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The Cochrane Database of Systematic... Aug 2010Antisocial personality disorder (AsPD) is associated with a wide range of disturbance including persistent rule-breaking, criminality, substance misuse, unemployment,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antisocial personality disorder (AsPD) is associated with a wide range of disturbance including persistent rule-breaking, criminality, substance misuse, unemployment, homelessness and relationship difficulties.
OBJECTIVES
To evaluate the potential beneficial and adverse effects of pharmacological interventions for people with AsPD.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1950 to September 2009), EMBASE (1980 to 2009, week 37), CINAHL (1982 to September 2009), PsycINFO (1872 to September 2009) , ASSIA (1987 to September 2009) , BIOSIS (1985 to September 2009), COPAC (September 2009), National Criminal Justice Reference Service Abstracts (1970 to July 2008), Sociological Abstracts (1963 to September 2009), ISI-Proceedings (1981 to September 2009), Science Citation Index (1981 to September 2009), Social Science Citation Index (1981 to September 2009), SIGLE (1980 to April 2006), Dissertation Abstracts (September 2009), ZETOC (September 2009) and the metaRegister of Controlled Trials (September 2009).
SELECTION CRITERIA
Controlled trials in which participants with AsPD were randomly allocated to a pharmacological intervention and a placebo control condition. Two trials comparing one drug against another without a placebo control are reported separately.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected studies. Two review authors independently extracted data. We calculated mean differences, with odds ratios for dichotomous data.
MAIN RESULTS
Eight studies met the inclusion criteria involving 394 participants with AsPD. Data were available from four studies involving 274 participants with AsPD. No study set out to recruit participants solely on the basis of having AsPD, and in only one study was the sample entirely of AsPD participants. Eight different drugs were examined in eight studies. Study quality was relatively poor. Inadequate reporting meant the data available were generally insufficient to allow any independent statistical analysis. The findings are limited to descriptive summaries based on analyses carried out and reported by the trial investigators. All the available data were derived from unreplicated single reports. Only three drugs (nortriptyline, bromocriptine, phenytoin) were effective compared to placebo in terms of improvement in at least one outcome. Nortriptyline was reported in one study as superior for men with alcohol dependency on mean number of drinking days and on alcohol dependence, but not for severity of alcohol misuse or on the patient's or clinician's rating of drinking. In the same study, both nortriptyline and bromocriptine were reported as superior to placebo on anxiety on one scale but not on another. In one study, phenytoin was reported as superior to placebo on the frequency and intensity of aggressive acts in male prisoners with impulsive (but not premeditated) aggression. In the remaining two studies, both amantadine and desipramine were not superior to placebo for adults with opioid and cocaine dependence, and desipramine was not superior to placebo for men with cocaine dependence.
AUTHORS' CONCLUSIONS
The body of evidence summarised in this review is insufficient to allow any conclusion to be drawn about the use of pharmacological interventions in the treatment of antisocial personality disorder.
Topics: Adult; Aggression; Alcohol-Related Disorders; Amantadine; Antisocial Personality Disorder; Anxiety; Bromocriptine; Desipramine; Female; Humans; Male; Nortriptyline; Phenytoin; Psychotropic Drugs; Randomized Controlled Trials as Topic
PubMed: 20687091
DOI: 10.1002/14651858.CD007667.pub2 -
CMAJ : Canadian Medical Association... Nov 2013Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effectiveness for mild cognitive impairment is unclear. We... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effectiveness for mild cognitive impairment is unclear. We conducted a systematic review to examine the efficacy and safety of cognitive enhancers for mild cognitive impairment.
METHODS
Our eligibility criteria were studies of the effects of donepezil, rivastigmine, galantamine or memantine on mild cognitive impairment reporting cognition, function, behaviour, global status, and mortality or harms. We identified relevant material by searching electronic databases (e.g., MEDLINE, Embase), the references of included studies, trial registries and conference proceedings, and by contacting experts. Two reviewers independently screened the results of the literature search, abstracted data and appraised risk of bias using the Cochrane risk-of-bias tool.
RESULTS
We screened 15,554 titles and abstracts and 1384 full-text articles. Eight randomized clinical trials and 3 companion reports met our inclusion criteria. We found no significant effects of cognitive enhancers on cognition (Mini-Mental State Examination: 3 randomized clinical trials [RCTs], mean difference [MD] 0.14, 95% confidence interval [CI] -0.22 to 0.50; Alzheimer's Disease Assessment Scale - cognition subscale: 3 RCTs, standardized MD -0.07, 95% CI-0.16 to 0.01]) or function (Alzheimer's Disease Cooperative Study activities of daily living inventory: 2 RCTs, MD 0.30, 95% CI -0.26 to 0.86). Cognitive enhancers were associated with higher risks of nausea, diarrhea and vomiting than placebo.
