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Journal of Attention Disorders Dec 2022Dysregulated emotional behavior occurs often in adults with ADHD. Analysis of clinical trials may guide clinical intervention and future research.
OBJECTIVE
Dysregulated emotional behavior occurs often in adults with ADHD. Analysis of clinical trials may guide clinical intervention and future research.
METHOD
Controlled trials of adult ADHD measuring emotional behavior were included if another study offered a comparable analysis of the same treatment method. Standardized Mean Difference (SMD) of effects were calculated, and the size of effects for emotional and non-emotional ADHD behavior were compared.
RESULTS
13 out of 14 studies of methylphenidate, atomoxetine, and lisdexamfetamine demonstrated significant improvement in emotional behavior measures, with small to high SMDs. The proportional effect on emotional versus non-emotional behavior ranged from 46% to 110% for methylphenidate, 56% to 129% for atomoxetine, and 36% to 96% for lisdexamfetamine.
CONCLUSION
Psychopharmacological treatments for ADHD are likely to improve emotional behavior, and available scales are sensitive to these effects. Studies dedicated to treatment of this domain of function can further refine clinical approaches.
Topics: Adult; Humans; Atomoxetine Hydrochloride; Lisdexamfetamine Dimesylate; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Treatment Outcome
PubMed: 35822610
DOI: 10.1177/10870547221110926 -
European Neuropsychopharmacology : the... Dec 2021Binge-Eating Disorder (BED) is the most common eating disorder in the United States. Lisdexamfetamine (LDX) was approved in 2015 by the FDA for treatment of BED and is... (Meta-Analysis)
Meta-Analysis Review
Lisdexamfetamine and binge-eating disorder: A systematic review and meta-analysis of the preclinical and clinical data with a focus on mechanism of drug action in treating the disorder.
Binge-Eating Disorder (BED) is the most common eating disorder in the United States. Lisdexamfetamine (LDX) was approved in 2015 by the FDA for treatment of BED and is the only drug approved for treating the disorder. There has been no systematic evaluation of the published clinical and preclinical evidence for efficacy of LDX in treating BED and the mechanisms responsible for the therapeutic action of the drug. To address this gap, we conducted a systematic review and meta-analysis using PRISMA guidelines. Fourteen clinical and seven preclinical articles were included. There is consistent evidence from clinical studies that LDX is an effective treatment for BED and that the drug reduces the BED symptoms and body weight of patients with the disorder. There is also consistent evidence from preclinical studies that LDX reduces food intake but no consistent evidence for a preferential reduction of palatable food consumption by the drug in rodents. The evidence on mechanism of action is more limited and suggests LDX may reduce binge eating by a combination of effects on appetite/satiety, reward, and cognitive processes, including attention and impulsivity/inhibition, that are mediated by catecholamine and serotonin mechanisms in the brain. There is an urgent need for adequately powered, placebo-controlled, behavioural and neuroimaging studies with LDX (recruiting patients and/or individuals with subclinical BED symptoms) to further investigate the mechanism of action of the drug in treating BED. An improved understanding of the behavioural and neurochemical mechanisms of action of LDX could lead to the development of improved drug therapies to treat BED.
Topics: Binge-Eating Disorder; Body Weight; Central Nervous System Stimulants; Humans; Impulsive Behavior; Lisdexamfetamine Dimesylate; Treatment Outcome
PubMed: 34461386
DOI: 10.1016/j.euroneuro.2021.08.001 -
Journal of Affective Disorders Sep 2021Globally, depression impacts nearly 300 million people, and roughly half do not achieve remission with standard first-line therapies. For such individuals, augmentation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Globally, depression impacts nearly 300 million people, and roughly half do not achieve remission with standard first-line therapies. For such individuals, augmentation strategies are often helpful at reducing the severity of depression. While there are many potential adjunctive medication choices, psychostimulants are among the more controversial options.
OBJECTIVES
The present review sought to clarify the comparative efficacy and safety of different stimulant-like medications to treat depression.
