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The Cochrane Database of Systematic... May 2017Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus, which can cause scarring. Many drugs have been used to treat this disease and some (such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus, which can cause scarring. Many drugs have been used to treat this disease and some (such as thalidomide, cyclophosphamide and azathioprine) are potentially toxic. This is an update of a Cochrane Review first published in 2000, and previously updated in 2009. We wanted to update the review to assess whether any new information was available to treat DLE, as we were still unsure of the effectiveness of available drugs and how to select the most appropriate treatment for an individual with DLE.
OBJECTIVES
To assess the effects of drugs for discoid lupus erythematosus.
SEARCH METHODS
We updated our searches of the following databases to 22 September 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant trials. Index Medicus (1956 to 1966) was handsearched and we approached authors for information about unpublished trials.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of drugs to treat people with DLE in any population group and of either gender. Comparisons included any drug used for DLE against either another drug or against placebo cream. We excluded laser treatment, surgery, phototherapy, other forms of physical therapy, and photoprotection as we did not consider them drug treatments.
DATA COLLECTION AND ANALYSIS
At least two reviewers independently extracted data onto a data extraction sheet, resolving disagreements by discussion. We used standard methods to assess risk of bias, as expected by Cochrane.
MAIN RESULTS
Five trials involving 197 participants were included. Three new trials were included in this update. None of the five trials were of high quality.'Risk of bias' assessments identified potential sources of bias in each study. One study used an inappropriate randomisation method, and incomplete outcome data were a concern in another as 15 people did not complete the trial. We found most of the trials to be at low risk in terms of blinding, but three of the five did not describe allocation concealment.The included trials inadequately addressed the primary outcome measures of this review (percentage with complete resolution of skin lesions, percentage with clearing of erythema in at least 50% of lesions, and improvement in patient satisfaction/quality of life measures).One study of fluocinonide cream 0.05% (potent steroid) compared with hydrocortisone cream 1% (low-potency steroid) in 78 people reported complete resolution of skin lesions in 27% (10/37) of participants in the fluocinonide cream group and in 10% (4/41) in the hydrocortisone group, giving a 17% absolute benefit in favour of fluocinonide (risk ratio (RR) 2.77, 95% CI 0.95 to 8.08, 1 study, n = 78, low-quality evidence). The other primary outcome measures were not reported. Adverse events did not require discontinuation of the drug. Skin irritation occurred in three people using hydrocortisone, and one person developed acne. Burning occurred in two people using fluocinonide (moderate-quality evidence).A comparative trial of two oral agents, acitretin (50 mg daily) and hydroxychloroquine (400 mg daily), reported two of the outcomes of interest: complete resolution was seen in 13 of 28 participants (46%) on acitretin and 15 of 30 participants (50%) on hydoxychloroquine (RR 0.93, 95% CI 0.54 to 1.59, 1 study, n = 58, low-quality evidence). Clearing of erythema in at least 50% of lesions was reported in 10 of 24 participants (42%) on acitretin and 17 of 25 (68%) on hydroxychloroquine (RR 0.61, 95% CI 0.36 to 1.06, 1 study, n = 49, low-quality evidence). This comparison did not assess improvement in patient satisfaction/quality of life measures. Participants taking acitretin showed a small increase in serum triglyceride, not sufficient to require withdrawal of the drug. The main adverse effects were dry lips (93% of the acitretin group and 20% of the hydroxychloroquine group) and gastrointestinal disturbance (11% of the acitretin group and 17% of the hydroxychloroquine group). Four participants on acitretin withdrew due to gastrointestinal events or dry lips (moderate-quality evidence).One trial randomised 10 people with DLE to apply a calcineurin inhibitor, pimecrolimus 1% cream, or a potent steroid, betamethasone 17-valerate 0.1% cream, for eight weeks. The study reported none of the primary outcome measures, nor did it present data on adverse events.A trial of calcineurin inhibitors compared tacrolimus cream 0.1% with placebo (vehicle) over 12 weeks in 14 people, but reported none of our primary outcome measures. In the tacrolimus group, five participants complained of slight burning and itching, and for one participant, a herpes simplex infection was reactivated (moderate-quality evidence).Topical R-salbutamol 0.5% cream was compared with placebo (vehicle) over eight weeks in one trial of 37 people with DLE. There was a significant improvement in pain and itch in the salbutamol group at two, four, six, and eight weeks compared to placebo, but the trial did not record a formal measure of quality of life. None of the primary outcome measures were reported. Changes in erythema did not show benefit of salbutamol over placebo, but we could not obtain from the trial report the number of participants with clearing of erythema in at least 50% of lesions. There were 15 events in the placebo group (experienced by 12 participants) and 24 in the salbutamol group (experienced by nine participants). None of the adverse events were considered serious (moderate-quality evidence).
