Early symptom non-improvement and aggravation are associated with the treatment response to SSRIs in MDD: a...

Early improvement in major depressive disorder is defined as a reduction of ≥20% in the 17-item Hamilton Depression Rating Scale (HAM-D-17) score at the second week after initiation of treatment, predicting long-term treatment response. However, there remains no effective strategy for switching medications when a patient fails to reach early improvement at the second week. This study focused on the predictive value of early symptom changes in each item of the HAM-D-17 scale for treatment response to selective serotonin reuptake inhibitor (SSRI) monotherapy and to provide a reference for switching antidepressants to enhance early treatment efficacy.

Our study was an observational, real-world study that enrolled 90 treatment-naïve patients experiencing their first episode of major depressive disorder in the outpatient department of Huashan Hospital. Patients who did not achieve the threshold of early improvement in the second week after starting treatment were switched to alternative SSRI monotherapy. Patient follow-up occurred at 2, 4, 8, and 12 weeks after the initiation of treatment. We analyzed the relationship between the change in each symptom on the HAM-D-17 scale and treatment efficacy.

Early improvement predicted the treatment response at 12 weeks (χ ²=19.249, P<0.001), whereas early non-improvement in insomnia and anxiety was associated with a poor response (OR =9.487, 95% CI: 1.312-68.588 and OR =12.947, 95% CI: 1.99-82.246, respectively). At week 2, general somatic symptom aggravation was associated with a poorer response (OR =73.337, 95% CI: 2.232->999.999); treatment-emergent headache and tremor were associated with treatment efficacy (t=-9.521, P<0.001 and t=3.660, P=0.001, respectively). In addition, the increase in suicidal thoughts, once treatment began, had no relationship with the treatment response (OR =0.821, P=0.872).

This study suggested that patients with early non-improvement in insomnia and anxiety were not suitable for switches in SSRI monotherapy. Patients with treatment-emergent symptoms, especially headaches and tremors, were not suitable for switching from monotherapy to another SSRI.