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The Cochrane Database of Systematic... Jan 2012Antipsychotic medication remains the mainstay of treatment for schizophrenia and has been in use for a long time. As evidenced by ongoing research and partial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic medication remains the mainstay of treatment for schizophrenia and has been in use for a long time. As evidenced by ongoing research and partial effectiveness of the antipsychotics on cognitive and negative symptoms, the search is on for drugs that may improve these domains of functioning for someone suffering from schizophrenia. Acetylcholinesterase inhibitors have long been in use for treating cognitive symptoms of dementia.
OBJECTIVES
The aim of the review was to evaluate the clinical effects, safety and cost effectiveness of acetylcholinesterase inhibitors for treating people with schizophrenia
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Register (February 2009), and inspected the references of all identified studies for further trials.
SELECTION CRITERIA
We included all clinical randomised trials comparing acetylcholinesterase inhibitors with antipsychotics or placebo either alone, or in combination, for schizophrenia and schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat (ITT) basis based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model.
MAIN RESULTS
The acetylcholinesterase inhibitor plus antipsychotic showed benefit over antipsychotic and placebo in the following outcomes.1. Mental state - PANSS negative symptoms average end point score (2 RCTs, n = 31, MD -1.69 95% CI -2.80 to -0.57), PANSS General Psychopathology average end point score (2 RCTs, n = 31, MD -3.86 95% CI -5.40 to -2.32), and improvement in depressive symptoms showed at least by one short-term study as measured by CDSS scale (data skewed).2. Cognitive domains - attention, (1 RCT, n = 73, MD 1.20 95% CI 0.14 to 2.26), visual memory (2 RCTs, n = 48 , MD 1.90 95% CI 0.52 to 3.28), verbal memory and language (3 RCTs, n = 42, MD 3.46 95% CI 0.67 to 6.26) and executive functioning (1 RCT, n = 24, MD 17.10 95% CI 0.70 to 33.50).3. Tolerability - EPSE: AIMS, (1 RCT, n = 35, MD 1.50 95% CI 1.04 to 1.96).No difference was noted between the two arms in other outcomes. The overall rate of participants leaving studies early was low (13.6 %) and showed no clear difference between the two groups.
AUTHORS' CONCLUSIONS
The results seem to favour the use of acetylcholinesterase inhibitors in combination with antipsychotics on a few domains of mental state and cognition, but because of the various limitations in the studies as mentioned in the main text, the evidence is weak. This review highlights the need for large, independent, well designed, conducted and reported pragmatic randomised studies.
Topics: Antipsychotic Agents; Cholinesterase Inhibitors; Donepezil; Galantamine; Humans; Indans; Phenylcarbamates; Piperidines; Psychotic Disorders; Randomized Controlled Trials as Topic; Rivastigmine; Schizophrenia; Schizophrenic Psychology
PubMed: 22258978
DOI: 10.1002/14651858.CD007967.pub2 -
BMJ Clinical Evidence Sep 2012Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired. (Review)
Review
INTRODUCTION
Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments on cognitive symptoms of dementia (Alzheimer's, Lewy body, or vascular)? What are the effects of treatments on behavioural and psychological symptoms of dementia (Alzheimer's, Lewy body, or vascular)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (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 49 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: acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine), antidepressants (clomipramine, fluoxetine, imipramine, sertraline), antipsychotics (haloperidol, olanzapine, quetiapine, risperidone), aromatherapy, benzodiazepines (diazepam, lorazepam), cognitive behavioural therapy (CBT), cognitive stimulation, exercise, ginkgo biloba, memantine, mood stabilisers (carbamazepine, sodium valproate/valproic acid), music therapy, non-steroidal anti-inflammatory drugs (NSAIDs), omega 3 (fish oil), reminiscence therapy, and statins.
Topics: Activities of Daily Living; Cognition Disorders; Dementia; Exercise; Humans; Indans; Memory; Music Therapy; Neuropsychological Tests; Personality Disorders
PubMed: 23870856
DOI: No ID Found -
Dementia and Geriatric Cognitive... Jan 2011Behavioural and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) greatly increase caregiver burden. The abilities of donepezil and memantine to...
