus placebo.In safety outcomes, only the risk ratios (RR) of pharyngitis (RR 1.04, 95% CI 0.18 to 5.89) and diarrhea (RR 1.39, 95% CI 0.62 to 3.16) are mild elevated between coenzyme Q10 therapy and placebo and there were no differences in the number of withdrawals due to adverse effects (RR 0.61, 95% CI 0.23 to 1.62).
AUTHORS' CONCLUSIONS
Coenzyme Q10 therapy with 1200 mg/d for 16 months was well tolerated by patients with Parkinson's disease. The improvements in ADL UPDRS and Schwab and England were positive, but it need to be further confirmed by larger sample. For total and other subscores of UPDRS, the effects of coenzyme Q10 seemed to be less clear.
Topics: Activities of Daily Living; Diarrhea; Humans; Neuroprotective Agents; Parkinson Disease; Pharyngitis; Randomized Controlled Trials as Topic; Ubiquinone; Vitamins
PubMed: 22592726
DOI: 10.1002/14651858.CD008150.pub3 -
Integrative Cancer Therapies 2022Remote medical scent detection of cancer and infectious diseases with dogs and rats has been an increasing field of research these last 20 years. If validated, the... (Review)
Review
BACKGROUND
Remote medical scent detection of cancer and infectious diseases with dogs and rats has been an increasing field of research these last 20 years. If validated, the possibility of implementing such a technique in the clinic raises many hopes. This systematic review was performed to determine the evidence and performance of such methods and assess their potential relevance in the clinic.
METHODS
Pubmed and Web of Science databases were independently searched based on PRISMA standards between 01/01/2000 and 01/05/2021. We included studies aiming at detecting cancers and infectious diseases affecting humans with dogs or rats. We excluded studies using other animals, studies aiming to detect agricultural diseases, diseases affecting animals, and others such as diabetes and neurodegenerative diseases. Only original articles were included. Data about patients' selection, samples, animal characteristics, animal training, testing configurations, and performances were recorded.
RESULTS
A total of 62 studies were included. Sensitivity and specificity varied a lot among studies: While some publications report low sensitivities of 0.17 and specificities around 0.29, others achieve rates of 1 sensitivity and specificity. Only 6 studies were evaluated in a double-blind screening-like situation. In general, the risk of performance bias was high in most evaluated studies, and the quality of the evidence found was low.
CONCLUSIONS
Medical detection using animals' sense of smell lacks evidence and performances so far to be applied in the clinic. What odors the animals detect is not well understood. Further research should be conducted, focusing on patient selection, samples (choice of materials, standardization), and testing conditions. Interpolations of such results to free running detection (direct contact with humans) should be taken with extreme caution. Considering this synthesis, we discuss the challenges and highlight the excellent odor detection threshold exhibited by animals which represents a potential opportunity to develop an accessible and non-invasive method for disease detection.
Topics: Humans; Dogs; Animals; Rats; Odorants; Neoplasms; Smell; Communicable Diseases; Randomized Controlled Trials as Topic
PubMed: 36541180
DOI: 10.1177/15347354221140516 -
BMJ Clinical Evidence May 2011Depression may affect up to 10% of the population, with half of affected people having recurrence of their symptoms. In mild to moderate depression, there is no reliable... (Review)
Review
INTRODUCTION
Depression may affect up to 10% of the population, with half of affected people having recurrence of their symptoms. In mild to moderate depression, there is no reliable evidence that any one treatment is superior in improving symptoms of depression, but the strength of evidence supporting different treatments varies. In severe depression, only prescription antidepressants and electroconvulsive therapy are known to improve symptoms.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in mild to moderate and severe depression, and in treatment-resistant depression? Which interventions reduce relapse rates? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 88 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressant drugs (tricyclic antidepressants [including low-dose tricyclic antidepressants], selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or venlafaxine), continuing prescription antidepressant drugs, electroconvulsive therapy, exercise, lithium augmentation, pindolol augmentation, and St John's wort.
Topics: Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depression; Depressive Disorder, Major; Double-Blind Method; Gene Library; Humans; Hypericum; United States Food and Drug Administration
PubMed: 21609510
DOI: No ID Found -
European Child & Adolescent Psychiatry Mar 2020Children and adolescents with major depressive disorder (MDD) appear to be more responsive to placebo than adults in randomized placebo-controlled trials (RCTs) of... (Meta-Analysis)
Meta-Analysis
Placebo response rates and potential modifiers in double-blind randomized controlled trials of second and newer generation antidepressants for major depressive disorder in children and adolescents: a systematic review and meta-regression analysis.
