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The Cochrane Database of Systematic... Apr 2021Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment. OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment.
SEARCH METHODS
We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature.
SELECTION CRITERIA
We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence.
MAIN RESULTS
The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported.
AUTHORS' CONCLUSIONS
Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.
Topics: Abortion, Spontaneous; Administration, Oral; Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Fertilization in Vitro; Humans; Live Birth; Ovarian Hyperstimulation Syndrome; Placebos; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 33851429
DOI: 10.1002/14651858.CD008605.pub4 -
The Cochrane Database of Systematic... Oct 2004As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to... (Review)
Review
BACKGROUND
As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase.
OBJECTIVES
To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.
SEARCH STRATEGY
Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted.
SELECTION CRITERIA
Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events.
MAIN RESULTS
Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration. Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels.
REVIEWERS' CONCLUSIONS
In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone.
Topics: Antiparkinson Agents; Benzophenones; Catechol O-Methyltransferase Inhibitors; Catechols; Enzyme Inhibitors; Humans; Levodopa; Nitriles; Nitrophenols; Parkinson Disease; Tolcapone
PubMed: 15495119
DOI: 10.1002/14651858.CD004554.pub2 -
The Cochrane Database of Systematic... 2003Abnormal involuntary movements known as dyskinesias are amongst the most disabling side-effects of levodopa therapy. It is thought that amantadine, an NMDA-receptor... (Review)
Review
BACKGROUND
Abnormal involuntary movements known as dyskinesias are amongst the most disabling side-effects of levodopa therapy. It is thought that amantadine, an NMDA-receptor antagonist, may reduce dyskinesias in patients with Parkinson's disease without worsening Parkinsonian symptoms.
OBJECTIVES
To compare the efficacy and safety of adjuvant amantadine therapy versus placebo in treating dyskinesia in patients with Parkinson's disease, already established on levodopa, and suffering from motor complications.
SEARCH STRATEGY
Electronic searches of The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), SCISEARCH (1974-2001), BIOSIS (1993-2001), GEROLIT (1979-2001), OLDMEDLINE (1957-1965), LILACS (1982-2001), MedCarib (17th Century - 2001), PASCAL (1973-2001), JICST-EPLUS (1985-2001), RUSSMED (1973-2001), DISSERTATION ABSTRACTS (2000-2001), SIGLE (1980-2001), ISI-ISTP (1990-2001), Aslib Index to Theses (2001), Clinicaltrials.gov (2001), metaRegister of Controlled Trials (2001), NIDRR (2001) and NRR (2001) were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of amantadine were contacted.
SELECTION CRITERIA
Randomised controlled trials comparing amantadine with placebo in the treatment of dyskinesia in patients with a clinical diagnosis of idiopathic Parkinson's disease.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by NC and KD onto standardised forms and disagreements were resolved by discussion.
MAIN RESULTS
Three randomised controlled trials were found comparing amantadine with placebo in the treatment of dyskinesia in patients with idiopathic Parkinson's disease. Three trials were excluded on the basis that they had no control group and a further three did not state whether they randomised the treatment that participants received. The included trials were double-blind cross-over studies involving a total of 53 patients. All three studies failed to present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. Two trials had no wash-out interval between the treatment periods. In view of the risk of a carry-over effect into the second arm, the results of these trials were not analysed. The final trial had a one week wash-out interval but only examined 11 participants. One study reported side-effects of amantadine in 8 of the 18 participants, including confusion and worsening of hallucinations. Another reported reversible edema of both feet in one of eleven participants.
REVIEWER'S CONCLUSIONS
Due to lack of evidence it is impossible to determine whether amantadine is a safe and effective form of treatment for levodopa-induced dyskinesias in patients with Parkinson's disease.
