title: Randomized double-blind placebo-controlled trial of lithium in youths with severe mood dysregulation.
abstract: OBJECTIVE
  The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD) by Leibenluft, has been the focus of increasing concern. We conducted the first randomized double-blind, placebo-controlled trial in SMD youth, choosing lithium on the basis of its potential in treating irritability and aggression and neuro-metabolic effects.
  
  
  METHODS
  SMD youths 7-17 years were tapered off their medications. Those who continued to meet SMD criteria after a 2-week, single-blind, placebo run-in were randomized to a 6-week double-blind trial of either lithium (n = 14) or placebo (n = 11). Clinical outcome measures were: (1) Clinical Global Impressions-Improvement (CGI-I) score less than 4 at trial's end and (2) the Positive and Negative Syndrome Scale (PANSS) factor 4 score. Magnetic resonance spectroscopy (MRS) outcome measures were myoinositol (mI), N-acetyl-aspartate (NAA), and combined glutamate/glutamine (GLX), all referenced to creatine (Cr).
  
  
  RESULTS
  In all, 45% (n = 20/45) of SMD youths were not randomized due to significant clinical improvement during the placebo run-in. Among randomized patients, there were no significant between-group differences in either clinical or MRS outcome measures.
  
  
  CONCLUSIONS
  Our study suggests that although lithium may not result in significant clinical or neurometabolic alterations in SMD youths, further SMD treatment trials are warranted given its prevalence.
authors.affiliation: E.P. Bradley Hospital, Bradley-Hasbro Children's Research Center, 1 Hoppin ST Coro West, Providence, RI 02903, USA. Daniel_Dickstein@Brown.edu
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Dickstein
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Towbin
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Van Der Veen
authors.forename: Brendan A
authors.initials: BA
authors.lastname: Rich
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brotman
authors.forename: Lisa
authors.initials: L
authors.lastname: Knopf
authors.forename: Laura
authors.initials: L
authors.lastname: Onelio
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
authors.forename: Ellen
authors.initials: E
authors.lastname: Leibenluft
mesh_terms: D000293:Adolescent; D018692:Antimanic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D002648:Child; D003401:Creatine / Q000378:metabolism; D003937:Diagnosis, Differential; D004311:Double-Blind Method; D005260:Female; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D019964:Mood Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D016037:Single-Blind Method
chemical_list: D018692:Antimanic Agents; D005973:Glutamine; D016651:Lithium Carbonate; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine