Effectiveness and Weight Effects of Open-Label Lamotrigine With and Without Concomitant Psychotropic Medications in Patients With Bipolar I Disorder

Michael N. ZarZar, MD; Jay Graham, PharmD; Jeremy Roberts; Thomas Thompson, MD; Kevin Nanry

Abstract

Background: Approximately half of all patients with diagnosed bipolar disorder are prescribed 2 or more psychotropic medications. Lamotrigine was approved in 2003 for the maintenance treatment of bipolar I disorder. This study examined comparative effects of lamotrigine with and without concomitant medications.
Methods: A post hoc analysis of data from a prospective, open-label study of lamotrigine in 1175 patients with bipolar I disorder evaluated the clinical response to and quality-of-life and weight effects of lamotrigine as monotherapy and in patients receiving concomitant valproate, lithium, antipsychotics, or antidepressants. The study was originally designed to assess the rate of rash among patients instructed to use specific dermatologic precautions compared with those receiving usual care. Lamotrigine was administered for 12 weeks, including a 5-week titration, with target dose of 200 mg/d, adjusted as necessary for concomitant medication(s). Evaluations at baseline and week 12 included the severity component of the Clinical Global Impression-Bipolar Version scale, the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form, and weight and body mass index (BMI).
Results: Efficacy data were available for 1139 patients. Symptoms and quality-of-life mean scores improved following treatment in all patient groups. Quality-of-life scores improved significantly more in patients not receiving than in those receiving concomitant antipsychotics. There were no changes in weight or BMI after lamotrigine monotherapy or adjuvant therapy. Most patients were satisfied with lamotrigine treatment.
Conclusion: Lamotrigine was effective and well tolerated and appeared to have no effect on body weight when given as monotherapy or as adjunctive therapy with valproate, antipsychotics, lithium, or antidepressants to outpatients with bipolar I disorder in a 12-week open-label study.

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Cite this: Effectiveness and Weight Effects of Open-Label Lamotrigine With and Without Concomitant Psychotropic Medications in Patients With Bipolar I Disorder - Medscape - May 22, 2007.

Table 1. Demographics, Concomitant Psychiatric Medication Use, and Patient Disposition (Safety Population)
	All Patients (N = 1175)
Demographics and Psychiatric Medication Use
Mean age (SD), years	42.2 (13.1)
Female, n (%)	757 (64)
Ethnicity, n (%) American Hispanic Black White Other	42 (4) 59 (5) 1055 (90) 19 (2)
Most common concomitant medications,* n (%) Lithium Valproate Bupropion Quetiapine Citalopram Clonazepam	267 (23) 260 (22) 249 (21) 163 (14) 142 (12) 141 (12)
Patient Disposition
Completed study, n (%)	867 (74)
Discontinued study prematurely, n (%) Adverse event Voluntary withdrawal (patient's decision) Lost to follow-up Protocol violation Other	180 (15) 42 (4) 38 (3) 28 (2) 20 (2)

*Patients could be using more than one concomitant medication.

Table 1. Demographics, Concomitant Psychiatric Medication Use, and Patient Disposition (Safety Population)
	All Patients (N = 1175)
Demographics and Psychiatric Medication Use
Mean age (SD), years	42.2 (13.1)
Female, n (%)	757 (64)
Ethnicity, n (%) American Hispanic Black White Other	42 (4) 59 (5) 1055 (90) 19 (2)
Most common concomitant medications,* n (%) Lithium Valproate Bupropion Quetiapine Citalopram Clonazepam	267 (23) 260 (22) 249 (21) 163 (14) 142 (12) 141 (12)
Patient Disposition
Completed study, n (%)	867 (74)
Discontinued study prematurely, n (%) Adverse event Voluntary withdrawal (patient's decision) Lost to follow-up Protocol violation Other	180 (15) 42 (4) 38 (3) 28 (2) 20 (2)

*Patients could be using more than one concomitant medication.

