A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group.

BACKGROUND Patients with rapid-cycling bipolar disorder are often treatment refractory. This study examined lamotrigine as maintenance monotherapy for rapid-cycling bipolar disorder. METHOD Lamotrigine was added to patients' current psychotropic regimens and titrated to clinical effect during an open-label treatment phase. Stabilized patients were tapered off other psychotropics and randomly assigned to lamotrigine or placebo monotherapy for 6 months. Time to additional pharmacotherapy for emerging symptoms was the primary outcome measure. Secondary efficacy measures included survival in study (time to any premature discontinuation), percentage of patients stable without relapse for 6 months, and changes in the Global Assessment Scale and Clinical Global Impressions-Severity scale. Safety was assessed from adverse event, physical examination, and laboratory data. RESULTS 324 patients with rapid-cycling bipolar disorder (DSM-IV criteria) received open-label lamotrigine, and 182 patients were randomly assigned to the double-blind maintenance phase. The difference between the treatment groups in time to additional pharmacotherapy did not achieve statistical significance in the overall efficacy population. However, survival in study was statistically different between the treatment groups (p = .036). Analyses also indicated a 6-week difference in median survival time favoring lamotrigine. Forty-one percent of lamotrigine patients versus 26% of placebo patients (p = .03) were stable without relapse for 6 months of monotherapy. Lamotrigine was well tolerated; there were no treatment-related changes in laboratory parameters, vital signs, or body weight. No serious rashes occurred. CONCLUSION This was the largest and only prospective placebo-controlled study of rapid-cycling bipolar disorder patients to date; results indicate lamotrigine monotherapy is a useful treatment for some patients with rapid-cycling bipolar disorder.

[1]  A J Rush,et al.  The Stanley Foundation Bipolar Treatment Outcome Network. II. Demographics and illness characteristics of the first 261 patients. , 2001, Journal of affective disorders.

[2]  J. Calabrese,et al.  A Randomized, Placebo-Controlled 12-Month Trial of Divalproex and Lithium in Treatment of Outpatients With Bipolar I Disorder , 2000 .

[3]  G. Sachs,et al.  The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000. , 2000, Postgraduate medicine.

[4]  J. Calabrese,et al.  Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. , 1999, The American journal of psychiatry.

[5]  J. Calabrese,et al.  Mood stabilizers and the evolution of maintenance study designs in bipolar I disorder. , 1999, The Journal of clinical psychiatry.

[6]  J. Calabrese,et al.  The efficacy of lamotrigine in rapid cycling and non–rapid cycling patients with bipolar disorder , 1999, Biological Psychiatry.

[7]  T. Suppes,et al.  Lamotrigine for the treatment of bipolar disorder: a clinical case series. , 1999, Journal of affective disorders.

[8]  S. Hoopes.  Lamotrigine in the treatment of affective disorders: A clinical experience , 1998, European Neuropsychopharmacology.

[9]  J. Calabrese,et al.  Clinical Studies on the Use of Lamotrigine in Bipolar Disorder , 1998, Neuropsychobiology.

[10]  C. Bowden.  New Concepts in Mood Stabilization: Evidence for the Effectiveness of Valproate and Lamotrigine , 1998, Neuropsychopharmacology.

[11]  R. Baldessarini,et al.  Lithium maintenance treatment of depression and mania in bipolar I and bipolar II disorders. , 1998, The American journal of psychiatry.

[12]  R. Suddath,et al.  Preliminary evidence of the reliability and validity of the prospective life-chart methodology (LCM-p). , 1997, Journal of psychiatric research.

[13]  L. Magliano,et al.  Validity of rapid cycling as a course specifier for bipolar disorder. , 1994, The American journal of psychiatry.

[14]  R. Spitzer.  Dsm-IV Casebook: A Learning Companion to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , 1994 .

[15]  J. Calabrese,et al.  Multisite data reanalysis of the validity of rapid cycling as a course modifier for bipolar disorder in DSM-IV. , 1994, The American journal of psychiatry.

[16]  David F. Smith,et al.  Seizure Severity and the Quality of Life , 1993, Epilepsia.

[17]  R. Post,et al.  Graphic representation of the life course of illness in patients with affective disorder. , 1988, The American journal of psychiatry.

[18]  R. Post,et al.  Ventricular-brain ratio and life course of illness in patients with affective disorder , 1988, Psychiatry Research.

[19]  L. Tondo,et al.  Course of the Manic-Depressive Cycle and Changes Caused by Treatments , 1980, Pharmakopsychiatrie, Neuro-Psychopharmakologie.

[20]  F. Goodwin,et al.  Rapid cycling in manic-depressives induced by tricyclic antidepressants. , 1979, Archives of general psychiatry.

[21]  J. Endicott,et al.  A diagnostic interview: the schedule for affective disorders and schizophrenia. , 1978, Archives of general psychiatry.

[22]  J. Fleiss,et al.  The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. , 1976, Archives of general psychiatry.

[23]  R. Fieve,et al.  Clinical factors in lithium carbonate prophylaxis failure. , 1974, Archives of general psychiatry.

[24]  M. Hamilton.  A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[25]  Charles L. Bowden,et al.  A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar i depression , 1999 .

[26]  L. Magliano,et al.  Long-term outcome of lithium prophylaxis in bipolar disorder: a 5-year prospective study of 402 patients at a lithium clinic. , 1998, The American journal of psychiatry.

[27]  M. Frye,et al.  Drug-Induced Switching in Bipolar Disorder , 1997 .

[28]  M. First,et al.  Structured clinical interview for DSM-IV axis I disorders : SCID-I: clinical version : administration booklet , 1997 .

[29]  Rush-Presbyterian-St. Luke's Medical Center and Others v. Hellenic Republic and Others , 1995, International Law Reports.