Topics: Amantadine; Antiparkinson Agents; Dyskinesias; Humans; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 12804468
DOI: 10.1002/14651858.CD003467 -
The Cochrane Database of Systematic... 2004Trifluoperazine is an inexpensive accessible 'high potency' antipsychotic drug, widely used to treat schizophrenia or related psychoses. (Review)
Review
BACKGROUND
Trifluoperazine is an inexpensive accessible 'high potency' antipsychotic drug, widely used to treat schizophrenia or related psychoses.
OBJECTIVES
To estimate the effects of trifluoperazine compared with placebo and other drugs.
SEARCH STRATEGY
Searches of the Cochrane Schizophrenia Group's register of trials (March 2002), supplemented with hand searching, reference searching, personal communication and contact with industry.
SELECTION CRITERIA
All clinical randomised trials involving people with schizophrenia and comparing trifluoperazine with any other treatment.
DATA COLLECTION AND ANALYSIS
Studies were reliably selected and quality rated and data was extracted. For dichotomous data, relative risks (RR) were estimated, with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, the number needed to treat (NNT) was calculated. We estimated heterogeneity (I-square technique) and publication bias.
MAIN RESULTS
1162 people from 13 studies were randomised to trifluoperazine or placebo. For global improvement, small short-term studies favoured trifluoperazine (n=95, 3 RCTs, RR 0.62 CI 0.49 to 0.78 NNT 3 CI 2 to 4). Loss to follow up was about 12% in both groups (n=280, 7 RCTs, RR 0.99 CI 0.62 to 1.57) and more people allocated trifluoperazine used antiparkinson drugs to alleviate movements disorders compared with placebo (n=195, 4 RCTs, RR 5.06 CI 2.49 to 10.27, NNH 4 CI 2 to 9). 2230 people from 49 studies were randomised to trifluoperazine or another older generation antipsychotic. Trifluoperazine was not clearly different in terms of 'no substantial improvement' (n=1016, 27 RCTs, RR 1.06 CI 0.98 to 1.14) or leaving the study early (n=930, 22 RCTs, RR 1.15 CI 0.83 to 1.58). Almost identical numbers of people reported at least one adverse event (60%) in each group (n=585, 14 RCTs, RR 0.99 CI 0.87 to 1.13), although trifluoperazine was more likely to cause extrapyramidal adverse effects overall when compared to low potency antipsychotics such as chlorpromazine (n=130, 3 RCTs, RR 1.66 CI 1.03 to 2.67, NNH 6 CI 3 to 121). One small study (n=38) found no clear differences between trifluoperazine and the atypical drug, sulpiride.
REVIEWER'S CONCLUSIONS
Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that trifluoperazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs. It has been claimed that trifluoperazine is effective at low doses for patients with schizophrenia but this does not appear to be based on good quality trial based evidence.
Topics: Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Trifluoperazine
PubMed: 14974020
DOI: 10.1002/14651858.CD003545.pub2 -
The Cochrane Database of Systematic... Jun 2018Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence... (Review)
Review
BACKGROUND
Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium.
OBJECTIVES
To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal.
SEARCH METHODS
We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials.