INTERPRETATION
Cognitive enhancers did not improve cognition or function among patients with mild cognitive impairment and were associated with a greater risk of gastrointestinal harms. Our findings do not support the use of cognitive enhancers for mild cognitive impairment.
Topics: Cholinesterase Inhibitors; Cognitive Dysfunction; Donepezil; Galantamine; Humans; Indans; Memantine; Nootropic Agents; Phenylcarbamates; Piperidines; Rivastigmine; Treatment Outcome
PubMed: 24043661
DOI: 10.1503/cmaj.130451 -
The Cochrane Database of Systematic... Dec 2014Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy. A variety of interventions for subjective fatigue are available, but little is known about their efficacy or the likelihood of any adverse effects for people with peripheral neuropathy.
OBJECTIVES
To assess the effects of drugs and physical, psychological or behavioural interventions for fatigue in adults or children with peripheral neuropathy.
SEARCH METHODS
On 5 November 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, LILACS and AMED. We also searched reference lists of all studies identified for inclusion and relevant reviews, and contacted the authors of included studies and known experts in the field to identify additional published or unpublished data. We also searched trials registries for ongoing studies.
SELECTION CRITERIA
We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs comparing any form of intervention for fatigue management in adults with peripheral neuropathy with placebo, no intervention or an alternative form of intervention for fatigue. Interventions considered included drugs, pacing and grading of physical activity, general or specific exercise, compensatory strategies such as orthotics, relaxation, counselling, cognitive and educational strategies.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed risk of bias and extracted study data. We contacted study authors for additional information. We collected information on adverse events from the included trials.
MAIN RESULTS
The review includes three trials, which were all at low risk of bias, involving 530 people with peripheral neuropathy. The effects of amantadine from one randomised, double-blind, placebo-controlled, cross-over trial comparing amantadine with placebo for the treatment of fatigue in 80 people with Guillain-Barré syndrome (GBS) were uncertain for the proportion of people achieving a favourable outcome six weeks post-intervention (odds ratio (OR) 0.56 (95% confidence interval (CI) 0.22 to 1.35, N = 74, P = 0.16). We assessed the quality of this evidence as low. Two parallel-group randomised double-blind, placebo-controlled trials comparing the effects of two doses of ascorbic acid with placebo for reducing fatigue in adults with Charcot-Marie-Tooth disease type 1A (CMT1A) showed that the effects of ascorbic acid at either dose are probably small (standardised mean difference (SMD) -0.12 (95% CI -0.32 to 0.08, n = 404, P = 0.25)) for change in fatigue after 12 to 24 months (moderate quality evidence). Neither ascorbic acid study measured fatigue at four to 12 weeks, which was our primary outcome measure. No serious adverse events were reported with amantadine. Serious adverse events were reported in the trials of ascorbic acid. However,risk of serious adverse events was similar with ascorbic acid and placebo.
AUTHORS' CONCLUSIONS
One small imprecise study in people with GBS showed uncertain effects of amantadine on fatigue. In two studies in people with CMT1A there is moderate-quality evidence that ascorbic acid has little meaningful benefit on fatigue. Information about adverse effects was limited, although both treatments appear to be well tolerated and safe in these conditions.There was no evidence available from RCTs to evaluate the effect of other drugs or other interventions for fatigue in either GBS, CMT1A or other causes of peripheral neuropathy. The cost effectiveness of different interventions should also be considered in future randomised clinical trials.
Topics: Adult; Amantadine; Ascorbic Acid; Charcot-Marie-Tooth Disease; Child; Fatigue; Guillain-Barre Syndrome; Humans; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic
PubMed: 25519471
DOI: 10.1002/14651858.CD008146.pub2 -
International Journal of Environmental... Feb 2022Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the second most common cause of optic nerve-related permanent visual loss in adults. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the second most common cause of optic nerve-related permanent visual loss in adults.
AIM
We aimed to analyze the efficacy of the noninvasive and minimally invasive therapeutic options of NAION.
