Interaction between Methylphenidate, Methadone and Different Antidepressant Drugs in Mice and Possible Clinical Implications

Miaad Bader, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Shaul Schreiber, Department of Psychiatry, Tel Aviv Sourasky Medical Center & Tel Aviv University Sackler Faculty of Medicine , Tel Aviv University, Tel Aviv, Israel
Vardit Rubovitch, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Chaim G. Pick, Department of Anatomy and Anthropology, Sackler Faculty of Medicine And Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel

Methylphenidate (MPH), a psychostimulant used for the treatment of attention deficit hyperactivity disorder (ADHD), is widely used by patients treated with antidepressants and / or methadone maintenance treatment. Preclinical studies in rats showed that MPH has an analgesic effect when given alone or in combination with morphine. In the present experiments we studied the interaction of acute doses of MPH with sub threshold doses of methadone and different antidepressant medications. Next, we studied the interaction of increasing doses of MPH with chronic methadone using implanted mini pumps. For these goals we performed the hot plate assay on mice. The addition of a sub threshold dose of venlafaxine, desipramine and clomipramine to MPH produced significant augmentation of MPH antinociceptive effect with each medication (p<0.05). No interactions were found when sub threshold doses of escitalopram and methadone were added to acute doses of MPH. On the other hand, addition of increasing doses of MPH to chronic methadone given for 2 weeks using osmotic mini pumps induced augmentation of the antinociceptive effect of chronic methadone exclusively at high dose of MPH. These findings may implicate the need of an excessive attention to the administration of MPH given to MMT patients. The findings of the no interaction between MPH and escitalopram may hint to the possibly safe co-administration of methylphenidate and SSRIs to depressed ADHD patients. Further studies are needed before these possible clinical implications can be validated. Supported by (i) The Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases. (ii) The Ari and Regine Aprijaskis Fund, at Tel-Aviv University. None of the authors has a conflict of interest related to this research.