The efficacy of licensed-indication use of donepezil and memantine monotherapies for treating behavioural and psychological symptoms of dementia in patients with Alzheimer's disease: systematic review and meta-analysis.
BACKGROUND/AIMS
Behavioural and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) greatly increase caregiver burden. The abilities of donepezil and memantine to manage BPSD within their licensed indications in AD were compared.
METHODS
A systematic review, random effects meta-analysis and Bucher indirect comparison were conducted.
RESULTS
Six randomised controlled studies (4 donepezil and 2 memantine) reported use within the licensed indication and had Neuropsychiatric Inventory (NPI) data suitable for meta-analysis. BPSD showed significant improvement with donepezil compared with placebo [weighted mean difference (WMD) in NPI -3.51, 95% confidence interval (CI) -5.75, -1.27], whereas this was not the case for memantine (WMD -1.65, 95% CI -4.78, 1.49). WMD in NPI for donepezil versus memantine favoured donepezil but was not statistically significant (-1.86, 95% CI -5.71, 1.99; p = 0.34).
CONCLUSION
Within its licensed indication, donepezil is efficacious for the management of BPSD in AD compared with placebo.
PubMed: 22163246
DOI: 10.1159/000330032 -
BMC Psychiatry Sep 2010Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime... (Review)
Review
BACKGROUND
Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime prevalence of visual hallucinations in patients with schizophrenia is much more common than conventionally thought and ranges from 24% to 72%. Cortical acetylcholine (ACh) depletion has been associated with visual hallucinations; the level of depletion being related directly to the severity of the symptoms. Current understanding of neurobiological visual processing and research in diseases with reduced cholinergic function, suggests that AChEI's may prove beneficial in treating visual hallucinations. This offers the potential for targeted drug therapy of clinically symptomatic visual hallucinations in patients with schizophrenia using acetylcholinesterase inhibition.
METHODS
A systematic review was carried out investigating the evidence for the effects of AChEI's in treating visual hallucinations in Schizophrenia.
RESULTS
No evidence was found relating to the specific role of AChEI's in treating visual hallucinations in this patient group.
DISCUSSION
Given the use of AChEI's in targeted, symptom specific treatment in other neuropsychiatric disorders, it is surprising to find no related literature in schizophrenia patients. The use of AChEI's in schizophrenia has investigated effects on cognition primarily with non cognitive effects measured more broadly.
CONCLUSIONS
We would suggest that more focused research into the effects of AChEI's on positive symptoms of schizophrenia, specifically visual hallucinations, is needed.
Topics: Cholinesterase Inhibitors; Donepezil; Galantamine; Hallucinations; Humans; Indans; Phenylcarbamates; Piperidines; Rivastigmine; Schizophrenia; Schizophrenic Psychology; Treatment Outcome
PubMed: 20822517
DOI: 10.1186/1471-244X-10-69 -
BMJ Clinical Evidence Apr 2010Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired. (Review)
Review
INTRODUCTION
Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments on cognitive symptoms of dementia (Alzheimer's, Lewy body, or vascular)? What are the effects of treatments on behavioural and psychological symptoms of dementia (Alzheimer's, Lewy body, or vascular)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (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 33 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: acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine), antidepressants (clomipramine, fluoxetine, imipramine, sertraline), antipsychotics (haloperidol, olanzapine, quetiapine, risperidone), aromatherapy, benzodiazepines (diazepam, lorazepam), cognitive behavioural therapy (CBT), cognitive stimulation, exercise, ginkgo biloba, memantine, mood stabilisers (carbamazepine, sodium valproate/valproic acid), music therapy, non-steroidal anti-inflammatory drugs (NSAIDs), omega 3 (fish oil), reminiscence therapy, and statins.
Topics: Alzheimer Disease; Anti-Inflammatory Agents, Non-Steroidal; Cholinesterase Inhibitors; Dementia; Galantamine; Humans; Memantine
PubMed: 21726471
DOI: No ID Found -
Dementia and Geriatric Cognitive... 2009The purpose of this systematic review was to compare the safety and tolerability of the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine and galantamine for... (Review)
Review
BACKGROUND/AIMS
The purpose of this systematic review was to compare the safety and tolerability of the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine and galantamine for treating mild to moderate Alzheimer's disease (AD) patients in routine clinical practice.
METHODS
Electronic databases (Cochrane Library, Medline, EMBASE; accessed October 2008) and manual bibliographic searches were conducted to identify head-to-head non-randomised studies examining ChEIs for the treatment of AD. Data were extracted by 2 independent reviewers.
RESULTS
Twelve head-to-head studies comparing ChEIs met the pre-specified inclusion criteria; 6 retrospective analyses and 6 prospective cohort studies. Donepezil was the most widely studied treatment and galantamine the least widely prescribed therapy. Fewer donepezil-treated subjects withdrew due to adverse events (AEs) compared with rivastigmine and galantamine-treated subjects. The incidence of gastrointestinal (GI) AEs was lower following treatment with donepezil compared with rivastigmine and galantamine. Non-GI (CNS and cardiovascular) AEs occurred at a low frequency, and had a similar incidence in subjects treated with the different ChEIs.
CONCLUSIONS
Subjects with mild to moderate AD treated in routine clinical practice with donepezil were more adherent to pharmacotherapy, and had a lower risk of GI AEs compared with rivastigmine or galantamine. This finding accords with results reported in the randomised clinical trial literature.
Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Evidence-Based Medicine; Galantamine; Humans; Indans; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Rivastigmine
PubMed: 19893314
DOI: 10.1159/000255578 -
The Cochrane Database of Systematic... Jul 2009Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant drugs that clinicians use for routine depression care.
OBJECTIVES
To assess the evidence for the efficacy, acceptability and tolerability of milnacipran in comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other newer antidepressive agents in the acute-phase treatment of major depression.
SEARCH STRATEGY
The Cochrane Collaboration Depression, Anxiety & Neurosis review group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were electronically searched in August 2008. References of relevant trials and other reviews were also checked. Trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished trials were hand-searched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied.
SELECTION CRITERIA
Randomised controlled trials comparing milnacipran with any other active antidepressive agents (including non-conventional agents such as herbal products like hypericum) as monotherapy in the acute phase of major depression were selected.
DATA COLLECTION AND ANALYSIS
Two reviewers independently checked eligibility, assessed methodological quality and extracted data from the eligible trials using a standardised data extraction form. The number of participants who responded to treatment or those who achieved remission were calculated on an intention-to-treat basis. Random-effects meta-analyses were conducted, combining data from the included trials.
MAIN RESULTS
A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis.Despite the size of this sample, the pooled 95% confidence intervals were rather wide and there were no statistically significant differences in efficacy, acceptability and tolerability when comparing milnacipran with other antidepressive agents. However, compared with TCAs, patients taking milnacipran were associated with fewer dropouts due to adverse events (OR 0.55; 95%CI 0.35 to 0.85). There was also some weak evidence to suggest that patients taking milnacipran experienced fewer adverse events of sleepiness/ drowsiness, dry mouth or constipation compared with TCAs.
AUTHORS' CONCLUSIONS
Currently, there is inadequate evidence to conclude whether milnacipran is superior, inferior or the same as other antidepressive agents in terms of efficacy, acceptability and tolerability in the acute phase treatment of major depression. However, there is some evidence in favour of milnacipran over TCAs in terms of dropouts due to adverse events (acceptability) and the rates of experiencing adverse events (tolerability). Information about other clinically meaningful outcomes such as cost-effectiveness and social functioning, including the ability to return to work, is lacking. Further study is needed to answer whether milnacipran would be the better choice of antidepressant for acute major depression.