SELECTION CRITERIA
Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1 study, very low-quality evidence); clonidine versus clonidine plus amantadine (RR 1.03, 95% CI 0.86 to 1.24; 69 participants, 1 study); clonidine versus buprenorphine in an inpatient setting (RR 1.04, 95% CI 0.90 to 1.20; 1 study, 35 participants, very low-quality evidence); methadone versus tramadol (RR 0.95, 95% CI 0.65 to 1.37; 1 study, 72 participants, very low-quality evidence); methadone versus methadone plus gabapentin (RR 1.17, 95% CI 0.96 to 1.43; 1 study, 40 participants, low-quality evidence), and tincture of opium versus methadone (1 study, 74 participants, low-quality evidence).Comparing different pharmacological treatments with each other, adding amantadine to clonidine decreased withdrawal scores rated at day 3 (mean difference (MD) -3.56, 95% CI -5.97 to -1.15; 1 study, 60 participants, very low-quality evidence). Comparing clonidine with buprenorphine in an inpatient setting, we found no difference in withdrawal symptoms rated by a physician (MD -1.40, 95% CI -2.93 to 0.13; 1 study, 34 participants, very low-quality evidence), and results in favour of buprenorpine when rated by participants (MD -11.80, 95% CI -15.56 to -8.04). Buprenorphine was superior to clonidine in controlling severe withdrawal symptoms in an outpatient setting (RR 0.35, 95% CI 0.19 to 0.64; 1 study, 76 participants). We found no difference in the comparison of methadone versus tramadol (MD 0.04, 95% CI -2.68 to 2.76; 1 study, 72 participants) and in the comparison of methadone versus methadone plus gabapentin (MD -2.20, 95% CI -6.72 to 2.32; 1 study, 40 participants).Comparing clonidine versus buprenorphine in an outpatient setting, more adverse effects were reported in the clonidine group (1 study, 76 participants). Higher numbers of participants in the clonidine group experienced hypotension at days 5 to 8, headache at days 1 to 8, sedation at days 5 to 8, dizziness and dry mouth at days 1 to 10, and nausea at days 1 to 9. Sweating was reported in a significantly higher number of participants in the buprenorphine group at days 1 to 10. We found no difference between groups for all the other comparisons considering this outcome.Comparing different dosages of the same pharmacological detoxification treatment, a high dose of clonidine (1 to 1.2 mg/day) did not differ from a low dose of clonidine (0.5 to 0.6 mg/day) in completion of treatment in an inpatient setting (RR 1.00, 95% CI 0.84 to 1.19; 1 study, 68 participants), however a higher number of participants with hypotension was reported in the high-dose group (RR 3.25, 95% CI 1.77 to 5.98). Gradual reduction of methadone was associated with more adverse effects than abrupt withdrawal of methadone (RR 2.25, 95% CI 1.02 to 4.94; 1 study, 20 participants, very low-quality evidence).
AUTHORS' CONCLUSIONS
Results did not support using any specific pharmacological approach for the management of opium withdrawal due to generally very low-quality evidence and small or no differences between treatments. However, it seems that opium withdrawal symptoms are significant, especially at days 2 to 4 after discontinuation of opium. All of the assessed medications might be useful in alleviating symptoms. Those who receive clonidine might experience hypotension.
Topics: Amantadine; Amines; Baclofen; Buprenorphine; Clonidine; Cyclohexanecarboxylic Acids; Gabapentin; Humans; Methadone; Opioid-Related Disorders; Opium; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Tramadol; gamma-Aminobutyric Acid
PubMed: 29929212
DOI: 10.1002/14651858.CD007522.pub2 -
The Cochrane Database of Systematic... Oct 2011Eye movement disorders may affect over 70% of stroke patients. These eye movement disorders can result in difficulty maintaining the normal ocular position and... (Review)
Review
BACKGROUND
Eye movement disorders may affect over 70% of stroke patients. These eye movement disorders can result in difficulty maintaining the normal ocular position and difficulty moving the eyes appropriately. The resulting functional disabilities include a loss of depth perception, reduced hand-to-eye co-ordination, marked difficulties with near tasks and reading and reduced ability to scan the visual environment. They can also impact on the effectiveness of rehabilitation therapy. There are a wide variety of different treatment interventions proposed for eye movement disorders after stroke. However, in the past, there has been a lack of evidence specific to the impact of interventions on the functional outcome of patients with stroke.
OBJECTIVES
To determine the effects of interventions for eye movement disorders on functional ability following stroke.
SEARCH STRATEGY
We searched the Cochrane Stroke Group Trials Register (February 2011), the Cochrane Eyes and Vision Group Trials Register (December 2009) and nine electronic bibliographic databases including CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to December 2009), EMBASE (1980 to December 2009), CINAHL (1982 to December 2009), AMED (1985 to December 2009), and PsycINFO (1967 to December 2009). We also searched reference lists and trials registers, handsearched journals and conference proceedings, and contacted experts.
