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The Cochrane Database of Systematic... Jan 2021Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial.
OBJECTIVES
To evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults.
SEARCH METHODS
In January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI.
MAIN RESULTS
We included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks. IR methylphenidate versus placebo We found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD -20.70, 95% CI -23.97 to -17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD -0.59, 95% CI -1.25 to 0.06; I = 69%; 2 trials, 138 participants; end scores). There is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD -0.57, 95% CI -0.85 to -0.28; 2 trials, 139 participants; I = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD -0.94, 95% CI -1.37 to -0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD -0.20, 95% CI -4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI -0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo. IR methylphenidate versus lithium Compared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI -3.11 to 4.31; 1 trial, 46 participants; end scores; Conners' Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD -0.80, 95% CI -4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD -1.20, 95% CI -3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium. Adverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively. We considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest.
AUTHORS' CONCLUSIONS
We found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.
Topics: Adult; Antidepressive Agents, Second-Generation; Anxiety; Attention Deficit Disorder with Hyperactivity; Bias; Bupropion; Central Nervous System Stimulants; Depression; Drug Delivery Systems; Female; Flavonoids; Humans; Lithium Compounds; Male; Methylphenidate; Middle Aged; Placebos; Plant Extracts; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33460048
DOI: 10.1002/14651858.CD013011.pub2 -
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 -
PloS One 2020This comprehensive review examined sex differences in prescription rates and efficacy or effectiveness of pharmacotherapy treatment in girls and women with attention...
OBJECTIVE
This comprehensive review examined sex differences in prescription rates and efficacy or effectiveness of pharmacotherapy treatment in girls and women with attention deficit hyperactivity disorder (ADHD), while identifying gaps in the scientific knowledge on this topic.
METHOD
A rigorous electronic database search was carried out in order to identify all published studies on female-specific effects of stimulants and non-stimulants in the treatment of ADHD. In total, 2672 studies were screened of which 21 studies (seven on prescription rates, 14 on effects of pharmacotherapy) met the inclusion criteria and were included for analysis.
RESULTS
In all seven studies on ADHD prescription rates, girls received significantly less prescriptions than boys, a difference however no longer seen in adults with the exception of one study. Each of the 14 studies on effectiveness / efficacy found at least one sex-difference in the effects of ADHD pharmacotherapy.
CONCLUSION
Several sex-differences are demonstrated in the prescription, usage and efficacy /effectiveness of both stimulant and non-stimulant ADHD pharmacotherapy. A single daily use of MPH may possibly not be optimal for girls with ADHD and ATX may be a promising medication for girls and women with ADHD. The robustness of this result requires further investigation.
Topics: Adolescent; Adult; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Databases, Factual; Drug Prescriptions; Female; Humans; Male; Men; Methylphenidate; Sex Characteristics; Young Adult
PubMed: 32946507
DOI: 10.1371/journal.pone.0239257 -
Journal of the American College of... Aug 2020Although the prevalence of attention-deficit/hyperactivity disorder (ADHD) has been stable over the past 3 decades, prescriptions of sympathomimetic stimulants have...
Although the prevalence of attention-deficit/hyperactivity disorder (ADHD) has been stable over the past 3 decades, prescriptions of sympathomimetic stimulants have steadily increased in the United States. This study consisted of a systematic review of PubMed articles screened for ADHD medications and potential cardiovascular toxicity as well as nondrug strategies for managing ADHD. The cumulative body of data showed that ADHD medications cause modest elevations in resting heart rate and blood pressure. Other adverse effects reported with ADHD stimulants included arrhythmia, nonischemic cardiomyopathy, Takotsubo cardiomyopathy, and sudden death. However, such reports did not imply causation, and there was a paucity of randomized trial evidence addressing long-term safety of ADHD medications, particularly among adults. Further studies are essential to clarify the risks and benefits of ADHD stimulant medications and to explore nonpharmacological options, including regular exercise and omega-3 fatty acids, which could be helpful for improving ADHD symptoms.
Topics: Attention Deficit Disorder with Hyperactivity; Cardiovascular Diseases; Cardiovascular System; Central Nervous System Stimulants; Humans
PubMed: 32792083
DOI: 10.1016/j.jacc.2020.05.081 -
World Psychiatry : Official Journal of... Jun 2020Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental dis-orders in this age...
Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects.
Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental dis-orders in this age group and are used not infrequently off-label. However, the adverse effects of these medications require special attention during developmentally sensitive periods of life. For this meta-review, we systematically searched network meta-analyses and meta-analyses of randomized controlled trials (RCTs), individual RCTs, and cohort studies reporting on 78 a priori selected adverse events across 19 categories of 80 psychotropic medications - including antidepressants, antipsychotics, anti-attention-deficit/hyperactivity disorder (ADHD) medications and mood stabilizers - in children and adolescents with mental disorders. We included data from nine network meta-analyses, 39 meta-analyses, 90 individual RCTs, and eight cohort studies, including 337,686 children and adolescents. Data on ≥20% of the 78 adverse events were available for six antidepressants (sertraline, escitalopram, paroxetine, fluoxetine, venlafaxine and vilazodone), eight antipsychotics (risperidone, quetiapine, aripiprazole, lurasidone, paliperidone, ziprasidone, olanzapine and asenapine), three anti-ADHD medications (methylphenidate, atomoxetine and guanfacine), and two mood stabilizers (valproate and lithium). Among these medications with data on ≥20% of the 78 adverse events, a safer profile emerged for escitalopram and fluoxetine among antidepressants, lurasidone for antipsychotics, methylphenidate among anti-ADHD medications, and lithium among mood stabilizers. The available literature raised most concerns about the safety of venlafaxine, olanzapine, atomoxetine, guanfacine and valproate. Nausea/vomiting and discontinuation due to adverse event were most frequently associated with antidepressants; sedation, extrapyramidal side effects, and weight gain with antipsychotics; anorexia and insomnia with anti-ADHD medications; sedation and weight gain with mood stabilizers. The results of this comprehensive and updated quantitative systematic meta-review of top-tier evidence regarding the safety of antidepressants, antipsychotics, anti-ADHD medications and mood stabilizers in children and adolescents can inform clinical practice, research and treatment guidelines.
PubMed: 32394557
DOI: 10.1002/wps.20765 -
CNS Drugs Apr 2020Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions.
METHODS
We systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use.
RESULTS
Our search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use.
CONCLUSIONS
No pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.
Topics: Amphetamine; Amphetamine-Related Disorders; Animals; Central Nervous System Stimulants; Humans; Methamphetamine; Substance-Related Disorders
PubMed: 32185696
DOI: 10.1007/s40263-020-00711-x -
Frontiers in Neurology 2019Aggression is a commonly reported problem following traumatic brain injury (TBI). It may present as verbal insults or outbursts, physical assaults, and/or property...
Aggression is a commonly reported problem following traumatic brain injury (TBI). It may present as verbal insults or outbursts, physical assaults, and/or property destruction. Aggressive behavior can fracture relationships and impede participation in treatment as well as a broad range of vocational and social activities, thereby reducing the individual's quality of life. Pharmacological intervention is frequently used to control aggression following TBI. The aim of this systematic review was to critically evaluate the evidence regarding efficacy of pharmacological interventions for aggression following TBI in adults. We reviewed studies in English, available before December 2018. MEDLINE, PubMed, CINAHL, EMBASE, PsycINFO, and CENTRAL databases were searched, with additional searching of key journals, clinical trials registries, and international drug regulators. The primary outcomes of interest were reduction in the severity of aggression and occurrence of harms. The secondary outcomes of interest were changes in quality of life, participation, psychological health (e.g., depression, anxiety), and cognitive function. Evidence quality was assessed using the Cochrane Risk of Bias tool and the Joanna Briggs Institute Critical Appraisal Instruments. Ten studies were identified, including five randomized controlled trials (RCTs) and five case series. There were positive, albeit mixed, findings for the RCTs examining the use of amantadine in reducing irritability ( = 2) and aggression ( = 2). There were some positive findings favoring methylphenidate in reducing anger ( = 1). The evidence for propranolol was weak ( = 1). Individual analysis revealed differential drug response across individuals for both methylphenidate and propranolol. The less rigorous studies administered carbamazepine ( = 2), valproic acid ( = 1), quetiapine ( = 1), and sertraline ( = 1), and all reported reductions in aggression. However, given the lack of a control group, it is difficult to discern treatment effects from natural change over time. This review concludes that a recommendation for use of amantadine to treat aggression and irritability in adults following TBI is appropriate. However, there is a need for further well-designed, adequately powered and controlled studies of pharmacological interventions for aggression following TBI.
