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Journal of the American Academy of... Jan 2020To review all literature on the nonmedical use (NMU) and diversion of prescription stimulants to better understand the characteristics, risk factors, and outcomes of NMU...
OBJECTIVE
To review all literature on the nonmedical use (NMU) and diversion of prescription stimulants to better understand the characteristics, risk factors, and outcomes of NMU and to review risk-reduction strategies.
METHOD
We systematically searched PubMed, PsycINFO, and SCOPUS from inception to May 2018 for studies containing empirical data about NMU and diversion of prescription stimulants. Additional references identified by the authors were also assessed for inclusion.
RESULTS
A total of 111 studies met inclusion criteria. NMU and diversion of stimulants are highly prevalent; self-reported rates among population samples range from 2.1% to 58.7% and from 0.7% to 80.0%, respectively. A variety of terms are used to describe NMU, and most studies have examined college students. Although most NMU is oral, non-oral NMU also occurs. The majority of NMU is associated with no, or minor, medical effects; however, adverse medical outcomes, including death, occur in some individuals, particularly when administered by non-oral routes. Although academic and occupational performance enhancement are the most commonly cited motivations, there is little evidence that academic performance is improved by NMU in individuals without attention-deficit/hyperactivity disorder.
CONCLUSION
NMU of stimulants is a significant public health problem, especially in college students, but variations in the terms used to describe NMU and inconsistencies in the available data limit a better understanding of this problem. Further research is needed to develop methods to detect NMU, identify individuals at greatest risk, study routes of administration, and devise educational and other interventions to help reduce occurrence of NMU. Colleges should consider including NMU in academic integrity policies.
Topics: Central Nervous System Stimulants; Humans; Prescriptions; Risk Factors; Risk Reduction Behavior; Substance-Related Disorders
PubMed: 31326580
DOI: 10.1016/j.jaac.2019.06.012 -
BMJ Open Jul 2019The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain...
OBJECTIVE
The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI).
METHODS
We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science and Prospero (up to 10 December 2018) for published and unpublished evidence on the risks and benefits of 9 prespecified medications classes used to control agitated behaviours following TBI. We included all randomised controlled trials, quasi-experimental and observational studies examining the effects of medications administered to control agitated behaviours in TBI patients. Included studies were classified into three mutually exclusive categories: (1) agitated behaviour was the presenting symptom; (2) agitated behaviour was not the presenting symptom, but was measured as an outcome variable; and (3) safety of pharmacological interventions administered to control agitated behaviours was measured.
RESULTS
Among the 181 articles assessed for eligibility, 21 studies were included. Of the studies suggesting possible benefits, propranolol reduced maximum intensities of agitation per week and physical restraint use, methylphenidate improved anger measures following 6 weeks of treatment, valproic acid reduced weekly agitated behaviour scale ratings and olanzapine reduced irritability, aggressiveness and insomnia between weeks 1 and 3 of treatment. Amantadine showed variable effects and may increase the risk of agitation in the critically ill. In three studies evaluating safety outcomes, antipsychotics were associated with an increased duration of post-traumatic amnesia (PTA) in unadjusted analyses. Small sample sizes, heterogeneity and an unclear risk of bias were limits.
CONCLUSIONS
Propranolol, methylphenidate, valproic acid and olanzapine may offer some benefit; however, they need to be further studied. Antipsychotics may increase the length of PTA. More studies on tailored interventions and continuous evaluation of safety and efficacy throughout acute, rehabilitation and outpatient settings are needed.
PROSPERO REGISTRATION NUMBER
CRD42016033140.
Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Humans; Psychomotor Agitation; Psychoses, Substance-Induced; Randomized Controlled Trials as Topic
PubMed: 31289093
DOI: 10.1136/bmjopen-2019-029604 -
Neuropsychiatric Disease and Treatment 2019While there is a very high rate of comorbidity of autism and ADHD, there are controversies about prescribing stimulants in children with autism. This is a systematic... (Review)
Review
While there is a very high rate of comorbidity of autism and ADHD, there are controversies about prescribing stimulants in children with autism. This is a systematic review about the effect of stimulants on irritability in children with both autism and ADHD. A systematic review was conducted to study the possible effect of stimulants on irritability in autism and ADHD using the databases of PubMed, Scopus, EMBASE, and ScienceDirect in September 2018. Eligible clinical trials of stimulants in the treatment of Autism and ADHD without restriction of language were included. The primary outcome was irritability score. The full texts of relevant articles were studied, and their references were scanned for any possible related article. Out of 1,315 citations, there were 26 relevant articles. Of the relevant articles, 16 were not interventional studies and were excluded. There were 10 interventional studies. None of them considered irritability as a main outcome. Also, none of them studied the effect of stimulants on irritability in autism plus ADHD. Current uncontrolled evidence about the association of stimulants with irritability is controversial. The current evidence is not enough to support or discourage the effect of stimulants on irritability in children and adolescents with both autism and ADHD. Well-designed controlled clinical trials need to be conducted for this ignored research area.