METHODS
We performed a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to 10 June 2019 to identify the studies that report on the effect of different therapies on visual acuity (VA) and visual field (VF). Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for these outcomes. The efficacy of steroids was investigated in quantitative, oxygen, steroid plus erythropoietin (EPO), levodopa/carbidopa, memantine, and heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP) therapies and other therapeutic modalities in qualitative synthesis.
RESULTS
Thirty-two studies were found to be eligible. We found that steroid therapy compared to control did not improve VA ( = 0.182, WMD = 0.14, 95% CI: -0.07, 0.35) or VF ( = 0.853, WMD = 0.16, 95% CI: -1.54, 1.86). Qualitative analysis could be performed for oxygen, steroid plus EPO, and HELP as well, however, none of them showed VA and VF benefit. Two individual studies found memantine and levodopa beneficial regarding VA.
CONCLUSION
Our systematic review did not reveal any effective treatment. Further investigations are needed to find therapy for NAION.
Topics: Adult; Humans; Levodopa; Memantine; Optic Neuropathy, Ischemic; Oxygen; Steroids; Visual Acuity
PubMed: 35270411
DOI: 10.3390/ijerph19052718 -
Health Technology Assessment... 2012Alzheimer’s disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK. (Review)
Review
The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (review of Technology Appraisal No. 111): a systematic review and economic model.
BACKGROUND
Alzheimer’s disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK.
OBJECTIVES
Review and update guidance to the NHS in England and Wales on the clinical effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine [acetylcholinesterase inhibitors (AChEIs)] and memantine within their licensed indications for the treatment of AD, which was issued in November 2006 (amended September 2007 and August 2009).
DATA SOURCES
Electronic databases were searched for systematic reviews and/or metaanalyses, randomised controlled trials (RCTs) and ongoing research in November 2009 and updated in March 2010; this updated search revealed no new includable studies. The databases searched included The Cochrane Library (2009 Issue 4, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, EconLit, ISI Web of Science Databases--Science Citation Index, Conference Proceedings Citation Index, and BIOSIS; the Centre for Reviews and Dissemination (CRD) databases--NHS Economic Evaluation Database, Health Technology Assessment, and Database of Abstracts of Reviews of Effects.
REVIEW METHODS
The clinical effectiveness systematic review was undertaken following the principles published by the NHS CRD. We included RCTs whose population was people with AD. The intervention and comparators depended on disease severity, measured by the Mini Mental State Examination (MMSE).
INTERVENTIONS
mild AD (MMSE 21-26)--donepezil, galantamine and rivastigmine; moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine and memantine; severe AD (MMSE < 10)--memantine. Comparators: mild AD (MMSE 21-26)--placebo or best supportive care (BSC); moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine, memantine, placebo or BSC; severe AD (MMSE < 10)--placebo or BSC. The outcomes were clinical, global, functional, behavioural, quality of life, adverse events, costs and cost-effectiveness. Where appropriate, data were pooled using pair-wise meta-analysis, multiple outcome measures, metaregression and mixedtreatment comparisons. The decision model was based broadly on the structure of the three-state Markov model described in the previous technology assessment report, based upon time to institutionalisation, parameterised with updated estimates of effectiveness, costs and utilities.
RESULTS
Notwithstanding the uncertainty of our results, we found in the base case that the AChEIs are probably cost saving at a willingness-to-pay (WTP) of £’30,000 per qualityadjusted life-year (QALY) for people with mild-to-moderate AD. For this class of drugs, there is a > 99% probability that the AChEIs are more cost-effective than BSC. These analyses assume that the AChEIs have no effect on survival. For the AChEIs, in people with mild to moderate AD, the probabilistic sensitivity analyses suggested that donepezil is the most cost-effective, with a 28% probability of being the most cost-effective option at a WTP of £’30,000 per QALY (27% at a WTP of £’20,000 per QALY). In the deterministic results, donepezil dominates the other drugs and BSC, which, along with rivastigmine patches, are associated with greater costs and fewer QALYs. Thus, although galantamine has a slightly cheaper total cost than donepezil (£’69,592 vs £’69,624), the slightly greater QALY gains from donepezil (1.616 vs 1.617) are enough for donepezil to dominate galantamine.The probability that memantine is cost-effective in a moderate to severe cohort compared with BSC at a WTP of £’30,000 per QALY is 38% (and 28% at a WTP of £’20,000 per QALY). The deterministic ICER for memantine is £’32,100 per/QALY and the probabilistic ICER is £’36,700 per/QALY.
