A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder

Joseph R. Calabrese, Charles L. Bowden, Gary Sachs, Lakshmi N. Yatham, Kirsten Behnke, Olli Pekka Mehtonen, Paul Montgomery, John Ascher, Walter Paska, Nancy Earl, Joseph DeVeaugh-Geiss

Research output: Contribution to journalArticle

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Abstract

Background: The anticonvulsant lamotrigine was previously shown to be effective for bipolar depression. This study assessed the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of mood episodes in bipolar disorder. Method: During an 8- to 16-week open-label phase, lamotrigine (titrated to 200 mg/day) was added to current therapy for currently or recently depressed DSM-IV-defined bipolar I outpatients (N = 966) and concomitant drugs were gradually withdrawn. Patients stabilized on open-label treatment (N = 463) were then randomly assigned to lamotrigine (50, 200, or 400 mg/day; N = 221), lithium (0.8-1.1 mEq/L; N = 121), or placebo (N = 121) monotherapy for up to 18 months. The primary outcome measure was time from randomization to intervention (addition of pharmacotherapy) for any mood episode (depressive, manic, hypomanic, or mixed). Data were gathered from September 1997 to August 2001. Results: Time to intervention for any mood episode was statistically superior (p = .029) for both lamotrigine and lithium compared with placebo-median survival times were 200, 170, and 93 days, respectively. Intervention for depression was more frequent than for mania by a factor of nearly 3:1. Lamotrigine was statistically superior to placebo at prolonging the time to intervention for a depressive episode (p = .047). The proportions of patients who were intervention-free for depression at 1 year were lamotrigine 57%, lithium 46%, and placebo 45%. Lithium was statistically superior to placebo at prolonging the time to intervention for a manic or hypomanic episode (p = .026). The proportions of patients who were intervention-free for mania at 1 year were lamotrigine 77%, lithium 86%, and placebo 72%. Headache was the most frequent adverse event for all 3 treatment groups. Conclusion: Lamotrigine and lithium were superior to placebo for the prevention of mood episodes in bipolar I patients, with lamotrigine predominantly effective against depression and lithium predominantly effective against mania.

Original languageEnglish (US)
Pages (from-to)1013-1024
Number of pages12
JournalJournal of Clinical Psychiatry
Volume64
Issue number9
StatePublished - Sep 1 2003

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Bipolar Disorder
Lithium
Placebos
Therapeutics
Depression
lamotrigine
Random Allocation
Diagnostic and Statistical Manual of Mental Disorders
Anticonvulsants
Headache
Outpatients
Outcome Assessment (Health Care)
Drug Therapy
Survival

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

Calabrese, J. R., Bowden, C. L., Sachs, G., Yatham, L. N., Behnke, K., Mehtonen, O. P., ... DeVeaugh-Geiss, J. (2003). A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. Journal of Clinical Psychiatry, 64(9), 1013-1024.

A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. / Calabrese, Joseph R.; Bowden, Charles L.; Sachs, Gary; Yatham, Lakshmi N.; Behnke, Kirsten; Mehtonen, Olli Pekka; Montgomery, Paul; Ascher, John; Paska, Walter; Earl, Nancy; DeVeaugh-Geiss, Joseph.

In: Journal of Clinical Psychiatry, Vol. 64, No. 9, 01.09.2003, p. 1013-1024.