PubMed: 31239689
DOI: 10.2147/NDT.S194022 -
Daru : Journal of Faculty of Pharmacy,... Dec 2019The study systematically reviewed the effectiveness of pharmacological treatments alone or combined with brief cognitive-behavioural therapy (BCBT) for treating Iranian... (Comparative Study)
Comparative Study
OBJECTIVES
The study systematically reviewed the effectiveness of pharmacological treatments alone or combined with brief cognitive-behavioural therapy (BCBT) for treating Iranian amphetamine abusers. The secondary aim was to review the efficacy of BCBT alone or combined with pharmacological treatments for treating amphetamine abusers in the world.
EVIDENCE ACQUISITION
Published trials were considered for inclusion. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Web of Science, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, Cochrane Drugs and Alcohol Group's Specialised Register of Trials, Embase, CINAHL, Scopus, PsychINFO, Iran Medex, Magiran and the Scientific Information Database were searched (January 2001 to March 2019). The reference lists of included studies were hand searched for more information. A systematic literature search in eight databases produced 10 trials.
RESULTS
Risperidone reduced positive psychotic symptoms while aripiprazole reduced negative psychotic symptoms. Methylphenidate reduced craving and depression compared with placebo. Topiramate reduced addiction severity and craving for methamphetamine abuse compared with placebo. Buprenorphine reduced methamphetamine craving more than methadone. Haloperidol and risperidone reduced psychosis. Riluzole reduced craving, withdrawal, and depression compared with placebo. Abstinence from amphetamine or reduction in amphetamine abuse was confirmed in four BCBT studies and one study which applied BCBT with a pharmacological treatment which were stable between two and 12-months. Other changes in BCBT studies were as follows: reduced polydrug use; drug injection, criminality and severity of amphetamine dependence at six-month follow-up; improved general functioning; mental health; stage of change as well as improved motivation to change in a pharmacological + BCBT study.
CONCLUSION
A review of trials indicates that pharmacological treatments and BCBT in a research setting outperform control conditions in treating amphetamines abuse and associated harms. Large-scale studies should determine if both treatments can be effective in clinical settings.
Topics: Amphetamine-Related Disorders; Aripiprazole; Clinical Trials as Topic; Cognitive Behavioral Therapy; Combined Modality Therapy; Humans; Iran; Methylphenidate; Risperidone
PubMed: 31228128
DOI: 10.1007/s40199-019-00282-3 -
Evidence-based Mental Health Aug 2019The comparative efficacy and tolerability of methylphenidate (MPH) and neurofeedback (NF) in individuals with attention-deficit/hyperactivity disorder (ADHD) remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The comparative efficacy and tolerability of methylphenidate (MPH) and neurofeedback (NF) in individuals with attention-deficit/hyperactivity disorder (ADHD) remains uncertain. This study aimed to fill this gap by means of a systematic review/meta-analysis.
METHODS
PubMed, OVID, ERIC, Web of Science, ClinialTrials.gov and a set of Chinese databases were searched until 22 August 2018. Standardised mean differences (SMD) were pooled using comprehensive meta-analysis software.
RESULTS
18 randomised controlled trials (RCTs) were included (778 individuals with ADHD in the NF arm and 757 in the MPH group, respectively; 13 studies in Chinese, five in English). At the study first endpoint, MPH was significantly more efficacious than NF on ADHD core symptoms (ADHD symptoms combined: SMD=-0.578, 95% CI (-1.063 to -0.092)) and on two neuropsychological parameters (inattention:-0.959 (-1.711 to -0.208); inhibition:-0.469 (-0.872 to -0.066)). Dropouts were significantly lower in NF versus MPH (OR=0.412, 0.186 to 0.913). Results were robust to sensitivity analyses, with two important exceptions: removing Chinese studies and non-funded studies, no differences emerged between MPH and NF, although the number of studies was small. At the study follow-up, MPH was superior to NF in some outcomes, but results were inconsistent across raters.