Children and adolescents with major depressive disorder (MDD) appear to be more responsive to placebo than adults in randomized placebo-controlled trials (RCTs) of second and newer generation antidepressants (SNG-AD). Previous meta-analyses obtained conflicting results regarding modifiers. We aimed to conduct a meta-analytical evaluation of placebo response rates based on both clinician-rating and self-rating scales. Based on the most recent and comprehensive study on adult data, we tested whether the placebo response rates in children and adolescents with MDD also increase with study duration and number of study sites. We searched systematically for published RCTs of SNG-AD in children and/or adolescents (last update: September 2017) in public domain electronic databases and additionally for documented studies in clinical trial databases. The log-transformed odds of placebo response were meta-analytically analyzed. The primary and secondary outcomes were placebo response rates at the end of treatment based on clinician-rating and self-rating scales, respectively. To examine the impact of study duration and number of study sites on placebo response rates, we performed simple meta-regression analyses. We selected other potential modifiers of placebo response based on significance in at least one previous pediatric meta-analysis and on theoretical considerations to perform explorative analyses. We applied sensitivity analyses with placebo response rates closest to week 8 to compare our data with those reported for adults. We identified 24 placebo-controlled trials (2229 patients in the placebo arms). The clinician-rated placebo response rates ranged from 22 to 62% with a pooled response rate of 45% (95% CI 41-50%). The number of study sites was a significant modifier in the simple meta-regression analysis [odds ratio (OR) 1.01, 95% CI 1.01-1.02, p = 0.0003, k = 24) with more study sites linked to a higher placebo response. Study duration was not significantly associated with the placebo response rate. The explorative simple analyses revealed that publication year may be an additional modifier. However, in the explorative multivariable analysis including the number of study sites and the publication year only the number of study sites reached a p value ≤ 0.05. The self-rated placebo response rates ranged from 1 to 68% with a pooled response rate of 26% (95% CI 10-54%) (k = 6; n = 396). This meta-analysis confirms a high pooled placebo response rate in children and adolescents based on clinician ratings, which exceeds that observed in the most recent meta-analysis of placebo effects in adults (36%; 95% CI 35-37%) published in 2016. However, and similar to findings in adults, the pooled response rates based on self-ratings were substantially lower. In accordance with previous meta-analyses, we corroborated the number of study sites as significant modifier. In comparison to the recent adult meta-analysis, the substantially lower number of pediatric studies entails a reduced power to detect modifiers. Future studies should provide more precise and homogenous information to support discovery of potential modifiers and consider no-treatment-if ethically permissible-to allow differentiation between placebo and spontaneous remission rates. If these differ, practicing clinicians should facilitate placebo effects as an addition to the verum effect to maximize benefits. Further research is required to explain the discrepant response rates between clinician and self-ratings.
Topics: Adolescent; Antidepressive Agents; Child; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 30535589
DOI: 10.1007/s00787-018-1244-7 -
Annali Dell'Istituto Superiore Di Sanita 2012The use of a complementary medicine approach, and specifically of the popular medicine Oscillococcinum, for the treatment of influenza-like syndromes remains... (Review)
Review
The use of a complementary medicine approach, and specifically of the popular medicine Oscillococcinum, for the treatment of influenza-like syndromes remains controversial. This brief paper analyses the currently available literature on this homeopathic preparation and the Cochrane Collaboration's 2006 systematic review, along with other recent studies, in order to clarify certain fundamental aspects of its use in the treatment of influenza. In the light of the reported findings, and applying the rigorous criteria of evidence-based medicine, we suggest that this medicine should be placed in category "BI".