Table 2. CGI-BP Overall Severity Scores
Regimen	Baseline Mean ± SD (n)	Week 12 Mean ± SD (n)	Change From Baseline Mean ± SD (n)
ITT population	3.4 ± 1.32 (1138)	2.4 ± 1.22 (1052)	-1.0 ± 1.29* (1051)
Lamotrigine monotherapy	3.6 ± 1.34 (226)	2.4 ± 1.24 (215)	-1.2 ± 1.33* (215)
Lamotrigine polytherapy	3.4 ± 1.32 (912)	2.4 ± 1.22 (837)	-1.1 ± 1.26* (837)
With concomitant valproate	3.2 ± 1.43 (249)	2.3 ± 1.26 (235)	-0.8 ± 1.40* (235)
Without concomitant valproate	3.5 ± 1.29 (889)	2.4 ± 1.21 (817)	-1.1 ± 1.25* (816)
With concomitant lithium	3.1 ± 1.36 (260)	2.2 ± 1.22 (241)	-0.9 ± 1.22* (241)
Without concomitant lithium	3.5 ± 1.30 (878)	2.4 ± 1.22 (811)	-1.1 ± 1.31* (810)
With concomitant antipsychotics	3.4 ± 1.39 (346)	2.4 ± 1.25 (325)	-1.0 ± 1.31* (324)
Without concomitant antipsychotics	3.5 ± 1.29 (n = 792)	2.4 ± 1.21 (n = 727)	-1.1 ± 1.28* (n = 727)
With concomitant antidepressants	3.4 ± 1.29 (758)	2.4 ± 1.22 (694)	-1.0 ± 1.28* (693)
Without concomitant antidepressants	3.5 ± 1.38 (380)	2.4 ± 1.23 (358)	-1.1 ± 1.32* (358)

*P < .0001 vs baseline.

Table 3. Q-LES-Q Scores (% Maximum Possible Score)
Regimen	Baseline Mean ± SD (n)	Week 12 Mean ± SD (n)	Change From Baseline Mean ± SD (n)
ITT population	50.6 ± 18.30 (1139)	60.9 ± 19.48 (914)	10.1 ± 20.07* (914)
Lamotrigine monotherapy	49.9 ± 18.324 (226)	61.8 ± 18.65 (184)	12.0 ± 20.13*^† (184)
Lamotrigine polytherapy	50.7 ± 18.30 (n = 913)	60.9 ± 19.54 (n = 730)	9.7 ± 20.04*^† (n = 730)
With concomitant valproate	53.1 ± 17.97 (249)	61.3 ± 20.59 (193)	7.9 ± 20.57* (193)
Without concomitant valproate	49.9 ± 18.34 (890)	60.8 ± 19.19 (721)	10.7 ± 19.91* (721)
With concomitant lithium	56.2 ± 18.07 (260)	63.2 ± 18.21 (217)	6.8 ± 18.74* (217)
Without concomitant lithium	48.9 ± 18.04 (879)	60.1 ± 19.81 (697)	11.2 ± 20.37* (697)
With concomitant antipsychotics	51.7 ± 18.29 (347)	58.8 ± 19.71 (283)	7.0 ± 19.83* (283)
Without concomitant antipsychotics	50.1 ± 18.29 (792)	61.8 ± 19.32 (631)	11.6 ± 20.03* (631)
With concomitant antidepressants	49.6 ± 18.09 (759)	60.3 ± 19.63 (613)	10.4 ± 20.20* (613)
Without concomitant antidepressants	52.4 ± 18.60 (380)	62.1 ± 19.14 (301)	9.7 ± 19.83* (301)

*P < .0001 vs baseline; ^† P < .05 vs without respective concomitant medication(s).

