Esketamine in a Patient With Major Depressive Disorder and Polysubstance Use: A Case Report.
Abdelazim Ali, Nahida Ahmed, Sona Varghese
Cureus October 1, 2025 DOI: 10.7759/cureus.93876 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Clinical case report Peer reviewed |
|---|---|
| Sample size | 1 |
| Population | 41-year-old man with recurrent major depressive disorder with suicidal ideation and polysubstance use disorder (daily morphine/prescription opioids; intermittent methamphetamine) |
| Intervention | Intranasal esketamine |
| Duration | 6-month follow-up |
| Topics | Depression Esketamine |
| Keywords | Clinical case report Craving reduction Esketamine intranasal Glutamatergic modulation Methamphetamine use disorder Polysubstance use disorder |
| Key findings | Intranasal esketamine adjunctive to an oral antidepressant was associated with rapid improvement in depressive symptoms, reduced craving, and sustained abstinence from opioids and methamphetamine over six months. |
Abstract
Major depressive disorder (MDD) frequently co-occurs with substance use disorders (SUDs), leading to poorer outcomes and limited options. Esketamine is approved for treatment-resistant depression (TRD); its effects on craving and abstinence in SUD are less explored. A 41-year-old man with recurrent MDD (suicidal ideation) and polysubstance use (daily morphine/prescription opioids; intermittent methamphetamine) failed multiple antidepressants and engaged in opioid-seeking behavior. Intranasal esketamine was initiated adjunctive to the ongoing oral antidepressant. At one month, depressive symptoms and craving markedly improved. At two months, he achieved abstinence from opioids and methamphetamine. At four months, he returned to work and started a business. At six months, he remained euthymic and abstinent. The Patient Health Questionnaire-9 (PHQ-9) scores dropped progressively from 24 at baseline to 4 at six months. Tolerability was good (transient dizziness, mild dissociation). Beyond rapid antidepressant effects, esketamine may reduce craving via glutamatergic modulation and synaptic plasticity. In conclusion, esketamine may offer dual benefits in TRD with comorbid SUD; however, controlled studies are needed.
Comparable studies
Other case reports and case series on esketamine for depression, most cited first.