Patients with anxious depression—major depressive disorder (MDD) with high levels of anxiety—are known to have a poorer response to commonly used antidepressants than those with MDD. A small study published in Depression & Anxiety now suggests intravenous (IV) ketamine may be able to reduce symptoms in patients with anxious depression. The study found patients with and without anxious depression experienced similar symptom improvements within 24 hours of receiving a ketamine infusion.

Naji C. Salloum, M.D., of Harvard Medical School and colleagues compared the effectiveness of IV ketamine to that of midazolam (preoperative sedative) in relieving symptoms of depression with anxiety. They randomized 99 patients with treatment-resistant depression to one of five arms: a single dose of IV ketamine (0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, or 1.0 mg/kg) or midazolam (0.045 mg/kg). Forty-five of those patients had anxious depression as defined by a Hamilton Depression Rating Scale Anxiety/Somatization score of at least 7.

Using several depression scales, the researchers evaluated the patients’ symptoms on the first and third days after treatment. Although all patients responded to their treatment (either ketamine or midazolam), those who had received ketamine experienced greater improvements in their symptoms. Furthermore, there were no significant differences in response between the anxious and nonanxious patients.

“[The] results of the present study did not demonstrate differential efficacy of ketamine for the treatment of either anxious or nonanxious depression, pointing to the possibility that intravenous ketamine treatment may be equally efficacious in treating subjects with or without anxious [treatment-resistant depression]. These results are still exploratory and future larger and adequately powered studies designed to specifically test this aim are warranted,” Salloum and colleagues wrote.

The researchers also noted that anxious patients experienced a lower level of dissociative symptoms 40 minutes after infusion compared to nonanxious patients, a phenomenon that they suggested may be attributable to a higher proportion of benzodiazepine use in patients with anxious depression.

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