METHODS
We conducted a systematic review and network meta-analysis of randomized, controlled trials (RCTs) using psychostimulant medications to treat adults with depression. Outcomes were pooled using rate ratios (RRs) for dichotomous outcomes (e.g., response, adverse events) and standardized mean differences (SMDs) for continuous outcomes (e.g., change in depression scores).
RESULTS
We identified 37 eligible studies (ranging from 1958 to 2016). We assessed nine psychostimulants: methylphenidate (n=14), dextroamphetamine (n=9), modafinil (n=6), lisdexamphetamine (n=3), methylamphetamine (n=3), pemoline (n=2), atomoxetine (n=1), desipramine (n=1), and imipramine (n=1). Overall, psychostimulants demonstrated efficacy for depression, reduced fatigue and sleepiness, and appeared well-tolerated. However, there was inconsistent evidence across particular psychostimulants. For example, the only psychostimulant which demonstrated efficacy for depression-in terms of both symptom severity and response rates-was methylphenidate.
CONCLUSIONS
While our review suggests that some psychostimulants-particularly methylphenidate-appear well-tolerated and demonstrate some efficacy for depression, as well as fatigue and sleepiness, the strength of evidence in our estimates was low to very low for most agents given the small sample sizes, few RCTs, and imprecision in most estimates. A lack of consistent evidence precludes a definitive hierarchy of treatments and points to a need for additional, high-quality RCTs.
Topics: Adult; Central Nervous System Stimulants; Depression; Fatigue; Humans; Methylphenidate; Network Meta-Analysis
PubMed: 34144366
DOI: 10.1016/j.jad.2021.05.119 -
Addiction (Abingdon, England) Feb 2024There is currently no standard of care for pharmacological treatment of amphetamine-type stimulant (ATS) use disorder (ATSUD). This systematic review with meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There is currently no standard of care for pharmacological treatment of amphetamine-type stimulant (ATS) use disorder (ATSUD). This systematic review with meta-analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo-controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD.
METHODS
Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random-effect meta-analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random-effect meta-analysis of continuous variables.
RESULTS
Ten RCTs (n = 561 participants) were included in the meta-analysis. Trials studied methylphenidate (n = 7), with daily doses of 54-180 mg, and dextroamphetamine (n = 3), with daily doses of 60-110 mg, for 2-24 weeks. PPs significantly decreased end-point craving [SMD -0.29; 95% confidence interval (CI) = -0.55, -0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85-1.01). No effect was observed for self-reported ATS use, retention in treatment, dropout following adverse events, early-stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79-0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention.
CONCLUSIONS
Among individuals with amphetamine-type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications.
Topics: Humans; Central Nervous System Stimulants; Methylphenidate; Substance-Related Disorders; Amphetamines; Prescriptions; Randomized Controlled Trials as Topic
PubMed: 37880829
DOI: 10.1111/add.16347 -
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 -
European Eating Disorders Review : the... Sep 2017Psychological and pharmacological interventions for binge-eating disorder have previously demonstrated efficacy (compared with placebo or waitlist control); thus, we... (Meta-Analysis)
Meta-Analysis Review
Psychological and pharmacological interventions for binge-eating disorder have previously demonstrated efficacy (compared with placebo or waitlist control); thus, we aimed to expand that literature with a review of comparative effectiveness. We searched MEDLINE,® EMBASE,® Cochrane Library, Academic OneFile, CINAHL® for binge-eating disorder treatment articles and selected studies using predetermined inclusion and exclusion criteria. Data were sufficient for network meta-analysis comparing two pharmacological interventions; psychological interventions were analysed qualitatively. In all, 28 treatment comparisons were included in this review: one pharmacological comparison (second-generation antidepressants versus lisdexamfetamine) and 26 psychological comparisons. Only three statistically significant differences emerged: lisdexamfetamine was better at increasing binge abstinence than second-generation antidepressants; therapist-led cognitive behavioural therapy was better at reducing binge-eating frequency than behavioural weight loss, but behavioural weight loss was better at reducing weight. The majority of other treatment comparisons revealed few significant differences between groups. Thus, patients and clinicians can choose from several effective treatment options. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
Topics: Antidepressive Agents, Second-Generation; Binge-Eating Disorder; Cognitive Behavioral Therapy; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28467032
DOI: 10.1002/erv.2517 -
Current Medical Research and Opinion Aug 2014Systematically review and synthesize the clinical evidence of treatments for attention deficit hyperactivity disorder (ADHD) by indirectly comparing established... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
Systematically review and synthesize the clinical evidence of treatments for attention deficit hyperactivity disorder (ADHD) by indirectly comparing established treatments in the UK with a drug recently approved in Europe (lisdexamfetamine [LDX]).
