ADHD in Patients With Bipolar Disorder: Genetics, Diagnosis, and Treatment

BIPOLAR UPDATE

Recent study results revealed that children with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) had a 10-fold increase in the incidence of later development of bipolar disorder (BD) compared with matched children without ADHD.¹ The comorbidity is common, has a more severe course than either diagnosis alone, and is associated with greater risk of suicide attempts.² Clinicians will have trouble determining which diagnosis best fits the patient, and it could be that the patient has both diagnoses. Often the patient (and/or prescriber) prefers the ADHD diagnosis and the stimulant medications used to treat it. They hope to avoid the BD diagnosis and medications used to treat it, because of the perceived stigma and complexity of treatment. The differential diagnosis is made by recognizing that bipolar (hypo)manias occur in discrete episodes of at least 4 to 7 days, whereas the hyperactivity and associated symptoms of ADHD are more or less constantly present as features of the individual’s temperament.

The comorbidity of ADHD and BD may involve overlapping genetics. In Sweden, 13,532 twin pairs (aged 9 to 12 years) were evaluated using parent-rated instruments for ADHD and hypomanic episodes.³ Overlapping symptoms were removed to aid in the analysis. The twin pairs were reassessed when aged 15 years and again when aged 18 years (N = 3013 pairs). They found that genetic factors associated with hypomania explained 25% to 42% of the likelihood of ADHD’s hyperactive/impulsive symptoms. There was less effect on the inattentive symptoms of ADHD. Monozygotic twins had a stronger association of the 2 conditions than dizygotic twins. The rest of the variance was presumed to be associated with causes of ADHD that do not contribute to causing hypomania.

The bottom line of these data is that it is important to take the time to diagnose bipolar disorder accurately in patients with a history of ADHD or who are presenting with current ADHD. Mood-stabilizing medications such as lithium will usually be indicated for the bipolar condition.

Stimulant treatment of ADHD when there is comorbid BD has been controversial. However, an important 2016 study by Viktorin and colleagues⁴ that may influence practice. This large observational study found that if patients are treated with methylphenidate for ADHD and their BD is not being treated with a mood stabilizer, the likelihood of manic switch over 3 to 6 months is multiplied by nearly 7-fold, compared with patients with bipolar disorder not treated with methylphenidate. However, if patients are on a bipolar mood stabilizer, the addition of methylphenidate was associated with reduced odds of becoming manic, compared with the control patients with BD who were not given a stimulant, with a hazard ratio of 0.6 (ie, a 40% reduction). Thus, it seemed that methylphenidate can be safe and effective for ADHD symptoms if the patient is on a mood stabilizer to manage the BD. Note that amphetamine products were not evaluated in this Scandinavian study; many European countries have not approved these agents.

In summary, it is critically important to carefully evaluate whether patients with ADHD also have BD. If you miss the bipolar diagnosis and treat the ADHD with a stimulant, the potential for harm (ie, induction of mania) is considerable. However, if the bipolar disorder is under control with a mood stabilizer, the use of a stimulant (at least methylphenidate) need not be avoided. Indeed, it may be quite helpful.

Dr Osser is associate professor of psychiatry, Harvard Medical School, and co-lead psychiatrist, US Department of Veterans Affairs, National Telemental Health Center, Bipolar Disorders Telehealth Program, Brockton, MA. He is a member of the Psychiatric Times^TM Editorial Board. The author reports no conflicts of interest concerning the subject matter of this article.

This article was originally posted ahead of print on October 30, 2020 under the title ADHD in Bipolar Patients: Genetics, Diagnosis, and Treatment, and has since been updated. -Ed

References

1. Meier SM, Pavlova B, Dalsgaard S, et al. Attention-deficit hyperactivity disorder and anxiety disorders as precursors of bipolar disorder onset in adulthood. Br J Psychiatry. 2018;213(3):555-560.

2. Lan W-H, Bai Y-M, Hsu J-W, et al. Comorbidity of ADHD and suicide attempts among adolescents and young adults with bipolar disorder: a nationwide longitudinal study. J Affect Disord. 2015;176:171-175.

3. Hosang GM, Lichtenstein P, Ronald A, Lundström, Taylor MJ. Association of genetic and environmental risks for attention-deficit/hyperactivity disorder with hypomanic symptoms in youths. JAMA Psychiatry. 2019;76(11):1150-1158.

4. Viktorin A, Rydén E, Thase ME, et al. The risk of treatment-emergent mania with methylphenidate in bipolar disorder. Am J Psychiatry. 2017;174(4):341-348.❒