Pharmacotherapeutic Management of Depression in Patients With Cancer: A Review of Mechanistic and Clinical Evidence.
Sepideh Hajivalizadeh, Kimia Farahmand, Kimia Kazemzadeh, Ghazaleh Hajivalizadeh, Ahmad Shamabadi
Cancer Reports May 1, 2026 DOI: 10.1002/cnr2.70587 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Interventions | celecoxib ketamine mirtazapine psilocybin methylphenidate |
| Topics | Depression |
| Keywords | Antidepressant Clinical trial Comorbidity Tumor |
| Key findings | A mechanism-informed approach targeting inflammation, HPA axis hyperactivity, and glutamate excitotoxicity is essential for managing depression in cancer patients, as conventional antidepressants show inconsistent efficacy. |
Abstract
Depression is a prevalent comorbidity in cancer, yet conventional treatments show inconsistent efficacy. This review sought to provide a mechanism-based framework for managing cancer-related depression by exploring its unique pathophysiology and evaluating promising pharmacotherapies based on their alignment with these biological pathways. This narrative review synthesized evidence on promising pharmacotherapies based on their ability to target the core biological mechanisms of cancer-related depression, including pro-inflammatory cytokine activity, hypothalamic-pituitary-adrenal axis hyperactivity, serotonin pathway disruption via indolamine-2,3-dioxygenase activation, and glutamate excitotoxicity. Interventions directly targeting inflammation (e.g., celecoxib) and glutamate modulation (e.g., ketamine) demonstrated encouraging early evidence. The effect of ketamine can also be due to its anti-inflammatory properties. Atypical antidepressants, such as mirtazapine, and the serotonergic psychedelic psilocybin also showed promising but preliminary benefits. In contrast, conventional selective serotonin reuptake inhibitors and tricyclic antidepressants yielded conflicting results. Other agents, including the psychostimulant methylphenidate, showed utility for specific symptoms like fatigue. A personalized, mechanism-informed approach targeting the core pathophysiological cascade of inflammation, hypothalamic-pituitary-adrenal axis hyperactivity, and glutamate excitotoxicity is essential for effectively managing depression in patients with cancer. This represents a necessary paradigm shift away from a one-size-fits-all treatment model.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cites 9
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis Psychiatry Research January 2, 2020
- Psilocybin‐assisted group therapy in patients with cancer diagnosed with a major depressive disorder Cancer December 18, 2023
and 4 more in the library