POPULATION
children and adolescents.
SETTING
Europe. Comparators: methylphenidate (MPH), atomoxetine (ATX), and dexamphetamine (DEX). Electronic databases and relevant conference proceedings were searched for randomized, controlled clinical trials evaluating efficacy and safety of at least one of the comparators and LDX. Quality assessments for each included trial were performed using criteria recommended by the Centre for Reviews and Dissemination. Network meta-analysis methods for dichotomous outcomes were employed to evaluate treatment efficacy.
MAIN OUTCOME MEASURES
Response, as defined by either a reduction from baseline of at least 25% in the ADHD Rating Scale [ADHD-RS] total score or, separately, as assessed on the Clinical Global Impression-Improvement [CGI-I] scale, and safety (all-cause withdrawals and withdrawal due to adverse events).
RESULTS
The systematic review found 32 trials for the meta-analysis, including data on LDX, ATX, and different formulations of MPH. No trials for DEX meeting the inclusion criteria were found. Sufficient data were identified for each outcome: ADHD-RS, 16 trials; CGI-I, 20 trials; all-cause withdrawals, 28 trials; and withdrawals due to adverse events, 27 trials. The relative probability of treatment response for CGI-I (95% confidence intervals [CI]) for ATX versus LDX was 0.65 (0.53-0.78); for long-acting MPH versus LDX, 0.82 (0.69-0.97); for intermediate release MPH versus LDX, 0.51 (0.40-0.65); and for short-acting MPH versus LDX, 0.62 (0.51-0.76). The relative probabilities of ADHD-RS treatment response also favored LDX.
CONCLUSIONS
For the treatment of ADHD, the synthesis of efficacy data showed statistically significant better probabilities of response with LDX than for formulations of MPH or ATX. The analysis of safety data proved inconclusive due to low event rates. These results may be limited by the studies included, which only investigated the short-term efficacy of medications in patients without comorbid disorders.
Topics: Adolescent; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dopamine Uptake Inhibitors; Europe; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Models, Statistical; Propylamines; Treatment Outcome
PubMed: 24627974
DOI: 10.1185/03007995.2014.904772 -
Health Technology Assessment... Jul 2006To assess the clinical and cost-effectiveness of oral methylphenidate hydrochloride (MPH), dexamfetaminesulphate (DEX) and atomoxetine (ATX) in children and adolescents... (Review)
Review
A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents.
OBJECTIVES
To assess the clinical and cost-effectiveness of oral methylphenidate hydrochloride (MPH), dexamfetaminesulphate (DEX) and atomoxetine (ATX) in children and adolescents (<18 years of age) diagnosed with attention deficit hyperactivity disorder (ADHD) (including hyperkinetic disorder).
DATA SOURCES
Electronic databases covering 1999--July 2004 for MPH, 1997--July 2004 for DEX and 1981--July 2004 for ATX.