LIMITATIONS
Trials were of 6 months maximum follow-up, lacked reporting of key outcomes, provided no subgroup analyses and used insensitive measures. Searches were limited to English language, The model does not include behavioural symptoms and there is uncertainty about the model structure and parameters.
CONCLUSIONS
The additional clinical effectiveness evidence identified continues to suggest clinical benefit from the AChEIs in alleviating AD symptoms, although there is debate about the magnitude of the effect. Although there is also new evidence on the effectiveness of memantine, it remains less supportive of this drug’s use than the evidence for AChEIs. The conclusions concerning cost-effectiveness are quite different from the previous assessment. This is because both the changes in effectiveness and costs between drug use and non-drug use underlying the ICERs are very small. This leads to highly uncertain results, which are very sensitive to change. RESEARCH PRIORITIES: RCTs to include mortality, time to institutionalisation and quality of life, powered for subgroup analysis.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Cost-Benefit Analysis; Donepezil; Dopamine Agents; Female; Galantamine; Humans; Indans; Male; Memantine; Middle Aged; Models, Economic; Phenylcarbamates; Piperidines; Rivastigmine; Technology Assessment, Biomedical
PubMed: 22541366
DOI: 10.3310/hta16210 -
Pharmaceuticals (Basel, Switzerland) May 2021The treatment of bipolar depression is hampered by the inadequate efficacy of antidepressants, moderate effect of mood stabilizers, and the side effects of some... (Review)
Review
The treatment of bipolar depression is hampered by the inadequate efficacy of antidepressants, moderate effect of mood stabilizers, and the side effects of some second-generation antipsychotics. There is limited evidence to date regarding the antidepressant effects of memantine in bipolar depression. The aim of the article was to provide a short review of preclinical and clinical studies on the antidepressant effect of memantine, and to present the case of a bipolar depression patient successfully treated with memantine. The described patient with bipolar disorder was unsuccessfully treated with two mood stabilizers. The addition of memantine at a dose of 20 mg/d to the treatment with lamotrigine and valproic acid resulted in a reduction in the severity of depression measured on the HDRS-17 scale by 35%, and by 47.1% after 7 weeks. The discussion presents experimental evidence for the antidepressant effect of memantine, as well as data from clinical trials in recurrent and bipolar depression. The presented case is the second report in the medical literature showing the antidepressant effect of memantine as an add-on treatment for bipolar depression. The described case and literature analysis indicate that memantine may be an effective and safe method of augmentation of mood stabilizing therapy in bipolar depression.
PubMed: 34070216
DOI: 10.3390/ph14050481 -
Therapeutic Advances in... Aug 2012The objective of this study was to conduct a systematic review and meta-analysis of randomized placebo-controlled trials of amantadine for the treatment of...
OBJECTIVE
The objective of this study was to conduct a systematic review and meta-analysis of randomized placebo-controlled trials of amantadine for the treatment of olanzapine-induced weight gain.
METHODS
Studies were identified using online searches of PUBMED/MEDLINE and Cochrane database (CENTRAL), along with websites recording trial information such as ClinicalTrials.gov, Controlled-trials.com, and Clinicalstudyresults.org. Study eligibility criteria included randomized, double-blind clinical trials comparing amantadine with placebo for olanzapine-induced weight gain with body weight as an outcome measure and study duration of at least 12 weeks. The methodological quality of included trials was assessed using the Jadad Scale. Separate meta-analyses were undertaken for each outcome (body weight and frequency of weight loss >7%) and treatment effects were expressed as weighted mean differences (WMD) and Mantel-Haenszel odds ratio for continuous and categorical outcomes, respectively.
RESULTS
A systematic review of literature revealed six studies that had assessed amantadine for olanzapine-induced weight gain. Of these, two studies (n = 144) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight and frequency of body weight loss >7%. For body weight change, WMD was -1.85 (95% confidence interval [CI] -3.31 to -0.39) kg with amantadine as compared with placebo; the overall effect was statistically significant (p = 0.01). For frequency of body weight loss >7%, Mantel-Haenszel odds ratio for weight loss was 3.72 (95% CI 1.19-11.62), favoring amantadine as compared with placebo, and the overall effect was significant (p = 0.02).
CONCLUSIONS
Existing data is limited to two studies, which support the efficacy of amantadine for olanzapine-induced weight gain and a significant proportion of patients might lose weight with amantadine compared with placebo.
