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Expert Review of Neurotherapeutics 2016Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard... (Review)
Review
Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder.
Topics: Adrenergic alpha-Agonists; Adult; Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bupropion; Central Nervous System Stimulants; Desipramine; Dopamine Agents; Droxidopa; Drug Combinations; Duloxetine Hydrochloride; Guanfacine; Histamine Agents; Humans; Lisdexamfetamine Dimesylate; Lithium Compounds; Lobeline; Mecamylamine; Memantine; Modafinil; Morpholines; Nicotinic Agonists; Nicotinic Antagonists; Nomifensine; Paroxetine; Pyridines; Pyridoxine; Pyrrolidonecarboxylic Acid; Quinazolinones; Reboxetine; Venlafaxine Hydrochloride; Wakefulness-Promoting Agents
PubMed: 26693882
DOI: 10.1586/14737175.2016.1135735 -
BMC Psychiatry Oct 2015Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood.... (Review)
Review
BACKGROUND
Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood. ADHD is associated with increased risk of co-morbid psychiatric disorders, including substance misuse. Many will be prescribed medication, namely methylphenidate, atomoxetine, dexamphetamine and lisdexamfetamine. If so, it is important to know if interactions exist and if they are potentially toxic.
METHODS
Three databases (Medline, EMBASE and PsychINFO) from a 22 year period (1992 - June 2014) were searched systematically. Key search terms included alcohol, substance related disorders, methylphenidate, atomoxetine, dexamphetamine, lisdexamfetamine, and death, which identified 493 citations (344 after removal of duplicates). The eligibility of each study was assessed jointly by two investigators, leaving 20 relevant articles.
RESULTS
We identified only a minimal increase in side-effects when ADHD medication (therapeutic doses) was taken with alcohol. None of the reviewed studies showed severe sequelae among those who had overdosed on ADHD medication and other coingestants, including alcohol.
CONCLUSIONS
The numbers across all the papers studied remain too low to exclude uncommon effects. Also, studies of combined effects with novel psychoactive substances have not yet appeared in the literature. Nevertheless, no serious sequelae were identified from combining ADHD medication with alcohol/illicit substances from the pre-novel psychoactive substance era.
Topics: Adolescent; Adrenergic Uptake Inhibitors; Alcohol Drinking; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Drug Interactions; Humans; Illicit Drugs; Lisdexamfetamine Dimesylate; Methylphenidate; Substance-Related Disorders
PubMed: 26517983
DOI: 10.1186/s12888-015-0657-9 -
Clinical and Experimental Obstetrics &... 2015To review treatment options for hair loss in women. (Review)
Review
PURPOSE
To review treatment options for hair loss in women.
MATERIALS AND METHODS
Suggestions for treatment were based on a thorough literature search plus the present authors' experience.
RESULTS
There are controlled studies that support the present authors' typical treatment regimen of identifying if there are increased androgens, and if so, identify the source (ovary and/or adrenal) and then suppress with drugs, e.g., oral contraceptives or glucocorticoids. If serum androgens are normal, agents that block dihydrotestosterone at the hair shaft level, e.g., spironolactone or 5a reductase inhibitors seem to be effective. However, a recent Cochrane systematic review concludes that the only drug proven to improve alopecia by randomized controlled studies using rigorous criteria is minoxidil.
CONCLUSIONS
The present authors will add minoxidil to their normal treatment paradigm based on this later study. The previous reasons for it was the quality of the hair produced (generally much shorter than other head hair). For alopecia related to inflammation, the present authors may have discovered a novel therapy--dextroamphetamine sulfate.
Topics: Alopecia; Central Nervous System Stimulants; Dextroamphetamine; Female; Humans; Minoxidil; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 26411201
DOI: No ID Found -
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 Psychiatry : the Journal of... Jun 2015There are few approved therapies for adults with attention-deficit/hyperactivity disorder (ADHD) in Europe. Lisdexamfetamine (LDX) is an effective treatment for ADHD;... (Meta-Analysis)
Meta-Analysis Review
Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: Estimates based on indirect analysis using a systematic review and meta-regression analysis.
BACKGROUND
There are few approved therapies for adults with attention-deficit/hyperactivity disorder (ADHD) in Europe. Lisdexamfetamine (LDX) is an effective treatment for ADHD; however, no clinical trials examining the efficacy of LDX specifically in European adults have been conducted. Therefore, to estimate the efficacy of LDX in European adults we performed a meta-regression of existing clinical data.
