New research on ketamine addresses its effectiveness compared to ECT and antipsychotics, the impact of placebo, and the benefits of combining ketamine with psychotherapy. The podcast also discusses studies comparing esketamine to quatypine and explores the confusing results of a ketamine trial. Additionally, a study on rapid fentanyl test strips and harm reduction approach is mentioned.
Ketamine works best for non-psychotic outpatients, while ECT is more suitable for hospitalized inpatients and individuals with psychotic depression.
Esketamine has proven to be more effective than quetiapine in treating treatment-resistant depression.
Deep dives
Comparing Ketamine to Other Treatments for Depression
Two recent studies compared ketamine directly to electroconvulsive therapy (ECT) for the treatment of depression. One study showed that ECT was slightly more effective, while the other study favored ketamine. The differences between the studies can be attributed to the types of patients enrolled and the quality of ECT delivered. The study that favored ECT included hospitalized inpatients and patients with psychotic depression, which is ECT's preferred treatment population. On the other hand, the study that favored ketamine focused on non-psychotic outpatients with depression. These studies clarify that ketamine works best for non-psychotic outpatients, while ECT is more suitable for hospitalized inpatients and individuals with psychotic depression.
Effectiveness of Esketamine Compared to Quetiapine in Treatment-Resistant Depression
A recent study compared esketamine (Spravato) to quetiapine in 676 patients with treatment-resistant depression. The study showed that esketamine was slightly more effective, resulting in a higher remission rate compared to quetiapine. While the difference was not large, esketamine demonstrated its benefits in patients who had failed two or more antidepressant trials, which defines treatment-resistant depression. Quetiapine, on the other hand, has mainly shown efficacy in patients who failed just one antidepressant. While esketamine requires ongoing maintenance therapy, quetiapine carries its own long-term risks such as diabetes, weight gain, and tardive dyskinesia. Overall, while esketamine is a controlled substance, it has proven to be more effective than quetiapine in treating treatment-resistant depression.
Questioning the Effectiveness of Ketamine
Meta-analyses have shown that ketamine has an ultra-high effect size compared to other psychiatric treatments, with a large impact on depression. However, further studies have raised doubts about the true effectiveness of ketamine. One recent analysis compared ketamine's benefits to saline drips as placebos and found a large effect size of 1.7 when compared to saline. However, when compared to an IV benzodiazepine, the effect size shrunk by more than 50% to 0.7, closer to the average effect size seen in other psychiatric treatments. Another study attempted to blind participants by administering ketamine or saline while they were under anesthesia for surgery. Surprisingly, both groups showed significant improvements, challenging the assumption that ketamine provides unique benefits. These findings highlight the need for further research to better understand the true effectiveness of ketamine and the potential role of psychological factors in its outcomes.
New research brings clarity to the big ketamine questions. How does it compare to ECT and antipsychotics? How much of it is placebo? Which is more effective – ketamine or esketamine? How do you sustain the benefits? Does it work better with psychotherapy?
Chris Aiken, MD, and Kellie Newsome, PMHNP have disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.
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