Effects on weight and outcome of long-term olanzapine-topiramate combination treatment in bipolar disorder.
ABSTRACT 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.
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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 · 2.15 Impact Factor
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ABSTRACT: The presence of comorbidity in major psychoses (e.g., schizophrenia and psychotic subtypes of bipolar disorder and major depressive disorder) seems to be the rule rather than the exception in both DSM-IV and ICD-10. Examining comorbidity in major psychoses, however, requires an investigation into the different levels of comorbidity (either full-blown and subsyndromal) which should be analyzed in both psychopathological and medical fields. On one hand, the high prevalence of psychiatric comorbidity in major psychoses may be the result of the current nosographic systems. On the other hand, it may stem from a common neurobiological substrate. In fact, comorbid psychopathological conditions may share a biological vulnerability, given that dysfunction in specific brain areas may be responsible for different symptoms and syndromes. The high rates of comorbidity in major psychoses require targeted pharmacological treatments in order to effectively act on both the primary diagnosis and comorbid conditions. Nevertheless, few controlled trials in comorbid major psychoses had been carried out and treatment recommendations in this field have mostly an empirical basis. The aim of the present article is to provide a comprehensive and updated overview in relation to epidemiological and clinical issues of comorbidity in major psychoses. KeywordsComorbidity–Major psychoses (MPs)–Schizophrenia (SK)–Bipolar disorder (BD)–Psychotic major depressive disorder (pMDD)European Archives of Psychiatry and Clinical Neuroscience 10/2011; 261(7):489-508. DOI:10.1007/s00406-011-0196-4 · 3.36 Impact Factor