Methylphenidate does not lead to treatment-emergent mania in bipolar patients who concomitantly receive mood-stabilizing medication, according to a new Swedish study.

Alexander Viktorin, PhD, of the Karolinska Institute in Stockholm and colleagues used Swedish national registries to identify 2 307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was then divided into patients who were or were not taking concomitant mood stabilizing medications (n=1 103 and n=718, respectively). Patients were required to have a period of nine months without receiving any doses of methylphenidate prior to medication initiation.

The researchers adjusted for individual-specific confounders, such as disorder severity, genetic makeup, and early environmental factors. The rate of mania was defined as hospitalization for mania or a new dispensation of stabilizing medication 0-3 months and 3-6 months after medication initiation following non-treated periods.

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To be classified as being on continuous mood-stabilizing treatment, a patient had to have at least two dispensations of a mood stabilizer during the 9 months preceding the initiation of methylphenidate treatment, of which at least one had to occur within the prior 6 months. To be classified as not using a mood stabilizer, the patient could not have any dispensations of aripiprazole, olanzapine, quetiapine, lamotrigine, lithium, valproate, carbamazepine, haloperidol, or risperidone during the six months preceding the initiation of methylphenidate treatment.

Patients receiving methylphenidate monotherapy displayed an increased rate of manic episodes (mania rate=0.08). During the three months after treatment initiation, the hazard ratio was 7.7, 95% CI=2.0-22.4; during the subsequent three months, the hazard ratio was 9.7, 95%, CI=2.9-31.7. In patients taking mood stabilizers, the mania rate (0.18) and risk of mania during the first three months was considerably lower (hazard ratio=0.6, 95% CI=0.4-0.9) and slightly reduced during the second three months (hazard ratio=0.9, 95% CI=0.5-1.7).

The researchers commented that 20% of patients with bipolar disorder may suffer from comorbid attention deficit hyperactivity disorder (ADHD), a condition that is successfully treated with methylphenidate in general population. Given this comorbidity, it’s “not surprising that 8.4% of all identified Swedish bipolar disorder patients received at least one prescription for methylphenidate during an 8-year period.”

Although stabilizing medications effectively treat mood episodes, they may worsen attention and concentration, thereby impairing everyday function and potentiating the impact of ADHD. For this reason, patients with comorbid bipolar disorder and ADHD may benefit from methylphenidate treatment, if it can be done without incurring the risk of mania. However, because of the risk of treatment-emergent mania in individuals with bipolar disorder, the researchers “recommend careful assessment to rule out bipolar disorder before initiating methylphenidate as a monotherapy.”

In those with established bipolar disorder who are taking mood-stabilizing medication, “it would appear that the combination of concomitant therapy of ADHD is both safe and feasible in the context of ongoing preventive therapy,” which the researchers call a “welcome” and “reassuring” finding.

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Viktorin A, Ryden E, Thase ME, et al. The risk of treatment-emergent mania with methylphenidate in bipolar disorder. Am J Psychiatry. 2016. doi: 10.1176/appi.ajp.2016.16040467.