Evidence-Based Reviews

What’s the best treatment for comorbid ADHD/bipolar mania?

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Consider the type of bipolar episode (Table 2).

For initial treatment of youths with BPD manic or mixed without psychosis, recent guidelines by Kowatch et al suggest using mood-stabilizer or atypical antipsychotic monotherapy. Youths who are more severely ill or present with psychosis may respond more favorably to a mood stabilizer plus an atypical antipsychotic.16,19

Individual patient traits will also determine whether a mood stabilizer or atypical antipsychotic is used and which agent within either medication class is chosen. For example:

  • If the patient is aggressive, risperidone may reduce aggression and manic symptoms. Among the atypicals, risperidone has the most evidence suggesting efficacy for aggressive behaviors in youths across psychiatric conditions.20
  • If an atypical antipsychotic is warranted and the patient’s weight is an issue, ziprasidone or aripiprazole would be preferred. These agents are considered weight-neutral compared with other atypicals.20

Other factors to consider include medication side effects, interactions, adherence, and cost.

Table 2

Mood stabilizer, atypical antipsychotic, or both with ADHD therapy?

Type of bipolar episodeRecommended psychotropics
Manic or mixed episode with psychosisMood stabilizer + atypical antipsychotic
Manic or mixed episode without psychosisMood stabilizer or atypical antipsychotic monotherapy first
  • if no response, switch to the other monotherapy
  • if partial response, augment one with the other
Prominent irritability without psychosisAtypical antipsychotic
Source: Adapted from references 18 and 19


If the child or adolescent with comorbid ADHD and BPD has acute manic symptoms, available data and expert opinion recommend starting treatment with a mood stabilizer or atypical antipsychotic.9,19,21 If ADHD symptoms persist after mood stabilization, a psychostimulant trial is warranted.

In practice, however, youngsters usually present with ADHD symptoms first. Psychostimulant treatment is initiated, ADHD symptoms are controlled, and the child’s academic and social functioning improve. Bipolar symptoms emerge later, often heralded by a depressive or mixed episode. Is it necessary to discontinue the psychostimulant and risk worsening ADHD symptoms before starting a mood stabilizer or atypical antipsychotic?

Clinical lore and one case report suggest that psychostimulants may destabilize mood.22,23 A 10-year-old boy with severe hyperactivity and family history of BPD experienced manic symptoms—rapid and pressured speech, grandiose delusions of identity, and tangentiality of thought processes—during methylphenidate treatment.22

Conversely, an analysis24 of children ages 7 to 10 from the National Institute of Mental Health Multimodal Treatment Study of Children with ADHD contradicts these assumptions. Although a clinical diagnosis of BPD was not assigned, 29 children (83% male) met the Diagnostic Interview Schedule for Children proxy for mania, 32 (88% male) met the Child Behavior Checklist proxy, and 7 met both proxies for mania.

The first month of methylphenidate treatment did not increase irritability, mood symptoms, or mania in the 54 children with ADHD and manic symptoms, compared with children with ADHD alone. The authors concluded that clinicians should not categorically avoid using stimulants in children with ADHD and some manic symptoms.

In a study by Pavuluri et al18 of pediatric bipolar type I disorder, 17 patients (mean age 11±4 years) received mood stabilizers—following a drug therapy algorithm that included risperidone—and typically received a psychostimulant after mood stabilization. This group was compared with 17 patients receiving “treatment as usual.”

The usual-treatment group remained on psychostimulant therapy after BPD intervention with a mood stabilizer and was less likely to receive an atypical antipsychotic. The algorithm treatment group showed better outcomes overall, specifically for mania and aggression.

Clearly, more studies are needed to determine the optimum treatment sequence with psychostimulants and mood stabilizers in youths with comorbid ADHD and BPD. With either approach, routinely monitor patients treated with psychostimulants for emerging or worsening bipolar symptoms.


Nonstimulants. Using psychostimulants is appropriate for ADHD in patients with stable bipolar symptoms. Evidence for using nonstimulants such as clonidine, guanfacine, or atomoxetine is less clear.

In a naturalistic study of 153 children and adolescent outpatients treated with atomoxetine, 51 (33%) experienced irritability, aggression, mania, or hypomania. Of these patients, 31 (61%) had a family history of a mood disorder, and 41 (80%) had a personal history of mood symptoms.25 Although these findings suggest that atomoxetine may be associated with mood exacerbation and hypomania, additional data are needed to determine whether atomoxetine may be used for ADHD symptoms in youths with comorbid BPD.

Atypical antipsychotics. Mood stabilization—particularly with atypical antipsychotics—often can address comorbid disruptive behaviors and aggressive symptoms. Combinations of atypical antipsychotics with psychostimulants are largely devoid of drug-drug interactions and metabolic interference, making them uncomplicated to use.

Though published studies of pediatric BPD have focused on three atypical antipsychotics—olanzapine, quetiapine, and risperidone—any agent in this class can be used in this population, with the choice often depending on how side effects are likely to affect individual patients (Table 3 ).

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