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The Cochrane Database of Systematic... Jun 2019Bipolar disorder is a common condition associated with high morbidity; developing efficacious, safe treatments is therefore essential. Lithium is an effective...
BACKGROUND
Bipolar disorder is a common condition associated with high morbidity; developing efficacious, safe treatments is therefore essential. Lithium is an effective maintenance treatment for bipolar disorder. It acts as mood stabiliser and reduces the risk of suicide. However, evidence assessing the efficacy of lithium in the treatment of acute mania is less robust. Current evidence-based guidelines cite multiple anti-dopaminergic and mood-stabilising agents as initial treatments: more definite evidence is needed to decide if lithium should be the first-line therapy.
OBJECTIVES
1. To assess the effects of lithium in comparison with placebo or other active treatment in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.2. To review the acceptability and tolerability of treatment with lithium in comparison with placebo or other active treatments in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, and PsycINFO. We also searched the World Health Organization trials portal (ICTRP) and ClinicalTrials.gov. We checked the reference lists of all included studies and relevant systematic reviews. We have incorporated studies from searches to 18 May 2018 into the current analyses.
SELECTION CRITERIA
Prospective randomised controlled studies comparing lithium with placebo or alternative drug treatment in treatment of acute mania. We included anyone with bipolar disorder, male and female, of any age.
DATA COLLECTION AND ANALYSIS
At least two review authors independently extracted data and assessed methodological quality. We used odds ratios (ORs) to analyse binary efficacy outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuously distributed outcomes. We used a fixed-effect model unless heterogeneity was moderate or substantial, in which case we used a random-effects model. We used Review Manager 5 to analyse data. We assessed the certainty of evidence for individual outcomes using the GRADE approach.
MAIN RESULTS
We found 36 randomised controlled studies comparing lithium with placebo, one of 12 drugs, or electroconvulsive therapy for treatment of acute mania. Studies included male and female participants (n = 4220), of all ages, who all fitted criteria for a manic episode within the context of a diagnosis of bipolar disorder.Risk of bias was variable; 12 studies had a high risk of bias in one domain and 27 gave inadequate information on randomisation leading to an 'unclear' rating for selection bias.Lithium versus placeboHigh-certainty evidence found that lithium was an effective treatment for acute mania and was more effective than placebo at inducing a response (OR 2.13, 95% confidence interval (CI) 1.73 to 2.63; participants = 1707; studies = 6; I = 16%; high-certainty evidence), or remission (OR 2.16, 95% CI 1.73 to 2.69; participants = 1597; studies = 5; I = 21%; high-certainty evidence).Lithium was more likely than placebo to cause tremor (OR 3.25, 95% CI 2.10 to 5.04; participants = 1241; studies = 6; I = 0%; high-certainty evidence), and somnolence (OR 2.28, 95% CI 1.46 to 3.58; participants = 1351; studies = 7; I = 0%; high-certainty evidence).There was insufficient evidence to determine the effect of lithium for all-cause dropouts (OR 0.76; 95% CI 0.46 to 1.25; participants = 1353; studies = 7; I = 75%; moderate-certainty evidence), and weight gain (OR 1.48, 95% CI 0.56 to 3.92; participants = 735, studies = 3; I= 51%; moderate-certainty evidence).Lithium versus antipsychotics or mood stabilisersFor the outcome of inducing a response, there was only very low-certainty evidence regarding lithium compared to haloperidol (MD -2.40, 95% CI -6.31 to 1.50; participants = 80; studies = 3; I = 95%), quetiapine (OR 0.66, 95% CI 0.28 to 1.55; participants = 335; studies = 2; I = 71%), and carbamazepine (SMD 0.21, 95% CI -0.18 to 0.60; participants = 102; studies = 3; I = 0%).Lithium was probably less likely to induce a response than olanzapine (OR 0.44, 95% CI 0.20 to 0.94; participants = 180; studies = 2; I = 0%; moderate-certainty evidence).Lithium may be less likely to induce a response than risperidone (MD 7.28, 95% CI 5.22 to 9.34; participants = 241; studies = 3; I = 49%; low-certainty evidence).There was no evidence of a difference between lithium and valproate (OR 1.22, 95% CI 0.87 to 1.70; participants = 607; studies = 5; I = 22%; moderate-certainty evidence).There was moderate-certainty evidence that lithium was more effective than topiramate at treating acute mania (OR 2.28, 95% CI 1.63 to 3.20; participants = 660; studies = 1).Data on adverse events for these comparisons contained too few studies to provide high-certainty evidence.
AUTHORS' CONCLUSIONS
This systematic review indicates that lithium is more effective than placebo as a treatment for acute mania but increases the risk for somnolence and tremor. Limited evidence suggests little or no difference between lithium and other mood stabilisers (valproate, carbamazepine) or antipsychotics (risperidone, quetiapine, haloperidol). Olanzapine may be an exception, as it is probably slightly more effective than lithium. There is uncertain evidence that risperidone may also be more effective than lithium. Lithium is probably more effective at treating acute mania than topiramate. When compared to placebo, lithium was more likely to cause adverse events. However, when compared to other drugs, too few studies provided data on adverse effects to provide high-certainty evidence. More, rigorously designed, large-scale studies are needed to definitively conclude if lithium is superior to other interventions in treating acute mania.
Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium Compounds; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 31152444
DOI: 10.1002/14651858.CD004048.pub4 -
The Cochrane Database of Systematic... Jun 2013Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs in the central nervous system. The present review is part of an update of a Cochrane review first published in 2004, and previously updated (conclusions not changed) in 2007.
OBJECTIVES
To describe and assess the evidence from controlled trials on the efficacy and tolerability of valproate (valproic acid or sodium valproate or a combination of the two) for preventing migraine attacks in adult patients with episodic migraine.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2012, Issue 12), PubMed/MEDLINE (1966 to 15 January 2013), MEDLINE In-Process (current week, 15 January 2013), and EMBASE (1974 to 15 January 2013) and handsearched Headache and Cephalalgia through January 2013.
SELECTION CRITERIA
Studies were required to be prospective, controlled trials of valproate taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data. For headache frequency data, we calculated mean differences (MDs) between valproate and comparator (placebo, active control, or valproate in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with ≥ 50% reduction in headache frequency), we calculated odds ratios (ORs) and, in select cases, risk ratios (RRs); we also calculated numbers needed to treat (NNTs). We calculated MDs for Migraine Disability Assessment (MIDAS) scores. We also summarised data on adverse events from placebo-controlled trials and calculated risk differences (RDs) and numbers needed to harm (NNHs).
MAIN RESULTS
Ten papers describing 10 unique trials met the inclusion criteria. Analysis of data from two trials (63 participants) showed that sodium valproate reduced headache frequency by approximately four headaches per 28 days as compared to placebo (MD -4.31; 95% confidence interval (CI) -8.32 to -0.30). Data from four trials (542 participants) showed that divalproex sodium (a stable combination of sodium valproate and valproic acid in a 1:1 molar ratio) more than doubled the proportion of responders relative to placebo (RR 2.18; 95% CI 1.28 to 3.72; NNT 4; 95% CI 2 to 11). One study of sodium valproate (34 participants) versus placebo supported the latter findings (RR for responders 2.83; 95% CI 1.27 to 6.31; NNT 3; 95% CI 2 to 9). There was no significant difference in the proportion of responders between sodium valproate versus flunarizine (one trial, 41 participants) or between divalproex sodium versus propranolol (one trial, 32 participants). Pooled analysis of post-treatment mean headache frequencies in two trials (88 participants) demonstrates a slight but significant advantage for topiramate 50 mg over valproate 400 mg (MD -0.90; 95% CI -1.58 to -0.22). For placebo-controlled trials of sodium valproate and divalproex sodium, NNHs for clinically important adverse events ranged from 7 to 14.
AUTHORS' CONCLUSIONS
Valproate is effective in reducing headache frequency and is reasonably well tolerated in adult patients with episodic migraine.
Topics: Adult; Anticonvulsants; Flunarizine; Fructose; Humans; Migraine Disorders; Propranolol; Randomized Controlled Trials as Topic; Topiramate; Valproic Acid
PubMed: 23797677
DOI: 10.1002/14651858.CD010611 -
Epileptic Disorders : International... Dec 2011In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects. Despite the... (Meta-Analysis)
Meta-Analysis Review
AIM
In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects. Despite the development of better tolerated new generation AEDs, phenobarbital is still widely used particularly in developing countries because of its low cost. The purpose of this review was to: (i) investigate whether phenobarbital can be safely used as an antiepileptic drug and (ii) determine the questions which need to be addressed in order to comprehensively and adequately evaluate the safety of phenobarbital for the treatment of epilepsy.
METHODS
The literature was searched using the Cochrane Central Register of randomised controlled trials (1800-2009), Medline (1966-2009), Embase (1966-2009) and three Chinese databases.
RESULTS
Twenty studies were finally included in this systematic review. The determination of adverse effects of combined antiepileptic drugs (AEDs) from different studies was complicated by numerous factors including study design, different descriptions of adverse events and a lack of standardised data collection. These factors may also have been responsible for the heterogeneity present in the meta-analysis. The data did not demonstrate any evidence of association between phenobarbital and a higher risk of adverse events. However, phenobarbital appeared to be associated with a higher rate of adverse drug reaction related withdrawal (ADR-related withdraw), compared to carbamazepine, valproic acid and phenytoin. This may have been due to a concern for possible adverse effects of phenobarbital.
CONCLUSIONS
Phenobarbital was associated with a higher rate of drug withdrawal although there was no evidence to suggest that phenobarbital caused more adverse events compared to carbamazepine, valproic acid or phenytoin. However, in the case of pregnant women, it is important for clinicians to evaluate the benefits and risks of phenobarbital administration before making a final recommendation. Furthermore, unified scales for the assessment of cognitive function should be applied for future studies particularly in children.
Topics: Anticonvulsants; Carbamazepine; Child; Cognition Disorders; Cohort Studies; Cross-Over Studies; Data Collection; Data Interpretation, Statistical; Epilepsy; Female; Humans; Male; Phenobarbital; Phenytoin; Pregnancy; Randomized Controlled Trials as Topic; Research; Research Design; Treatment Outcome; Valproic Acid
PubMed: 21926048
DOI: 10.1684/epd.2011.0444 -
BMJ Open Jul 2014To determine whether valproate (VPA) monotherapy influences homocysteine metabolism in patients with epilepsy. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine whether valproate (VPA) monotherapy influences homocysteine metabolism in patients with epilepsy.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
We searched all articles in English through PubMed, Web of Science and EMBASE published up to August 2013 concerning the homocysteine levels in VPA monotherapeutic patients with epilepsy.
PARTICIPANTS
VPA-treated patients with epilepsy (n=266) and matched healthy controls (n=489).
OUTCOME MEASURES
Heterogeneity between studies was assessed using I(2) statistics. Pooled standardised mean difference (SMD) and 95% CIs were calculated using a random effect model.
RESULTS
A total of eight eligible studies were enrolled in our meta-analysis. We compared the plasma levels of homocysteine in VPA-treated patients with epilepsy and healthy controls. There was significant heterogeneity in the estimates according to the I(2) test (I(2)=65.6%, p=0.005). Plasma homocysteine levels in VPA-treated patients with epilepsy were significantly higher than in healthy controls under a random effect model. (SMD, 0.62; 95% CI 0.32 to 0.92). Further subgroup analyses suggested that no significant differences were present when grouped by ethnicity and age, but the risk of heterogeneity in the West Asian group (I(2)=47.4%, p=0.107) was diminished when compared with that of the overall group (I(2)=65.6%, p=0.005).
CONCLUSIONS
Our meta-analysis indicates that VPA monotherapy is associated with the increase in plasma homocysteine levels in patients with epilepsy. Whether this association is influenced by ethnicity needs further research.
Topics: Anticonvulsants; Epilepsy; Homocysteine; Humans; Valproic Acid
PubMed: 25031190
DOI: 10.1136/bmjopen-2014-004936 -
Medical Acupuncture Apr 2019A Cochrane Systematic Review published by Linde et al. in 2016 found moderate evidence suggesting that acupuncture is "at least non-inferior" to conventional... (Review)
Review
A Cochrane Systematic Review published by Linde et al. in 2016 found moderate evidence suggesting that acupuncture is "at least non-inferior" to conventional prophylactic drug treatments (flunarizine, metoprolol, and valproic acid) for episodic migraine prophylaxis. The evidence for the efficacy of these conventional treatments must be verified to strengthen and validate the original comparison made in Linde et al.'s 2016 review. The aim of the current authors' systematic review was to verify the efficacy of the conventional treatments used in Linde et al.'s 2016 comparison with acupuncture. Search strategies were applied to find studies that could verify the efficacy of conventional treatments for treating episodic migraines. Relevant outcomes and dosages were extracted from the retrieved studies. Each study's quality was assessed, using the Cochrane's collaboration tool for assessing risk of bias and the Cochrane GRADE [Grading of Recommendations Assessment, Development, and Evaluation] scale. There is high-quality evidence suggesting that prophylactic drug treatment, at the treatment dosage ranges used in Linde et al.'s 2016 review, reduced headache frequency at a 3-month follow-up, compared to placebo. Headache frequency at a 6-month follow-up, and responses (at least 50% reduction of headache frequency) at 3-month and 6-month follow-ups could not be assessed. These findings strengthened Linde et al.'s 2016 comparison of conventional treatments and acupuncture for reducing headache frequency at a 3-month follow-up. For episodic migraine prophylaxis, moderate evidence suggests that acupuncture is "at least non-inferior," to now-, conventional treatments. This raises significant questions in the debate concerning claims that acupuncture is a placebo-based treatment and the prescriptions of proven conventional treatments that have similar effects as acupuncture.
PubMed: 31031874
DOI: 10.1089/acu.2019.1337 -
British Journal of Clinical Pharmacology Jul 2016The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in... (Comparative Study)
Comparative Study Meta-Analysis Review
AIMS
The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients.
METHOD
A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects.
RESULTS
The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta-analysis. The combined results from the meta-analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03-0.42]: χ(2) = 1.76: I(2) = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14-2.99]: χ(2) = 8.79: I(2) = 77%).
CONCLUSIONS
The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.
Topics: Anticonvulsants; Craniotomy; Humans; Levetiracetam; Perioperative Care; Phenytoin; Piracetam; Seizures; Supratentorial Neoplasms; Valproic Acid
PubMed: 26945547
DOI: 10.1111/bcp.12926 -
Health Technology Assessment... Oct 2007To determine the clinical effectiveness and cost-effectiveness of pharmacological and/or psychosocial interventions for the prevention of relapse in people with bipolar... (Review)
Review
OBJECTIVES
To determine the clinical effectiveness and cost-effectiveness of pharmacological and/or psychosocial interventions for the prevention of relapse in people with bipolar disorder.
DATA SOURCES
Major electronic databases were searched up to September 2005.
REVIEW METHODS
Systematic reviews were undertaken on the clinical and economic effectiveness of treatments. An analysis was performed using the methods of mixed treatment comparison (MTC) to enable indirect comparisons to be made between the treatments. An economic model of treatments for the prevention of relapse in bipolar disorder was developed.
RESULTS
Forty-five trials were included in the clinical effectiveness review; all but one studied adults. This review found that for the prevention of all relapses, lithium, valproate, lamotrigine and olanzapine performed better than placebo, with lithium and lamotrigine having the strongest evidence. For depressive relapse prevention, valproate, lamotrigine and imipramine performed better than placebo, with evidence strongest for lamotrigine and weakest for imipramine. For manic relapses, lithium and olanzapine performed significantly better than placebo. The MTC found that the best treatment for bipolar I patients with mainly depressive symptoms was valproate, followed by lithium plus imipramine. For bipolar I patients with mainly manic symptoms, olanzapine was the best treatment. From the studies investigating psychosocial interventions, there were few data for each comparison and outcome. The evidence suggests that cognitive behaviour therapy (CBT), in combination with usual treatment, is effective for the prevention of relapse. Group psychoeducation and possibly family therapy may also have roles as adjunctive therapy for preventing relapse. The results from the decision analytic model developed on the cost-effectiveness of long-term maintenance treatments of bipolar I patients suggest that the choice of treatment is dependent upon a number of factors: the previous episode history of a patient and the mortality benefit assumed for lithium strategies. The results from the base-case analysis for patients with a recent history of depression suggest that valproate, lithium and the combination of lithium and imipramine are potentially cost-effective depending upon the amount that a decision-maker is willing to pay for additional health gain. Using conventional amounts that the NHS is prepared to pay for health gain, then the lithium-based strategies appear to be potentially cost-effective for this group. For patients with a recent history of mania, the choice of pharmacological intervention appears to be between olanzapine and lithium monotherapy. Again using conventional threshold as a reference point, the results suggest that lithium is the most cost-effective therapy. Excluding the additional mortality benefit associated with lithium-based strategies resulted in all treatments for patients with a recent history of a depressive episode being dominated by valproate and, in the case of patients with a recent history of a manic episode, by olanzapine.
CONCLUSIONS
Lithium, valproate, lamotrigine and olanzapine are effective as maintenance therapy for the prevention of relapse in bipolar disorder. Olanzapine and lithium are efficacious for the prevention of manic relapses and valproate, lamotrigine and imipramine for the prevention of depressive relapse. There is some evidence that CBT, group psychoeducation and family therapy might be beneficial as adjuncts to pharmacological maintenance treatments. Insufficient information is available regarding the relative tolerability of the treatments or their relative effects on suicide rate and mortality. For patients with a recent depressive episode, valproate, lithium monotherapy and the combination of lithium and imipramine are potentially cost-effective. For patients with a recent manic episode, olanzapine and lithium monotherapy are potentially cost-effective. The cost-effectiveness estimates in both groups of patients were shown to be sensitive to the assumption of a reduced suicidal risk associated with lithium-based strategies. Further research is needed into the adverse effects of all treatments and the differential effects of agents. Good-quality trials of valproate, of combination therapy, e.g. lithium plus a selective serotonin reuptake inhibitor antidepressant, of psychosocial interventions and of the disorder in children are also required.
Topics: Adult; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Cognitive Behavioral Therapy; Cost-Benefit Analysis; Databases, Bibliographic; Female; Humans; Lamotrigine; Lithium; Male; Models, Economic; Olanzapine; Outcome and Process Assessment, Health Care; Randomized Controlled Trials as Topic; Secondary Prevention; Triazines; Valproic Acid
PubMed: 17903393
DOI: 10.3310/hta11390 -
The Cochrane Database of Systematic... May 2018Despite the high prevalence of apathy in Alzheimer's disease (AD), and its harmful effects, there are currently no therapies proven to treat this symptom. Recently, a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite the high prevalence of apathy in Alzheimer's disease (AD), and its harmful effects, there are currently no therapies proven to treat this symptom. Recently, a number of pharmacological therapies have been investigated as potential treatments for apathy in AD.
OBJECTIVES
Objective 1: To assess the safety and efficacy of pharmacotherapies for the treatment of apathy in Alzheimer's disease (AD).Objective 2: To assess the effect on apathy of pharmacotherapies investigated for other primary outcomes in the treatment of AD.
SEARCH METHODS
We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), MEDLINE, Embase, CINAHL, PsycINFO, LILACS, ClinicalTrials.gov and the World Health Organization (WHO) portal, ICTRP on 17 May 2017.
SELECTION CRITERIA
Eligible studies were double-blind, randomized, placebo-controlled trials (RCTs) investigating apathy as a primary or secondary outcome in people with AD.
DATA COLLECTION AND ANALYSIS
Three review authors extracted data. We assessed the risks of bias of included studies using Cochrane methods, and the overall quality of evidence for each outcome using GRADE methods. We calculated mean difference (MD), standardized mean difference (SMD) or risk ratio (RR) with 95% confidence intervals on an intention-to-treat basis for all relevant outcome measures.
MAIN RESULTS
We included 21 studies involving a total of 6384 participants in the quantitative analyses. Risk of bias is very low to moderate. All studies reported appropriate methods of randomization and blinding. Most studies reported appropriate methods of allocation concealment. Four studies, three with methylphenidate and one with modafinil, had a primary aim of improving apathy. In these studies, all participants had clinically significant apathy at baseline. Methylphenidate may improve apathy compared to placebo. This finding was present when apathy was assessed using the apathy evaluation scale (AES), which was used by all three studies investigating methylphenidate: MD -4.99, 95% CI -9.55 to -0.43, n = 145, 3 studies, low quality of evidence, but not when assessed with the neuropsychiatric inventory (NPI)-apathy subscale, which was used by two of the three studies investigating methylphenidate: MD -0.08, 95% CI -3.85 to 3.69, n = 85, 2 studies, low quality of evidence. As well as having potential benefits for apathy, methylphenidate probably also slightly improves cognition (MD 1.98, 95% CI 1.06 to 2.91, n = 145, 3 studies, moderate quality of evidence), and probably improves instrumental activities of daily living (MD 2.30, 95% CI 0.74 to 3.86, P = 0.004, n = 60, 1 study, moderate quality of evidence), compared to placebo. There may be no difference between methylphenidate and placebo in the risk of developing an adverse event: RR 1.28, 95% CI 0.67 to 2.42, n = 145, 3 studies, low quality of evidence. There was insufficient evidence from one very small study of modafinil to determine the effect of modafinil on apathy assessed with the FrSBe-apathy subscale: MD 0.27, 95% CI -3.51 to 4.05, n = 22, 1 study, low quality of evidence. In all other included studies, apathy was a secondary outcome and participants were not selected on the basis of clinically significant apathy at baseline. We considered the evidence on apathy from these studies to be indirect and associated with publication bias. There was low or very low quality of evidence on cholinesterase inhibitors (ChEIs) (six studies), ChEI discontinuation (one study), antipsychotics (two studies), antipsychotic discontinuation (one study), antidepressants (two studies), mibampator (one study), valproate (three studies) and semagacestat (one study).
AUTHORS' CONCLUSIONS
Methylphenidate may demonstrate a benefit for apathy and may have slight benefits for cognition and functional performance in people with AD, but this finding is associated with low-quality evidence. Our meta-analysis is limited by the small number of studies within each drug class, risk of bias, publication bias, imprecision and inconsistency between studies. Additional studies should be encouraged targeting people with AD with clinically significant apathy which investigate apathy as a primary outcome measure, and which have a longer duration and a larger sample size. This could increase the quality of evidence for methylphenidate, and may confirm whether or not it is an effective pharmacotherapy for apathy in AD.
Topics: Alanine; Alzheimer Disease; Antidepressive Agents; Apathy; Azepines; Benzhydryl Compounds; Biphenyl Compounds; Central Nervous System Stimulants; Cholinesterase Inhibitors; Humans; Methylphenidate; Modafinil; Randomized Controlled Trials as Topic; Sulfonamides; Valproic Acid
PubMed: 29727467
DOI: 10.1002/14651858.CD012197.pub2 -
The Cochrane Database of Systematic... Jun 2013Faecal incontinence (leakage of bowel motions or stool) is a common symptom which causes significant distress and reduces quality of life. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Faecal incontinence (leakage of bowel motions or stool) is a common symptom which causes significant distress and reduces quality of life.
OBJECTIVES
To assess the effects of drug therapy for the treatment of faecal incontinence. In particular, to assess the effects of individual drugs relative to placebo or other drugs, and to compare drug therapy with other treatment modalities.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Register of Trials, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE in process, and handsearching of journals and conference proceedings (searched 21 June 2012) and the reference lists of relevant articles.
SELECTION CRITERIA
All randomised or quasi-randomised controlled trials were included in this systematic review.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened abstracts, extracted data and assessed risk of bias of the included trials.
