Irritability Strongly Linked to Suicidal Behavior in Major Depression

Fran Lowry

June 08, 2020

Irritability in adults with major depressive disorder (MDD) and stimulant use disorder (SUD) is strongly linked to suicidality and should be assessed by clinicians.

Three clinical trials of adults with MDD and one trial of adults with SUD showed that the link between irritability and suicidality was stronger than the association between depression severity and suicidal behaviors.

"Irritability is an important construct that is not often studied in adults with major depressive disorder," Manish K. Jha, MD, Icahn School of Medicine at Mount Sinai, New York City, told Medscape Medical News.

"If you look at current diagnostic convention, irritability is not considered a symptom of major depressive episodes in adults, but below age 18, it is considered one of the two main symptoms," Jha said.

The findings were presented at the virtual American Society of Clinical Psychopharmacology (ASCP) 2020 Annual Meeting.

Clinically Useful

Irritability is assessed using age-related norms of behavior, Jha said.

"The best way to conceptualize it is that it is the propensity to get angry easily or more frequently as compared to peers in response to frustration. I have a 2½-year old, and if he throws a tantrum, that is perfectly age appropriate. But if I do the same thing, it would be extreme irritability. The pediatric literature uses the word 'grouchiness,' but it is a little bit difficult to define, in part because it hasn't been studied extensively," he said.

To better understand the potential association between irritability and suicidality, the investigators reviewed results of three trials involving adults with MDD. These trials were the Combining Medications to Enhance Depression Outcomes (CO-MED) trial, which included 665 patients; the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) trial, which included 296 patients; and the Suicide Assessment Methodology Study (SAMS), which included 266 patients.

They also examined the Stimulant Reduction Intervention Using Dosed Exercise (STRIDE) study, which was conducted in 302 adults with SUD.

All studies assessed irritability using the Concise Associated Symptom Tracking scale, a 5-point Likert scale. The trials also assessed suicidality with the Concise Health Risk Tracking Suicidal Thoughts.

The investigators found that irritability and suicidality were positively correlated. The association between irritability and suicidality was two to 11 times stronger than the link to overall depression.

Higher irritability at baseline predicted higher levels of suicidality at week 9 in CO-MED (P = .011), EMBARC (P < .0001), and STRIDE (P = .007), but not in SAMS (P = .21).

Greater reduction in irritability from baseline to week 4 predicted lower levels of suicidality at week 8 in CO-MED (P = .007), EMBARC (P < .0001), and STRIDE (P < .0001), but not in SAMS (P = .065).

Similarly, lower baseline levels and greater reductions in irritability were associated with lower levels of suicidality at week 28 of CO-MED, week 16 of EMBARC, and week 36 of STRIDE.

Jha speculated that by treating irritability, it may be possible to lower rates of subsequent suicidal ideation, and he believes that measuring irritability in MDD "has clinical utility."

Common and Disabling Symptom

Commenting on the study for Medscape Medical News, Sanjay J. Mathew, MD, professor of psychiatry and behavioral sciences, Baylor College of Medicine, Houston, Texas, said the findings provide further support that irritability is a relatively common and disabling symptom associated with major depression.

"The presence of significant irritability was associated with higher levels of suicidal ideation and is therefore highly relevant for clinicians to assess," said Mathew, who was not part of the study.

"Early improvements in irritability are associated with better longer-term outcomes with antidepressant treatments, and this highlights the need for careful clinical evaluation early on in the course of antidepressant therapy, ideally within the first 2 weeks," he said.

Jha reports financial relationships with ACADIA Pharmaceuticals and Janssen Research & Development. Mathew reports financial relationships with Allergan, Vistagen, Janssen, Clexio, and Biohaven.

American Society of Clinical Psychopharmacology (ASCP) 2020 Annual Meeting: Abstract 3002163, presented May 30, 2020

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