Major depressive disorder (MDD) impacts about 280 million individuals worldwide, making it a leading cause of disability and diminished quality of life. Among those with MDD, approximately one-third experience treatment-resistant depression (TRD), defined as a lack of response to at least two antidepressant treatments.
Esketamine, administered as a nasal spray, has emerged as a rapid-acting treatment for TRD. It can be combined with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). Recent research by Italian and German scientists, published in JAMA Psychiatry, evaluated which combination—esketamine with SSRI or SNRI—yields better clinical outcomes for TRD.
The analysis involved over 55,000 patients from more than 90 healthcare facilities across 20 countries. Using propensity score matching to ensure comparability, participants were divided into two groups: those receiving esketamine with SSRI and those receiving it with SNRI. Each group contained a balanced representation of genders, with an average age of 46. The SSRIs used included citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and vilazodone, while the SNRI group included desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine.
The study tracked key clinical outcomes, including all-cause mortality rates, hospitalizations, depressive relapses, and suicide attempts over a five-year period. Findings indicated that patients treated with esketamine and SNRI experienced lower rates of all-cause mortality (5.3%) compared to those on the SSRI combination (9.1%). Additionally, hospitalizations were minimal in the SNRI group (0.1%) versus a slightly higher rate in the SSRI group (0.2%). Rates of depressive relapse were also lower in the SNRI cohort (14.8%) compared to those receiving SSRIs (21.2%).
Survival rates over five years showed a notable difference: 91.4% for the SNRI group versus 86.9% for the SSRI group. Both treatment combinations reduced instances of suicide attempts, but the SNRI combination recorded a lower percentage (0.5%) compared to the SSRI group (0.3%).
These results underscore the importance of selecting the appropriate antidepressant combination for treating TRD. The researchers stress that understanding the distinct effects of these combinations is vital for customizing treatment plans for patients suffering from this challenging condition. The study’s findings may help clinicians optimize treatment strategies for individuals facing treatment-resistant depression.
