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Child Psychiatrist /Adult Psychiatrist

Off-Label Use of ADHD Medications for Patients With Bipolar Disorder

Keypoint: ADHD medications do not increase mania for patients with bipolar disorder when used alongside mood stabilizers.


A systematic review published in Bipolar Disorders found that adjunctive attention-deficit/hyperactivity disorder (ADHD) medications are effective in improving comorbid ADHD symptoms – but not overall cognition – among patients with bipolar disorder.


ADHD Medications

Both bipolar disorder and ADHD have overlapping psychopathology and potentially similar pathophysiology. The 2 disorders are also frequently comorbid and have both been associated with cognitive impairments due to abnormal dopamine and norepinephrine signaling. Because ADHD medications are effective in improving cognition and daily functioning among patients with ADHD, they are also sometimes used off-label for the treatment of ADHD symptoms and cognitive impairment among patients with bipolar disorder.


To evaluate the effectiveness and safety of established and off-label use of ADHD medications for cognition and/or comorbid ADHD symptoms among patients with bipolar disorder, investigators from the International Society for Bipolar Disorders (ISBD) conducted a systematic review of the literature. The ISBD searched publication databases through June 2023 for relevant studies that examined ADHD pharmacotherapy among patients with bipolar disorder and reported on both changes in neurocognitive function or ADHD symptoms as an outcome and side effects experienced by patients.


The investigators included a total of 17 studies comprising 2136 patients. Of the included studies, 12 examined stimulant ADHD medications and 5 evaluated nonstimulant medications. The 2 most commonly studied medications were armodafinil (k=4; n=1581) and methylphenidate (k=4; n=84).


In the studies of methylphenidate, patients received between 5 and 40 milligrams per day administered in 2 daily doses in combination with mood-stabilizing medications (primarily lithium). Methylphenidate was found to be more effective than placebo among children and adolescents at reducing symptoms of ADHD in 2 studies. However, methylphenidate did not significantly improve mood symptoms in 1 of the included studies. Further, a study of children and adolescents with bipolar disorder did not report significant effects of methylphenidate on ADHD symptoms relative to placebo. Among adults, methylphenidate was not favored over placebo for the outcomes of cognition or mania.


In a placebo-controlled trial that evaluated the effect of other stimulant medications on ADHD symptoms in pediatric bipolar disorder, the use of amphetamine salts (5 mg/d) adjunctive to divalproex sodium was associated with significant reductions in ADHD symptoms compared with placebo.


For nonstimulant ADHD medications, clonidine (0.2-0.6 mg/d, dosed twice daily) with lithium or valproate sodium among adults was associated with significant reductions in the severity of manic symptoms and sleep disturbances, but no change was observed in cognition.


The interventions were generally well-tolerated, especially when administered as an adjunctive with mood-stabilizing agents. However, review authors could not come to a consensus on nonpsychiatric side effects due to heterogeneity and uncertainty regarding how the studies monitored these side effects.


The review authors concluded, “Given this good safety profile of the medications and paucity of research into their possible cognitive benefits, we encourage further research into the pro-cognitive potential of these medications in [bipolar disorder].”


The major limitation of this review is that the investigators could not conduct a meta-analysis due to study heterogeneity and limited data.


Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Note: This article originally appeared on Psychiatry Advisor

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