Research output: Contribution to journalArticle

Calabrese, JR, Bowden, CL, Sachs, G, Yatham, LN, Behnke, K, Mehtonen, OP, Montgomery, P, Ascher, J, Paska, W, Earl, N & DeVeaugh-Geiss, J 2003, 'A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder', Journal of Clinical Psychiatry, vol. 64, no. 9, pp. 1013-1024.
Calabrese, Joseph R. ; Bowden, Charles L. ; Sachs, Gary ; Yatham, Lakshmi N. ; Behnke, Kirsten ; Mehtonen, Olli Pekka ; Montgomery, Paul ; Ascher, John ; Paska, Walter ; Earl, Nancy ; DeVeaugh-Geiss, Joseph. / A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. In: Journal of Clinical Psychiatry. 2003 ; Vol. 64, No. 9. pp. 1013-1024.
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abstract = "Background: The anticonvulsant lamotrigine was previously shown to be effective for bipolar depression. This study assessed the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of mood episodes in bipolar disorder. Method: During an 8- to 16-week open-label phase, lamotrigine (titrated to 200 mg/day) was added to current therapy for currently or recently depressed DSM-IV-defined bipolar I outpatients (N = 966) and concomitant drugs were gradually withdrawn. Patients stabilized on open-label treatment (N = 463) were then randomly assigned to lamotrigine (50, 200, or 400 mg/day; N = 221), lithium (0.8-1.1 mEq/L; N = 121), or placebo (N = 121) monotherapy for up to 18 months. The primary outcome measure was time from randomization to intervention (addition of pharmacotherapy) for any mood episode (depressive, manic, hypomanic, or mixed). Data were gathered from September 1997 to August 2001. Results: Time to intervention for any mood episode was statistically superior (p = .029) for both lamotrigine and lithium compared with placebo-median survival times were 200, 170, and 93 days, respectively. Intervention for depression was more frequent than for mania by a factor of nearly 3:1. Lamotrigine was statistically superior to placebo at prolonging the time to intervention for a depressive episode (p = .047). The proportions of patients who were intervention-free for depression at 1 year were lamotrigine 57{\%}, lithium 46{\%}, and placebo 45{\%}. Lithium was statistically superior to placebo at prolonging the time to intervention for a manic or hypomanic episode (p = .026). The proportions of patients who were intervention-free for mania at 1 year were lamotrigine 77{\%}, lithium 86{\%}, and placebo 72{\%}. Headache was the most frequent adverse event for all 3 treatment groups. Conclusion: Lamotrigine and lithium were superior to placebo for the prevention of mood episodes in bipolar I patients, with lamotrigine predominantly effective against depression and lithium predominantly effective against mania.",
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AU - Behnke, Kirsten

AU - Mehtonen, Olli Pekka

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N2 - Background: The anticonvulsant lamotrigine was previously shown to be effective for bipolar depression. This study assessed the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of mood episodes in bipolar disorder. Method: During an 8- to 16-week open-label phase, lamotrigine (titrated to 200 mg/day) was added to current therapy for currently or recently depressed DSM-IV-defined bipolar I outpatients (N = 966) and concomitant drugs were gradually withdrawn. Patients stabilized on open-label treatment (N = 463) were then randomly assigned to lamotrigine (50, 200, or 400 mg/day; N = 221), lithium (0.8-1.1 mEq/L; N = 121), or placebo (N = 121) monotherapy for up to 18 months. The primary outcome measure was time from randomization to intervention (addition of pharmacotherapy) for any mood episode (depressive, manic, hypomanic, or mixed). Data were gathered from September 1997 to August 2001. Results: Time to intervention for any mood episode was statistically superior (p = .029) for both lamotrigine and lithium compared with placebo-median survival times were 200, 170, and 93 days, respectively. Intervention for depression was more frequent than for mania by a factor of nearly 3:1. Lamotrigine was statistically superior to placebo at prolonging the time to intervention for a depressive episode (p = .047). The proportions of patients who were intervention-free for depression at 1 year were lamotrigine 57%, lithium 46%, and placebo 45%. Lithium was statistically superior to placebo at prolonging the time to intervention for a manic or hypomanic episode (p = .026). The proportions of patients who were intervention-free for mania at 1 year were lamotrigine 77%, lithium 86%, and placebo 72%. Headache was the most frequent adverse event for all 3 treatment groups. Conclusion: Lamotrigine and lithium were superior to placebo for the prevention of mood episodes in bipolar I patients, with lamotrigine predominantly effective against depression and lithium predominantly effective against mania.

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