Prazosin addition to fluvoxamine: A preclinical study and open clinical trial in OCD

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• 作者：Matthijs G.P. Feenstra^a ; ^b ; ¹ ; André ; Klompmakers^a ; ^b ; ¹ ; Martijn Figee^a ; ¹ ; Sjoerd Fluitman^a ; Nienke Vulink^a ; Herman G.M. Westenberg^c ; ² ; Damiaan Denys^a ; ^b ; ^{ddenys@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Dopamine ; Serotonin ; Prefrontal cortex ; Augmentation ; Obsessive compulsive disorder
• 刊名：European Neuropsychopharmacology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：26
• 期：2
• 页码：310-319
• 全文大小：1060 K

文摘

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-HT_1A 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 α_1-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.