Anna Tiihonen Möller1,2, Torbjörn Bäckström3, Sigrid Nyberg3, Hans Peter Söndergaard4, Lotti Helström4,5. 1. Department of Clinical Science and Education, Karolinska Institutet, Solna, Sweden. anna.moller@ki.se. 2. Department of Obstetrics and Gynecology, Stockholm South Hospital, SE-118 83, Stockholm, Sweden. anna.moller@ki.se. 3. Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. 4. Department of Clinical Science and Education, Karolinska Institutet, Solna, Sweden. 5. Department of Obstetrics and Gynecology, Stockholm South Hospital, SE-118 83, Stockholm, Sweden.
Abstract
RATIONALE: The use of benzodiazepines in treating anxiety symptoms in patients with posttraumatic stress disorder (PTSD) has been debated. Studies on other anxiety disorders have indicated changed sensitivity to GABA-A receptor active substances. OBJECTIVE: In the present study, we investigated the GABA receptor sensitivity in PTSD patients. METHODS: Injections of allopreganolone, diazepam, and flumazenil were carried out, each on separate occasions, in 10 drug naïve patients with PTSD compared to 10 healthy controls. Effects were measured in saccadic eye velocity (SEV) and in subjective ratings of sedation. RESULTS: The PTSD patients were less sensitive to allopregnanolone compared with healthy controls. This was seen as a significant difference in SEV between the groups (p = 0.047). Further, the patients were less sensitive to diazepam, with a significant less increase in sedation compared to controls (p = 0.027). After flumazenil injection, both patients and controls had a significant agonistic effect on SEV, leading to decreased SEV after injection. The patients also responded with an increase in sedation after flumazenil injection, while this was not seen in the controls. CONCLUSIONS: Patients with PTSD have a changed sensitivity to GABA-A receptor active substances. As a consequence of this, benzodiazepines and other GABA-A receptor active compounds such as sleeping pills will be less useful for this group of patients.
RATIONALE: The use of benzodiazepines in treating anxiety symptoms in patients with posttraumatic stress disorder (PTSD) has been debated. Studies on other anxiety disorders have indicated changed sensitivity to GABA-A receptor active substances. OBJECTIVE: In the present study, we investigated the GABA receptor sensitivity in PTSDpatients. METHODS: Injections of allopreganolone, diazepam, and flumazenil were carried out, each on separate occasions, in 10 drug naïve patients with PTSD compared to 10 healthy controls. Effects were measured in saccadic eye velocity (SEV) and in subjective ratings of sedation. RESULTS: The PTSDpatients were less sensitive to allopregnanolone compared with healthy controls. This was seen as a significant difference in SEV between the groups (p = 0.047). Further, the patients were less sensitive to diazepam, with a significant less increase in sedation compared to controls (p = 0.027). After flumazenil injection, both patients and controls had a significant agonistic effect on SEV, leading to decreased SEV after injection. The patients also responded with an increase in sedation after flumazenil injection, while this was not seen in the controls. CONCLUSIONS:Patients with PTSD have a changed sensitivity to GABA-A receptor active substances. As a consequence of this, benzodiazepines and other GABA-A receptor active compounds such as sleeping pills will be less useful for this group of patients.
Authors: Hal A Droogleever Fortuyn; Frank van Broekhoven; Paul N Span; Torbjörn Bäckström; Frans G Zitman; Robbert J Verkes Journal: Psychoneuroendocrinology Date: 2004-11 Impact factor: 4.905
Authors: Carina Seah; Michael S Breen; Tom Rusielewicz; Heather N Bader; Changxin Xu; Christopher J Hunter; Barry McCarthy; P J Michael Deans; Mitali Chattopadhyay; Jordan Goldberg; Frank Desarnaud; Iouri Makotkine; Janine D Flory; Linda M Bierer; Migle Staniskyte; Scott A Noggle; Laura M Huckins; Daniel Paull; Kristen J Brennand; Rachel Yehuda Journal: Nat Neurosci Date: 2022-10-20 Impact factor: 28.771
Authors: Matthew J Girgenti; Jiawei Wang; Dingjue Ji; Dianne A Cruz; Murray B Stein; Joel Gelernter; Keith A Young; Bertrand R Huber; Douglas E Williamson; Matthew J Friedman; John H Krystal; Hongyu Zhao; Ronald S Duman Journal: Nat Neurosci Date: 2020-12-21 Impact factor: 24.884