title: Prazosin addition to fluvoxamine: A preclinical study and open clinical trial in OCD.
abstract: The efficacy of selective serotonin reuptake inhibitors (SRIs) in psychiatric disorders may be "augmented" through the addition of atypical antipsychotic drugs. A synergistic increase in dopamine (DA) release in the prefrontal cortex has been suggested to underlie this augmentation effect, though the mechanism of action is not clear yet. We used in vivo microdialysis in rats to study DA release following the administration of combinations of fluvoxamine (10 mg/kg) and quetiapine (10 mg/kg) with various monoamine-related drugs. The results confirmed that the selective 5-HT1A antagonist WAY-100635 (0.05 mg/kg) partially blocked the fluvoxamine-quetiapine synergistic effect (maximum DA increase dropped from 325% to 214%). A novel finding is that the α1-adrenergic blocker prazosin (1 mg/kg), combined with fluvoxamine, partially mimicked the effect of augmentation (maximum DA increase 205%; area-under-the-curve 163%). As this suggested that prazosin augmentation might be tested in a clinical study, we performed an open clinical trial of prazosin 20 mg addition to SRI in therapy-resistant patients with obsessive-compulsive disorder applying for neurosurgery. A small, non-significant reduction in Yale Brown Obsessive Compulsive Scale (Y-BOCS) scores was observed in 10 patients and one patient was classified as a responder with a reduction in Y-BOCS scores of more than 25%. We suggest that future clinical studies augmenting SRIs with an α1-adrenergic blocker in less treatment resistant cases should be considered. The clinical trial "Prazosin in combination with a serotonin reuptake inhibitor for patients with Obsessive Compulsive disorder: an open label study" was registered at 24/05/2011 under trial number ISRCTN61562706: http://www.controlled-trials.com/ISRCTN61562706.
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands; Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Matthijs G P
authors.initials: MGP
authors.lastname: Feenstra
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands; Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: André
authors.initials: A
authors.lastname: Klompmakers
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Figee
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Fluitman
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: Vulink
authors.affiliation: Department of Psychiatry, UMC Utrecht, Rudolf Magnus Institute of Neuroscience, The Netherlands.
authors.forename: Herman G M
authors.initials: HGM
authors.lastname: Westenberg
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands; Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. Electronic address: ddenys@gmail.com.
authors.forename: Damiaan
authors.initials: D
authors.lastname: Denys
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use*; D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use; D011224:Prazosin / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D055815:Young Adult
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000928:Antidepressive Agents; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D016666:Fluvoxamine; D004298:Dopamine; D011224:Prazosin
keywords: Augmentation; Dopamine; Obsessive compulsive disorder; Prefrontal cortex; Serotonin