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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 -
JAMA Psychiatry Feb 2024Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose escalation beyond US Food and Drug Administration recommendations is associated with positive risk benefits is unclear.
OBJECTIVE
To investigate the impact, based on averages, of stimulant doses on treatment outcomes in adults with ADHD and to determine, based on averages, whether unlicensed doses are associated with positive risk benefits compared with licensed doses.
DATA SOURCES
Twelve databases, including published (PubMed, Cochrane Library, Embase, Web of Sciences) and unpublished (ClinicalTrials.gov) literature, up to February 22, 2023, without language restrictions.
STUDY SELECTION
Two researchers independently screened records to identify double-blinded randomized clinical trials of stimulants against placebo in adults (18 years and older) with ADHD.
DATA EXTRACTION AND SYNTHESIS
Aggregate data were extracted and synthesized in random-effects dose-response meta-analyses and network meta-analyses.
MAIN OUTCOME MEASURES
Change in ADHD symptoms and discontinuations due to adverse events.
RESULTS
A total of 47 randomized clinical trials (7714 participants; mean age, 35 (SD, 11) years; 4204 male [56%]) were included. For methylphenidate, dose-response curves indicated additional reductions of symptoms with increments in doses, but the gains were progressively smaller and accompanied by continued additional risk of adverse events dropouts. Network meta-analyses showed that unlicensed doses were associated with greater reductions of symptoms compared with licensed doses (standardized mean difference [SMD], -0.23; 95% CI, -0.44 to -0.02; very low certainty of evidence), but the additional gain was small and accompanied by increased risk of adverse event dropouts (odds ratio, 2.02; 95% CI, 1.19-3.43; moderate certainty of evidence). For amphetamines, the dose-response curve approached a plateau and increments in doses did not indicate additional reductions of symptoms, but there were continued increments in the risk of adverse event dropouts. Network meta-analysis did not identify differences between unlicensed and licensed doses for reductions of symptoms (SMD, -0.08; 95% CI, -0.24 to 0.08; very low certainty of evidence).
CONCLUSIONS AND RELEVANCE
Based on group averages, unlicensed doses of stimulants may not have positive risk benefits compared with licensed doses for adults with ADHD. In general, practitioners should consider unlicensed doses cautiously. Practitioners may trial unlicensed doses if needed and tolerated but should be aware that there may not be large gains in the response to the medication with those further increments in dose. However, the findings are averages and will not generalize to every patient.
Topics: Adult; Male; Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Amphetamines; Treatment Outcome
PubMed: 37878348
DOI: 10.1001/jamapsychiatry.2023.3985 -
The Cochrane Database of Systematic... Apr 2023Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity,... (Review)
Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity, and impulsivity, and is associated with long-term social, academic, and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Research has shown that children and adolescents with ADHD have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA. These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD. This review is an update of a previously published Cochrane Review. Overall, there was little evidence that PUFA supplementation improved symptoms of ADHD in children and adolescents.
OBJECTIVES
To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents.
SEARCH METHODS
We searched 13 databases and two trials registers up to October 2021. We also checked the reference lists of relevant studies and reviews for additional references.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials that compared PUFA with placebo or PUFA plus alternative therapy (medication, behavioural therapy, or psychotherapy) with the same alternative therapy alone in children and adolescents (aged 18 years and under) diagnosed with ADHD.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was severity or improvement of ADHD symptoms. Our secondary outcomes were severity or incidence of behavioural problems; quality of life; severity or incidence of depressive symptoms; severity or incidence of anxiety symptoms; side effects; loss to follow-up; and cost. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 37 trials with more than 2374 participants, of which 24 trials were new to this update. Five trials (seven reports) used a cross-over design, while the remaining 32 trials (52 reports) used a parallel design. Seven trials were conducted in Iran, four each in the USA and Israel, and two each in Australia, Canada, New Zealand, Sweden, and the UK. Single studies were conducted in Brazil, France, Germany, India, Italy, Japan, Mexico, the Netherlands, Singapore, Spain, Sri Lanka, and Taiwan. Of the 36 trials that compared a PUFA to placebo, 19 used an omega-3 PUFA, six used a combined omega-3/omega-6 supplement, and two used an omega-6 PUFA. The nine remaining trials were included in the comparison of PUFA to placebo, but also had the same co-intervention in the PUFA and placebo groups. Of these, four trials compared a combination of omega-3 PUFA plus methylphenidate to methylphenidate. One trial each compared omega-3 PUFA plus atomoxetine to atomoxetine; omega-3 PUFA plus physical training to physical training; and an omega-3 or omega-6 supplement plus methylphenidate to methylphenidate; and two trials compared omega-3 PUFA plus dietary supplement to dietary supplement. Supplements were given for a period of between two weeks and six months. Although we found low-certainty evidence that PUFA compared to placebo may improve ADHD symptoms in the medium term (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.47 to 2.60; 3 studies, 191 participants), there was high-certainty evidence that PUFA had no effect on parent-rated total ADHD symptoms compared to placebo in the medium term (standardised mean difference (SMD) -0.08, 95% CI -0.24 to 0.07; 16 studies, 1166 participants). There was also high-certainty evidence that parent-rated inattention (medium-term: SMD -0.01, 95% CI -0.20 to 0.17; 12 studies, 960 participants) and hyperactivity/impulsivity (medium-term: SMD 0.09, 95% CI -0.04 to 0.23; 10 studies, 869 participants) scores were no different compared to placebo. There was moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups (RR 1.02, 95% CI 0.69 to 1.52; 8 studies, 591 participants). There was also moderate-certainty evidence that medium-term loss to follow-up was likely similar between groups (RR 1.03, 95% CI 0.77 to 1.37; 13 studies, 1121 participants).
