title: Amantadine Effect on Perceptions of Irritability after Traumatic Brain Injury: Results of the Amantadine Irritability Multisite Study.
abstract: This study examines the effect of amantadine on irritability in persons in the post-acute period after traumatic brain injury (TBI). There were 168 persons ≥6 months post-TBI with irritability who were enrolled in a parallel-group, randomized, double-blind, placebo-controlled trial receiving either amantadine 100 mg twice daily or equivalent placebo for 60 days. Subjects were assessed at baseline and days 28 (primary end-point) and 60 of treatment using observer-rated and participant-rated Neuropsychiatric Inventory (NPI-I) Most Problematic item (primary outcome), NPI Most Aberrant item, and NPI-I Distress Scores, as well as physician-rated Clinical Global Impressions (CGI) scale. Observer ratings between the two groups were not statistically significantly different at day 28 or 60; however, observers rated the majority in both groups as having improved at both intervals. Participant ratings for day 60 demonstrated improvements in both groups with greater improvement in the amantadine group on NPI-I Most Problematic (p<0.04) and NPI-I Distress (p<0.04). These results were not significant with correction for multiple comparisons. CGI demonstrated greater improvement for amantadine than the placebo group (p<0.04). Adverse event occurrence did not differ between the two groups. While observers in both groups reported large improvements, significant group differences were not found for the primary outcome (observer ratings) at either day 28 or 60. This large placebo or nonspecific effect may have masked detection of a treatment effect. The result of this study of amantadine 100 mg every morning and noon to reduce irritability was not positive from the observer perspective, although there are indications of improvement at day 60 from the perspective of persons with TBI and clinicians that may warrant further investigation.
authors.affiliation: 1 Department of Physical Medicine and Rehabilitation, Indiana University School of Medicine , and Rehabilitation Hospital of Indiana, Indianapolis, Indiana.|2 Department of Physical Medicine and Rehabilitation, Carolinas Rehabilitation, Carolinas HealthCare System , Charlotte, North Carolina.
authors.forename: Flora M
authors.initials: FM
authors.lastname: Hammond
authors.affiliation: 3 TIRR Memorial Hermann , Houston, Texas.
authors.forename: Mark
authors.initials: M
authors.lastname: Sherer
authors.affiliation: 1 Department of Physical Medicine and Rehabilitation, Indiana University School of Medicine , and Rehabilitation Hospital of Indiana, Indianapolis, Indiana.
authors.forename: James F
authors.initials: JF
authors.lastname: Malec
authors.affiliation: 4 Spaulding Rehabilitation Hospital , Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Ross D
authors.initials: RD
authors.lastname: Zafonte
authors.affiliation: 2 Department of Physical Medicine and Rehabilitation, Carolinas Rehabilitation, Carolinas HealthCare System , Charlotte, North Carolina.
authors.forename: Marybeth
authors.initials: M
authors.lastname: Whitney
authors.affiliation: 5 University of Washington , Seattle, Washington.|7 University of Texas Southwestern Medical School , Dallas, Texas.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bell
authors.affiliation: 5 University of Washington , Seattle, Washington.
authors.forename: Sureyya
authors.initials: S
authors.lastname: Dikmen
authors.affiliation: 6 Department of Physical Medicine and Rehabilitation, The Ohio State University , Columbus, Ohio.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bogner
authors.affiliation: 6 Department of Physical Medicine and Rehabilitation, The Ohio State University , Columbus, Ohio.
authors.forename: Jerry
authors.initials: J
authors.lastname: Mysiw
authors.affiliation: 2 Department of Physical Medicine and Rehabilitation, Carolinas Rehabilitation, Carolinas HealthCare System , Charlotte, North Carolina.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Pershad
mesh_terms: D000328:Adult; D000547:Amantadine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care
chemical_list: D015259:Dopamine Agents; D000547:Amantadine
keywords: aggression; agitation; amantadine; brain injuries; irritability