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PloS One 2020Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD.
METHODS
We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework.
RESULTS
Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration.
CONCLUSIONS
Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs.
REGISTRATION
PROSPERO no. CRD 42015026049.
Topics: Adult; Amphetamine; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Bayes Theorem; Bupropion; Central Nervous System Stimulants; Dextroamphetamine; Drug-Related Side Effects and Adverse Reactions; Female; Guanfacine; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Modafinil; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 33085721
DOI: 10.1371/journal.pone.0240584 -
Journal of Sleep Research Aug 2021Graduate medical education (GME) training commonly requires residents and fellows to engage in night float shift work. This review aims to assess the effectiveness of...
Graduate medical education (GME) training commonly requires residents and fellows to engage in night float shift work. This review aims to assess the effectiveness of interventions for trainees when preparing for, completing, and recovering from working night float shifts. We reviewed all available studies published prior to September 2019 using PubMed, Scopus, CINAHL, the Cochrane library, PsycINFO, and Google Scholar databases. We included all original, primary research articles assessing either non-pharmacological or pharmacological interventions on the chronobiological and physiological effects of night float shift work among GME trainees. Five studies (n = 179 patients) met inclusion criteria. Interventions included melatonin in the morning before sleep after night float shifts, napping during night float shifts, modafinil after a night of sleep deprivation, and caffeinated energy drinks after 6 consecutive night float shifts. Melatonin improved one measure of attention. A 2-hr nap was associated with improved speed related to task switching. Modafinil improved performance in tests of cognition. Caffeinated energy drinks led to improvement in select driving performance variables and reaction time. Effect sizes for outcome variables were calculated. Heterogeneity among the studies precluded combining the data in a meta-analysis. According to GRADE criteria, the quality of the evidence in these studies was low or very low. Our findings suggest GME trainees may benefit from utilising a limited number of interventions when preparing for or recovering from night float shift work. More investigation is needed to identify interventions that could help GME trainees adapt to and recover from working night float shifts.
Topics: Adaptation, Physiological; Attention; Caffeine; Education, Medical, Graduate; Energy Drinks; Fatigue; Humans; Melatonin; Modafinil; Reaction Time; Sleep; Sleep Deprivation; Sleep Disorders, Circadian Rhythm; Work Schedule Tolerance
PubMed: 33058426
DOI: 10.1111/jsr.13212 -
Expert Opinion on Pharmacotherapy Feb 2021Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic... (Comparative Study)
Comparative Study
INTRODUCTION
Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. Treatment of narcolepsy remains challenging and current therapy is strictly symptomatically based.
AREAS COVERED
The present manuscript is based on an extensive Internet and PubMed search from 1990 to 2020. It is focused on the clinical and pharmacological properties of pitolisant in the treatment of narcolepsy.
EXPERT OPINION
Currently there is no cure for narcolepsy. Although efforts have been made, current treatments do not always allow to obtain an optimal control of symptoms. Pitolisant is an antagonist/inverse agonist of the histamine H3 autoreceptor. Its mechanism of action is novel and distinctive compared to the other available therapies for narcolepsy. Clinical trials suggest that pitolisant administered at a dose of ≤36 mg/day is an effective treatment option for narcolepsy, reducing EDS and cataplexy. Pitolisant is available as oral tablets and offers a convenient once-daily regimen. Pitolisant is generally well tolerated and showed minimal abuse potential in animals and humans. Long-term studies comparing the effectiveness and tolerability of pitolisant with active drugs (e.g. modafinil, sodium oxybate) are needed.
Topics: Animals; Cataplexy; Humans; Modafinil; Narcolepsy; Piperidines; Sleep; Sodium Oxybate; Treatment Outcome
PubMed: 32941089
DOI: 10.1080/14656566.2020.1817387 -
Journal of Child Psychology and... Jun 2021Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The... (Meta-Analysis)
Meta-Analysis
Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis.
BACKGROUND
Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta-analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation.
METHODS
We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha-2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random-effects model.
RESULTS
Twenty-five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent-rated: standardized mean difference [SMD] = -.63, 95%CI = -.95,-.30; teacher-rated: SMD = -.81, 95%CI = -1.43,-.19) and inattention (parent-rated: SMD = -.36, 95%CI = -.64,-.07; teacher-rated: SMD = -.30, 95%CI = -.49,-.11). Atomoxetine reduced inattention (parent-rated: SMD = -.54, 95%CI = -.98,-.09; teacher/investigator-rated: SMD = -0.38, 95%CI = -0.75, -0.01) and parent-rated hyperactivity (parent-rated: SMD = -.49, 95%CI = -.76,-.23; teacher-rated: SMD = -.43, 95%CI = -.92, .06). Indirect evidence for significant reductions in hyperactivity with second-generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events.