METHODS
A systematic review identified US- and Europe-based randomized efficacy trials of LDX, atomoxetine (ATX), or osmotic-release oral system methylphenidate (OROS-MPH) in children/adolescents and adults. A meta-regression model was then fitted to the published/calculated effect sizes (Cohen's d) using medication, geographical location, and age group as predictors. The LDX effect size in European adults was extrapolated from the fitted model. Sensitivity analyses performed included using adult-only studies and adding studies with placebo designs other than a standard pill-placebo design.
RESULTS
Twenty-two of 2832 identified articles met inclusion criteria. The model-estimated effect size of LDX for European adults was 1.070 (95% confidence interval: 0.738, 1.401), larger than the 0.8 threshold for large effect sizes. The overall model fit was adequate (80%) and stable in the sensitivity analyses.
CONCLUSION
This model predicts that LDX may have a large treatment effect size in European adults with ADHD.
Topics: Adult; Attention; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Europe; Female; Follow-Up Studies; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Regression Analysis; Treatment Outcome
PubMed: 25725594
DOI: 10.1016/j.eurpsy.2015.01.001 -
Drug Design, Development and Therapy 2014Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD).
OBJECTIVES
This systematic review was undertaken to summarize LDX efficacy, acceptability, and tolerability in adult ADHD. All randomized controlled trials (RCTs) of lisdexamfetamine compared with placebo were included for synthesis. Clinical trials published between January 1991 and January 2014 were evaluated.
METHODS
The database of MEDLINE(®), EMBASE™, CINAHL(®), PsycINFO(®) and Cochrane Controlled Trials Register were searched in January 2014. Studies were also searched in ClinicalTrials.gov and the EU Clinical Trials Register database. Study eligibility criteria, participants, and interventions were considered. All RCTs of LDX vs placebo reporting final results of: 1) severity of ADHD symptoms and executive function deficit, 2) response or remission rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse events were included. The language of the papers was not restricted. All abstracts of studies gathered from the database were examined. After excluding irrelevant trials, the full text version of relevant studies were assessed and extracted for outcomes of interest. Examination of risks of bias, based on the Cochrane bias assessment, was carried out. The efficacy outcomes consisted of the mean end point or change scores for ADHD rating scales, the response rate, and the remission rate. The overall discontinuation rate and the discontinuation rate due to adverse events were measured for acceptability and tolerability, respectively. A random effect model was applied for the synthesis of relative risks (RRs), and weighted mean differences or standardized mean differences (SMDs) with 95% confidence intervals (CIs).
RESULTS
A total of 806 final study or safety participants were included. The dosage of lisdexamfetamine was 30 to 70 mg/day. The pooled mean scores of mean change and mean end point scores between LDX- and placebo-treated groups also had a significant difference (SMD [95% CI] of -0.97 [-1.15, -0.78], I(2)=18%). The pooled response rates for adult ADHD between the two groups had a significant difference (RR [95% CI] of 1.99 [1.50, 2.63], I(2)=0%). Based on the Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A), the pooled end point mean scores for the Global Executive Composite (GEC) for the LDX-treated groups was greater than that of placebo-treated groups (MD [95% CI] of -9.20 [-14.11, -4.29], I(2)=34%). The pooled overall discontinuation rates between the two groups had no significant difference (RR [95% CI] of 0.82 [0.59, 1.14], I(2)=0%). Similarly, the pooled discontinuation rates due to adverse events between the two groups was not significantly different (RR [95% CI] of 1.77 [0.71, 4.40], I(2)=0%).
CONCLUSION
The number of included studies was limited (five RCTs), but based on this meta-analysis, LDX is efficacious and well tolerated in the treatment of adult ADHD. Additionally, it also improved the executive function deficits in this population. However, its acceptability is no higher than placebo. These findings should be carefully interpreted and considered as preliminary outcomes. To confirm these results, further studies are warranted. LDX is a viable alternative psychostimulant for adult ADHD.
Topics: Attention Deficit Disorder with Hyperactivity; Databases, Factual; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Placebos; Registries
PubMed: 25336914
DOI: 10.2147/DDDT.S68393 -
CNS Drugs Jun 2014Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of... (Review)
Review
BACKGROUND
Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD).
METHODS
A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]).
RESULTS
In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX.
