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History of episodic heavy alcohol use predicts antidepressant effectiveness of ketamine

Aaishah R. Raquib; Vy Nguyen; Joshua C. Brown; Amanda E. Sedgewick; Stephen Seiner; Joseph J. Taylor; Shan H. Siddiqi; Robert C. Meisner
Psychopharmacology · Vol. 243, Issue 7 · pp. 1693-1699 · 2026

Abstract

Rationale Antidepressant response to ketamine is greatest in patients with a family history of alcohol use disorder (AUD), but it remains unclear if this trend holds true for a personal history of alcohol use. Objective We hypothesized that a personal history of episodic heavy drinking would positively correlate with antidepressant response to ketamine. Methods In a retrospective cohort study, patients with Major Depressive Disorder (MDD) received intravenous ketamine. To assess specificity, patients receiving electroconvulsive therapy (ECT) at the same center were also studied. Depression was quantified using the Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR), And alcohol use was quantified using the Alcohol Use Disorder Identification Test question 3 (AUDIT-3). Results Of 225 patients evaluated for ketamine, 178 completed the AUDIT-3 And completed the initial course of three treatments. Of 2577 that received ECT, 1851 received at least 10 treatments. Across both groups, patients were between age 16 And 90. With ketamine, history of past-year episodic heavy drinking was associated with greater improvement in QIDS-SR with a significant Group x Time interaction after the first three treatments (F(12,502) = 2.25, p = 0.0089), four treatments (F(16,632) = 2.56, p = 0.0007), and five treatments (F(20,757) = 2.22, p = 0.0016). This effect was not seen with ECT after 5 treatments (F(4,2283) = 0.91, p = 0.46), 10 treatments (F(8,3939) = 1.63, p = 0.11), or 20 treatments (F(16,7154) = 1.50, p = 0.09). There was An interaction after 15 treatments (F(12,5113) = 1.93, p = 0.027), although this did not survive multiple comparisons correction. Conclusions In patients with trMDD, history of episodic heavy drinking predicted antidepressant effectiveness of ketamine, but not ECT. These results may assist in patient selection for ECT vs. ketamine.

Bibliographic Information

JournalPsychopharmacology
PublisherSpringer
Publication Date2026-07-01
Publication Year2026
Volume243
Issue7
Pages1693-1699
Document TypeJournal Article
Print ISSN0033-3158
eISSN1432-2072
DOI10.1007/s00213-025-06918-4

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NARA Access Coverage1959-01-01~Current
Journal Homepagehttps://www.springer.com/journal/213
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