CONCLUSIONS
Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long-term continuation is undertaken to help guide clinical decision-making regarding treatment of co-occurring ADHD symptoms in children and youth with ASD.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Central Nervous System Stimulants; Child; Guanfacine; Humans; Methylphenidate
PubMed: 32845025
DOI: 10.1111/jcpp.13305 -
The Journal of Clinical Psychiatry Jul 2020To review the efficacy of antidepressants and other therapeutic agents for the treatment of cognitive impairment in adults with major depressive disorder (MDD).
OBJECTIVE
To review the efficacy of antidepressants and other therapeutic agents for the treatment of cognitive impairment in adults with major depressive disorder (MDD).
DATA SOURCES
We conducted a database search of MEDLINE, PsycINFO, and Embase through Ovid on May 7, 2019. The year of publication was not restricted. The search terms "Major Depressive Disorder," "depress*," "cognit*," and "therapeutics" were used.
STUDY SELECTION
The studies included in this review were clinical trials of antidepressants and other therapeutic agents in MDD populations. Participants were aged between 18 and 65 years and had a DSM-III, -IV, or -5 diagnosis of MDD. In total, 2,045 research papers were screened, 53 full-text articles were assessed, and 26 articles were eligible to be included in this systematic review.
DATA EXTRACTION
The data and quality of research papers were assessed and screened by 2 independent reviewers. Discrepancies were resolved through a third reviewer.
RESULTS
Overall, studies demonstrated that tricyclic antidepressants do not have procognitive effects, while vortioxetine and bupropion have demonstrated procognitive effects in MDD populations relative to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Several non-antidepressant agents, such as modafinil, amphetamines, and erythropoietin, have also demonstrated significant positive effects on cognition in depression.
CONCLUSIONS
Present-day antidepressants and other agents have demonstrated procognitive effects in MDD, but the findings between various agents are mixed. Further research looking at objective measures of cognitive performance would be helpful to obtain more definitive results regarding the efficacy of therapeutics for cognitive impairment in MDD.
Topics: Antidepressive Agents; Cognitive Dysfunction; Depressive Disorder, Major; Humans; Psychotropic Drugs
PubMed: 32726521
DOI: 10.4088/JCP.19r13200 -
European Neuropsychopharmacology : the... Sep 2020Modafinil, methyphenidate (MPH) and d-amphetamine (d-amph) are putative cognitive enhancers. However, efficacy of cognitive enhancement has yet to be fully established.... (Meta-Analysis)
Meta-Analysis
How effective are pharmaceuticals for cognitive enhancement in healthy adults? A series of meta-analyses of cognitive performance during acute administration of modafinil, methylphenidate and D-amphetamine.
Modafinil, methyphenidate (MPH) and d-amphetamine (d-amph) are putative cognitive enhancers. However, efficacy of cognitive enhancement has yet to be fully established. We examined cognitive performance in healthy non-sleep-deprived adults following modafinil, MPH, or d-amph vs placebo in 3 meta-analyses, using subgroup analysis by cognitive domain; executive functions (updating, switching, inhibitory control, access to semantic/long term memory), spatial working memory, recall, selective attention, and sustained attention. We adhered to PRISMA. We identified k = 47 studies for analysis; k = 14 studies (64 effect sizes) for modafinil, k = 24 studies (47 effect sizes) for Methylphenidate, and k = 10 (27 effect sizes) for d-amph. There was an overall effect of modafinil (SMD=0.12, p=.01). Modafinil improved memory updating (SMD=0.28, p=.03). There was an overall effect of MPH (SMD=0.21, p=.0004) driven by improvements in recall (SMD=0.43, p=.0002), sustained attention (SMD=0.42, p=.0004), and inhibitory control (SMD=0.27, p=.03). There were no effects for d-amph. MPH and modafinil show enhancing effects in specific sub-domains of cognition. However, data with these stimulants is far from positive if we consider that effects are small, in experiments that do not accurately reflect their actual use in the wider population. There is a user perception that these drugs are effective cognitive enhancers, but this is not supported by the evidence so far.
Topics: Adult; Cognition; Dextroamphetamine; Drug Administration Schedule; Female; Healthy Volunteers; Humans; Male; Mental Recall; Methylphenidate; Modafinil; Nootropic Agents; Pharmaceutical Preparations
PubMed: 32709551
DOI: 10.1016/j.euroneuro.2020.07.002 -
CNS Spectrums Jul 2020Depression is considered to be the most difficult to treat phase of bipolar disorder as patients experience residual symptoms causing long-term disability. This work...
