Randomized double-blind placebo-controlled trial of lithium in youths with severe mood dysregulation.
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.
Dickstein
Daniel P
DP
E.P. Bradley Hospital, Bradley-Hasbro Children's Research Center, 1 Hoppin ST Coro West, Providence, RI 02903, USA. Daniel_Dickstein@Brown.edu
Towbin
Kenneth E
KE
Van Der Veen
Jan Willem
JW
Rich
Brendan A
BA
Brotman
Melissa A
MA
Knopf
Lisa
L
Onelio
Laura
L
Pine
Daniel S
DS
Leibenluft
Ellen
E
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
D018692:Antimanic Agents; D005973:Glutamine; D016651:Lithium Carbonate; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine