title: Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model.
abstract: 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.
authors.affiliation: Behavioral Neuroscience Lab, Bruce and Ruth Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Aga-Mizrachi
authors.affiliation: Behavioral Neuroscience Lab, Bruce and Ruth Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Cymerblit-Sabba
authors.affiliation: Department of Psychiatry, Emek Medical Center, Afula, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Gurman
authors.affiliation: Department of Psychiatry, Emek Medical Center, Afula, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Balan
authors.affiliation: Department of Psychiatry, Emek Medical Center, Afula, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Shwam
authors.affiliation: Department of Psychiatry, Emek Medical Center, Afula, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Deshe
authors.affiliation: Department of Psychiatry, Emek Medical Center, Afula, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Miller
authors.affiliation: Department of Psychiatry, Emek Medical Center, Afula, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Gorodetsky
authors.affiliation: Department of Psychiatry, Emek Medical Center, Afula, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Heinrich
authors.affiliation: Department of Psychiatry, Emek Medical Center, Afula, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Tzezana
authors.affiliation: Behavioral Neuroscience Lab, Bruce and Ruth Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Zubedat
authors.affiliation: Behavioral Neuroscience Lab, Bruce and Ruth Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Grinstein
authors.affiliation: 1] Behavioral Neuroscience Lab, Bruce and Ruth Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel [2] Department of Psychiatry, Emek Medical Center, Afula, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Avital
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D003891:Desipramine