CONCLUSIONS
Due to the risk of bias of included studies, the results of the sensitivity analysis excluding Chinese and non-funded studies, and the mixed findings on at the follow-up endpoint, further high quality studies are needed to assess the comparative efficacy and acceptability of NF and MPH in individuals with ADHD.
TRIAL REGISTRATION NUMBER
CRD42018090256.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate; Neurofeedback; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic
PubMed: 31221690
DOI: 10.1136/ebmental-2019-300088 -
Current Neuropharmacology 2019Advances in basic and molecular biology have promoted the use of cell cultures in a wide range of areas, including the evaluation of drug efficacy, safety and toxicity. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Advances in basic and molecular biology have promoted the use of cell cultures in a wide range of areas, including the evaluation of drug efficacy, safety and toxicity.
OBJECTIVE
This article aims to provide a general overview of the methodological parameters of cell cultures used to investigate therapeutic options for Attention Deficit Hyperactivity Disorder.
METHOD
A systematic search was performed in the electronic databases PubMed, Scopus, and DOAJ. In vitro experimental studies using cell cultures were included.
RESULTS
A total of 328 studies were initially identified, with 16 included for qualitative synthesis. Seven studies used neuronal cells (SH-SY5Y neuroblastoma and PC12 cell line) and nine used nonneuronal cells. All the studies described the culture conditions, but most studies were inconsistent with regard to reporting results and raw data. Only one-third of the studies performed cell viability assays, while a further 30% conducted gene expression analysis. Other additional tests included electrophysiological evaluation and transporter activity. More than 50% of the studies evaluated the effects of drugs such as methylphenidate and atomoxetine, while plant extracts were assessed in four studies and polyunsaturated fatty acids in one.
CONCLUSION
We suggested a flowchart to guide the planning and execution of studies, and a checklist to be completed by authors to allow the standardized reporting of results. This may guide the elaboration of laboratory protocols and further in vitro studies.
Topics: Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Cell Culture Techniques; Cells, Cultured; Central Nervous System Stimulants; Child; Humans; Methylphenidate; Neurons
PubMed: 31079591
DOI: 10.2174/1570159X17666190409143155 -
Revista de Neurologia May 2019Methylphenidate is a widely-used drug for the treatment of attention deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders. Sustained-attention...
INTRODUCTION
Methylphenidate is a widely-used drug for the treatment of attention deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders. Sustained-attention deficits and poorer task performance in these disorders have been associated with default mode network (DMN) dysfunction in fMRI studies. DMN is a set of brain areas more activated during the resting-state. Under the execution of external tasks, there is an attenuation of DMN activity. In healthy individuals, DMN and task-positive network are anticorrelated. It has been suggested that methylphenidate could normalize the attenuated task-related DMN deactivation in attention- and inhibitory control-related disorders and that such normalization could improve task performance.
PATIENTS AND METHODS
To explore the hypothesis of DMN deactivation after methylphenidate administration, we conducted a systematic review of the literature.
RESULTS
After a systematic search, 12 studies were included in this review. For eligibility, studies were required to measure the effects of methylphenidate administration on the DMN activity. Eleven studies showed evidence of MPH-induced improvements in brain areas related to DMN. The results suggest a normalization of brain circuits in individuals with DMN dysfunction.
CONCLUSIONS
Our preliminary findings strongly suggest methylphenidate improves DMN dysfunction presented in ADHD and other neuropsychiatric disorders. Further studies are needed to better understand this effect and expand comprehension of methylphenidate action mechanisms.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate; Nerve Net; Task Performance and Analysis
PubMed: 31070233
DOI: 10.33588/rn.6810.2018487 -
BMJ Open Mar 2019To assess the methodological advantages and disadvantages of parallel and crossover designs in randomised clinical trials on methylphenidate for children and adolescents... (Meta-Analysis)
Meta-Analysis
Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder: a systematic review and meta-analyses.
OBJECTIVE
To assess the methodological advantages and disadvantages of parallel and crossover designs in randomised clinical trials on methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).
DESIGN
Secondary analyses of a Cochrane systematic review.
SETTING AND PARTICIPANTS
We searched relevant databases up to March 2015 and included data from parallel and crossover randomised trials assessing children and adolescents up to 18 years with ADHD.
INTERVENTIONS
Methylphenidate compared with placebo or no-treatment interventions.