BACKGROUND
Depression is considered to be the most difficult to treat phase of bipolar disorder as patients experience residual symptoms causing long-term disability. This work aims to explore the role of add-on stimulant and stimulant-like medication in resistant bipolar depression patients.
METHODS
Systematic review of add-on stimulants and stimulant-like drugs in resistant bipolar depression by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analysis was performed using the random-effects models. Heterogeneity was evaluated with Cochran's Q and I2 statistics.
RESULTS
Six randomized controlled trials of add-on modafinil, armodafinil, and lisdexamphetamine (LDX) (n = 813) vs placebo (n = 815) in the treatment of resistant bipolar depression were included. These drugs were more likely to induce remission from an episode of resistant bipolar depression (relative risk [RR] = 1.37; 95% confidence interval [CI]: 1.06-1.77; number needed to treat for an additional beneficial outcome = 16). Moreover, they did not induce more dropouts than placebo (RR = 1.04; 95% CI: 0.91-1.18), nor did they increase the risk of adverse effects (53/772 vs 41/771) at the end of treatment (RR = 1.30; 95% CI: 0.81-2.10; number needed to treat for an additional harmful outcome = 62). Suicidality and manic switch were not affected by active treatment. Heterogeneity was low (Cochran's Q: P > .05), but sometimes with a large CI.
CONCLUSIONS
LDX, modafinil, and armodafinil seem to offer a reasonably well-tolerated and safe treatment in resistant bipolar depression. Treatment guidelines should, therefore, be revised to include these medications earlier in the therapeutic algorithm for resistant acute bipolar depression. Further research is, however, necessary for the elucidation of the clinical usefulness of these and other similar compounds.
PubMed: 32641179
DOI: 10.1017/S109285292000156X -
Psychopharmacology Aug 2020Agonist-based pharmacologic intervention is an accepted approach in treatment of opioid and tobacco use disorders. (Meta-Analysis)
Meta-Analysis
RATIONALE
Agonist-based pharmacologic intervention is an accepted approach in treatment of opioid and tobacco use disorders.
OBJECTIVES
We conducted a systematic review and meta-analysis to evaluate usefulness of an agonist approach as treatment of (psycho)stimulant use disorder (PSUD).
METHODS
We reviewed PubMed/Medline, LILACS, and ClinicalTrials.gov databases searching for randomized, double-blind, placebo-controlled, parallel-design studies evaluating outcomes of individuals treated for cocaine- or amphetamine-type substance use disorder. We combined results of all trials that included the following prescription psychostimulants (PPs): modafinil, methylphenidate, or amphetamines (mixed amphetamine salts, lisdexamphetamine, and dextroamphetamine). The combined sample consisted of 2889 patients. Outcomes of interest included the following: drug abstinence (defined as 2-3 weeks of sustained abstinence and the average maximum days of consecutive abstinence), percentage of drug-negative urine tests across trial, and retention in treatment. We conducted random-effects meta-analyses and assessed quality of evidence using the GRADE system.
RESULTS
Thirty-eight trials were included. Treatment with PPs increases rates of sustained abstinence [risk ratio (RR) = 1.45, 95% confidence interval (CI) = (1.10, 1.92)] and duration of abstinence [mean difference (MD) = 3.34, 95% CI = (1.06, 5.62)] in patients with PSUD, particularly those with cocaine use disorder (very low-quality evidence). Prescription amphetamines were particularly efficacious in promoting sustained abstinence in patients with cocaine use disorder [RR = 2.44, 95% CI = (1.66, 3.58)], and higher doses of PPs were particularly efficacious for treatment of cocaine use disorder [RR = 1.95, 95% CI = (1.38, 2.77)] (moderate-quality evidence). Treatment with prescription amphetamines also yielded more cocaine-negative urines [MD = 8.37%, 95% CI = (3.75, 12.98)]. There was no effect of PPs on the retention in treatment.
CONCLUSION
Prescription psychostimulants, particularly prescription amphetamines given in robust doses, have a clinically significant beneficial effect to promote abstinence in the treatment of individuals with PSUD, specifically the population with cocaine use disorder.
Topics: Amphetamine; Central Nervous System Stimulants; Cocaine; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Modafinil; Prescription Drugs; Randomized Controlled Trials as Topic; Substance-Related Disorders; Treatment Outcome
PubMed: 32601988
DOI: 10.1007/s00213-020-05563-3 -
Neurocritical Care Aug 2020Amantadine and modafinil are neurostimulants that may improve cognitive and functional recovery post-stroke, but the existing study results vary, and no comprehensive...
