Intranasal esketamine plus oral antidepressant for treatment-resistant depression: acute induction and maintenance relapse-prevention outcomes in a systematic review and meta-analysis
Frontiers in Psychiatry July 3, 2026 Jingqiang Xie, Chunying Pu, Mingyue Sun
For people with treatment-resistant depression, adding intranasal esketamine to an oral antidepressant produces a modest but rapid reduction in depressive symptoms within two days, with greater symptom reduction at four weeks compared to placebo nasal spray plus an oral antidepressant. The combination therapy also increases the likelihood of response and remission, and improves daily functioning. Among those who initially respond, continued esketamine treatment halves the risk of relapse. However, acute treatment increases side effects, including dissociation and elevated blood pressure, and more patients discontinue due to adverse events. These findings support the use of esketamine under medical supervision with careful individual benefit-risk assessment.