Agitated Depression and the Potential Response to Gama-Amino Butyric Acid Agonist: A Case Series and Literature Review

Purpose/Background: Agitated depression is a specific variant of depressive disorder characterized by marked psychomotor agitation, including prominent restlessness and pacing, intense anxiety, irritability, and insomnia. These symptoms can be severe, and patients might be at increased risk of suicide. Authors have suggested that agitated depression can worsen with the use of antidepressants but can respond to options such as electroconvulsive therapy (ECT), lithium, anticonvulsants, antipsychotics, and benzodiazepines. Appropriate identification of this variant of depressive disorder is essential for proper treatment, as some of these patients might be labeled as resistant to treatment due to the worsening or lack of response to several antidepressant trials. Methods/Procedure: Summary of 2 recent cases and literature review on agitated depression symptoms and treatment. Finding/Results: Our 2 patients presented with symptoms of depressed mood, increased anxiety, irritability, poor sleep, poor appetite, restlessness, rumination, indecisiveness, and psychosis. Both patients had worsening symptoms with the use of various antidepressants but improved with the use of lorazepam and olanzapine. We review literature describing this variant of depressive disorder and its suggested treatment. Implication/Conclusion: Agitated depression has been poorly characterized in the literature. The criteria suggested by Koukopoulos et al (Acta Psychiatr Scand. 2007;115:50-57) and the provisional criteria for melancholia, as indicated by Mahgoub et al (Front Psychiatry. 2024;15:1372136), might help recognize this variant of depressive disorder. These patients might have a poor response or worsen with the use of antidepressants while responding to options like gamma-amino butyric acid (GABA) agonists, antipsychotics, and ECT.