Amantadine and modafinil are neurostimulants that may improve cognitive and functional recovery post-stroke, but the existing study results vary, and no comprehensive review has been published. This systematic review describes amantadine and modafinil administration practices post-stroke, evaluates timing and impact on clinical effectiveness measures, and identifies the incidence of potential adverse drug effects. A librarian-assisted search of the MEDLINE (PubMed) and EMBASE databases identified all English-language publications with "amantadine" or "modafinil" in the title or abstract from inception through February 1, 2020. Publications meeting predefined Patient, Intervention, Comparator, Outcome (PICO) criteria were included: Patients (≥ 18 years of age post-stroke); Intervention (amantadine or modafinil administration); Comparison (pretreatment baseline or control group); Outcomes (cognitive or functional outcome). Amantadine and modafinil administration practices, cognitive and functional outcomes, and incidence of potential adverse drug effects were collected following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance. Quantitative analyses were not performed due to heterogeneity in the clinical effectiveness measures; descriptive data are presented as number (percent) or median (interquartile range). Of 12,620 publications initially identified, 10 amantadine publications (n = 121 patients) and 12 modafinil publications (n = 120 patients) were included. Amantadine was initiated 39 (16, 385) days post-stroke, with most common initial doses of 100 mg once or twice daily (range 100-200 mg/day), and final daily dose of 200 (188, 200) mg/day. Modafinil was initiated 170 (17, 496) days post-stroke, with initial and final daily doses of 100 (100, 350) mg/day and 200 (100, 350) mg/day, respectively. The most common indication was consciousness disorders for amantadine (n = 3/10 publications; 30%) and fatigue for modafinil (n = 5/12; 42%). Forty unique clinical effectiveness measures (1.8 per study) with 141 domains (6.4 per study) were described across all studies. A positive response in at least one clinical effectiveness measure was reported in 70% of amantadine publications and 83% of modafinil publications. Only one publication each for amantadine (10%; n = 5 patients) and modafinil (8%; n = 21 patients) studied acutely hospitalized or ICU patients; both were randomized studies showing improvements in neurocognitive function for amantadine and fatigue for modafinil. Potential adverse drug effects were reported in approximately 50% of publications, most commonly visual hallucinations with amantadine (2% of patients) and dizziness (5% of patients) and dry eyes or mouth (5% of patients). Amantadine and modafinil may improve cognitive and functional recovery post-stroke, but higher-quality data are needed to confirm this conclusion, especially in the acute care setting.
Topics: Amantadine; Central Nervous System Stimulants; Dopamine Agents; Humans; Modafinil; Recovery of Function; Stroke
PubMed: 32394130
DOI: 10.1007/s12028-020-00977-5 -
Therapeutic Drug Monitoring Apr 2020The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among...
BACKGROUND
The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among high-risk substance users. Various phenethylamines and NPS are also highly used in populations with mental disorders, depression, or attention deficit hyperactivity disorder (ADHD). Moreover, NPS use is highly prevalent among men and women with risky sexual behavior. Considering these specific populations and their frequent concurrent use of drugs, such as antidepressants, ADHD medication, and antiretrovirals, reports on potential interactions between these drugs, and phenethylamines 4-FA and 2C-B, were reviewed.
METHODS
The authors performed a systematic literature review on 4-FA and 2C-B interactions with antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, bupropion, venlafaxine, phenelzine, moclobemide, and tranylcypromine), ADHD medications (atomoxetine, dexamphetamine, methylphenidate, and modafinil), and antiretrovirals.
RESULTS
Limited literature exists on the pharmacokinetics and drug-drug interactions of 2C-B and 4-FA. Only one case report indicated a possible interaction between 4-FA and ADHD medication. Although pharmacokinetic interactions between 4-FA and prescription drugs remain speculative, their pharmacodynamic points toward interactions between 4-FA and ADHD medication and antidepressants. The pharmacokinetic and pharmacodynamic profile of 2C-B also points toward such interactions, between 2C-B and prescription drugs such as antidepressants and ADHD medication.
CONCLUSIONS
A drug-drug (phenethylamine-prescription drug) interaction potential is anticipated, mainly involving monoamine oxidases for 2C-B and 4-FA, with monoamine transporters being more specific to 4-FA.
Topics: Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Depressive Disorder; Dimethoxyphenylethylamine; Drug Interactions; Humans; Phenethylamines; Prescription Drugs
PubMed: 32022784
DOI: 10.1097/FTD.0000000000000725