AUTHORS' CONCLUSIONS
Fluocinonide cream may be more effective than hydrocortisone in clearing DLE skin lesions. Hydroxychloroquine and acitretin appear to be of equal efficacy in terms of complete resolution, although adverse effects might be more frequent with acitretin, and clearing of erythema in at least 50% of lesions occurred less often in participants applying acitretin. Moderate-quality evidence found adverse events were minor on the whole. There is not enough reliable evidence about other drugs used to treat DLE. Overall, the quality of the trials and levels of uncertainty were such that there is a need for further trials of sufficient duration comparing, in particular, topical steroids with other agents.
Topics: Acitretin; Albuterol; Calcineurin Inhibitors; Dermatologic Agents; Fluocinonide; Humans; Hydrocortisone; Hydroxychloroquine; Lupus Erythematosus, Discoid; Randomized Controlled Trials as Topic; Tacrolimus; Treatment Outcome
PubMed: 28476075
DOI: 10.1002/14651858.CD002954.pub3 -
Journal of Psychopharmacology (Oxford,... Jan 2024Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT),... (Review)
Review
Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug-drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects.
Topics: Humans; Hallucinogens; Psilocybin; Mescaline; N,N-Dimethyltryptamine; Drug Interactions; Lysergic Acid Diethylamide
PubMed: 37982394
DOI: 10.1177/02698811231211219 -
Neuropsychopharmacology Reports Mar 2024To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis... (Meta-Analysis)
Meta-Analysis
AIM
To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD.
METHODS
Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI).
RESULTS
Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation.
CONCLUSIONS
Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.
Topics: Humans; Aged; Depressive Disorder, Major; Japan; Antidepressive Agents; Duloxetine Hydrochloride; Venlafaxine Hydrochloride; Randomized Controlled Trials as Topic
PubMed: 38318955
DOI: 10.1002/npr2.12422 -
The Cochrane Database of Systematic... Dec 2018Amphetamine-type stimulants (ATS) refer to a group of synthetic stimulants including amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA) and related... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Amphetamine-type stimulants (ATS) refer to a group of synthetic stimulants including amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA) and related substances. ATS are highly addictive and prolonged use may result in a series of mental and physical symptoms including anxiety, confusion, insomnia, mood disturbances, cognitive impairments, paranoia, hallucinations and delusion.Currently there is no widely accepted treatment for ATS-use disorder. However, cognitive-behavioural treatment (CBT) is the first-choice treatment. The effectiveness of CBT for other substance-use disorders (e.g. alcohol-, opioid- and cocaine-use disorders) has been well documented and as such this basic treatment approach has been applied to the ATS-use disorder.
OBJECTIVES
To investigate the efficacy of cognitive-behavioural treatment for people with ATS-use disorder for reducing ATS use compared to other types of psychotherapy, pharmacotherapy, 12-step facilitation, no intervention or treatment as usual.
SEARCH METHODS
We identified randomised controlled trials (RCT) and quasi-RCTs comparing CBT for ATS-use disorders with other types of psychotherapy, pharmacotherapy, 12 step facilitation or no intervention. We searched the Cochrane Drugs and Alcohol Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, Embase and five other databases up to July 2018. In addition, we examined reference lists of eligible studies and other systematic reviews. We contacted experts in the field.
SELECTION CRITERIA
Eligibility criteria consisted of RCTs and quasi-RCTs comparing CBT versus other types of interventions with adult ATS users (aged 18 years or older) diagnosed by any explicit diagnostic system. Primary outcomes included abstinence rate and other indicators of drug-using behaviours.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Only two studies met the eligibility criteria. Both studies were at low risk of selection bias and reporting bias. In one study, almost half of participants in the intervention group dropped out and this study was at high risk of attrition bias. The studies compared a single session of brief CBT or a web-based CBT to a waiting-list control (total sample size across studies of 129). Results were mixed across the studies. For the single-session brief CBT study, two out of five measures of drug use produced significant results, percentage of abstinent days in 90 days (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.02 to 2.11) and dependence symptoms (standardised mean difference (SMD) -0.59, 95% CI -1.16 to -0.02). Little confidence could be placed in the results from this study give the small sample size (25 participants per group) and corresponding large CIs around the observed effects. For the web-based CBT, there was no significant difference across different outcomes. Neither study reported adverse effects. The meta-analytic mean across these two trials for drug use was not significant (SMD -0.28, 95% CI -0.69 to 0.14). In summary, overall quality of evidence was low and there was insufficient evidence to conclude that CBT is effective, or ineffective, at treating ATS use.
