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Updated: Mar 30, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Interaction between methylphenidate, methadone and different antidepressant drugs on antinociception in mice, and
Shaul Schreiber1, Miaad Bader2, Vardit Rubovitch2
1a Department of Psychiatry , Tel Aviv Sourasky Medical Center & Tel Aviv University Sackler Faculty of Medicine , Tel Aviv , Israel.
Objectives:
Methylphenidate (MPH), a psychostimulant used for treatment of attention deficit hyperactivity disorder (ADHD), is widely used by patients on antidepressants and methadone maintenance treatment (MMT). Preclinical studies showed MPH to exert analgesic effects when given alone or with morphine.
Methods:
Using the hotplate assay on mice, we studied the interaction of acute doses of MPH with sub-threshold doses of methadone and different antidepressant medications and the interaction of increasing doses of MPH with chronic methadone.
Results:
Adding a sub-threshold dose of venlafaxine, desipramine or clomipramine to MPH produced significant augmentation of MPH antinociception with each medication (P < 0.05). No such interactions were found between escitalopram and acute methadone. However, addition of increasing doses of MPH to chronic methadone given for 2 weeks using ALZET osmotic mini pumps induced augmentation of the antinociceptive effect of chronic methadone exclusively at high dose of MPH (7.5 mg/kg).
Conclusions:
These findings may implicate the need of an excessive attention to the administration of MPH to MMT patients. The no interaction found between MPH and escitalopram may hint to the possibly safe co-administration of MPH and selective serotonin reuptake inhibitors (SSRIs) to depressed ADHD patients. Further studies are needed in order to validate these possible clinical implications.
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