title: Does nefazodone improve both depression and Parkinson disease? A pilot randomized trial.
abstract: Some of the selective serotonin reuptake inhibitors (SSRI)-induced motor side effects are mediated by stimulating 5-HT2 receptors in the basal ganglia, probably because serotonin inhibits the subsequent neuronal dopamine release. We hypothesized that nefazodone, a serotonin 2 antagonist/reuptake inhibitor (SARI) that selectively blocks 5-HT2 receptors, could disrupt the aforementioned inhibitory pathway. Therefore, increased dopamine levels in the postsynaptic milieu and an improvement in the motor symptoms in depressed patients with Parkinson disease (PD) should be observed. This study was designed to determine whether nefazodone has a dual activity as an antidepressant and as an agent capable of reducing the extrapyramidal symptoms in depressed parkinsonian patients. Depressed patients with PD were randomly assigned to 2 therapeutic groups: nefazodone or fluoxetine. Patients were evaluated by a psychiatrist and were blindly assessed by a neurologist with an array of scales. Patients on nefazodone (n = 9) showed a significant improvement over time in the total Unified Parkinson Disease Rating Scale score (UPDRS) (part II + part III) (P = 0.004) and in the UPDRS subscore part III (P = 0.003). None of these scores changed over time in the fluoxetine group (n = 7). Both, nefazodone and fluoxetine were equally effective as antidepressants: Beck Depression Inventory scores significantly improved (P < 0.001), with no significant differences between treatment groups (P = 0.97). If our results can be confirmed in a larger clinical trial, nefazodone ought to be considered over fluoxetine given its secondary beneficial effects regarding the reduction of extrapyramidal symptoms in depressed PD patients.
authors.affiliation: Department of Neurology, Consorci Sanitari Creu Roja a Catalunya, L' Hospitalet de Llobregat, Barcelona, Spain. Asuncion.Avila@chcr.scs.es
authors.forename: Asunción
authors.initials: A
authors.lastname: Avila
authors.forename: Xavier
authors.initials: X
authors.lastname: Cardona
authors.forename: Montserrat
authors.initials: M
authors.lastname: Martin-Baranera
authors.forename: Plácida
authors.initials: P
authors.lastname: Maho
authors.forename: Francesc
authors.initials: F
authors.lastname: Sastre
authors.forename: Juan
authors.initials: J
authors.lastname: Bello
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D003863:Depression / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D010865:Pilot Projects; D010879:Piperazines; D011446:Prospective Studies; D016037:Single-Blind Method; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D014230:Triazoles; C051752:nefazodone