REVIEW METHODS
Selected studies were assessed using modified criteria based on CRD Report No. 4. Clinical effectiveness data were reported separately for each drug and by the type of comparison. Data for MPH were also analysed separately based on whether it was administered as an immediate release (IR) or extended release (ER) formulation. For all drugs, the data were examined by dose. Data for the core outcomes of hyperactivity (using any scale), Clinical Global Impression [as a proxy of quality of life (QoL)] and adverse events were reported. For crossover studies, the mean and standard deviation (SD) for each outcome were data extracted for end of trial data (i.e. baseline data were not considered). For parallel studies, change scores were reported where given, otherwise means and SDs were presented for end of trial data. In addition, mean differences with 95% confidence intervals were calculated for each study. For adverse events, self-ratings were reported when used, otherwise, parent reports were utilised. Percentages of participants reporting adverse events were used to calculate numbers of events in each treatment arm. All the clinical effectiveness data and economic evaluations (including accompanying models) included in the company submissions were assessed. A new model was developed to assess the cost-effectiveness of the alternative treatments in terms of cost per quality-adjusted life-year. To achieve this, a mixed treatment comparison model was used to estimate the differential mean response rates. Monte Carlo simulation was used to reflect uncertainty in the cost-effectiveness results.
RESULTS
In total, 65 papers met the inclusion criteria. The results suggest that MPH and DEX are effective at reducing hyperactivity and improving QoL (as determined by Clinical Global Impression) in children, although the reliability of the MPH study results is not known and there were only a small number of DEX studies. There was consistent evidence that ATX was superior to placebo for hyperactivity and Clinical Global Impression. Studies on ATX more often reported the study methodology well, and the results were likely to be reliable. Very few studies made direct head-to-head comparisons between the drugs or examined a non-drug intervention in combination with MPH, DEX or ATX. Adequate and informative data regarding the potential adverse effects of the drugs were also lacking. The results of the economic evaluation clearly identified an optimal treatment strategy of DEX first-line, followed by IR-MPH for treatment failures, followed by ATX for repeat treatment failures. Where DEX is unsuitable as a first-line therapy, the optimal strategy is IR-MPH first-line, followed by DEX and then ATX. For patients contraindicated to stimulants, ATX is preferred to no treatment. For patients in whom a midday dose of medication is unworkable, ER-MPH is preferred to ATX, and ER-MPH12 appears more cost-effective than ER-MPH8. As identified in the clinical effectiveness review, the reporting of studies was poor, therefore this should be borne in mind when interpreting the model results.
CONCLUSIONS
Drug therapy seems to be superior to no drug therapy, no significant differences between the various drugs in terms of efficacy or side effects were found, mainly owing to lack of evidence, and the additional benefits from behavioural therapy (in combination with drug therapy) are uncertain. Given the lack of evidence for any differences in effectiveness between the drugs, the economic model tended to be driven by drug costs, which differed considerably. Future trials examining MPH, DEX and ATX should include the assessment of tolerability and safety as a priority. Longer term follow-up of individuals participating in trials could further inform policy makers and health professionals. Such data could potentially distinguish between these drugs in a clinically useful way. In addition, research examining whether somatic complaints are actually related to drug treatment or to the disorder itself would be informative.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Cost-Benefit Analysis; Dextroamphetamine; Humans; Methylphenidate; Models, Economic; Propylamines; Treatment Outcome
PubMed: 16796929
DOI: 10.3310/hta10230 -
Drug and Alcohol Dependence Oct 2018Demand for treatment for amphetamine use is increasing internationally. Establishing effective pharmacotherapy provides broader treatment options for people who are... (Review)
Review
BACKGROUND
Demand for treatment for amphetamine use is increasing internationally. Establishing effective pharmacotherapy provides broader treatment options for people who are dependent on amphetamine and may encourage engagement in evidence-based behavioral treatment. This study aimed to identify medicines that have potential in improving treatment outcomes for people who are dependent on amphetamines.
