Adjunctive Brexpiprazole May Improve Anger, Irritability in MDD Patients

Improvements in anger and irritability were displayed after 6 weeks of adjunctive treatment
Improvements in anger and irritability were displayed after 6 weeks of adjunctive treatment

Irritability and anger symptoms for patients with major depressive disorder (MDD) may be improved with adjunctive brexpiprazole treatment. Those are the findings of a new, 8-week, open label study conducted at 15 sites across the United States between October 2013 and July 2014.

In total, 54 patients matched the criteria for study inclusion; by being diagnosed with MDD according to DSM-IV-TR criteria and having their current major depressive episode (MDE) confirmed using the Mini International Neuropsychiatric Interview.

The study included a 6-week period of open-label treatment with the patient's current antidepressant and adjunctive treatment with brexpiprazole. After the 6 weeks patients discontinued the brexpiprazole treatment while continuing their regular antidepressant, and had a 4-week follow-up period. 

Throughout, treatment with the regular antidepressant remained the same, while brexpiprazole was titrated up from 1mg once daily for 1 week, followed by 2mg once daily for 1 week and increased to the target dose of 3mg once daily for 4 weeks. 

Changes in levels of irritability, were measured using the Sheehan Irritability Scale, Sheehan Irritability Scale item 1, and IDS-C item 6; the Monetary Choice Questionnaire and Barratt Impulsiveness Scale, version 11 were used to measure impulsivity; while the Kellner Symptom Questionnaire and Anger Attacks Questionnaire were used to measure anger and hostility. 

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Results showed that irritability symptoms had improved by week 6 with brexpiprazole treatment. Sheehan Irritability Scale scores decreased from baseline, with a mean change of –21.1 (95%CI, –26.3 to –16.0), mean Sheehan Irritability Scale item 1 score decreased to –3.5 (95% CI, –4.2 to –2.7), and mean IDS-C item 6 score decreased –1.2 (95% CI, –1.5 to –1.0). 

No change was noted in the Monetary Choice Questionnaire during the first 6 weeks of treatment with adjunctive brexpiprazole, although symptoms worsened when brexpiprazole was discontinued. At week 6 the average Kellner Symptom Questionnaire anger-hostility scores improved by 7.7 points (95% –9.6 to –5.9). At week 10 – after discontinuation of brexpiprazole – the mean score change was 1.2 points (95% CI, –0.8 to 3.2), which indicated no further improvements once patients stopped taking brexpiprazole.

In addition to improvements in irritability and anger issues, a number of barometers also showed a consistent improvement in the severity of depressive symptoms. At week 6 there was a decrease from baseline in mean IDS-C score of –17.8 (95% CI, –21.0 to –14.6); a decrease in the mean Kellner Symptom Questionnaire depression subscale score of –7.7 (95% CI, –9.6 to –5.8), and a decrease in the MADRS total score of –14.2 (95% CI, –16.7 to –11.6). 

From week 6 to week 10, when brexpiprazole was discontinued, the Kellner Symptom Questionnaire showed a worsening of depressive symptoms with a mean change of 2.1 points (95% CI, 0.1 to 4.2).

The authors concluded, “adjunctive treatment with brexpiprazole may represent a strategy for the treatment of irritability symptoms in patients with MDD.” They also declared that their results should be viewed as preliminary and that further studies should use a larger sample size that excludes the possibility of any placebo responses.

For more information visit Psychiatrist.com.


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