AUTHORS' CONCLUSIONS
Although we found low-certainty evidence that children and adolescents receiving PUFA may be more likely to improve compared to those receiving placebo, there was high-certainty evidence that PUFA had no effect on total parent-rated ADHD symptoms. There was also high-certainty evidence that inattention and hyperactivity/impulsivity did not differ between PUFA and placebo groups. We found moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups. There was also moderate-certainty evidence that follow-up was similar between groups. It is important that future research addresses the current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, and short follow-up times.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Quality of Life; Fatty Acids, Unsaturated; Methylphenidate; Fatty Acids, Omega-3; Amphetamine
PubMed: 37058600
DOI: 10.1002/14651858.CD007986.pub3 -
Annals of Internal Medicine Nov 2020Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries.
PURPOSE
To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs).
DATA SOURCES
MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020.
STUDY SELECTION
Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries.
DATA EXTRACTION
Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
DATA SYNTHESIS
The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence).
LIMITATIONS
Only English-language studies were included. The number of head-to-head comparisons was limited.
CONCLUSION
Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms.
PRIMARY FUNDING SOURCE
National Safety Council. (PROSPERO: CRD42018094412).
Topics: Acetaminophen; Acute Pain; Administration, Oral; Administration, Topical; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Comparative Effectiveness Research; Diclofenac; Drug Eruptions; Gastrointestinal Diseases; Humans; Musculoskeletal System; Nervous System Diseases; Network Meta-Analysis; Patient Satisfaction; Physical Functional Performance; Randomized Controlled Trials as Topic
PubMed: 32805127
DOI: 10.7326/M19-3601 -
Expert Opinion on Pharmacotherapy 2023The data suggests that in children and adolescents, bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) may be strongly correlated. Even though... (Review)
Review
INTRODUCTION
The data suggests that in children and adolescents, bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) may be strongly correlated. Even though drugs for ADHD and BD are largely accepted, there is relatively little research on the management of comorbidity in children and adolescents, particularly in terms of safety. We provide a synthesis of these findings because one hasn't been made yet.
AREAS COVERED
As a primary outcome, we wanted to determine whether stimulant or non-stimulant treatment of children and adolescents with ADHD and comorbid BD was effective. As a secondary outcome, we wanted to determine tolerability, especially the risk of mood switch.
EXPERT OPINION
The findings of this systematic review suggest that methylphenidate, when used with a mood stabilizer, may be safe and not significantly increase the risk of a manic switch or psychotic symptoms when used to treat ADHD that co-occurs with a BD. In situations where stimulants are ineffective or have low tolerance, atomoxetine also seems to be a good alternative, and also in cases of co-morbid anxiety, oppositional defiant disorder, conduct disorders, ICT disorders, and substance use disorders. Additional research with a higher level of evidence is necessary to corroborate these preliminary findings.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Atomoxetine Hydrochloride; Methylphenidate; Central Nervous System Stimulants
PubMed: 37300473
DOI: 10.1080/14656566.2023.2224920 -
European Neuropsychopharmacology : the... Jul 2023Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal... (Meta-Analysis)
Meta-Analysis
Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.
Topics: Humans; Selegiline; Depressive Disorder, Major; Monoamine Oxidase Inhibitors; Attention Deficit Disorder with Hyperactivity; Methylphenidate
PubMed: 37087864
DOI: 10.1016/j.euroneuro.2023.03.012 -
Progress in Neuro-psychopharmacology &... Jul 2023Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with cognitive, social, and academic impairment. Neurotrophins, particularly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with cognitive, social, and academic impairment. Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), have been implicated in the pathophysiology of ADHD and response to stimulant treatment. This review aims to investigate the relationship between BDNF levels in ADHD before and after treatment with stimulants in childhood.
METHODS
This systematic review followed PRISMA-P guidelines and included 19 studies from PubMed, EMBASE, Cochrane, Capes Periodic, and Lilacs databases. The studies were evaluated for risk of bias and level of evidence.
RESULTS
There was no significant difference in peripheral BDNF levels in ADHD children before or after methylphenidate treatment. Additionally, there was no statistically significant difference in BDNF levels between children with ADHD and controls.
DISCUSSION
Understanding the role of BDNF in ADHD may provide insight into the disorder's pathophysiology and facilitate the development of biological markers for clinical use.
CONCLUSION
Our findings suggest that BDNF levels are not significantly affected by methylphenidate treatment in ADHD children and do not differ from controls.
SYSTEMATIC REVIEW REGISTRATION
"Brain-derived neurotrophic factor (BDNF) levels in children and adolescents before and after stimulant use: a systematic review". Number CRD42021261519.
Topics: Adolescent; Child; Humans; Attention Deficit Disorder with Hyperactivity; Brain-Derived Neurotrophic Factor; Central Nervous System Stimulants; Methylphenidate
PubMed: 37044279
DOI: 10.1016/j.pnpbp.2023.110761 -
Journal of Attention Disorders Oct 2023To report the characteristics associated with response to methylphenidate (MPH) in children and adolescents with ADHD. (Review)
Review
OBJECTIVE
To report the characteristics associated with response to methylphenidate (MPH) in children and adolescents with ADHD.
METHODS
Studies reporting potentials predictors of response to MPH were searched in Medline and Embase from January 1998 to March 2022. Narrative synthesis was performed.
RESULTS
Fifty-seven reports of 46 studies totaling 6,656 ADHD patients were included. No association appears between response to MPH and age, gender, MPH dosage, ADHD subtype, comorbidities nor socioeconomic status when considering a specific patient. No conclusion could be drawn about body weight, ADHD severity, intelligence quotient, and parental symptoms of depression or ADHD.
CONCLUSIONS
None of these potential predictors have proven their usefulness to predict response to MPH on an individual basis in clinical practice. In research, potential predictors should be measured, their association with response to MPH assessed, in order to control for confounding variables when modeling response to MPH.
Topics: Humans; Child; Adolescent; Methylphenidate; Central Nervous System Stimulants; Attention Deficit Disorder with Hyperactivity; Intelligence Tests; Parents; Treatment Outcome
PubMed: 37243373
DOI: 10.1177/10870547231177234 -
Alcohol-medication interactions: A systematic review and meta-analysis of placebo-controlled trials.Neuroscience and Biobehavioral Reviews Jan 2022Alcohol and other xenobiotics may limit the therapeutic effects of medications. We aimed at investigating alcohol-medication interactions (AMI) after the exclusion of... (Meta-Analysis)
Meta-Analysis Review
Alcohol and other xenobiotics may limit the therapeutic effects of medications. We aimed at investigating alcohol-medication interactions (AMI) after the exclusion of confounding effects related to other xenobiotics. We performed a systematic review and meta-analysis of controlled studies comparing the effects induced by alcohol versus placebo on pharmacodynamic and/or pharmacokinetic parameters of approved medications. Certainty in the evidence of AMI was assessed when at least 3 independent studies and at least 200 participants were available. We included 107 articles (3097 participants): for diazepam, cannabis, opioids, and methylphenidate, we found significant AMI and enough data to assign the certainty of evidence. Alcohol consumption significantly increases the peak plasma concentration of diazepam (low certainty; almost 290 participants), cannabis (high certainty; almost 650 participants), opioids (low certainty; 560 participants), and methylphenidate (moderate certainty; 290 participants). For most medications, we found some AMI but not enough data to assign them the certainty grades; for some medications, we found no differences between alcohol and placebo in any outcomes evaluated. Our results add further evidence for interactions between alcohol and certain medications after the exclusion of confounding effects related to other xenobiotics. Physicians should advise patients who use these specific medications to avoid alcohol consumption. Further studies with appropriate control groups, enough female participants to investigate sex differences, and elderly population are needed to expand our knowledge in this field. Short phrases suitable for indexing terms.
Topics: Aged; Female; Humans; Methylphenidate; Randomized Controlled Trials as Topic
PubMed: 34826511
DOI: 10.1016/j.neubiorev.2021.11.019 -
Psychological Medicine Jan 2022There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This... (Meta-Analysis)
Meta-Analysis Review
There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63-2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06-1.56), guanfacine (OR = 1.43, 95% CI = 1.12-1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09-1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.
Topics: Child; Humans; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Guanfacine; Central Nervous System Stimulants; Methylphenidate; Drug-Related Side Effects and Adverse Reactions; Comorbidity; Headache; Randomized Controlled Trials as Topic
PubMed: 34635194
DOI: 10.1017/S0033291721004141