PubMed: 23983968
DOI: 10.1177/2045125312440441 -
Systematic Reviews Oct 2021The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in... (Review)
Review
PURPOSE
The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in patients with multiple sclerosis.
METHODS
A systematic review of literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines in the MEDLINE, LILACS, EMBASE, and COCHRANE databases. Articles were filtered based on title and abstract considering the selection criteria and subsequently filtered by full-text reading. The resulting articles were evaluated using the Joanna Briggs Institute Quality Tools. Study characteristics and results were extracted and presented in structured tables to conduct a narrative synthesis.
RESULTS
A total of 2852 published articles were extracted using our strategy. After removing duplicates, 2841 articles were screened based on title and abstract, 102 articles were evaluated using quality tools, and 69 articles were filtered by full-text reading. Through this search strategy, 60 articles met all the inclusion criteria and seven articles, through a search update conducted in the same manner, were included. This resulted in 67 articles meeting the inclusion criteria, of which 11 were experimental and 56 were observational. The therapies related to ocular TEAEs were alemtuzumab, amantadine, fingolimod, steroids, CTLA-4 Ig, estriol, interferon β, natalizumab, hyperbaric oxygen, rituximab, siponimod, teriflunomide, and tovaxin. Fingolimod and siponimod were commonly associated with macular edema, interferon β was associated with retinopathy, alemtuzumab was associated with thyroid eye disease, amantadine was associated with corneal edema, and steroids were associated with acute retinal necrosis. Opportunistic infections were also found, and there was one life-threatening case.
CONCLUSIONS
Our search revealed different methodological assessments of the topic. However, longitudinal studies regarding ocular TEAEs related to multiple sclerosis therapy are necessary to provide evidence-based recommendations, especially in understudied regions such as Latin America and Africa. Physicians should monitor ocular symptoms in patients being treated for multiple sclerosis and consider an interdisciplinary approach.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO ID CRD42020106886.
Topics: Africa; Humans; Multiple Sclerosis
PubMed: 34711264
DOI: 10.1186/s13643-021-01782-7 -
The Cochrane Database of Systematic... Jan 2018Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures.
OBJECTIVES
1. To determine the effects of any of the following drugs for antipsychotic-induced TD in people with schizophrenia or other chronic mental illnesses.i. Drugs which influence the noradrenergic system.ii. Dopamine receptor agonists.iii. Dopamine receptor antagonists.iv. Dopamine-depletor drugs.v. Drugs that increase the production or release of dopamine.2. To examine whether any improvement occurred with short periods of intervention (less than 6 weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.3. To examine if there was a differential effect for the various compounds.4. To examine whether the use of non-antipsychotic catecholaminergic drugs are most effective in those with more recent onset TD (less than five years).
SEARCH METHODS
We retrieved 712 references from searching the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We selected studies if they were randomised controlled trials focusing on people with schizophrenia or other chronic mental illnesses and antipsychotic-induced tardive dyskinesia. We compared the use of catecholaminergic interventions versus placebo, no intervention, or any other intervention for the treatment of antipsychotic-induced tardive dyskinesia.
DATA COLLECTION AND ANALYSIS
We independently extracted data from these trials and we estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assumed that people who left the studies early had no improvement.