MAIN RESULTS
Sixteen trials were identified, including 558 participants. Eleven trials were of cross-over design. Eleven trials included only people with faecal incontinence related to liquid stool (either chronic diarrhoea, following ileoanal pouch or rectal surgery, or due to use of a weight-reducing drug). Two trials were amongst people with weak anal sphincters, one in participants with faecal impaction and bypass leakage, and one in geriatric patients. In one trial there was no specific cause for faecal incontinence.Seven trials tested anti-diarrhoeal drugs to reduce faecal incontinence and other bowel symptoms (loperamide, diphenoxylate plus atropine, and codeine). Six trials tested drugs that enhance anal sphincter function (phenylepinephrine gel and sodium valproate). Two trials evaluated osmotic laxatives (lactulose) for the treatment of faecal incontinence associated with constipation in geriatric patients. One trial assessed the use of zinc-aluminium ointment for faecal incontinence. No studies comparing drugs with other treatment modalities were identified.There was limited evidence that antidiarrhoeal drugs and drugs that enhance anal sphincter tone may reduce faecal incontinence in patients with liquid stools. Loperamide was associated with more adverse effects (such as constipation, abdominal pain, diarrhoea, headache and nausea) than placebo. However, the dose may be titrated to the patient's symptoms to minimise side effects while achieving continence. The drugs acting on the sphincter sometimes resulted in local dermatitis, abdominal pain or nausea. Laxative use in geriatric patients reduced faecal soiling and the need for help from nurses.Zinc-aluminium ointment was associated with improved quality of life, with no reported adverse effects. However, the observed improvement in quality of life was seen in the placebo group as well as the treatment group.It should be noted that all the included trials in this review had small sample sizes and short duration of follow-up. 'Risk of bias' assessment was unclear for most of the domains as there was insufficient information. There were no data suitable for meta-analysis.
AUTHORS' CONCLUSIONS
The small number of trials identified for this review assessed several different drugs in a variety of patient populations. The focus of most of the included trials was on the treatment of diarrhoea, rather than faecal incontinence. There is little evidence to guide clinicians in the selection of drug therapies for faecal incontinence. Larger, well-designed controlled trials, which use the recommendations and principles set out in the CONSORT statement, and include clinically important outcome measures, are required.
Topics: Adult; Antidiarrheals; Diarrhea; Epinephrine; Fecal Incontinence; Gastrointestinal Agents; Humans; Lactulose; Randomized Controlled Trials as Topic; Valproic Acid; Zinc Compounds
PubMed: 23757096
DOI: 10.1002/14651858.CD002116.pub2 -
Seizure Oct 2021Serotonin syndrome (SS) is a drug‑induced, potentially fatal, clinical syndrome resulting from drugs that have serotonergic properties. Several antiepileptic drugs... (Review)
Review
Serotonin syndrome (SS) is a drug‑induced, potentially fatal, clinical syndrome resulting from drugs that have serotonergic properties. Several antiepileptic drugs (AEDs) are known to have serotonergic properties and it can be hypothesized that such AEDs can cause SS. This study aims to review the literature on SS in patients receiving AEDs. We performed a systematic review of Scopus and MEDLINE/PUBMED for case reports and case series of SS where patients had received at least one AED at the onset of symptoms. The cases published in the English literature between 1 January 1991 and 1 April 2021 were included. Initial search identified 1263 articles of which 63 (76 patients) were included in the final analysis. Most of the included cases (53 cases, 70%) have been published in the last 10 years. The mean age of the 76 patients was 40.6 ± 17.8 years, and 51% of cases were females. These patients had been exposed to a total of 8 different types of AEDs. Valproic acid was the most common drug (29, 38%), followed by lamotrigine (22, 29%), gabapentin (16, 21%), pregabalin (seven, 9%), topiramate (five, 7%) and carbamazepine (two, 3%). There has been one case each with phenytoin and oxcarbazepine. Seven (9%) patients received more than one AEDs. Most patients (67, 88%) also received other serotoninergic agents. Only nine (12%) patients were on AEDs alone. The most common clinical condition for using AEDs was psychiatric disorders (36 patients, 47.3%), followed by migraine (17, 22.4%), other painful conditions (15, 19.7%), epilepsy (7, 9.2%), and perioperative conditions (8, 10.5%). Death was reported in two patients. We suggest that AEDs, because of their serotonergic properties, may induce SS, especially in patients who are on another serotonergic agent.
Topics: Adult; Anticonvulsants; Carbamazepine; Female; Humans; Middle Aged; Oxcarbazepine; Serotonin Syndrome; Topiramate; Young Adult
PubMed: 34153897
DOI: 10.1016/j.seizure.2021.06.004