title: A novel treatment for tinnitus and tinnitus-related cognitive difficulties using computer-based cognitive training and D-cycloserine.
abstract: OBJECTIVE
  Tinnitus affects more than 40 million people in the Unites States, and cognitive difficulties are among the most commonly associated symptoms.
  
  
  OBJECTIVE
  To test the feasibility and preliminarily the effectiveness of using a putative neuroplasticity-enhancing drug, D-cycloserine, to facilitate a computer-assisted CT program for improving tinnitus bother and related cognitive difficulties.
  
  
  METHODS
  Double-blind, randomized clinical trial at an outpatient academic medical center of 34 participants aged 35 to 65 years with subjective, unilateral or bilateral, nonpulsatile tinnitus of at least 6 months' duration.
  
  
  METHODS
  Five weeks of twice-weekly computer-based CT with either 250 mg D-cycloserine or placebo orally prior to computer CT sessions.
  
  
  METHODS
  Difference in the change in Tinnitus Functional Index (TFI) score between the 2 groups.
  
  
  RESULTS
  After excluding 1 participant lost to follow-up, 1 who withdrew, 1 who did not complete 90% of sessions, and 1 outlier, 30 participants were included in the analysis. The D-cycloserine plus CT group showed a significant improvement in median TFI score (-5.8 [95% CI, -9.4 to -1.1]) and self-reported cognitive deficits (-4.5 [95% CI, -11.5 to -1.0]), but the placebo group did not (-1.0 [95% CI, -11.7 to 4.9] and -2.0 [95% CI, -5.1 to 2.0], respectively). After controlling for age and duration of tinnitus, there was no significant difference in TFI score change between the 2 groups (P = .41). After confounders were controlled for, the D-cycloserine group demonstrated a significantly greater improvement in self-reported cognitive deficits as compared with the placebo group (P = .03). No serious adverse events were reported.
  
  
  CONCLUSIONS
  Use of a computer-based CT program with a putative neuroplasticity-sensitizing drug, D-cycloserine, was feasible and well tolerated. With the limited sample size, the adjuvant use of D-cycloserine was no more effective than placebo at improving tinnitus bother. The finding that D-cycloserine use was more effective than placebo at improving self-reported cognitive difficulties could be important given the high rate of concern for cognitive deficits in patients with tinnitus. D-cycloserine and other putative neuroplasticity-facilitating agents could be investigated in the future as a strategy to enhance neuroplasticity-based tinnitus treatments.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01550796.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri2Doris Duke Clinical Research Fellowship, Washington University School of Medicine, St Louis, Missouri3Stanford Medical Scholars Fellowship, St.
authors.forename: James G
authors.initials: JG
authors.lastname: Krings
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Andre
authors.initials: A
authors.lastname: Wineland
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Dorina
authors.initials: D
authors.lastname: Kallogjeri
authors.affiliation: Department of Psychology, Washington University in St Louis, St Louis, Missouri.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rodebaugh
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Joyce
authors.initials: J
authors.lastname: Nicklaus
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lenze
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Jay F
authors.initials: JF
authors.lastname: Piccirillo
mesh_terms: D000328:Adult; D000368:Aged; D003072:Cognition Disorders / Q000209:etiology / Q000628:therapy*; D015928:Cognitive Behavioral Therapy / Q000379:methods; D003523:Cycloserine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D014012:Tinnitus / Q000150:complications / Q000628:therapy*
chemical_list: D003523:Cycloserine