CONCLUSIONS
The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Clinical Trials, Phase III as Topic; Dextroamphetamine; Dose-Response Relationship, Drug; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Randomized Controlled Trials as Topic; Time Factors
PubMed: 24788672
DOI: 10.1007/s40263-014-0166-2 -
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 -
American Journal of Alzheimer's Disease... Mar 2014The objective of this review is to summarize the current data on the pharmacological treatments for frontotemporal dementias from randomized controlled trials. A... (Review)
Review
The objective of this review is to summarize the current data on the pharmacological treatments for frontotemporal dementias from randomized controlled trials. A systematic search of 4 major databases, PubMed, Medline, PsychINFO and Cochrane, found a total of 9 randomized controlled, double-blinded clinical trials. Of these, 2 trials used the selective serotonin reuptake inhibitor (SSRI), paroxetine; 1 trial used trazodone; 2 trials used stimulants (methylphenidate and dextroamphetamine); 1 trial used the acetylcholinesterase inhibitor, galantamine; 2 trials used the N-methyl-d-aspartate antagonist, memantine; and 1 trial used the neuropeptide oxytocin. The analysis of the available data indicates that SSRIs, trazodone, and the amphetamines may be effective in reducing some behavioral symptoms, but none of these medications had an impact on cognition. Available data indicate that these medications were well tolerated in all the trials.
Topics: Cognition; Dopamine Agents; Frontotemporal Dementia; Humans; Memantine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 24164931
DOI: 10.1177/1533317513507375 -
The Cochrane Database of Systematic... Sep 2013Amphetamine dependence is a public health problem with medical, psychiatric, cognitive, legal and socioeconomic consequences. To date, no pharmacological treatment has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amphetamine dependence is a public health problem with medical, psychiatric, cognitive, legal and socioeconomic consequences. To date, no pharmacological treatment has been approved for this disorder, and psychotherapy remains the mainstay of treatment. In recent years, psychostimulants have been investigated as a possible replacement therapy.
OBJECTIVES
To evaluate the efficacy and safety of psychostimulant medications for amphetamine abuse or dependence. The influences of type of drug, type of dependence, comorbid disorders, clinical trial risk of bias and publication of data were also studied.
SEARCH METHODS
Relevant trials were searched in the following sources: PubMed (January 1966 to 6 June 2012), EMBASE (January 1988 to 6 June 2012), CENTRAL (The Cochrane Library, Issue 5 of 12, May 2012), PsycINFO (January 1985 to 6 June 2012) and the Specialised Register of the Cochrane Drug and Alcohol Group (June 2012). We also searched the reference lists of retrieved trials, the list of studies citing the included trials and the main electronic registers of ongoing trials (ClinicalTrials.gov, International Clinical Trials Registry Platform and EU Clinical Trials Register). Finally, we contacted investigators to request information about unpublished trials. Searches included non-English language literature.
SELECTION CRITERIA
All randomised, placebo-controlled, parallel-group clinical trials investigating the efficacy or safety of psychostimulants for amphetamine dependence or abuse conducted in an outpatient setting.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
Eleven studies were included in the review (791 participants). Studied psychostimulants included dexamphetamine, bupropion, methylphenidate and modafinil. No significant differences were found between psychostimulants and placebo for any of the studied efficacy outcomes. Overall retention in studies was low (50.4%). Psychostimulants did not reduce amphetamine use (mean difference (MD) -0.26, 95% confidence interval (CI) -0.85 to 0.33) or amphetamine craving (MD 0.07, 95% CI -0.44 to 0.59) and did not increase sustained abstinence (relative risk (RR) 1.12, 95% CI 0.84 to 1.49). The proportion of adverse events inducing dropout was similar for psychostimulants and placebo (risk difference (RD) 0.01, 95% CI -0.03 to 0.04). The main findings did not change in any subgroup analysis.
AUTHORS' CONCLUSIONS
Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy for amphetamine abuse or dependence. Future research could change this conclusion, as the numbers of included studies and participants are limited and information on relevant outcomes, such as efficacy according to the severity of dependence or craving, is still missing.
Topics: Amphetamine-Related Disorders; Benzhydryl Compounds; Bupropion; Central Nervous System Stimulants; Dextroamphetamine; Humans; Methylphenidate; Modafinil; Randomized Controlled Trials as Topic
PubMed: 23996457
DOI: 10.1002/14651858.CD009695.pub2