Duloxetine-bupropion combination for treatment-resistant atypical depression: a double-blind, randomized, placebo-controlled trial.
The efficacy, safety, and tolerability of combined bupropion versus placebo using duloxetine as active reference drug, in patients with a DSM-IV diagnosis of major depression with atypical features and a history of treatment resistance, were evaluated in this preliminary six-week study. Patients (n=46) had a baseline Hamilton Depression Scale (HAM-D) ≥14 and were randomly assigned to 150/300 mg/day bupropion vs. placebo, which was added to 60 to 120 mg/day duloxetine depending on baseline depression severity. Atypical features of depression were assessed using the additional eight-item module of the Structured Interview Guide for the HAM-D with the Atypical Depression Supplement. By week 6, only five (21.7%) patients receiving duloxetine+placebo vs. six (26.1%) patients on the bupropion combination achieved response. No significant difference in final HAM-D scores between the two groups was observed between those patients achieving response. The presence of a higher number of atypical features significantly predicted non-response, with the relevant binary logistic regression model correctly classifying 17 out 22 (77.3%) of non-responders [Exp(B)=0.294; p=0.016] vs. 17 out 23 (73.9%) [Exp(B)=0.353; p=0.028] non-responder cases in the "+placebo" and "+bupropion" groups, respectively. In those patients receiving bupropion, treatment-emergent adverse events leading to withdrawal were more common among those receiving lower doses of the combination drug, and no life-threating dangers were noted. Additional studies, including an adequate course of duloxetine trial, are nonetheless aimed to allow a firm conclusion about the usefulness of the combination of duloxetine and bupropion for treatment-resistant cases of major depression with atypical features.
Department of Education Science, University of Catania, Catania, Italy. Electronic address: dott.fornaro@gmail.com.
Michele
M
Fornaro
Department of Neurosciences, Ophthalmology and Genetics - Section of Psychiatry, University of Genova, Genoa, Italy. Electronic address: matteomartino9@gmail.com.
Matteo
M
Martino
Department of Neurosciences, Ophthalmology and Genetics - Section of Psychiatry, University of Genova, Genoa, Italy. Electronic address: chiaramattei@gmail.com.
Chiara
C
Mattei
Department of Neurosciences, Ophthalmology and Genetics - Section of Psychiatry, University of Genova, Genoa, Italy. Electronic address: davideprestia@alice.it.
Davide
D
Prestia
Department of Neurosciences, Ophthalmology and Genetics - Section of Psychiatry, University of Genova, Genoa, Italy. Electronic address: sailing_boat@libero.it.
Valentina
V
Vinciguerra
Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "ASL 4", Teramo, Italy. Electronic address: dodebera@aliceposta.it.
Domenico
D
De Berardis
Department of Education Science, University of Catania, Catania, Italy. Electronic address: depasqua@unict.it.
Concetta
C
De Pasquale
Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University School of Medicine" Federico II" of Naples, Italy. Electronic address: felix_ias@hotmail.com.
Felice
F
Iasevoli
Department of Neurosciences, Ophthalmology and Genetics - Section of Psychiatry, University of Genova, Genoa, Italy. Electronic address: sergiomungo@libero.it.
Sergio
S
Mungo
Department of Neurosciences, Ophthalmology and Genetics - Section of Psychiatry, University of Genova, Genoa, Italy. Electronic address: prof.fornaro@gmail.com.
Pantaleo
P
Fornaro
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D016642:Bupropion / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068736:Duloxetine Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D013876:Thiophenes / Q000627:therapeutic use*; D055815:Young Adult
D000928:Antidepressive Agents; D013876:Thiophenes; D016642:Bupropion; D000068736:Duloxetine Hydrochloride
Atypical depression; Bupropion; Duloxetine; Placebo-controlled; Randomized trial (RCT); Treatment-resistant depression