This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Depersonalization disorder (DPD) is a chronic, disabling psychiatric condition that is characterized by feelings of estrangement, detachment, and disconnection from one's sense of self. Currently, there are no approved pharmacological agents for the treatment of DPD. Recent controlled trials of both SSRI and lamotrigine in DPD unfortunately proved negative. State-of-the-art psychopharmacologic treatment for the disorder is currently conducted without proven efficacy or systematic guidelines for any medication. Pharmacologists usually attempt to use a variety of marketed medications on the basis of the symptom and comorbidity profile of each individual patient. However, based both on theoretical reasoning and case report data, there is reason to hypothesize that the NMDA partial glycine agonist D-cycloserine (DCS) and the 5HT2A and C antagonist cyproheptadine (CH) may have some efficacy in the treatment of DPD. We therefore propose to conduct a pilot crossover medication treatment study consisting of an 8-week open treatment arm with DCS and an 8-week open treatment arm with CH, administered in randomized sequence with a 2-week washout period in 15 subjects currently suffering from DSM-IV depersonalization.
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