PRIMARY AND SECONDARY OUTCOMES
The primary outcomes were teacher-rated ADHD symptoms and serious adverse events. The secondary outcomes were non-serious adverse events.
RESULTS
We included 38 parallel trials (n=5111) and 147 crossover trials (n=7134). When comparing methylphenidate with placebo or no-treatment on ADHD symptoms, we found no differences between the end of parallel trials and the first-period from crossover trials (Χ²=1.06, df=1, p=0.30, I²=5.5%). We also found no differences when combining the end of first-period crossover trials with the end of parallel trials and comparing them to the end of last-period crossover trials (Χ²=3.25, df=1, p=0.07, I²=69.2%). We found no differences in serious and non-serious adverse events, and no risk of period and carryover effects. However, only two trials contributed data to the latter analyses.
CONCLUSIONS
Both parallel and crossover trials seem suitable for investigating methylphenidate in children and adolescents with ADHD, with comparable estimates on ADHD symptom severity and adverse events. However, parallel trials might still offer ethical and statistical advantages over crossover trials.
Topics: Adolescent; Child; Female; Humans; Male; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Methylphenidate; Randomized Controlled Trials as Topic
PubMed: 30928951
DOI: 10.1136/bmjopen-2018-026478 -
Neuropsychiatric Disease and Treatment 2018This systematic review aimed to evaluate the efficacy of neurofeedback (NF) compared to stimulant medication in treating children and adolescents with... (Review)
Review
This systematic review aimed to evaluate the efficacy of neurofeedback (NF) compared to stimulant medication in treating children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Included in this review are eight randomized controlled trials that compared an NF condition, either alone or combined with medication, to a medication condition, which was mainly methylphenidate. Outcome measures included behavioral assessments by parents and teachers, self-reports, neurocognitive measures, electroencephalogram power spectra and event-related potentials. When only trials are considered that include probably blinded ratings or those that are sham-NF or semi-active controlled or those that employed optimally titration procedures, the findings do not support theta/beta NF as a standalone treatment for children or adolescents with ADHD. Nevertheless, an additive treatment effect of NF was observed on top of stimulants and theta/beta NF was able to decrease medication dosages, and both results were maintained at 6-month follow-up. This review concludes that the present role of NF in treating children diagnosed with ADHD should be considered as complementary in a multimodal treatment approach, individualized to the needs of the child, and may be considered a viable alternative to stimulants for a specific group of patients. Particularly patients with the following characteristics may benefit from NF treatment: low responders to medication, intolerable side effects due to medication, higher baseline theta power spectra and possibly having no comorbid psychiatric disorders. Future research should prioritize the identification of markers that differentiate responders from nonresponders to NF treatment, the potential of NF to decrease stimulant dosage, the standardization of NF treatment protocols and the identification of the most favorable neurophysiological treatment targets.
PubMed: 30464474
DOI: 10.2147/NDT.S178839 -
BMJ Open Science 2018Attention-deficit/hyperactivity disorder (ADHD) is a prevalent condition related to several negative outcomes, and its pathophysiology is still poorly understood. The...
Behavioural effects of methylphenidate in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis protocol.
INTRODUCTION
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent condition related to several negative outcomes, and its pathophysiology is still poorly understood. The spontaneously hypertensive rats (SHRs) are the most commonly used animal model of ADHD. How ever, its validity, and especially its predictive validity, has been questioned. Therefore, the current protocol discloses the background, aims and methods of a systematic review and meta-analysis of studies reporting the behavioural effects of methylphenidate (MPH), the most commonly prescribed treatment for ADHD, in the SHR.
SEARCH STRATEGY
Studies will be identified through a literature search using three different electronic databases: Medline, Embase and Web of Science. There will be no language restrictions. All s tudies that administered MPH to SHR and evaluated locomotion, attention, impulsivity or memory will be included.
SCREENING AND ANNOTATION
Studies will be prescreened based on title and abstract, and a full-text review will be performed if necessary. Screening will be performed by two authors, and any disagreement will be discussed with a third author.
DATA MANAGEMENT AND REPORTING
Data extraction will be performed by two independent authors according to a standardised form. Studies will be grouped according to the behavioural outcomes reported, and a meta-analysis will be performed for each group. The influence of predefined covariates on the effects of MPH will be evaluated using meta-regression and sensitivity analyses. Data will be reported following PRISMA guidelines.
PubMed: 35047675
DOI: 10.1136/bmjos-2018-000001