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. 2017 Apr 1;174(4):341-348.
doi: 10.1176/appi.ajp.2016.16040467. Epub 2016 Oct 3.

The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder

Alexander Viktorin  1 , Eleonore Rydén  1 , Michael E Thase  1 , Zheng Chang  1 , Cecilia Lundholm  1 , Brian M D'Onofrio  1 , Catarina Almqvist  1 , Patrik K E Magnusson  1 , Paul Lichtenstein  1 , Henrik Larsson  1 , Mikael Landén  1
Affiliations

The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder

Alexander Viktorin et al. Am J Psychiatry. .

Erratum in

  • CORRECTION.
    [No authors listed] [No authors listed] Am J Psychiatry. 2016 Nov 1;173(11):1154. doi: 10.1176/appi.ajp.2016.17311correction. Am J Psychiatry. 2016. PMID: 27798994 No abstract available.

Abstract

Objective: The authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder.

Method: Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods.

Results: Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted.

Conclusions: No evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolar patients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.

Keywords: ADHD; Attention Deficit Hyperactivity Disorder; Bipolar disorder; Methylphenidate; Mood Disorders; Stimulants.

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Figures

Figure 1.
Figure 1.. Design of the study*
* The design permits within-individuai comparisons of mania after initiation of methylphenidate treatment with a preceding nontreatment period. The follow-up time is divided into 0–3 months and 3–6 months to assess both acute (switch) and longer-term effects.
See this image and copyright information in PMC

Comment in

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