Topiramate versus Valproate Sodium as Adjunctive Therapies to a Combination of Lithium and Risperidone for Adolescents with Bipolar I Disorder: Effects on Weight and Serum Lipid Profiles

Article excerpt

Objective: To compare the effects of topiramate versus valproate sodium as an add-on therapy to a combination of lithium and risperidone (Li+Ris) on body weight and serum lipid profile in children and adolescents with bipolar disorder.

Methods: In a single-blind randomized clinical trial, thirty children and adolescents with bipolar disorder type I in the manic or mixed phase ,treated with the combination of Li+Ris at therapeutic doses for at least 4 weeks who had the indication of add-on therapy due to a recurrent episode; a partial response or non response in the current episode or relapse were included. Participants were randomly assigned to receive either topiramate or sodium valproate as the third drug add-on therapy for a total of 6 weeks. Weight, height and serum lipid profiles were determined at baseline and at the end of week 6.

Results: Differences in the mean levels of lipid profiles at baseline and after week 6 evaluation were not significant in both treatment groups.

BMI z-score increased in both treatment groups, being significant only in the Li+Ris/Valproate group, increasing from (mean SD) 0.38 0.55 to 0.72 1.23 (p<0.05). Between group changes in BMI z-score was not significant.Among the BMI percentile categories, participants in the normal weight subgroup showed a significant increase in BMI z-score during the 6 week trial, compared to overweight/obese subgroup, in both Li+Ris/Valproate and Li+Ris/Topiramate treatment groups. Elevated mean serum level of triglyceride and a high proportion of participants with elevated total cholesterol (≥ 170 mg/dl), triglyceride (≥ 110 mg/dl), and BMI percentile 85-<95 at baseline (before randomization) and at the end of 6 week study were noted.

Conclusion: When topiramate and valproate sodium are used for six weeks as adjunctive treatment to a combination of Li+Ris, they act alike on lipid milieu of children and adolescents with bipolar disorder.

Both Li+Ris/Valproate and Li+Ris/Topiramate therapies can lead to an increase in BMI z-score. This increase is statistically significant with Li+Ris/Valproate therapy. This suggests that topiramate could attenuate the ongoing weight gain from lithium and risperidone .

In this study, the majority of participants who gained weight were those with BMI less than 85th percentile. This suggests that normal weight patients may have greater weight gain potential than overweight/obese patients.High proportion of metabolic abnormalities among the patients at baseline, which remained elevated throughout the trial, warrants cardiometabolic monitoring in this population.

Keywords: Body weight, Lipids, Lithium, Risperidone, Topiramate, Valproate sodium

Iran J Psychiatry 2012; 7:1-10

Bipolar disorder (BD) in children and adolescents is a chronic psychiatric condition (1) requiring long term pharmacotherapy with conventional mood stabilizers including lithium and antiepileptic drugs (AEDs) and/or antipsychotics (2). Adults with BD are known to have a higher prevalence of medical co-morbidities including obesity, metabolic and cardiovascular illnesses (3-7) related to the disorder itself or to its treatment (5, 8). Less is known about metabolic and cardiovascular co-morbidities in children and adolescents with BD; however, greater prevalence of obesity/overweight (8,9), cardiovascular and metabolic risk factors is also reported in this group (8). Atherosclerotic cardiovascular disease is a well known consequence of abnormal lipid profiles both in adult and adolescent populations (10, 11).Additionally, children and adolescents may be more vulnerable and have an accelerated development of such adverse effects when compared with adults (12- 14). Furthermore, obesity in adolescents is a reason for nonadherence to treatment (15) and is associated with increased psychiatric burden (9)

Current treatment guidelines suggest that valproate sodium is effective both as monotherapy in acute treatment of children and adolescents with manic or mixed episodes without psychosis and as augmentation therapy for those with a partial response to monotherapy, or with psychotic symptoms (2). …