AUTHORS' CONCLUSIONS
Currently, there is not enough evidence to establish the efficacy of CBT for ATS-use disorders because of a paucity of high-quality research in this area.
Topics: Adult; Amphetamine-Related Disorders; Amphetamines; Cognitive Behavioral Therapy; Female; Humans; Male; Patient Dropouts; Randomized Controlled Trials as Topic; Sample Size; Waiting Lists
PubMed: 30577083
DOI: 10.1002/14651858.CD011315.pub2 -
Orphanet Journal of Rare Diseases Jan 2024The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk of gastroschisis in offspring.
METHODS
PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I statistic for heterogeneity and publication bias was calculated.
RESULTS
Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I = 39.4%).
CONCLUSIONS
These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.
Topics: Female; Humans; Pregnancy; Aspirin; Contraceptives, Oral; Gastroschisis; Ibuprofen; Phenylpropanolamine; Pseudoephedrine; Observational Studies as Topic
PubMed: 38287353
DOI: 10.1186/s13023-023-02992-z -
Seizure Feb 2021Dravet syndrome (DS) is an infantile-onset developmental and epileptic encephalopathy syndrome with limited treatment options. We aimed to evaluate the efficacy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dravet syndrome (DS) is an infantile-onset developmental and epileptic encephalopathy syndrome with limited treatment options. We aimed to evaluate the efficacy and tolerability of fenfluramine in patients with Dravet syndrome using meta-analytical techniques.
METHODS
We searched for relevant randomized controlled trials and non-randomized studies involving children with Dravet syndrome on fenfluramine therapy in MEDLINE, CENTRAL, EMBASE, Google Scholar and Web of Science database (31 July 2020). The primary outcome for the efficacy of fenfluramine was reduction in monthly convulsive seizure frequency. We carried out a random effect meta-analysis focusing on efficacy and safety variables. Only Randomized Controlled Trials (RCT) were included in the meta-analysis. The risk of bias was assessed for each study, and GRADE was used to assess the quality of evidence for each outcome.
RESULTS
Of 61 publications initially screened, 12 were reviewed as full-text. Seven articles including 2 RCTs, 4 uncontrolled studies (3 prospective and one retrospective study), and one case report described responses to fenfluramine in 144 DS patients (54 % male, mean age of 8.8 years, median dose of 0.4 mg/kg/day). Fenfluramine was found to be more efficacious than placebo, in terms of mean convulsive and total seizure frequency reduction (mean difference: -45.3 % (95 % CI: -48.1 %, -42.4 %, p < 0.00001) and -39.7 % (-46.7 %, -32.7 %, p < 0.00001)). A greater proportion of patients in the fenfluramine arm achieved >25 %, >50 %, >75 % and 100 % seizure reductions (odds ratios: 6.5 (3.7, 11.5, p < 0.00001), 10.6 (5.3, 21.3, p < 0.00001), 22.7(6.9, 75.3, p < 0.00001) and 9.3(1.7, 51.4, p = 0.01) respectively). The incidence of serious adverse events was not greater in the fenfluramine groups (OR: 1.02 (0.5, 2.19, p = 0.96)).
CONCLUSION
Fenfluramine appears to be a safe and efficacious antiseizure medication in patients with Dravet syndrome.
Topics: Child; Epilepsies, Myoclonic; Female; Fenfluramine; Humans; Infant; Male; Seizures; Spasms, Infantile; Treatment Outcome
PubMed: 33461030
DOI: 10.1016/j.seizure.2020.12.016 -
The Cochrane Database of Systematic... Aug 2015Neuropathic pain, which is caused by nerve damage, is increasing in prevalence worldwide. This may reflect improved diagnosis, or it may be due to increased incidence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuropathic pain, which is caused by nerve damage, is increasing in prevalence worldwide. This may reflect improved diagnosis, or it may be due to increased incidence of diabetes-associated neuropathy, linked to increasing levels of obesity. Other types of neuropathic pain include post-herpetic neuralgia, trigeminal neuralgia, and neuralgia caused by chemotherapy. Antidepressant drugs are sometimes used to treat neuropathic pain; however, their analgesic efficacy is unclear. A previous Cochrane review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining chronic neuropathic pain in the first instance. Venlafaxine is a reasonably well-tolerated antidepressant and is a serotonin reuptake inhibitor and weak noradrenaline reuptake inhibitor. Although not licensed for the treatment of chronic or neuropathic pain in most countries, it is sometimes used for this indication.
