Irritability, Anger Indicators of Complex, Severe Depression

Megan Brooks

September 12, 2013

Symptoms of irritability and anger during a major depressive episode (MDE) appear to be clinical markers for a significantly more complex, chronic, and severe form of major depressive disorder, a new study indicates.

Results from the longitudinal observational investigation of patients with unipolar MDEs showed that those with current overt irritability/anger were significantly more likely to have increased depressive severity, longer duration of the index MDE, poorer impulse control, and a more chronic and severe long-term course of illness.

Overt irritability and anger were also associated with higher rates of lifetime comorbid substance abuse and anxiety disorder, more antisocial and personality disorders, greater psychosocial impairment, reduced life satisfaction, and a higher rate of bipolar II disorder in relatives.

The study findings strongly suggest that "concurrent anger/irritability symptoms are important indicators of increased severity, chronicity, and complexity of unipolar major depression," the authors, led by Lewis L. Judd, MD, University of California, San Diego, write.

The study was published online September 11 in JAMA Psychiatry.

Prevalent and Telling

Symptoms of irritability or anger are not central to the diagnosis of unipolar MDEs. Yet, "as a clinician with considerable experience in treating major depressive disorder, I became very impressed with the amount of irritability and anger comorbid with MDEs," Dr. Judd told Medscape Medical News. "We set about to find out what was the impact of this comorbidity on the depressive disorder itself."

Dr. Lewis Judd

The investigators examined the prevalence of overtly expressed irritability/anger in MDE and its association with illness presentation and long-term course in 536 patients followed for up to 31 years.

The researchers found that more than half (292 of 536, or 54.5%) exhibited overt irritability/anger during the first unipolar MDE evaluated at entry into the study.

"Although the irritable group did not have more MDEs prior to study intake or during follow-up, their study intake MDEs lasted longer, and their prospectively observed course of affective illness was significantly more chronic (more time symptomatic) and severe (more of follow-up in a major affective episode)," the authors write.

"In addition to a greater symptomatic burden of illness and psychosocial dysfunction, they also had significantly more comorbidities with anxiety and substance use disorders," they add.

The findings were not explained by comorbidity or other manic spectrum symptoms. There was no association between irritability/anger and increased suicidal ideation or behavior.

These patients need "closer clinical monitoring," the study team notes.

They add that the treatment plan for this population "should include specific strategies to address anger management issues, as well as the frequently associated problems of comorbid anxiety disorder, substance abuse disorder, poor impulse control, and psychosocial impairment when these are present."

Distinct MDD Subtype?

"The most important finding in this paper is that it confirms...that the majority of people with irritability and depression do not have bipolar disorder," Roy H. Perlis, MD, director of the Bipolar Clinical Program at Massachusetts General Hospital and associate professor of psychiatry at Harvard Medical School in Boston, who was not involved in the study, told Medscape Medical News.

The finding that irritability is primarily a marker of greater depression severity is "quite consistent with what multiple previous studies have reported," he added.

Dr. Judd and colleagues believe their findings "support the possibility" that unipolar depression with overt irritability/anger may be a marker for a distinct subtype of unipolar MDD. "Correlates such as poor anger management, poor impulse control, increased substance abuse, and greater long-term psychosocial dysfunction raise the question of whether MDEs with irritability/anger arise from a distinct biological substrate," they write.

They call for further research is to explore how combinations of biological mechanisms, personality vulnerabilities, poor social circumstances, or prior trauma may be involved in the pathogenesis of MDE with overt irritability/anger.

"Findings from such research could lead to the identification of a distinct subtype of unipolar MDD, along with specific diagnostic tools and more effective treatments," they conclude.

The initial funding source for the database used in this study was the National Institute of Mental Health. The authors' disclosures are listed in the original article. Dr. Perlis reports no relevant financial relationships.

JAMA Psychiatry. Published online September 11, 2013. Abstract


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