Interaction of different antidepressants with acute and chronic methadone in mice, and possible clinical implications

Shaul Schreiber*, Yonatan Barak, Avner Hostovsky, Renana Baratz-Goldstein, Ina Volis, Vardit Rubovitch, Chaim G. Pick

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p<0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn.

Original languageEnglish
Pages (from-to)598-604
Number of pages7
JournalJournal of Molecular Neuroscience
Issue number4
StatePublished - Apr 2014


FundersFunder number
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
Tel Aviv University


    • Acute and chronic methadone administration
    • Antinociceptive effect
    • Hot plate
    • Mice
    • SSRIs
    • Tricyclic antidepressants


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