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 via PubMed
Summary
AI-generated from the abstractA 41-year-old man with treatment-resistant depression and polysubstance use (daily opioids and intermittent methamphetamine) received intranasal esketamine alongside his existing antidepressant. Depressive symptoms and craving markedly improved within one month. By two months he had stopped using opioids and methamphetamine. At six months he remained in remission and abstinent, with PHQ-9 scores dropping from 24 to 4. Side effects were transient dizziness and mild dissociation. The authors suggest esketamine may reduce craving through glutamatergic modulation and synaptic plasticity, offering dual benefits for depression and substance use, but note that controlled studies are needed.
Study at a glance
| 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 |
| Key finding | 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.