Topics: Absenteeism; Adolescent; Adult; Animals; Child; Complex Mixtures; Double-Blind Method; Ducks; Female; Fever; Homeopathy; Humans; Influenza, Human; Liver; Male; Middle Aged; Myocardium; Pain; Randomized Controlled Trials as Topic; Tissue Extracts; Treatment Outcome; Young Adult
PubMed: 22456024
DOI: 10.4415/ANN_12_01_17 -
The Cochrane Database of Systematic... May 2018Cerebral palsy occurs in up to 2.1 of every 1000 live births and encompasses a range of motor problems and movement disorders. One commonly occurring movement disorder... (Review)
Review
BACKGROUND
Cerebral palsy occurs in up to 2.1 of every 1000 live births and encompasses a range of motor problems and movement disorders. One commonly occurring movement disorder amongst those with cerebral palsy is dystonia: sustained or intermittent involuntary muscle spasms and contractions that cause twisting, repetitive movements and abnormal postures. The involuntary contractions are often very painful and distressing and cause significant limitations to activity and participation.Oral medications are often the first line of medical treatment for dystonia. Trihexyphenidyl is one such medication that clinicians often use to treat dystonia in people with cerebral palsy.
OBJECTIVES
To assess the effects of trihexyphenidyl in people with dystonic cerebral palsy, according to the World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) domains of impairment, activity and participation. We also assessed the type and incidence of adverse effects in people taking the drug.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, eight other databases and two trials registers in May 2017, and we checked reference lists and citations to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials comparing oral trihexyphenidyl versus placebo for dystonia in cerebral palsy. We included studies in children and adults of any age with dystonic cerebral palsy, either in isolation or with the associated movement disorders of spasticity, ataxia, chorea, athetosis and/or hypotonia. We included studies regardless of whether or not the study authors specified the method used to diagnose dystonia in their study population. Primary outcomes were change in dystonia and adverse effects. Secondary outcomes were: activity, including mobility and upper limb function; participation in activities of daily living; pain; and quality of life.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified one study, which was set in Australia, that met the inclusion criteria. This was a randomised, double-blind, placebo-controlled, cross-over trial in 16 children (10 boys and 6 girls) with predominant dystonic cerebral palsy and a mean age of 9 years (standard deviation 4.3 years, range 2 to 17 years). We considered the trial to be at low risk of selection, performance, detection, attrition, reporting and other sources of bias. We rated the GRADE quality of the evidence as low.We found no difference in mean follow-up scores for change in dystonia as measured by the Barry Albright Dystonia Scale (BADS), which assesses eight body regions for dystonia on a 5-point scale (0 = none to 4 = severe), resulting in a total score of 0 to 32. The BADS score was 2.67 points higher (95% confidence interval (CI) -2.55 to 7.90; low-quality evidence), that is, worse dystonia, in the treated group. Trihexyphenidyl may be associated with an increased risk of adverse effects (risk ratio 2.54, 95% CI 1.38 to 4.67; low-quality evidence).There was no difference in mean follow-up scores for upper limb function as measured by the Quality of Upper Extremity Skills Test, which has four domains that collectively assess 36 items (each scored 1 or 2) and produces a total score of 0 to 100. The score in the treated group was 4.62 points lower (95% CI -10.98 to 20.22; low-quality evidence), corresponding to worse function, than in the control group. We found low-quality evidence for improved participation (as represented by higher scores) in the treated group in activities of daily living, as measured by three tools: 18.86 points higher (95% CI 5.68 to 32.03) for the Goal Attainment Scale (up to five functional goals scored on 5-point scale (-2 = much less than expected to +2 = much more than expected)), 2.91 points higher (95% CI 1.01 to 4.82) for the satisfaction subscale of the Canadian Occupational Performance Measure (COPM; satisfaction with performance in up to five problem areas scored on a 10-point scale (1 = not satisfied at all to 10 = extremely satisfied)), and 2.24 points higher (95% CI 0.64 to 3.84) for performance subscale of the COPM (performance in up to five problem areas scored on a 10-point scale (1 = not able to do to; 10 = able to do extremely well)).The study did not report on pain or quality of life.
AUTHORS' CONCLUSIONS
At present, there is insufficient evidence regarding the effectiveness of trihexyphenidyl for people with cerebral palsy for the outcomes of: change in dystonia, adverse effects, increased upper limb function and improved participation in activities of daily living. The study did not measure pain or quality of life. There is a need for larger randomised, controlled, multicentre trials that also examine the effect on pain and quality of life in order to determine the effectiveness of trihexyphenidyl for people with cerebral palsy.
Topics: Adolescent; Anti-Dyskinesia Agents; Cerebral Palsy; Child; Child, Preschool; Dystonia; Female; Humans; Male; Trihexyphenidyl
PubMed: 29763510
DOI: 10.1002/14651858.CD012430.pub2