Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model

S. Aga-Mizrachi, A. Cymerblit-Sabba, O. Gurman, A. Balan, G. Shwam, R. Deshe, L. Miller, N. Gorodetsky, N. Heinrich, O. Tzezana, S. Zubedat, D. Grinstein, A. Avital

Research output: Contribution to journalArticlepeer-review


Antidepressant medication constitutes the first line pharmacological treatment for posttraumatic stress disorder (PTSD), however, because many patients display no beneficial drug effects it has been suggested that combinations of antidepressants with additional drugs may be necessary. The defining symptoms of PTSD include re-experiencing, avoidance and hyperarousal. In addition, PTSD patients were shown to become easily distracted and often suffer from poor concentration together with indications of comorbidity with attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) is the most common and effective drug treatment for ADHD, thus we aimed to investigate the effects of MPH treatment, by itself or in combination with the antidepressants fluoxetine (FLU) or desipramine (DES). We modified an animal model of PTSD by exposing rats to chronic stress and evaluating the subsequent development of behavioral PTSD-like symptoms, as well as the effects on proinflammatory cytokines, which were implicated in PTSD. We report that while FLU or DES had a beneficial effect on avoidance and hyperarousal symptoms, MPH improved all three symptoms. Moreover, the combination of MPH with DES produced the most dramatic beneficial effects. Serum levels of interleukin-1β (IL-1β) and IL-6 were elevated in the PTSD-like group compared with the control group, and were decreased by MPH, FLU, DES or the combination drug treatments, with the combination of DES+MPH producing the most complete rescue of the inflammatory response. Considering the versatile symptoms of PTSD, our results suggest a new combined treatment for PTSD comprising the antidepressant DES and the psychostimulant MPH.

Original languageEnglish
Article numbere447
JournalTranslational Psychiatry
Issue number9
StatePublished - 1 Jan 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Macmillan Publishers Limited.

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry


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