Trial PaperAnxiety DisordersBipolar DisorderDepressive DisordersSchizophreniaMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Safety & Risk ManagementKetamine

Central nervous system-related safety and tolerability of add-on ketamine to antidepressant medication in treatment-resistant depression: focus on the unique safety profile of bipolar depression

In an observational study of 49 treatment‑resistant inpatients with major depressive disorder and bipolar disorder, add‑on intravenous ketamine was associated with transient psychomimetic and dissociative symptoms—notably more intense in patients taking citalopram or classic mood‑stabilisers (lamotrigine, valproate, lithium)—with no lasting sequelae; the authors conclude ketamine in TRD, particularly bipolar depression, requires close CNS safety and tolerability monitoring.

1 linked clinical trial

Ask Blossom about this paper

Authors

  • Wiesław Cubała

Published

Therapeutic Advances in Psychopharmacology
individual Study

Abstract

Background

There is evidence supporting the use of ketamine in treatment-resistant depression (TRD). However, there are some safety and tolerability concerns associated with ketamine. This study aimed to investigate ketamine’s safety and tolerability to the central nervous system and to assess the relationship between dissociative symptomology and psychometric outcomes during and after intravenous ketamine treatment concurrent with treatment by varying psychotropic medications in treatment-refractory inpatients with major depressive disorder (MDD) and bipolar disorder (BP).

Methods

A total of 49 patients with MDD and BP were included in this study. The subjects were administered ketamine and were assessed for changes using an observational protocol.

Results

No antidepressants were associated with psychomimetic symptomatology except for citalopram ( p = 0.019). Patients treated with citalopram showed a higher intensity of psychomimetic symptomatology. The use of classic mood-stabilizers was significantly associated with an increase in psychomimetic symptomatology according to the Brief Psychiatric Rating Scale (BPRS; lamotrigine p = 0.009, valproate p = 0.048, lithium p = 0.012). No sequelae were observed.

Conclusions

Despite the limitations that this study may be underpowered due to the small sample size, the sample consisted of a heterogeneous TRD population in a single site, and there no blinding of who underwent only acute ketamine administration, our observations indicate ketamine use requires close safety and tolerability monitoring with regards to psychomimetic and dissociative symptoms in TRD-BP and careful management for MDD patients. ClinicalTrials.gov identifier: NCT04226963

Unlocked with Blossom Pro

Research Summary of 'Central nervous system-related safety and tolerability of add-on ketamine to antidepressant medication in treatment-resistant depression: focus on the unique safety profile of bipolar depression'

Editorial

βBlossom's Take

This paper is useful as a safety counterweight to efficacy-focused ketamine studies. It shows that transient psychomimetic and dissociative symptoms can vary with background medication, which matters in real-world TRD and bipolar depression where ketamine is often used alongside other psychotropics rather than in isolation.

Add-on ketamine in treatment-resistant depression was linked to transient CNS side effects, with stronger psychomimetic symptoms in some background medication groups

Sourced

How did central nervous system safety and tolerability look during adjunctive intravenous ketamine in a small treatment-resistant inpatient sample?

49
patients included
citalopram p = 0.019
antidepressant linked to higher psychomimetic symptom intensity
lamotrigine p = 0.009
mood stabiliser associated with increased BPRS psychomimetic symptomatology
valproate p = 0.048
mood stabiliser associated with increased BPRS psychomimetic symptomatology
lithium p = 0.012
mood stabiliser associated with increased BPRS psychomimetic symptomatology

Background medication groups reported as associated with greater psychomimetic symptomatology

lamotrigine
p = 0.009
valproate
p = 0.048
lithium
p = 0.012
Study snapshot figure.

Single-site observational study of 49 treatment-resistant inpatients receiving add-on intravenous ketamine. These numbers describe reported associations with psychomimetic symptoms and the absence of observed sequelae, not a controlled causal estimate of ketamine safety or efficacy.

Expert Research Summary

Go Pro to unlock section-by-section summaries, Blossom's editorial take, and the complete research toolkit.

See Pro Plans

Study Details

Your Personal Research Library

Go Pro to save papers, add notes, rate research, and organize custom shelves.

See Pro Plans