MAIN RESULTS
There are 10 included trials (N = 261) published between 1973 and 2010; eight are new from the 2015 and 2017 update searches. Forty-eight studies are excluded. Participants were mostly chronically mentally ill inpatients in their 50s, and studies were primarily of short (2 to 6 weeks) duration. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment and generation of the sequence. Studies were also not clearly blinded and we are unsure if data are incomplete or selectively reported, or if other biases were operating.One small, three-arm trial found that both alpha-methyldopa (N = 20; RR 0.33, 95% CI 0.14 to 0.80; low-quality evidence) and reserpine (N = 20; RR 0.52 95% CI 0.29 to 0.96; low-quality evidence) may lead to a clinically important improvement in tardive dyskinesia symptoms compared with placebo after 2 weeks' treatment, but found no evidence of a difference between alpha-methyldopa and reserpine (N = 20; RR 0.60, 95% CI 0.19 to 1.86; very low quality evidence). Another small trial compared tetrabenazine and haloperidol after 18 weeks' treatment and found no evidence of a difference on clinically important improvement in tardive dyskinesia symptoms (N = 13; RR 0.93, 95% CI 0.45 to 1.95; very low quality evidence). No study reported on adverse events.For remaining outcomes there was no evidence of a difference between any of the interventions: alpha-methyldopa versus placebo for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence), celiprolol versus placebo for leaving the study early (1 RCT; N = 35; RR 5.28, 95% CI 0.27 to 102.58; very low quality evidence) and quality of life (1 RCT; N = 35; RR 0.87, 95% CI 0.68 to 1.12; very low quality evidence), alpha-methyldopa versus reserpine for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; not estimable, no reported events; very low quality evidence), reserpine or carbidopa/levodopa versus placebo for deterioration of tardive dyskinesia symptoms (2 RCTs; N = 37; RR 1.18, 95% CI 0.35 to 3.99; very low quality evidence), oxypertine versus placebo for deterioration of mental state (1 RCT; N = 42; RR 2.20, 95% CI 0.22 to 22.45; very low quality evidence), dopaminergic drugs (amantadine, bromocriptine, tiapride, oxypertine, carbidopa/levodopa) versus placebo for leaving the study early (6 RCTs; N = 163; RR 1.29, 95% CI 0.65 to 2.54; very low quality evidence), and tetrabenazine versus haloperidol for deterioration of tardive dyskinesia symptoms (1 RCT; N = 13; RR 1.17, 95% CI 0.09 to 14.92) and leaving the study early (1 RCT; N = 13; RR 0.23, 95% CI 0.01 to 4.00).
AUTHORS' CONCLUSIONS
Although there has been a large amount of research in this area, many studies were excluded due to inherent problems in the nature of their cross-over designs. Usually data are not reported before the cross-over and the nature of TD and its likely response to treatments make it imprudent to use this data. The review provides little usable information for service users or providers and more well-designed and well-reported studies are indicated.
Topics: Adrenergic Uptake Inhibitors; Anti-Dyskinesia Agents; Antipsychotic Agents; Celiprolol; Disease Progression; Dopamine Antagonists; Dyskinesia, Drug-Induced; Haloperidol; Humans; Methyldopa; Randomized Controlled Trials as Topic; Reserpine; Tetrabenazine; Tiapamil Hydrochloride
PubMed: 29342497
DOI: 10.1002/14651858.CD000458.pub3 -
Journal of Affective Disorders Jun 2016Acetylcholinesterase inhibitors (AceI) and memantine might prove useful in bipolar disorder (BD) given their neuroprotective and pro-cognitive effects, as highlighted by... (Meta-Analysis)
Meta-Analysis Review
Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions.
BACKGROUND
Acetylcholinesterase inhibitors (AceI) and memantine might prove useful in bipolar disorder (BD) given their neuroprotective and pro-cognitive effects, as highlighted by several case reports. We aimed to systematically review the efficacy and safety of AceI and memantine across multiple outcome dimensions in BD.
METHODS
Systematic PubMed and SCOPUS search until 04/17/2015 without language restrictions. Included were randomized controlled trials (RCTs), open label studies and case series of AceI or memantine in BD patients reporting quantitative data on depression, mania, psychotic symptoms, global functioning, or cognitive performance. We summarized results using a best-evidence based synthesis.
RESULTS
Out of 214 hits, 12 studies (RCTs=5, other designs=7, total n=422) were included. Donepezil (studies=5; treated=102 vs. placebo=21): there was strong evidence for no effect on mania and psychotic symptoms; low evidence indicating no effect on depression. Galantamine (studies=3; treated=21 vs. controls=20) (placebo=10, healthy subjects=10): there was strong evidence for no effect on mania; moderate evidence for no effect on depression; low evidence for no effect on global functioning. Memantine (studies=4; treated=152 vs. placebo=88): there was conflicting evidence regarding efficacy for mania, depression and global functioning.
LIMITATIONS
Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics.
CONCLUSION
There is limited but converging evidence of no effect of AceI in BD, and conflicting evidence about memantine in BD. Too few studies of mostly medium/low quality and lacking sufficient numbers of patients in specific mood states, especially mania, contributed data, focusing solely on short-term/medium-term treatment, necessitating additional high-quality research to yield more definite results.
Topics: Adult; Bipolar Disorder; Case-Control Studies; Cholinesterase Inhibitors; Clinical Trials as Topic; Depression; Depressive Disorder; Donepezil; Evidence-Based Medicine; Excitatory Amino Acid Antagonists; Female; Galantamine; Humans; Indans; Male; Memantine; Middle Aged; Piperidines; Psychotic Disorders; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27010579
DOI: 10.1016/j.jad.2016.03.034