Effects on Weight and Outcome of Long-term Olanzapine-Topiramate Combination Treatment in Bipolar Disorder

Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 08/2004; 24(4):374-8. DOI: 10.1097/
Source: PubMed


Olanzapine is an effective drug for the long-term treatment of bipolar disorder but is associated with burdensome weight gain. Topiramate is a novel anticonvulsant that may induce weight loss in some patients. This is the first study to address the long-term efficacy and impact on weight of the combination of olanzapine and topiramate in bipolar patients. Twenty-six Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar spectrum patients received olanzapine plus topiramate cotherapy for treatment of their manic (n = 14), hypomanic (n = 6), depressive (n = 2), and mixed (n = 1) symptoms for 1 year. Three rapid cycling patients were also enrolled despite being euthymic. Efficacy was assessed with the Young Mania Rating Scale, the Hamilton Depression Rating Scale, and the Modified Clinical Global Impressions for Bipolar Disorder. Weight, body mass index, and side effects were collected at every visit. Thirteen (50%) patients completed the 1-year follow-up. By intent-to-treat, patients significantly improved from baseline in Young Mania Rating Scale scores (P < 0.0001), Hamilton Depression Rating Scale (P < 0.05), and Modified Clinical Global Impressions for Bipolar Disorder subscales (mania P < 0.0001, depression P < 0.05, overall P < 0.0001). Most patients gained weight during the first month of combined treatment (mean weight gain 0.7 +/- 0.6 kg), but at the 12-month endpoint, the mean weight change was -0.5 +/- 1.1 kg. The combination of olanzapine and topiramate was efficacious for the long-term treatment of bipolar patients and appeared to carry some benefits for controlling weight gain. Given the limitations of the open, uncontrolled design, further trials are warranted with this combination.

19 Reads
  • Source
    • "kg/m 2 ; both were statistically signifi cant compared with weight gain observed in the patients receiving either lithium or VPA. A more recent study by Vieta et al (2004) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Topiramate (TPM) is one of the novel antiepileptic drugs and exhibits a wide range of mechanisms of action. Efficacy of TPM has been demonstrated in partial-onset seizures and primary generalized seizures in adults and children, as both monotherapy and adjunctive therapy. More recently, TPM has been proposed as an add-on treatment for patients with lithium-resistant bipolar disorder, especially those displaying rapid-cycling and mixed states. This paper reviews the multiple mechanisms of action and the tolerability profile of TPM in the light of its therapeutic potential in affective disorders. Studies of TPM in bipolar disorder are evaluated, and the efficacy and tolerability issues as a mood stabilizing agent are discussed.
    Neuropsychiatric Disease and Treatment 01/2007; 2(4):475-88. DOI:10.2147/nedt.2006.2.4.475 · 1.74 Impact Factor
  • Source
    • "As this patient was treated during this weight loss period with topiramate, a drug well known for its weight reducing properties and increasingly used in obese patients(Wilding et al., 2004). What is more, topiramate has recently been found to be of some utility particularly in patients with drug induced weight gain (Vieta et al., 2004). "

  • Source
    • "The mean weight of patients decreased by 1.1 kg by the end of the study. The same team examined the effect of the co-administration of topiramate and olanzapine over a 12 months interval [26]. Thirteen patients completed 12 months of treatment and their mania and depression ratings improved significantly. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The weight-gain caused by many psychotropic drugs is a major cause for poor compliance with such medications and could also increase cardio-vascular morbidity among psychiatric patients. Recent reports have shown that the anticonvulsant topiramate causes weight loss in various patient groups. The drug has also shown effectiveness in open trials as a mood stabilizer in patients with affective disorders, but not in controlled trials in the acute treatment of mania. We used topiramate to treat 12 patients with affective disorders who had a body-mass index > 30 kg/m2. Topiramate was prescribed as part of our routine clinical practice, as an add-on medication, or as a replacement of a mood stabilizer. Patients' weight was recorded in 1 to 2 monthly intervals. Patients were followed up for between 6 and 12 months. The final dose of topiramate varied from 200 to 600 mg/day. Topiramate was effective in reducing the weight in 10 out of the 12 patients. At six months the 12 patients had lost a mean of 7.75 kg (SD = 6.9 kg, p < 0.001) and at 12 months 9 patients had lost a mean of 9.61 kg (SD = 6.7 kg, p = 0.003). Three patients stopped the treatment: one due to side effects, one due to possible side effects, and one suffered a manic relapse and showed no sustained weight loss. There were no other clear changes in the course of illness of the patients. The evidence of a strong weight-reducing potential of topiramate is indisputable and clinically significant. Topiramate could be considered in the treatment of bipolar patients who are overweight, or whose concerns about weight gain compromise their compliance with long-term prophylactic medication. So far there is no evidence that topiramate has anti-manic effect and it should not be used as monotherapy.
    BMC Psychiatry 02/2005; 5(1):19. DOI:10.1186/1471-244X-5-19 · 2.21 Impact Factor
Show more