Impact of Lamotrigine and Lithium on Weight in Obese and Nonobese Patients With Bipolar I Disorder

Stanford University, Palo Alto, California, United States
American Journal of Psychiatry (Impact Factor: 12.3). 08/2006; 163(7):1199-201. DOI: 10.1176/appi.ajp.163.7.1199
Source: PubMed


This study assessed weight changes in a large cohort of patients with bipolar disorder who were treated with randomly assigned maintenance monotherapies.
A post hoc analysis was conducted to assess the effects of lamotrigine, lithium, and placebo administration on body weight in obese and nonobese patients with bipolar disorder from two double-blind, placebo-controlled, 18-month studies.
Mean changes in weight among obese patients (N=155) at week 52 were -4.2, +6.1, and -0.6 kg with lamotrigine, lithium, and placebo, respectively (lamotrigine versus lithium and lithium versus placebo). Among nonobese patients (N=399), mean changes in weight (kg) at week 52 were -0.5, +1.1, and +0.7 with lamotrigine, lithium, and placebo, respectively, with no significant differences among groups.
Obese patients with bipolar I disorder lost weight while taking lamotrigine and gained weight while taking lithium.

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Available from: Charles L Bowden, Jan 28, 2016
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    • "A 7-year follow-up study reported that weight increased during the first 1–2 years of prophylactic lithium treatment and remained constant thereafter (Vestergaard et al., 1988). A 1-year follow-up study found that 155 obese patients with bipolar I disorder lost weight (– 4.2 kg) while taking lamotrigine and gained weight (6.1 kg) while taking lithium (Bowden et al., 2006), whereas there was no significant weight change in 399 nonobese patients. The prevalence of weight gain with VPA treatment is estimated to occur in 3–20% of patients and ranges between 3–10 kg over a period of 3–12 months (Pijl and Meinders, 1996; Bowden, 2003). "
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    ABSTRACT: Side effects are among the most frequent reasons preventing patients from taking their medication. Although the management of side effects is an important issue in clinical practice, particularly in patients with physical comorbidities, research on clinical management of side effects is rather scattered. The aim of this article was to provide an overview on the prevalence and management of various side effects of mood-stabilizing drugs. In December 2012, we carried out a PubMed search for publications reporting side effects in patients with bipolar disorder. Naturalistic studies describing the prevalence of side effects in treatment with mood stabilizers are sparse. We describe the prevalence of neurological, gastrointestinal, metabolic, thyroid, dermatological, nephrogenic, cognitive, sexual, hematological, hepatogenic, and teratogenic side effects of lithium, valproate, carbamazepine, and lamotrigine and discuss their clinical management. There are specific strategies that aim at reducing side effects, but, to date, studies on the efficacy of these interventions are lacking. With age, the renal elimination and hepatic metabolism of drugs reduce and comedication and somatic comorbidity increase, making elderly patients particularly susceptible to side effects. Most side effects can be managed by striving for the lowest possible dose without losing efficacy by lowering the dose below the therapeutic window. Specific measurements to limit certain side effects are available and may ameliorate treatment adherence.
    Full-text · Article · Jul 2013 · International clinical psychopharmacology
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    • "Interestingly, in a study that assessed weight changes with either lamotrigine or lithium in both obese and nonobese patients with bipolar I disorder, those who were obese lost weight ( À 4.2 kg) while taking lamotrigine and gained weight (6.1 kg) while taking lithium, but only minimal differences between the two drugs were observed among nonobese patients ( À 0.5 kg with lamotrigine versus 1.1 kg with lithium) (Bowden et al., 2006). Although the reasons for these results are unclear, it may be secondary to obese versus nonobese patients being predisposed to gaining more weight while on lithium (Bowden et al., 2006). Because weight gain, per se, is only one sign of metabolic dysfunction, it is important to investigate the effects of any drug on the risk of developing metabolic syndrome, as well as the individual metabolic parameters that comprise metabolic syndrome. "
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    ABSTRACT: BACKGROUND: Bipolar I disorder (BPD) patients are often overweight or obese, and likely to have metabolic syndrome. Several medications used to treat BPD are associated with increased body weight and/or worsening metabolic parameters. METHODS: Metabolic data were analyzed from two efficacy studies of aripiprazole plus the mood stabilizers, lithium/valproate (Study CN138-189), or lamotrigine (Study CN138-392), in the long-term treatment (52 weeks) of BPD. Changes in body weight, individual metabolic parameters, and incidence of metabolic syndrome were assessed. RESULTS: In the lithium/valproate study, modest increases in body weight were observed at Week 52 in both groups: 1.7±0.8kg in the lithium/valproate group, and 1.6±0.7kg in the adjunctive aripiprazole group; this difference was nonsignificant. In the lamotrigine study, decreases in body weight were observed at Week 52 with lamotrigine alone (-2.2±1.0kg), whereas a modest increase was observed when combined with aripiprazole (0.4±1.0kg). In both studies, rates of metabolic syndrome at 52 weeks did not increase from baseline with aripiprazole, and median changes from baseline in individual metabolic syndrome parameters were similar with both mood stabilizer monotherapy and the addition of aripiprazole as an adjunctive therapy. LIMITATIONS: This was a post-hoc analysis, and a low percentage of patients completed the lamotrigine study. CONCLUSIONS: Aripiprazole plus a mood stabilizer has minimal impact on metabolic changes in predominantly overweight/obese BPD patients over a 52-week period. In both studies, modest mean increases in weight with the addition of aripiprazole were not accompanied by increased rates of metabolic syndrome or changes in metabolic parameters.
    Full-text · Article · Dec 2012 · Journal of Affective Disorders
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    • "The Bowden study (Level III/B) [78] at 12 weeks ranks valproate slightly ahead of lithium (1.1 kg vs 0.2 kg). Quantitative data obtained from two different publications [79], [80] and the clinical impressions of the expert panel support the ranking of valproate slightly ahead of lithium. "
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    ABSTRACT: Psychotropic medication use is associated with weight gain. While there are studies and reviews comparing weight gain for psychotropics within some classes, clinicians frequently use drugs from different classes to treat psychiatric disorders. To undertake a systematic review of all classes of psychotropics to provide an all encompassing evidence-based tool that would allow clinicians to determine the risks of weight gain in making both intra-class and interclass choices of psychotropics. We developed a novel hierarchical search strategy that made use of systematic reviews that were already available. When such evidence was not available we went on to evaluate randomly controlled trials, followed by cohort and other clinical trials, narrative reviews, and, where necessary, clinical opinion and anecdotal evidence. The data from the publication with the highest level of evidence based on our hierarchical classification was presented. Recommendations from an expert panel supplemented the evidence used to rank these drugs within their respective classes. Approximately 9500 articles were identified in our literature search of which 666 citations were retrieved. We were able to rank most of the psychotropics based on the available evidence and recommendations from subject matter experts. There were few discrepancies between published evidence and the expert panel in ranking these drugs. Potential for weight gain is an important consideration in choice of any psychotropic. This tool will help clinicians select psychotropics on a case-by-case basis in order to minimize the impact of weight gain when making both intra-class and interclass choices.
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