Table 4. Mean Weight (lb)
Regimen	Baseline Mean ± SD (n)	Week 12 Mean ± SD (n)	Change From Baseline Mean ± SD (n)
Safety population	188.1 ± 48.21 (1174)	188.9 ± 48.41 (894)	-0.2 ± 8.10 (894)
Lamotrigine monotherapy	181.4 ± 50.00 (238)	183.6 ± 52.40 (178)	0.7 ± 9.26 (178)
Adjunctive lamotrigine	190.0 ± 47.62 (936)	190.5 ± 47.27 (716)	-0.2 ± 7.80 (716)
With concomitant valproate	199.1 ± 49.07 (259)	199.1 ± 49.34 (190)	-0.2 ± 6.83 (190)
Without concomitant valproate	184.7 ± 47.53 (915)	186.1 ± 47.82 (704)	-0.0 ± 8.42 (704)
With concomitant lithium	184.8 ± 43.12 (267)	186.12 ± 43.1 (215)	0.22± 8.76 (215)
Without concomitant lithium	188.32 ± 49.48 (907)	189.2 ± 49.87 (679)	-0.22 ± 7.88 (679)
With concomitant antipsychotics	192.7 ± 47.31 (351)	193.8 ± 46.80 (275)	-0.4 ± 8.00 (275)
Without concomitant antipsychotics	186.1 ± 48.48 (823)	186.7 ± 49.01 (619)	0.0 ± 8.16 (619)
With concomitant antidepressants	188.5 ± 47.55 (777)	188.3 ± 48.55 (599)	-0.2 ± 7.69 (599)
Without concomitant antidepressants	187.2 ± 49.52 (397)	188.7 ± 52.29 (295)	-0.0 ± 8.90 (295)

*P < .05 vs baseline

Table 5. Mean BMI (kg/m²)
Regimen	Baseline Mean ± SD (n)	Week 12 Mean ± SD (n)	Change From Baseline Mean ± SD (n)
Safety population	30.1 ± 7.23 (1174)	30.2 ± 7.25 (894)	-0.0 ± 1.34 (894)
Lamotrigine monotherapy	28.7 ± 7.37 (238)	28.7 ± 7.71 (178)	0.1 ± 1.54 (178)
Adjunctive lamotrigine	30.5 ± 7.16 (936)	30.5 ± 7.09 (716)	-0.1 ± 1.29 (716)
With concomitant valproate	31.4 ± 7.27 (259)	31.5 ± 7.54 (190)	-0.0 ± 1.41 (190)
Without concomitant valproate	29.8 ± 7.18 (915)	29.8 ± 7.13 (704)	-0.0 ± 1.07 (704)
With concomitant lithium	1.2 ± 6.08 (267)	29.4 ± 6.06 (215)	0.0 ± 1.47 (215)
Without concomitant lithium	30.4 ± 7.52 (907)	30.4 ± 7.57 (679)	-0.0 ± 1.30 (679)
With concomitant antipsychotics	31.4 ± 7.27 (259)	31.5 ± 7.54 (190)	-0.1 ± 1.34 (275)
Without concomitant antipsychotics	29.7 ± 7.18 (823)	29.7 ± 7.19 (619)	0.0 ± 1.34 (619)
With concomitant antidepressants	30.4 ± 7.16 (777)	30.4 ± 6.94 (599)	-0.0 ± 1.47 (599)
Without concomitant antidepressants	29.5 ± 7.35 (397)	29.6 ± 7.82 (295)	-0.0 ± 1.27 (295)

*P < .05 vs baseline.

Table 6. Drug-Related Adverse Events (% of Patients) Occurring in 5% or More of Any Group
Adverse Event	All Subjects (N = 1175)	Lithium		Lamotrigine		Valproate		Antipsychotics		Antidepressants
Adverse Event	All Subjects (N = 1175)	Yes (n = 267)	No (n = 908)	Monotherapy (n = 238)	Adjunctive (n = 937)	Yes (n = 260)	No (n = 915)	Yes (n = 352)	No (n = 823)	Yes (n = 778)	No (n = 397)
Headache	5	6	5	6	5	4	5	3	6	5	5
Rash	4	4	4	6	4	5	4	4	4	3	6
Dizziness	4	3	4	3	4	5	3	3	4	4	3
Tremor	2	2	2	0	2	5	1	2	2	2	1
Insomnia	3	5	3	4	3	2	4	4	3	3	4
Nausea	3	5	3	3	3	2	4	3	3	4	3

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