OBJECTIVES
To assess the analgesic efficacy of, and the adverse effects associated with the clinical use of, venlafaxine for chronic neuropathic pain in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via The Cochrane Library, and MEDLINE and EMBASE via Ovid up to 14 August 2014. We reviewed the bibliographies of any randomised trials identified and review articles, contacted authors of one excluded study and searched www.clinicaltrials.gov to identify additional published or unpublished data. We also searched the meta-Register of controlled trials (mRCT) (www.controlled-trials.com/mrct) and the WHO International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/) for ongoing trials but did not find any relevant trials.
SELECTION CRITERIA
We included randomised, double-blind studies of at least two weeks' duration comparing venlafaxine with either placebo or another active treatment in chronic neuropathic pain in adults. All participants were aged 18 years or over and all included studies had at least 10 participants per treatment arm. We only included studies with full journal publication.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted data using a standard form and assessed study quality. We intend to analyse data in three tiers of evidence as described by Hearn 2014, but did not find any first-tier evidence (ie evidence meeting current best standards, with minimal risk of bias) or second-tier evidence, that was considered at some risk of bias but with adequate participant numbers (at least 200 in the comparison). Third-tier evidence is that arising from studies with small numbers of participants; studies of short duration, studies that are likely to be of limited clinical utility due to other limitations, including selection bias and attrition bias; or a combination of these.
MAIN RESULTS
We found six randomised, double-blind trials of at least two weeks' duration eligible for inclusion. These trials included 460 participants with neuropathic pain, with most participants having painful diabetic neuropathy. Four studies were of cross-over design and two were parallel trials. Only one trial was both parallel design and placebo-controlled. Mean age of participants ranged from 48 to 59 years. In three studies (Forssell 2004, Jia 2006 and Tasmuth 2002), only mean data were reported. Comparators included placebo, imipramine, and carbamazepine and duration of treatment ranged from two to eight weeks. The risk of bias was considerable overall in the review, especially due to the small size of most studies and due to attrition bias. Four of the six studies reported some positive benefit for venlafaxine. In the largest study by Rowbotham, 2004, 56% of participants receiving venlafaxine 150 to 225 mg achieved at least a 50% reduction in pain intensity versus 34% of participants in the placebo group and the number needed to treat for an additional beneficial outcome was 4.5. However, this study was subject to significant selection bias. Known adverse effects of venlafaxine, including somnolence, dizziness, and mild gastrointestinal problems, were reported in all studies but were not particularly problematic and, overall, adverse effects were equally prominent in placebo or other active comparator groups.
AUTHORS' CONCLUSIONS
We found little compelling evidence to support the use of venlafaxine in neuropathic pain. While there was some third-tier evidence of benefit, this arose from studies that had methodological limitations and considerable risk of bias. Placebo effects were notably strong in several studies. Given that effective drug treatments for neuropathic pain are in current use, there is no evidence to revise prescribing guidelines to promote the use of venlafaxine in neuropathic pain. Although venlafaxine was generally reasonably well tolerated, there was some evidence that it can precipitate fatigue, somnolence, nausea, and dizziness in a minority of people.
Topics: Adult; Analgesics, Non-Narcotic; Antidepressive Agents, Second-Generation; Carbamazepine; Humans; Imipramine; Middle Aged; Neuralgia; Off-Label Use; Patient Dropouts; Randomized Controlled Trials as Topic; Venlafaxine Hydrochloride
PubMed: 26298465
DOI: 10.1002/14651858.CD011091.pub2 -
International Journal of Clinical... Apr 2015To describe the efficacy and safety of lisdexamfetamine dimesylate (LDX) for the treatment of binge eating disorder (BED). (Review)
Review
Lisdexamfetamine for binge eating disorder in adults: a systematic review of the efficacy and safety profile for this newly approved indication - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
OBJECTIVE
To describe the efficacy and safety of lisdexamfetamine dimesylate (LDX) for the treatment of binge eating disorder (BED).
