Pharmacological reports : PRMay 20, 2026

New psychiatric side effects reported by patients during ketamine treatment for major depression

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated May 21, 2026

Abstract

Sleep disturbances were reported by 28 inpatient individuals receiving ketamine for treatment-resistant depression.

Nighttime sleep problems increased by the 7th infusion and persisted for some individuals at follow-up.
Appetite and weight changes peaked early in treatment, with increased appetite reported by 7 participants and decreased appetite by 6 at the 3rd infusion.
Early waking was observed across multiple timepoints, affecting 3 to 4 participants.
Mood, cognitive, and most somatic symptoms were reported by 2 to 4 participants, indicating they were relatively rare.
Suicidal ideation was minimal, observed in only 1 participant at the 3rd infusion and follow-up.

Simplified

BACKGROUND: Treatment-resistant depression (TRD) poses a significant therapeutic challenge, with remission often unattainable. Recognition and detection of treatment-emergent adverse events (TEAEs) are essential, as these events may significantly influence the quality of treatment response. This knowledge aids in personalizing care and selecting the best treatment strategy.

METHODS: In a retrospective analysis of an observational study of inpatients (n = 28) with TRD, who were administered 8 ketamine infusions as an add-on therapy, psychiatric TEAEs were assessed using the Inventory of Depressive Symptomatology Self-Report 30 (IDS SR-30) and defined as symptoms that were not present at baseline but emerged during ketamine administration. The protocol was registered at ClinicalTrials.gov on Jan 2, 2020 (NCT04226963).

RESULTS: Sleep disturbances were the most consistently reported psychiatric TEAEs, with nighttime sleep problems increasing by the 7th infusion and persisting at follow-up (n = 5), and early waking reported across timepoints (n = 3-4). Appetite and weight changes were also observed, with both increased and decreased appetite peaking early in treatment (n = 7 and n = 6 at the 3rd infusion) and persisting at lower levels at follow-up. In contrast, mood, cognitive, and most somatic symptoms were rare (≤ 2-4 participants), and suicidal ideation was minimal (n = 1 at the 3rd infusion and follow-up).

CONCLUSIONS: This study identified sleep disturbances, appetite changes, and weight fluctuations as common patient-reported TEAEs during ketamine use for TRD inpatients. These preliminary results highlight the need for larger, controlled trials to gain a comprehensive understanding of ketamine's psychiatric safety profile.

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Funding

Competing interests

Declarations. Competing interests: Krzysztof Pastuszak has no conflict of interestMichał Pastuszak received research support from Beckley Psytech, Compass Pathways, Definium Therapeutics, GH Research, MSD. Aleksander Kwaśny received research support from Beckley Psytech, Compass Pathways, Definium Therapeutics, GH Research, MSD. Alina Wilkowska has received research support from Angelini, Biogen, Eli Lilly and Company, Janssen- Cilag, Lundbeck, Polpharma, Sanofi, Termedia, Valeant, Bristol Myers Squibb.Wiesław Jerzy Cubała has received grants: Acadia, Alkermes, Allergan, Angelini, Auspex Pharmaceuticals, Beckley Psytech, BMS, Celon, Cephalon, Compass Pathways, Cortexyme, Ferrier, Forest Laboratories, GedeonRichter, GH Research, GWPharmaceuticals, HMNC Brain Health, IntraCellular Therapies, Janssen, KCR, Lilly, Lundbeck, MindMed (Definium), Minerva, MSD, NIH, Neumora, Novartis, Orion, Otsuka, Recognify Life Sciences, Sanofi, Seaport, Servier; Honoraria: Adamed, Angelini, AstraZeneca, BMS, Celon, GH Research, GSK, Janssen, KRKA, Lekam, Lundbeck, Minerva, NeuroCog, Novartis, Orion, Pfizer, Polfa Tarchomin, Sanofi, Servier, Zentiva; Advisory boards: Angelini, Celon (ended 2021), Douglas Pharmaceuticals, GH Research, Janssen, MSD, Novartis, Polpharma, Sanofi, Tasman Therapeutics.

PubMed

New psychiatric side effects reported by patients during ketamine treatment for major depression

Abstract

Full Text

Funding

Competing interests

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