Recent studies have examined new treatment approaches for depression, OCD, and schizophrenia, and assessed their efficacy and limitations.
In his editor's note published in the March issue of the American Journal of Psychiatry, Ned H. Kalin, MD, of the Department of Psychiatry at the University of Wisconsin School of Medicine and Public Health, highlighted studies from the issue; namely, intranasally administered esketamine's short-lived antidepressant effects, the potential benefits of multisession daily transcranial direct current stimulation (tDCS), the limited impact of high-dose ondansetron for OCD, the cognitive advantages of the newly approved schizophrenia drug, Cobenfy (xanomeline/trospium), and D-cycloserine-enhanced intermittent theta burst stimulation (iTBS) for OCD.
First, Dr. Kalin discussed a systematic review that found intranasally administered esketamine added to other antidepressant treatments had initial antidepressant effects, which declined after 4 days and were mostly absent after 4 weeks. The magnitude of esketamine's antidepressant effect was comparable to adjunctive atypical antipsychotics, but little evidence supports its ability to reduce suicidal ideation or behavior.
He continued with a discussion on another study that investigated the feasibility of repeated tDCS sessions for major depression, in which stimulation was applied five times daily over 5 weeks in 28 patients. The researchers in this study noted that Hamilton Depression Rating Scale scores dropped by 29% at 1 week and 26.2% at 4 weeks. While no serious adverse events occurred, common side effects included headaches (68%), contact dermatitis (64%), and fatigue (57%), in addition to discomfort at the application site, which was experienced by all patients. The open-label design limited definitive conclusions about efficacy.
Next, Dr. Kalin cited a double-blind, randomized, placebo-controlled trial that assessed high-dose ondansetron (24 mg/day) in 51 patients with OCD and tic disorders. The drug did not significantly improve symptoms compared with placebo, though greater improvement was noted in patients also taking SSRIs or other psychotropic medications. Functional MRI analyses did not confirm expected reductions in insula and sensorimotor cortex activation. Constipation was the most common side effect. It affected 52% of ondansetron recipients compared with 3% of the placebo group.
Cobenfy (xanomeline/trospium) improved cognitive function in patients with schizophrenia, as shown in two phase III trials with 150 treated patients and 157 on placebo. Significant improvements were observed in executive function, visual memory, sustained attention, and verbal recall and recognition among participants classified as cognitively impaired (ie, patients who scored at least one standard deviation lower than normative data). These improvements were measured using the Cambridge Neuropsychological Test Automated Battery composite score and occurred independently of improvements in psychotic symptoms.
Finally, Dr. Kalin described a pilot study that tested whether D-cycloserine enhanced iTBS effects for OCD. In a randomized, triple-blind, placebo-controlled trial, 24 patients received sham TBS plus placebo (n = 5), sham TBS plus d-cycloserine (n = 3), TBS plus placebo (n = 6), and TBS plus d-cycloserine (n = 10). Patients who received iTBS and D-cycloserine experienced significantly greater symptom improvement as measured by the Yale-Brown Obsessive Compulsive Scale than those in other groups, though no significant reductions in depression symptoms were observed across treatment arms.
"The papers in this issue of the Journal present new data and ideas about innovative treatment strategies that are directly relevant to clinical practice and at the same time highlight avenues for further research," Dr. Kalin concluded.
The article notes that funding information can be found in the April 2024 issue of the Journal.