DATA SOURCES
The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrials.gov and http://www.clinicaltrialsregister.eu for the search terms 'lisdexamfetamine' and 'binge', and by also querying the Web of Science (Thomson Reuters) and Embase (Elsevier) commercial databases, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information.
STUDY SELECTION
All available clinical reports of studies were identified.
DATA EXTRACTION
Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.
DATA SYNTHESIS
LDX is a central nervous system stimulant indicated for the treatment of moderate to severe BED. The recommended dose range is 50-70 mg/day. Approval for the treatment of BED was based on a clinical development programme that included an 11-week Phase II proof-of-concept, placebo-controlled study, testing fixed doses of LDX 30, 50 and 70 mg/day, and two 12-week Phase III placebo-controlled studies examining LDX 50-70 mg/day. Statistically significant reductions in binge eating days/week, the primary outcome measure, were observed for LDX doses of 50 and 70 mg/day, with effect sizes in the Phase III trials ranging from 0.83 to 0.97. The pooled NNT for response across all trials (as defined by a Clinical Global Impressions-Improvement score of 'very much improved' or 'much improved') for LDX vs. placebo was 3 (95% CI 3-4), and NNT for remission (as defined by 4-week cessation of binge eating) for LDX vs. placebo was 4 (95% CI 4-6). Reductions in weight ranged between 5.2% and 6.25% for LDX 50 or 70 mg/day. Discontinuation rates because of adverse events (AEs) were low; NNH for discontinuation because of an AE for LDX vs. placebo was 44 (95% CI 23-1971). The most commonly encountered AEs (incidence ≥ 10% and greater than the rate for placebo) were dry mouth, decreased appetite, insomnia and headache, with NNH values vs. placebo of 4 (95% CI 3-5), 11 (95% CI 8-17), 11 (95% CI 8-18) and 19 (95% CI 11-75), respectively.
CONCLUSIONS
LDX is the first pharmacological agent that has received regulatory approval for the treatment of BED. LDX 50 or 70 mg/day significantly reduced BED symptoms as measured by the number of binge eating days per week. Effect sizes were highly robust. Pending clinical trials include a long-term study examining maintenance of efficacy.
Topics: Antipsychotic Agents; Binge-Eating Disorder; Central Nervous System Stimulants; Clinical Trials as Topic; Dopamine Uptake Inhibitors; Humans; Lisdexamfetamine Dimesylate; Numbers Needed To Treat
PubMed: 25752762
DOI: 10.1111/ijcp.12639 -
The Cochrane Database of Systematic... Jan 2018Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures.
OBJECTIVES
1. To determine the effects of any of the following drugs for antipsychotic-induced TD in people with schizophrenia or other chronic mental illnesses.i. Drugs which influence the noradrenergic system.ii. Dopamine receptor agonists.iii. Dopamine receptor antagonists.iv. Dopamine-depletor drugs.v. Drugs that increase the production or release of dopamine.2. To examine whether any improvement occurred with short periods of intervention (less than 6 weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.3. To examine if there was a differential effect for the various compounds.4. To examine whether the use of non-antipsychotic catecholaminergic drugs are most effective in those with more recent onset TD (less than five years).
SEARCH METHODS
We retrieved 712 references from searching the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We selected studies if they were randomised controlled trials focusing on people with schizophrenia or other chronic mental illnesses and antipsychotic-induced tardive dyskinesia. We compared the use of catecholaminergic interventions versus placebo, no intervention, or any other intervention for the treatment of antipsychotic-induced tardive dyskinesia.
DATA COLLECTION AND ANALYSIS
We independently extracted data from these trials and we estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assumed that people who left the studies early had no improvement.