Topics: Antidepressive Agents; Cyclopropanes; Depressive Disorder, Major; Humans; Milnacipran; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 19588396
DOI: 10.1002/14651858.CD006529.pub2 -
The Cochrane Database of Systematic... Jan 2009Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). Acetylcholine is a chemical found in the brain that has an important... (Review)
Review
BACKGROUND
Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). Acetylcholine is a chemical found in the brain that has an important role in memory, attention, reason and language. Rivastigmine is a "pseudo-irreversible" inhibitor of acetylcholinesterase, which is thought to maintain levels of acetylcholine. Rivastigmine can improve cognitive function and slow the decline of AD in the general population over time. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population.
OBJECTIVES
To determine the effectiveness and safety of rivastigmine for people with DS who develop AD.
SEARCH STRATEGY
CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of rivastigmine as well as experts in the field, to ask about reports of unpublished or ongoing trials.
SELECTION CRITERIA
Randomised controlled trials of participants with DS and AD in which treatment with rivastigmine was administered compared with a placebo group.
DATA COLLECTION AND ANALYSIS
No study was identified which met inclusion criteria for this review.
MAIN RESULTS
No study was identified which met inclusion criteria for this review.
AUTHORS' CONCLUSIONS
As there are no included trials, recommendations cannot be made about rivastigmine for AD in DS. Well-designed, adequately powered studies are required.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Down Syndrome; Humans; Phenylcarbamates; Rivastigmine
PubMed: 19160344
DOI: 10.1002/14651858.CD007658 -
The Cochrane Database of Systematic... Jan 2009Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). There is an understanding that an increase in L-glutamate contributes to... (Review)
Review
BACKGROUND
Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). There is an understanding that an increase in L-glutamate contributes to the pathogenesis of cerebral ischemias and AD. Memantine acts as an antagonist of N-methyl-D-aspartate (NMDA) type receptors, which is thought to reduce abnormal activation of glutamate neurotransmission. It binds with a low affinity to the NMDA receptor and so should not prevent learning and the formation of memory. Memantine can improve cognitive function and slow the decline of AD in the general population over time, and is the subject of this review. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population.
OBJECTIVES
To determine the effectiveness and safety of memantine for people with DS who develop AD.
SEARCH STRATEGY
CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of memantine, as well as experts in the field, to ask about reports of unpublished or ongoing trials.
SELECTION CRITERIA
Randomised controlled trials of participants with DS and AD in which treatment with memantine was administered compared with a placebo group.
DATA COLLECTION AND ANALYSIS
No study was identified which met the inclusion criteria for this review.
MAIN RESULTS
No study was identified which met inclusion criteria for this review, however there is an on-going randomised controlled study being conducted in the UK and data are expected in 2009.
AUTHORS' CONCLUSIONS
As there are no included trials, recommendations cannot be made about memantine for AD in DS. Well-designed, adequately powered studies are required.
Topics: Alzheimer Disease; Down Syndrome; Humans; Memantine; Receptors, N-Methyl-D-Aspartate
PubMed: 19160343
DOI: 10.1002/14651858.CD007657 -
The Cochrane Database of Systematic... Jan 2009Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). Acetylcholine is a chemical found in the brain that has an important... (Review)
Review
BACKGROUND
Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). Acetylcholine is a chemical found in the brain that has an important role in memory, attention, reason and language. Galantamine both inhibits the activity of acetylcholinesterase and increases the level of acetylcholine. Galantamine can improve cognitive function and slow the decline of AD in the general population over time. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population.
OBJECTIVES
To determine the effectiveness and safety of galantamine for people with DS who develop AD.
SEARCH STRATEGY
CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of galantamine as well as experts in the field, to ask about reports of unpublished or ongoing trials.
SELECTION CRITERIA
Randomised controlled trials of participants with DS and AD in which treatment with galantamine was administered compared with a placebo group.
DATA COLLECTION AND ANALYSIS
No study was identified which met inclusion criteria for this review.
MAIN RESULTS
No study was identified which met inclusion criteria for this review.
AUTHORS' CONCLUSIONS
As there are no included trials, recommendations cannot be made about galantamine for AD in DS. Well-designed, adequately powered studies are required.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Down Syndrome; Galantamine; Humans
PubMed: 19160342
DOI: 10.1002/14651858.CD007656