SELECTION CRITERIA
Randomised trials in adults after stroke where the intervention was specifically targeted at improving the eye movement disorder or improving the ability of the participant to cope with the eye movement disorder. The primary outcome was functional ability in activities of daily living. Secondary outcomes included functional ability in extended activities of daily living, eye movement measures, balance, falls, depression or anxiety, discharge destination or residence after stroke, quality of life and social isolation, adverse events, and death.
DATA COLLECTION AND ANALYSIS
Two authors independently screened abstracts, extracted data and appraised trials. We undertook assessment of methodological quality for allocation concealment, blinding of outcome assessor, method of dealing with missing data, and other potential sources of bias.
MAIN RESULTS
Two studies (28 participants but only five were people with stroke) met the inclusion criteria and were included in this review. Both studies investigated pharmacological interventions for disorders of eye movement in patients with stroke. It was not appropriate to pool data and we were not able to draw conclusions from these studies. We found no other randomised studies which investigated interventions for disorders of eye movement in patients with stroke.
AUTHORS' CONCLUSIONS
There is insufficient evidence to reach conclusions about the effectiveness of interventions for patients with eye movement disorders after stroke. High quality research in the form of well-designed randomised trials are urgently required.
Topics: Activities of Daily Living; Adult; Humans; Muscarinic Antagonists; Ocular Motility Disorders; Randomized Controlled Trials as Topic; Stroke; Trihexyphenidyl
PubMed: 21975780
DOI: 10.1002/14651858.CD008389.pub2 -
Movement Disorders : Official Journal... Aug 2021Advanced Parkinson's disease is inconsistently defined, and evidence is lacking in relation to device-aided therapies. To update existing reviews of intrajejunal... (Review)
Review
Advanced Parkinson's disease is inconsistently defined, and evidence is lacking in relation to device-aided therapies. To update existing reviews of intrajejunal infusion of levodopa/carbidopa (LCIG), we performed a literature search for relevant articles (to November 3, 2020) using PubMed supplemented by hand searching. Retrieved articles were categorized by relevance to identified research questions, including motor complications and symptoms; nonmotor symptoms; functioning, quality of life, and caregiver burden; optimal timing of treatment initiation and administration duration; discontinuation; and complications. Most eligible studies (n = 56) were open-label, observational studies including relatively small patient numbers. LCIG consistently reduces OFF time and increased ON time without troublesome dyskinesia with varying effects regarding ON time with troublesome dyskinesia and the possibility of diphasic dyskinesia. More recent evidence provides some increased support for the benefits of LCIG in relation to nonmotor symptoms, quality of life, activities of daily living, and reduced caregiver burden. Patient age does not appear to significantly impact the effectiveness of LCIG. Discontinuation rates with LCIG (~17%-26%) commonly relate to device-related issues, although the ability to easily discontinue LCIG may represent a potential benefit. LCIG may be a favorable option for patients with advanced Parkinson's disease who show predominant nonmotor symptoms and vulnerability to complications of other advanced therapy modalities. Larger, well-controlled studies, including precise investigation of cost effectiveness, would further assist treatment selection. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Activities of Daily Living; Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Parkinson Disease; Quality of Life
PubMed: 33899262
DOI: 10.1002/mds.28595 -
The International Journal of... Dec 2014We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease.
METHODS
We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects.
RESULTS
Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=-0.13), activity of daily living scores (standardized mean difference=-0.10), and global assessment scores (standardized mean difference=-0.15). In addition, cognitive function scores (standardized mean difference=-0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects.
CONCLUSIONS
Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated.
Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antiparkinson Agents; Cholinesterase Inhibitors; Cognition; Combined Modality Therapy; Female; Humans; Male; Memantine; Treatment Outcome
PubMed: 25548104
DOI: 10.1093/ijnp/pyu115 -
Canadian Respiratory Journal Oct 2003To evaluate the efficacy and safety of amantadine and rimantadine, the first generation antivirals, for the prophylaxis of influenza virus. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the efficacy and safety of amantadine and rimantadine, the first generation antivirals, for the prophylaxis of influenza virus.
DATA SOURCES
A systematic search of the English language literature using MEDLINE, EMBASE, Current Contents and the Cochrane database from 1966 to April 2002, as well as a manual search of references from retrieved articles, were performed.
STUDY SELECTION
Prospective, randomized, controlled clinical trials evaluating amantadine and rimantadine for prophylaxis of naturally occurring influenza A illness were considered. The control arm used either a placebo or an antiviral agent.
DATA EXTRACTION
Each trial was assessed by two authors to determine the adequacy of randomization and description of withdrawals. Efficacy data were extracted according to a predefined protocol. Discrepancies in data extraction among the investigators were solved by consensus. Nine prophylaxis studies of amantadine and rimantadine met the criteria for this systematic review.
DATA SYNTHESIS
Seven amantadine versus placebo trials (n=1797), three rimantadine versus placebo trials (n=688) and two amantadine versus rimantadine studies (n=455) were included for the meta-analysis on the prevention of influenza A illness. The summary of results for the relative odds of illness indicated a 64% reduction in the amantadine group compared with placebo (OR 0.36, 95% CI 0.23 to 0.55, P< or =0.001), a 75% reduction in illness for the rimantadine group compared with placebo (OR 0.25, 95% CI 0.07 to 0.97, P=0.05) and no significant differences in the odds of illness for the amantadine versus rimantadine groups (OR 1.15, 95% CI 0.57 to 2.32, P=0.32). The summary of results examining adverse events showed significantly higher odds of central nervous system adverse reactions and premature withdrawal from the clinical trials in the amantadine-treated group than in the placebo-treated group. Compared with the placebo-treated group, the rimantadine-treated group did not have a significantly higher rate of withdrawal or central nervous system events. However, there was a significant increase in the odds of gastrointestinal adverse events for those treated with rimantadine compared with those treated with placebo (OR 3.34, 95% CI 1.17 to 9.55, P=0.03). In the comparative trials of amantadine to rimantadine, rimantadine was associated with an 82% reduction in the odds of central nervous system events (OR 0.18, 95% CI 0.03 to 1.00, P=0.05) and a 60% reduction in the odds of discontinuing treatment (OR 0.40, 95% CI 0.20 to 0.79, P=0.009).
CONCLUSION
This meta-analysis demonstrates that amantadine and rimantadine are superior to placebo in the prevention of influenza A illness. Both antiviral agents have an increased number of adverse events compared with placebo; however, the use of amantadine is associated with significantly higher numbers of central nervous system events and treatment withdrawals compared with rimantadine. Thus, rimantadine should be the preferred agent in this class for the prevention of influenza A virus infection and should be made available in Canada.
Topics: Amantadine; Antiviral Agents; Canada; Data Interpretation, Statistical; Drug Administration Schedule; Humans; Influenza A virus; Influenza, Human; Randomized Controlled Trials as Topic; Rimantadine
PubMed: 14571290
DOI: 10.1155/2003/453183 -
PloS One 2015We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD).
METHODS
The meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes.
RESULTS
Nine studies including 2433 patients that met the study's inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=-0.27, 95% confidence interval (CI)=-0.39 to -0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95% CI=-0.22 to -0.01, p=0.03), activities of daily living (SMD=-0.09, 95% CI=-0.19 to -0.00, p=0.05), global function assessment (SMD=-0.18, 95% CI=-0.27 to -0.09, p=0.0001), and stage of dementia (SMD=-0.23, 95% CI=-0.33 to -0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17¬ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups.
CONCLUSIONS
Memantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.
Topics: Activities of Daily Living; Alzheimer Disease; Humans; Memantine; Publication Bias; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25860130
DOI: 10.1371/journal.pone.0123289