American Society of Clinical Psychopharmacology Annual Meeting
American Society of Clinical Psychopharmacology Annual Meeting
Source/Disclosures
Source:

Jha M, et al. Clinical utility of targeting anger and irritability to guide novel therapeutics for patients with depression. Presented at: American Society of Clinical Psychopharmacology Annual Meeting; May 29-30, 2020 (virtual meeting).

Disclosures: Chin Fatt reports no relevant financial disclosures. Jha reports serving as research grant principal investigator for Acadia Pharmaceuticals and Janssen Research & Development. Healio Psychiatry could not confirm relevant financial disclosures for Fava at time of publication. Murrough reports serving on advisory boards of five pharmaceutical companies; consultant roles for two pharmaceutical companies and Global Medical Education; serving as research grant principal investigator for Avanir Pharmaceuticals; and that his spouse serves as a consultant for Medavante-Prophase.
June 03, 2020
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Treatments lacking to address impact of irritability on mental health, experts say

Source/Disclosures
Source:

Jha M, et al. Clinical utility of targeting anger and irritability to guide novel therapeutics for patients with depression. Presented at: American Society of Clinical Psychopharmacology Annual Meeting; May 29-30, 2020 (virtual meeting).

Disclosures: Chin Fatt reports no relevant financial disclosures. Jha reports serving as research grant principal investigator for Acadia Pharmaceuticals and Janssen Research & Development. Healio Psychiatry could not confirm relevant financial disclosures for Fava at time of publication. Murrough reports serving on advisory boards of five pharmaceutical companies; consultant roles for two pharmaceutical companies and Global Medical Education; serving as research grant principal investigator for Avanir Pharmaceuticals; and that his spouse serves as a consultant for Medavante-Prophase.
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Specific treatments are needed to target irritability, according to presenters at the American Society of Clinical Psychopharmacology Annual Meeting.

Manish Jha, MD, assistant professor in the departments of psychiatry and neuroscience at Icahn School of Medicine at Mount Sinai, said novel study findings suggest irritability may play a significant role in mental health.

woman gripping forhead in aggravation
Source: Adobe Stock

“About 6% of adults with major depressive disorder had a marked increase of about five points in irritability [on the Concise Associated Symptom Tracking Scale] after their health presentation was initiated,” Jha said during the virtual meeting. “Most of this increase happened within the first 4 weeks. ...Those with worsened irritability during the first few weeks of treatment were much less likely to be in remission, so early worsening predicted score outcomes later on.”

Specifically, Jha and colleagues found that individuals with more than an average improvement in irritability by week 4 were significantly more likely to be in remission for depression, with early reduction or improvement in irritability having predicted much higher improvement in depression outcomes 4 weeks later.

Results of one study showed that approximately 40% to 50% of adults with MDD exhibited significant irritability during their depressive episode, and antidepressant treatments tended to improve irritability by approximately 20% to 25%, Jha noted.

Irritability also may be associated with suicidality, according to Jha. Research has shown that moderate irritability, even in the presence of low anxiety or depression, significantly predicted suicidal ideation or suicide attempts among children aged 13 to 17 years.

“Conversely, in the absence of irritability, depression and anxiety were not a significant predictor, suggesting that the link between irritability and suicide-related outcomes may be stronger than the link between overall depression and suicide-related outcomes,” Jha said. “Similar findings have been reported in epidemiological studies where earlier assessments of irritability have predicted suicide-related outcomes over much longer periods of time.”

James Murrough

James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Icahn School of Medicine, provided an overview of research into ketamine’s potential for addressing irritability.

“If irritability is related to suicide risk and is modifiable by intervention, that makes a very strong case that we need to look at this [issue], and perhaps ketamine or other glutamatergic modulators are relevant,” Murrough said. “Ketamine is a rapid antidepressant, and there’s an emerging story and signal of its anti-suicidal-ideation effects. It appears to have activity against irritability, which is associated with reduced suicidal ideation.”

Cherise Chin Fatt, PhD, assistant professor in the department of psychiatry at University of Texas Southwestern Medical Center, presented data from a large randomized clinical trial that concluded it is possible to identify neural circuits associated with concurrent symptoms of irritability and those that predict changes in irritability with antidepressant medications vs. placebo.

She also outlined next steps for research in this area.

“Our next step is to learn from developmental literature, where we’re able to probe the effects of environments using the impact of childhood trauma and of deficits and instrumental learning using the probabilistic reward tasks,” Chin Fatt said. “Lastly, we can look at the overlap with other symptom measures, such as anger attack, aggression, anhedonia and anxiety.”

Maurizio Fava, MD
Maurizio Fava

Maurizio Fava, MD, director of the division of clinical research at Massachusetts General Hospital Research Institute, provided an overview of the important clinical aspects of irritability, as well as anger attacks, in relation to MDD.

“Irritability is common among both adolescent and adult MDD, affecting about one-third of depressed patients,” Fava said. “There is greater severity with earlier age of onset, higher comorbidity with anxiety disorders and greater chronicity. Anger attacks are more common in MDD... [However], the risk [for] emergence of anger attacks is no greater on antidepressants than on placebo, and improvement in irritability is a very important point.”