METHODS
Medline, PsycINFO, Embase and the Cochrane Database of Systematic Reviews were searched from 1997 to 2012 and again from 2013 to 2016. Studies on medications for amphetamine/methamphetamine dependence treatment were selected and assessed by two independent researchers. A meta-narrative review approach was used to synthesize results.
RESULTS
A total of 49 studies investigating 20 potential pharmacotherapies were eligible for inclusion. Of these, 35 studies related to 33 level II quality randomized controlled trials (RCTs). Five medications were subject to multiple RCTs. Four of these medicines demonstrated some limited evidence of benefit for reducing amphetamine use: methylphenidate (as reported in three studies), bupropion (in three studies), modafinil (two studies), and naltrexone (one study). Four RCTs of dexamphetamine suggest its benefit on secondary outcomes such as treatment retention, but not for reducing amphetamine use. Six other medicines indicate the potential for efficacy, but the number of studies is too small to draw conclusions.
CONCLUSIONS
No medicine has as yet demonstrated sufficient, consistent evidence of effectiveness to support its use in routine treatment. High study drop-out and poor medication adherence limits the strength of evidence and raises important clinical questions about how to improve treatment engagement and outcomes.
Topics: Amphetamine; Amphetamine-Related Disorders; Dextroamphetamine; Humans; Medication Adherence; Methylphenidate; Modafinil; Naltrexone; Randomized Controlled Trials as Topic
PubMed: 30173086
DOI: 10.1016/j.drugalcdep.2018.06.038 -
Neuropsychopharmacology : Official... Jun 2010Antipsychotic-related weight gain and metabolic effects are a critical outcome for patients requiring these medications. A literature search using MEDLINE, Web of... (Meta-Analysis)
Meta-Analysis Review
Antipsychotic-related weight gain and metabolic effects are a critical outcome for patients requiring these medications. A literature search using MEDLINE, Web of Science, PsycNET, and EMBASE for randomized, open and double-blind, placebo-controlled trials of medications targeting antipsychotic-induced weight gain was performed. Primary outcome measures were change and endpoint values in body weight and body mass index (BMI). Secondary outcomes included >or=7% weight gain, all-cause discontinuation, change in waist circumference, glucose and lipid metabolism parameters, and psychiatric symptoms. Sensitivity analyses were conducted to explain heterogeneity of the results. Across 32 studies including 1482 subjects, 15 different medications were tested: amantadine, dextroamphetamine, d-fenfluramine, famotidine, fluoxetine, fluvoxamine, metformin, nizatidine, orlistat, phenylpropanolamine, reboxetine, rosiglitazone, sibutramine, topiramate, and metformin+sibutramine. Compared with placebo, metformin had the greatest weight loss (N=7, n=334, -2.94 kg (confidence interval (CI:-4.89,-0.99)), followed by d-fenfluramine (N=1, n=16, -2.60 kg (CI:-5.14,-0.06)), sibutramine (N=2, n=55, -2.56 kg (CI:-3.91,-1.22)), topiramate (N=2, n=133, -2.52 kg (CI:-4.87,-0.16)), and reboxetine (N=2, n=79, -1.90 kg (CI:-3.07,-0.72)). Weight loss remained significant with metformin initiation after weight gain had occurred, but not when started concomitantly with antipsychotics. Nausea rates were not higher with any treatment compared with placebo. In all, 5 of 15 psychopharmacologic interventions aimed at ameliorating antipsychotic-induced weight gain outperformed placebo. Results were most robust for metformin, although these were modest and heterogeneous. Only one (negative) combination treatment study was available and head-to-head studies are absent. None of the agents were able to entirely reverse weight gain because of antipsychotics. At present, no treatment has sufficient evidence to recommend broad clinical usage. Antipsychotics with no or minimal cardiometabolic liability, as well as interventions that prevent or normalize adverse antipsychotic cardiometabolic effects are needed.
Topics: Animals; Antidepressive Agents; Databases, Factual; Humans; Hypoglycemic Agents; Metabolic Diseases; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 20336059
DOI: 10.1038/npp.2010.21