PubMed: 31849802
DOI: 10.3389/fneur.2019.01169 -
Scientific Reports Nov 2019Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with intellectual disability in children, and may further compromise learning. Methylphenidate is a... (Meta-Analysis)
Meta-Analysis
Therapeutic effects of methylphenidate for attention-deficit/hyperactivity disorder in children with borderline intellectual functioning or intellectual disability: A systematic review and meta-analysis.
Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with intellectual disability in children, and may further compromise learning. Methylphenidate is a first-line treatment for ADHD, however no previous meta-analysis has evaluated its overall efficacy for ADHD in children with comorbid intellectual disability (ID) or borderline intellectual functioning. The PubMed/MEDLINE, Cochrane CENTRAL and ScienceDirect databases were systematically searched from inception through 2018/7/15 for clinical studies that investigated the effects of methylphenidate in children with ADHD and ID. A random-effects model meta-analysis was used for data synthesis. Eight studies (average Jadad score = 2.5) enrolling 242 participants receiving methylphenidate and 181 participants receiving placebo were included. The meta-analysis showed that methylphenidate led to a significant improvement in ADHD symptoms relative to placebo (Hedges' g = 0.878, p < 0.001). Meta-regression analysis pointed to an association between the dose of methylphenidate and overall improvement in ADHD severity (slope = 1.334, p < 0.001). Finally, there was no significant difference in drop-out rate [odds ratio (OR) = 1.679, p = 0.260] or rate of treatment discontinuation due to adverse events (OR = 4.815, p = 0.053) between subjects receiving methylphenidate and those taking placebos. Our study suggests that methylphenidate retains its efficacy in children with ADHD and borderline intellectual functioning or ID.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Intellectual Disability; Methylphenidate; Odds Ratio; Placebo Effect; Severity of Illness Index; Treatment Outcome
PubMed: 31685858
DOI: 10.1038/s41598-019-52205-6 -
Frontiers in Pharmacology 2019Apathy is one of the most prevalent neuropsychiatric symptoms encountered in Alzheimer's disease (AD) and may be an early sign in the development of dementia persisting...
Apathy is one of the most prevalent neuropsychiatric symptoms encountered in Alzheimer's disease (AD) and may be an early sign in the development of dementia persisting over the disease course. It has been associated with poor disease outcome, impaired daily functioning, and significant caregiver distress. Early diagnosis and timely treatment of apathy in AD are of great importance. However, approved agents for apathy are still missing. Within this context, we conducted an extensive electronic search in the databases included in the National Library of Medicine, PsychInfo, and Google Scholar for studies that have investigated the effect of pharmacological treatments in apathy in AD. There were no limitations regarding study design and all care settings were considered for inclusion. Structured measures for level of evidence and study quality were employed to evaluate the results. A total of 1,607 records were identified; 1,483 records remained after the removal of duplicates and were screened; 166 full-text articles were selected and assessed for eligibility and a remaining 90 unique studies and relevant reviews were included in the qualitative synthesis. Acetylcholinesterase inhibitors, gingko biloba, and methylphenidate were found to be successful in reducing apathy in patients with AD. Methodological heterogeneity in the studies and the small amount of studies where apathy was the primary outcome are limiting factors to assess for group effects. Pharmacological treatment of apathy in AD is an underexplored field. Standardized and systematic efforts are needed to establish a possible treatment benefit. Elucidating the pathophysiology of apathy and its components or subtypes will inform disease models and mechanistic drug studies that can quantify a benefit from specific agents for specific AD groups.
PubMed: 31680942
DOI: 10.3389/fphar.2019.01108 -
Current Neuropharmacology 2020To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia.
OBJECTIVE
To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia.
METHODS
We conducted two researches on the PubMed, Scopus and Embase using the keywords ("elderly") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine") and then ("Alzheimer" OR "dementia") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine").
RESULTS
Twenty-nine papers met all the eligibility criteria. The results are encouraging as 81.5% of the studies showed clinical improvement of the investigated condition.
CONCLUSION
Amphetamines and methylphenidate are probably effective strategies for different conditions in the elderly population. However, further studies are needed to provide more robust evidence on efficacy, dosage and safety for this population.
Topics: Aged; Amphetamine; Dementia; Depressive Disorder, Major; Humans; Lisdexamfetamine Dimesylate; Methylphenidate
PubMed: 31660835
DOI: 10.2174/1570159X17666191010093021