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

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 s...

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Bibliographic Details
Published in:	Translational psychiatry Vol. 4; no. 9; p. e447
Main Authors:	Aga-Mizrachi, S, Cymerblit-Sabba, A, Gurman, O, Balan, A, Shwam, G, Deshe, R, Miller, L, Gorodetsky, N, Heinrich, N, Tzezana, O, Zubedat, S, Grinstein, D, Avital, A
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 23-09-2014 Nature Publishing Group
Subjects:	13/21 631/443 64/86 692/699/476 Animals Antidepressive Agents, Tricyclic - pharmacology Behavioral Sciences Biological Psychology Central Nervous System Stimulants - pharmacology Desipramine - pharmacology Disease Models, Animal Drug Therapy, Combination Male Medicine Medicine & Public Health Methylphenidate - pharmacology Neurosciences Original original-article Pharmacotherapy Psychiatry Rats Rats, Wistar Stress Disorders, Post-Traumatic - drug therapy Treatment Outcome
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2158-3188 2158-3188
DOI:	10.1038/tp.2014.82