“Instead of raising the chemical, we’re resetting the thermostat” – Greg Mattingly, MD

During Psych Congress 2023 (September 6-10, 2023; Nashville, TN) this week, an exceptional session offered a unique opportunity to hear from providers and a real patient in an interactive setting to discuss rapid-acting antidepressants (RAADs).

Although more than 30 antidepressants are currently available to patients, these often fail to provide a response. Patients successfully reach remission in even fewer cases. Common residual symptoms include emotional blunting, problems with eating, sleeping, or cognition, fatigue, anhedonia, lack of motivation, and suicidal ideations. Of these, emotional blunting, anhedonia, low motivation, and cognitive problems stand out as major obstacles preventing treatment success. These can persist for up to 3 years even after remission, and cognitive symptoms, in particular, are a predictor for relapse. Persistent depression increases the risk of suicidality. Indeed, when looking at a heat map of suicide rates from 2002-2004 compared to 2014-2016, as shown during this session, it was abundantly clear that the battle against depression is being lost, panelists said.

Agents with a faster onset of action stand out as one of the critical unmet needs in the antidepressant arsenal. Fortunately, several novel mechanisms under investigation show promise to fill this void. These include N-methyl-D-aspartate (NMDA) antagonists, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) modulators, neural steroids, triple reuptake inhibitors, and several others. For both clinicians and patients, the future of pharmacotherapeutics looks very optimistic.

Women are a notable category of patients who may benefit greatly from RAADS, especially postpartum women. Dr Dalthorp presented valuable information on the differences in women that may cause additional vulnerability to depression. Epidemiological studies have identified fluctuating hormone levels as a cause for increased risk of mood disorders in women's life phases such as puberty, menstruation, infertility treatment, pregnancy, postpartum, and menopausal transition. The statistics on gender differences in mental health reflect this vulnerability. According to statistics shown during the session, 1 in 5 women are treated for depression compared to 1 in 10 men. Furthermore, 29% of women received treatment for a mental health problem compared to only 17% of men. Research also shows that stress response is highly gender-specific, causing greater sensitivity, more prominent responses, and longer recovery periods in women. Dr Dalthorp also shared a heartwarming review written by a patient, thanking her clinical team for changing her life. The patients said she felt relief within days and could return from a very dark place to feel like herself again.

Between this patient feedback and the personal testimony shared by the patient panel member, the session demonstrated the clear value to patients of experiencing rapid response to antidepressant treatment. When patients feel relief faster, they can return to their lives and better care for themselves and their families. The emergence of RAADs thus offers new hope for patients struggling with depression.

Reference:
Mattingly G, Baig A, Dalthorp R, Meier C. Expert panel: real-world impact of rapid-acting antidepressants. Presented at: Psych Congress; September 6-10, 2023; Nashville, TN.