Risk for Instability Increased in Patients With Major Depressive Disorder and Comorbid ADHD

woman with emotional problems, blurry
woman with emotional problems, blurry
In patients with major depression, having a comorbid diagnosis of ADHD may be associated with bipolar disorder diathesis, mixed features, and multiple psychiatric comorbidities.

In patients with major depression, having a comorbid diagnosis of attention-deficit/hyperactivity disorder (ADHD) is associated with bipolar diathesis, mixed features, multiple psychiatric comorbidities, and a more unstable disease course, according to a study published in the Journal of Affective Disorders.

Giulia Vannucchi, MD, from the Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy, and CREA, Research and Clinical Center, San Sebastiano Foundation and NEUROFARBA Department, University of Florence, Florence, Italy, and colleagues evaluated a sample of 2777 patients with a major depressive episode (MDE) who were enrolled in the multinational study BRIDGE-II-Mix Study to find patients who met the criteria for ADHD. Investigators identified 61 patients (2.20%) who had comorbid ADHD. These patients were compared with patients without ADHD.

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Patients with ADHD had a higher number of hypomanic or manic symptoms during depressive episodes than those without ADHD, and mixed depression was more common in those with ADHD as well. The investigators noted a number of features associated with ADHD in MDE, including a family history of bipolar disorder in first-degree relatives (36.7% vs 14.7% for ADHD-positive and ADHD-negative participants, respectively) and a personal history of antidepressant-induced hypomanic or manic switches. Patients with MDE who were ADHD positive were more likely to have an onset before the age of 20 (23.0%) than those without ADHD (12.0%). The presence of ADHD was also associated with a greater number of depressive and affective episodes, atypical depressive features, higher rates of bipolarity specifier, and psychiatric comorbidities with eating, anxiety, and borderline personality disorders.

The authors suggest that the complex presentation of ADHD co-occurring with MDE may represent a specific phenotype that requires a different treatment approach. They note that these findings also suggest that providers consider ADHD screening for patients with depression presenting with mixed features, a familial history of bipolar disorder, and a highly complicated clinical picture with comorbidity and adverse or poor response to antidepressants.

The authors call for further prospective studies to confirm the hypothesis that emotional dysregulation associated with adult ADHD may play a pivotal role in the relationships among MDE, bipolarity, mixed features, and other comorbid psychiatric disorders.


Vannucchi G, Medda P, Pallucchini A, et al. The relationship between attention deficit hyperactivity disorder, bipolarity and mixed features in major depressive patients: evidence from the BRIDGE-II-Mix Study. J Affect Disord. 2018;246:346-354.