Lamotrigine adjunctive therapy to lithium and divalproex in depressed patients with rapid cycling bipolar disorder and a recent substance use disorder: a 12-week, double-blind, placebo-controlled pilot study.
OBJECTIVE
To pilot the efficacy and safety data of lamotrigine adjunctive therapy to lithium and divalproex in patients with rapid-cycling bipolar disorder (RCBD) and a recent substance use disorder (SUD).


METHODS
Structured clinical interviews were used to ascertain DSM-IV diagnosis of RCBD, SUDs, and other Axis I disorders. Patients who did not meet the criteria for a bimodal response after up to 16-weeks of open-label treatment with lithium plus divalproex, as measured by MADRS (Montgomery-Asberg Depression Rating Scale) ≤ 19, YMRS ( Young Mania Rating Scale) ≤ 12 and GAF (Global Assessment of Functioning) = 51 for 4 weeks, were randomized to a 12- week, double-blind addition of lamotrigine or placebo to lithium plus divalproex. Primary and secondary outcomes were analyzed with ANCOVA, t-test, or chi-square/Fisher's exact.


RESULTS
Of 98 patients enrolled into the study, 36 were randomized to receive lamotrigine (n = 18) or placebo (n ± 18), and 8 patients per arm completed the study. No patient discontinued due to adverse events. The change in MADRS total score from baseline to endpoint was -9.1 ± 11.2 in lamotrigine-treated patients versus -4.5 ± 13.1 in placebo-treated patients (p = 0.27). There were no significant differences in changes in YMRS total scores and rates of response or remission.


CONCLUSIONS
Lamotrigine adjunctive therapy was well tolerated in patients previously non-responsive to initial treatment of lithium plus divalproex. A larger study is warranted to determine the efficacy and safety of adjunctive lamotrigine versus placebo in RCBD with a recent SUD.
Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Zuowei
Z
Wang
Keming
K
Gao
David E
DE
Kemp
Philip K
PK
Chan
Mary Beth
MB
Serrano
Carla
C
Conroy
Yiru
Y
Fang
Stephen J
SJ
Ganocy
Robert L
RL
Findling
Joseph R
JR
Calabrese
D000328:Adult; D000704:Analysis of Variance; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D016009:Chi-Square Distribution; D003863:Depression / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D000077213:Lamotrigine; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009820:Ohio; D010865:Pilot Projects; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012074:Remission Induction; D019966:Substance-Related Disorders / Q000150:complications* / Q000523:psychology; D013997:Time Factors; D016896:Treatment Outcome; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D018692:Antimanic Agents; D018020:Lithium Compounds; D010919:Placebos; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine
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