Stimulant Dosing in the Community Treatment of Adult Attention-Deficit/Hyperactivity Disorder

Olfson, Mark; Marcus, Steven C.; Zhang, Huabin F.; Wan, George J.

doi:10.1097/jcp.0b013e31816740be

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…Scrutiny has increased, in part, due to the burgeoning use of prescription stimulants among adults [1-3]. Older adults using prescription stimulants [4] may be particularly vulnerable to adverse cardiovascular events, given their higher background rate of cardiovascular events and comorbid conditions, higher doses of stimulants [2,5], and slower drug elimination [6]. …”

Section: Introductionmentioning

confidence: 99%

Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review

Westover

Halm

2012

BMC Cardiovasc Disord

125

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BackgroundThere is increasing concern that prescription stimulants may be associated with adverse cardiovascular events such as stroke, myocardial infarction, and sudden death. Public health concerns are amplified by increasing use of prescription stimulants among adults.MethodsThe objective of this study was to conduct a systematic review of the evidence of an association between prescription stimulant use and adverse cardiovascular outcomes. PUBMED, MEDLINE, EMBASE and Google Scholar searches were conducted using key words related to these topics (MESH): ADHD; Adults; Amphetamine; Amphetamines; Arrhythmias, Cardiac; Cardiovascular Diseases; Cardiovascular System; Central Nervous Stimulants; Cerebrovascular; Cohort Studies; Case–control Studies; Death; Death, Sudden, Cardiac; Dextroamphetamine; Drug Toxicity; Methamphetamine; Methylphenidate; Myocardial Infarction; Stimulant; Stroke; Safety. Eligible studies were population-based studies of children, adolescents, or adults using prescription stimulant use as the independent variable and a hard cardiovascular outcome as the dependent variable.ResultsTen population-based observational studies which evaluated prescription stimulant use with cardiovascular outcomes were reviewed. Six out of seven studies in children and adolescents did not show an association between stimulant use and adverse cardiovascular outcomes. In contrast, two out of three studies in adults found an association.ConclusionsFindings of an association between prescription stimulant use and adverse cardiovascular outcomes are mixed. Studies of children and adolescents suggest that statistical power is limited in available study populations, and the absolute risk of an event is low. More suggestive of a safety signal, studies of adults found an increased risk for transient ischemic attack and sudden death/ventricular arrhythmia. Interpretation was limited due to differences in population, cardiovascular outcome selection/ascertainment, and methodology. Accounting for confounding and selection biases in these studies is of particular concern. Future studies should address this and other methodological issues.

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Section: Introductionmentioning

confidence: 99%

Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review

Westover

Halm

2012

BMC Cardiovasc Disord

125

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“…Other strategies to augment response to stimulants (eg, switching to other stimulant class) should be considered and may be implemented rather than simply raising the dose beyond the licensed range . Therefore, our study provides support for expert opinion that licensed doses may be sufficient for most patients and calls into question the widespread use of unlicensed doses in routine practice, despite earlier reports …”

Section: Discussionmentioning

confidence: 55%

“…10 Therefore, our study provides support for expert opinion that licensed doses may be sufficient for most patients 10,11,48 and calls into question the widespread use of unlicensed doses in routine practice, 49 despite earlier reports. 50 The quality of evidence was not high, which underscores the importance of additional studies evaluating the impact of unlicensed doses of stimulants on the treatment outcomes of adults with ADHD. Flexible-dose RCTs may be particularly appropriate to study the risk-benefits of escalation to unlicensed doses because they ensure that participants receive optimal doses.…”

Section: Discussionmentioning

confidence: 99%

Treatment Outcomes With Licensed and Unlicensed Stimulant Doses for Adults With Attention-Deficit/Hyperactivity Disorder

Farhat,

Flores,

Avila-Quintero

et al. 2024

JAMA Psychiatry

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ImportanceStimulants (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.ObjectiveTo 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 SourcesTwelve databases, including published (PubMed, Cochrane Library, Embase, Web of Sciences) and unpublished (ClinicalTrials.gov) literature, up to February 22, 2023, without language restrictions.Study SelectionTwo 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 SynthesisAggregate data were extracted and synthesized in random-effects dose-response meta-analyses and network meta-analyses.Main Outcome MeasuresChange in ADHD symptoms and discontinuations due to adverse events.ResultsA 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 RelevanceBased 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.

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Risk of Incident Psychosis and Mania With Prescription Amphetamines

Moran,

Skinner,

Shinn

et al. 2024

AJP

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Stimulant Dosing in the Community Treatment of Adult Attention-Deficit/Hyperactivity Disorder

Cited by 3 publications

References 13 publications

Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review

Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review

Treatment Outcomes With Licensed and Unlicensed Stimulant Doses for Adults With Attention-Deficit/Hyperactivity Disorder

Risk of Incident Psychosis and Mania With Prescription Amphetamines

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