Background
Fluctuations in mood are quintessential features of bipolar disorder; however, previous
studies have seldom examined the extent to which pharmacotherapies for bipolar disorder
may reduce or ameliorate daily or weekly mood variability. The anticonvulsant lamotrigine
has demonstrated efficacy for relapse prevention in bipolar disorder, but its possible
mood-stabilizing properties on a day-to-day or week-to-week basis have not previously
been investigated.
Methods
Weekly mood shifts were examined over 26 weeks using patients’ self-reported prospective
Life Chart Method (LCM) data obtained as part of a previously reported randomized
relapse prevention comparison of lamotrigine monotherapy or placebo in 182 bipolar
patients with DSM-IV rapid cycling. Generalized estimating equation (GEE) analyses
were used to compare treatment arms for subjects who achieved euthymia across weeks.
Results
After adjusting for potential confounding factors, a final GEE model revealed that
subjects taking lamotrigine were 1.8 times more likely than those taking placebo to
achieve euthymia, as measured by LCM, at least once per week over 6 months (95% confidence
interval [CI] = 1.03–3.13). Subjects taking lamotrigine had an increase of .69 more
days per week euthymic as compared with those taking placebo (p = .014).
Conclusions
Achievement of euthymia across weeks represents a novel paradigm shift in gauging
the mood-stabilizing properties of a psychotropic agent. The present findings demonstrate
the utility of the prospective Life Chart Method for assessing longitudinal mood stability
during randomized clinical trials for bipolar disorder. The results lend support to
the potential mood-stabilizing properties of lamotrigine monotherapy for bipolar disorder.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Evidence of chaotic mood variation in bipolar disorder.Arch Gen Psychiatry. 1995; 52: 947-959
- Divalproex sodium treatment of women with borderline personality disorder and bipolar II disorder: A double-blind placebo-controlled pilot study.J Clin Psychiatry. 2002; 63: 442-446
- Lamotrigine treatment of aggression in female-borderline patients: A randomized, double-blind, placebo-controlled study.J Clin Psychopharmacol. 2005; 19: 287-291
- Borderline personality disorder in patients with bipolar disorder and response to lamotrigine.J Affect Disord. 2004; 79: 297-303
- The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000.Postgrad Med. 2000 (Spec No:1–104)
- On defining “mood stabilizer.”.Bipolar Disord. 2001; 3: 154-158
- What makes a drug a primary mood stabilizer?.Mol Psychiatry. 2002; 7: S8-S14
- What is a mood stabilizer?.Am J Psychiatry. 2004; 161: 3-18
- Subsyndromal symptoms in bipolar disorder.Arch Gen Psychiatry. 1992; 49: 371-376
- Subsyndromal depression is associated with functional impairment in patients with bipolar disorder.J Clin Psychiatry. 2002; 63: 807-811
- Predictors of recurrence in bipolar disorder: Primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).Am J Psychiatry. 2006; 163: 217-224
- Influence of sub-syndromal symptoms after remission from manic or mixed episodes.Br J Psychiatry. 2006; 189: 515-519
- Incidence and time course of sub-syndromal symptoms in patients with bipolar I disorder: An evaluation of two placebo-controlled maintenance trials.J Clin Psychiatry. 2006; 67: 1721-1728
- A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder.J Clin Psychiatry. 2004; 65: 432-441
- A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression.J Clin Psychiatry. 1999; 60: 79-88
- A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders.J Clin Psychopharmacol. 2000; 20: 607-614
- Graphic representation of the life course of illness in patients with affective disorder.Am J Psychiatry. 1988; 145: 844-848
- The longitudinal course of recurrent affective illness: Life chart data from research patients at the NIMH.Acta Psychiatr Scand Suppl. 1985; 317: 1-34
- A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder.J Clin Psychiatry. 2000; 61: 841-850
- A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder.Am J Psychiatry. 2005; 162: 2152-2161
- Bipolar rapid cycling: Focus on depression as its hallmark.J Clin Psychiatry. 2001; 62: 34-41
- The long-term course of rapid-cycling bipolar disorder.Arch Gen Psychiatry. 2003; 60: 914-920
- Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-I/P, version 2.0).New York State Psychiatric Institute, Biometrics Research Department, New York1995
- A rating scale for depression.J Neurol Neurosurg Psychiatry. 1960; 23: 56-62
- A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia.Arch Gen Psychiatry. 1978; 35: 837-844
- Preliminary evidence of the reliability and validity of the prospective life-charting methodology (LCM-p).J Psychiatr Res. 1997; 31: 593-603
- Validation of the prospective NIMH-Life-Chart (NIMH-LCM-p) for longitudinal assessment of bipolar illness.Psychol Med. 2000; 30: 1391-1397
- Utility of the daily prospective National Institute of Mental Health Life-Chart Method (NIMH-LCM-p) ratings in clinical trials of bipolar disorder.Depress Anxiety. 2002; 15: 1-9
- Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers.Am J Psychiatry. 2006; 163: 232-239
- Morbidity in 258 bipolar outpatients followed for 1 year with daily prospective ratings on the NIMH Life Chart Method.J Clin Psychiatry. 2003; 64: 680-690
- Duration and stability of the rapid cycling course: A long-term personal follow-up of 109 patients.J Affect Disord. 2003; 73: 75-85
- Comparison of population-averaged and subject-specific approaches for analyzing repeated binary outcomes.Am J Epidemiol. 1998; 147: 694-703
- A comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder.J Clin Psychiatry. 2002; 63: 1148-1155
- A randomized, placebo-controlled, 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder.Arch Gen Psychiatry. 2000; 57: 481-489
- Relapse prevention in bipolar I disorder: 18 month comparison of olanzapine plus mood stabilizer v. mood stabilizer alone.Br J Psychiatry. 2004; 184: 337-345
- Unique design issues in clinical trials of patients with bipolar affective disorder.J Psychiatr Res. 2003; 37: 61-73
- On the meaning and measurement of affective instability: Clues from chaos theory.Biol Psychiatry. 1999; 45: 261-269
- Affective instability as rapid cycling: Theoretical and clinical implications for borderline personality and bipolar spectrum disorders.Bipolar Disord. 2006; 8: 1-14
- Borderline personality features and instability of daily negative affect and self-esteem.J Person. 2004; 72: 111-137
- Characterizing affective instability in borderline personality disorder.Am J Psychiatry. 2002; 159: 784-788
- Affective instability and impulsivity in borderline personality and bipolar II disorders: Similarities and differences.J Psychiatr Res. 2001; 35: 307-312
- Do patients with borderline personality disorder belong to the bipolar spectrum?.J Affect Disord. 2001; 67: 221-228
- Bipolar disorder with comorbid cluster B personality disorder features: Impact on suicidality.J Clin Psychiatry. 2005; 66: 339-3345
Article info
Publication history
Published online: June 02, 2007
Accepted:
December 22,
2006
Received in revised form:
December 17,
2006
Received:
August 3,
2006
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
