title: Low-frequency repetitive transcranial magnetic stimulation in the right prefrontal cortex combined with partial sleep deprivation in treatment-resistant depression: a randomized sham-controlled trial.
abstract: BACKGROUND
  Sham-controlled low-frequency repetitive transcranial magnetic stimulation (rTMS) was used in patients with pharmacoresistant major depression as an added treatment along with partial sleep deprivation (PSD). In addition, the potential predictive role of brain-derived neurotrophic factor genetic polymorphism on treatment response was analyzed.
  
  
  METHODS
  We recruited 19 female patients (48.3 ± 8.6 years old) with treatment-resistant unipolar major depression (Hamilton Depression Rating Scale [HDRS] score ≥20) who were on a stable antidepressant treatment. They received either 1-Hz rTMS or sham stimulation over the right dorsolateral prefrontal cortex (intensity of 110% of the threshold; 3000 stimuli per protocol; and 10 daily sessions). Additionally, PSD was applied once per week during the treatment. The patients were evaluated (HDRS and Clinical Global Impression Scale) by a blind rater at baseline (B) and after 2 and 3 weeks (W2 and W3) of treatment for short-term outcome. Long-term evaluations were performed after 12 (W12) and 24 weeks (W24) for patients who received active stimulation.
  
  
  RESULTS
  Eleven patients in the active group showed a significant HDRS score reduction from 30.09 ± 3.53 (B) to 16.73 ± 5.71 (W3) compared to the lack of therapeutic response in the sham-treated patients. The long-term follow-up for the active group included 64% of the responders at W12 and 55% at W24. Full remission (HDRS ≤10) was achieved in 5 of 11 patients. Four of these 5 patients with long-term sustained remission expressed the Val66Val genotype.
  
  
  CONCLUSIONS
  Our study suggests a clinically relevant response, persisting for up to 6 months, from 1-Hz rTMS over the right dorsolateral prefrontal cortex and PSD in patients with pharmacoresistant major depression. The brain-derived neurotrophic factor Val66Val homozygous genotype may be related to a better treatment outcome.
authors.affiliation: From the *Psychiatric Hospital, Clinical Hospital Center "Dr Dragisa Misovic", Belgrade, Serbia; †Faculty of Biology, University of Belgrade, Belgrade, Serbia; ‡Department of Human Genetics and Prenatal Diagnostics, Clinical Hospital Center "Zvezdara", Belgrade, Serbia; §Institute for Medical Research, University of Belgrade, Belgrade, Serbia; ║School of Medicine, University of Belgrade, Belgrade, Serbia; and ¶Department of Clinical Neurophysiology, Medical Faculty of Military Medical Academy, University of Defense, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Krstić
authors.forename: Ivana
authors.initials: I
authors.lastname: Buzadžić
authors.forename: Slađan D
authors.initials: SD
authors.lastname: Milanović
authors.forename: Nela V
authors.initials: NV
authors.lastname: Ilić
authors.forename: Sanja
authors.initials: S
authors.lastname: Pajić
authors.forename: Tihomir V
authors.initials: TV
authors.lastname: Ilić
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000523:psychology / Q000628:therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity; D017397:Prefrontal Cortex; D012892:Sleep Deprivation / Q000523:psychology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D019208:Brain-Derived Neurotrophic Factor