2019 Annual Meeting Coverage: Rapid-Acting Antidepressants: Deconstructing One and Constructing Another

Presenter Nolan Williams, MD Article contribution by: Diana Wertz, MD

Dr. Nolan Williams gave a wonderfully informative lecture on recent advances involving rapid-acting antidepressants for treatment resistant depression (TRD). The talk started off with a discussion of how ECT is a powerful and effective treatment for TRD with remission rates of 50%. However, it is often not available or offered to eligible patients and it presents long-term sustainability issues in that most people will relapse within 8 weeks without further ECT. Discussion then turned to the use of ketamine as a rapid acting antidepressant with a 23.8% remission rate, a 50% response rate and anti-suicidal effects in up to half of treated patients. Ketamine impacts many different neuronal systems including NMDA/AMPA, glutamate, and the opioid system. Many in the audience were interested in recent research conducted by Dr. Williams suggesting that activation of the endogenous opioid system is necessary for the antidepressant effects of ketamine. The dissociative effects of ketamine do not appear to be sufficient to lead to clinical improvement. This led to a discussion of the pros and cons of using ketamine clinically with some people expressing concern about the potential for addiction while also acknowledging the benefit for many patients with intense suicidal depression.

The lecture then turned to a discussion of new developments in Transcranial Magnetic Stimulation (TMS). Dr. Williams explained the history behind both repetitive TMS (rTMS) and accelerated theta burst stimulation (TBS) which was recently approved in 2016 for TRD. For traditional rTMS approximately 30% of patients remit and 50% respond after an initial course of treatment. 62% of patients maintain the response at 6 months and 84% maintain the response if maintenance TMS is provided. Dr. Williams went on to explain that TBS can be applied much quicker and in condensed periods of time compared to traditional rTMS with no loss of efficacy. This allows for accelerated treatment such that a course of TBS treatment is complete in 5 days (with only 2 hours of stimulation) compared to 6 weeks of rTMS treatment. Interestingly, Dr. Williams presented research that suggests if TBS is applied multiple times per day there is evidence of long-term potentiation which may lead to longer term durability of response to treatment. Dr. Williams also presented some preliminary research involving the use of new pulse sequences for TBS in which very treatment resistant patients achieved 85% remission rates. Most remarkably, the side effects are mild (headache), no cognitive side effects were noted in patients and there appeared to be good durability at 15 weeks. The talk ended with a question session where many expressed hope and excitement about these new developments for TRD.

Newsletter Reference: 
March/April 2019


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