MAIN RESULTS
There are 10 included trials (N = 261) published between 1973 and 2010; eight are new from the 2015 and 2017 update searches. Forty-eight studies are excluded. Participants were mostly chronically mentally ill inpatients in their 50s, and studies were primarily of short (2 to 6 weeks) duration. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment and generation of the sequence. Studies were also not clearly blinded and we are unsure if data are incomplete or selectively reported, or if other biases were operating.One small, three-arm trial found that both alpha-methyldopa (N = 20; RR 0.33, 95% CI 0.14 to 0.80; low-quality evidence) and reserpine (N = 20; RR 0.52 95% CI 0.29 to 0.96; low-quality evidence) may lead to a clinically important improvement in tardive dyskinesia symptoms compared with placebo after 2 weeks' treatment, but found no evidence of a difference between alpha-methyldopa and reserpine (N = 20; RR 0.60, 95% CI 0.19 to 1.86; very low quality evidence). Another small trial compared tetrabenazine and haloperidol after 18 weeks' treatment and found no evidence of a difference on clinically important improvement in tardive dyskinesia symptoms (N = 13; RR 0.93, 95% CI 0.45 to 1.95; very low quality evidence). No study reported on adverse events.For remaining outcomes there was no evidence of a difference between any of the interventions: alpha-methyldopa versus placebo for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence), celiprolol versus placebo for leaving the study early (1 RCT; N = 35; RR 5.28, 95% CI 0.27 to 102.58; very low quality evidence) and quality of life (1 RCT; N = 35; RR 0.87, 95% CI 0.68 to 1.12; very low quality evidence), alpha-methyldopa versus reserpine for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; not estimable, no reported events; very low quality evidence), reserpine or carbidopa/levodopa versus placebo for deterioration of tardive dyskinesia symptoms (2 RCTs; N = 37; RR 1.18, 95% CI 0.35 to 3.99; very low quality evidence), oxypertine versus placebo for deterioration of mental state (1 RCT; N = 42; RR 2.20, 95% CI 0.22 to 22.45; very low quality evidence), dopaminergic drugs (amantadine, bromocriptine, tiapride, oxypertine, carbidopa/levodopa) versus placebo for leaving the study early (6 RCTs; N = 163; RR 1.29, 95% CI 0.65 to 2.54; very low quality evidence), and tetrabenazine versus haloperidol for deterioration of tardive dyskinesia symptoms (1 RCT; N = 13; RR 1.17, 95% CI 0.09 to 14.92) and leaving the study early (1 RCT; N = 13; RR 0.23, 95% CI 0.01 to 4.00).
AUTHORS' CONCLUSIONS
Although there has been a large amount of research in this area, many studies were excluded due to inherent problems in the nature of their cross-over designs. Usually data are not reported before the cross-over and the nature of TD and its likely response to treatments make it imprudent to use this data. The review provides little usable information for service users or providers and more well-designed and well-reported studies are indicated.
Topics: Adrenergic Uptake Inhibitors; Anti-Dyskinesia Agents; Antipsychotic Agents; Celiprolol; Disease Progression; Dopamine Antagonists; Dyskinesia, Drug-Induced; Haloperidol; Humans; Methyldopa; Randomized Controlled Trials as Topic; Reserpine; Tetrabenazine; Tiapamil Hydrochloride
PubMed: 29342497
DOI: 10.1002/14651858.CD000458.pub3 -
Drug and Alcohol Review Jan 2023Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to... (Meta-Analysis)
Meta-Analysis Review
ISSUES
Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to assess the efficacy of pharmacotherapy for methamphetamine withdrawal, the first comprehensive meta-analysis since 2008.
APPROACH
MEDLINE (1966-2020), CINAHL (1982-2020), PsychINFO (1806-2020) and EMBASE (1947-2020) were systematically searched. Studies were included if they were randomised controlled trials (RCT) investigating pharmacological treatments for methamphetamine withdrawal, reviewing outcomes of treatment discontinuation, mental health outcomes, withdrawal symptoms (including craving) and patient safety. The relative risk (RR) and weighted mean difference (MD) were used to meta-analyse dichotomous and continuous data respectively, with 95% confidence intervals. Risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted.
KEY FINDINGS
Nine RCTs of six medications (n = 242 participants) met inclusion criteria, however, only six trials of four medications (n = 186) could be meta-analysed. Mean sample size across studies was 27 participants, and 88% of participants were male. The quality of evidence in this review varies from low to very low on GRADE assessments. Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD -0.49, 95% CI -0.80, -0.17), compared with placebo, however, this medication is no longer approved. No other medications improved any domain when compared with placebo. Due to lack of reporting safety profiles could not be established.
CONCLUSIONS
There is insufficient evidence to indicate any medication is effective for the treatment of methamphetamine withdrawal. The poor quality of the evidence indicates a need for better powered, high-quality trials.
Topics: Male; Humans; Female; Substance Withdrawal Syndrome; Methamphetamine; Randomized Controlled Trials as Topic
PubMed: 35862266
DOI: 10.1111/dar.13511