title: An open pilot study of zonisamide augmentation in major depressive patients not responding to a low dose trial with duloxetine: preliminary results on tolerability and clinical effects.
abstract: BACKGROUND
  Despite multiple antidepressant options, major depressive disorder (MDD) still faces high non-response rates, eventually requiring anticonvulsant augmentation strategies too. The aim of this study was to explore such a potential role for zonisamide.
  
  
  METHODS
  A total of 40 MDD outpatients diagnosed using the Diagnostic and Statistical Manual for Mental Disorders, fourth edition criteria entered a 24 week open trial receiving duloxetine 60 mg/day for the first 12 weeks and subsequently (weeks 12 to 24) augmentation with zonisamide 75 mg/day if they did not respond to the initial monotherapy. Efficacy and tolerability were assessed using the Hamilton Scales for Anxiety and Depression (a 12 week score ≥50% vs baseline defined 'non-response'), the Arizona Sexual Experience Scale, the Patient Rated Inventory of Side Effects and the Young Mania Rating Scale.
  
  
  RESULTS
  At week 12, 15 patients out of 39 (38.5%) were responders, and 1 had dropped out; remarkably, 14 patients out of 24 (58.3%) had achieved response by week 24. Poor concentration and general malaise were associated with non-response both at week 12 and 24 (P = 0.001), while loss of libido and reduced energy were prominent among final timepoint non-responders. Patients receiving zonisamide also experienced weight reduction (2.09 ± 12.14 kg; P = 0.001) independently of the outcome.
  
  
  CONCLUSIONS
  Although only a preliminary study due to strong methodological limitations, and thus requiring confirmation by further controlled investigations, the current results indicate zonisamide may be a potential augmentation option for some depressed patients receiving low doses of duloxetine.
authors.affiliation: Department of Neuroscience, Section of Psychiatry, University of Genova, Genoa, Italy. matteomartino9@libero.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Fornaro
authors.forename: Matteo
authors.initials: M
authors.lastname: Martino
authors.forename: Bruna
authors.initials: B
authors.lastname: Dalmasso
authors.forename: Salvatore
authors.initials: S
authors.lastname: Colicchio
authors.forename: Marzia
authors.initials: M
authors.lastname: Benvenuti
authors.forename: Giulio
authors.initials: G
authors.lastname: Rocchi
authors.forename: Andrea
authors.initials: A
authors.lastname: Escelsior
authors.forename: Giulio
authors.initials: G
authors.lastname: Perugi