Effects on weight and outcome of long-term olanzapine-topiramate combination treatment in bipolar disorder.

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.

Clinical value of 99mTc-HMPAO SPECT in depressed bipolar I patients.

Regional cerebral blood flow was studied in 17 bipolar I depressed patients (DSM-IV criteria) with single photon emission computed tomography (SPECT). Visual analysis of images revealed no abnormality in eight patients and abnormal findings in nine patients. In the nine patients with abnormal findings, all showed regional decreases of the uptake of (99m)Tc-D,L-hexamethylpropylene amine oxime (HMPAO, four in the frontal region, two in the basal ganglia, and three in both the frontal region and the basal ganglia). The patients with visible SPECT abnormalities had significantly higher scores on the Hamilton Rating Scale for Depression (HDRS).

Adjunctive topiramate in bipolar II disorder.

We evaluated the efficacy and safety of adjunctive topiramate in bipolar II patients who were either treatment-resistant to or unable to tolerate lithium, carbamazepine or valproate. Nineteen DSM-IV bipolar II patients received increasing doses of open-label topiramate as adjunctive therapy for their hypomanic (n=15) or depressive (n=4) symptoms. Sixteen patients completed the 12-week follow-up. There were highly significant improvements in YMRS, HDRS and CGI-BP-M scores (p=0.0001). Of the fifteen hypomanic patients, eight (53%) were rated as responders to topiramate (50% reduction in YMRS scores), and five (33%) met criteria for remission (YMRS score pound 8). Two of the four patients with a depressive episode at study entry (50%) were rated as responders (50% reduction in HDRS score), and one (25%) achieved remission (HDRS score pound 6). Topiramate was generally well tolerated. One third of the patients experienced weight loss. These preliminary results suggest that adjunctive topiramate may be useful in treating bipolar II disorder.

A randomized trial on the efficacy of group psychoeducation in the prophylaxis of recurrences in bipolar patients whose disease is in remission.

BACKGROUND: Studies on individual psychotherapy indicate that some interventions may reduce the number of recurrences in bipolar patients. However, there has been a lack of structured, well-designed, blinded, controlled studies demonstrating the efficacy of group psychoeducation to prevent recurrences in patients with bipolar I and II disorder. METHODS: One hundred twenty bipolar I and II outpatients in remission (Young Mania Rating Scale score <6, Hamilton Depression Rating Scale-17 score <8) for at least 6 months prior to inclusion in the study, who were receiving standard pharmacologic treatment, were included in a controlled trial. Subjects were matched for age and sex and randomized to receive, in addition to standard psychiatric care, 21 sessions of group psychoeducation or 21 sessions of nonstructured group meetings. Subjects were assessed monthly during the 21-week treatment period and throughout the 2-year follow-up. RESULTS: Group psychoeducation significantly reduced the number of relapsed patients and the number of recurrences per patient, and increased the time to depressive, manic, hypomanic, and mixed recurrences. The number and length of hospitalizations per patient were also lower in patients who received psychoeducation. CONCLUSION: Group psychoeducation is an efficacious intervention to prevent recurrence in pharmacologically treated patients with bipolar I and II disorder.

Quetiapine in the treatment of rapid cycling bipolar disorder.

INTRODUCTION: This prospective open-label study assessed the impact of add-on quetiapine in the treatment of rapid cycling bipolar patients. METHODS: Fourteen rapid cycling bipolar patients were treated with quetiapine, which was added to their ongoing medication regimen for 112 +/- 33 days. At the beginning of the study, five were manic, three were in a mixed state, three were depressed, two hypomanic and one was euthymic. Patients were assessed prospectively with a modified version of the Clinical Global Impression Scale for Bipolars (CGI-BP), the Young Scale for mania (YMRS) and the Hamilton Scale for Depression (HDRS). RESULTS: A significant reduction of the following scale scores was observed: a 1.8 point reduction for the general CGI-BP (p = 0.013), a -1.3 point for the mania subscale (p = 0.016), a -1.01 point for the YMRS (p = 0.025). Improvement in depressive symptoms was not significant, neither in the CGI-BP (-1 point, p = 0.074) nor in the HDRS (-5.2 points, p = NS). The most common side-effect was sedation (n = 6, 43%). Doses of quetiapine were significantly reduced by the end of the study (443 +/- 235 mg/day versus 268 +/- 190 mg/day, p = 0.008) and they also differed according to the initial episode to be treated (720 +/- 84 mg/day for mania, and 183 +/- 29 mg/day for depression, p = 0.023). CONCLUSIONS: Quetiapine could possibly be an effective treatment for rapid cycling bipolar patients. Adequate doses for acute episodes could significantly differ according to the episode polarity and the length of treatment.

Nuevos eutimizantes: cuestiones metodológicas relativas a los ensayos clínicos controlados con placebo / New euthymic agents : methodological issues relative to placebo-controlled clinical trials

En los últimos años hemos asistido al desarrollo de nuevas indicaciones para los psicofármacos con especial impacto en el tratamiento de los trastornos bipolares. Las experiencias de los organismos reguladores, incluyendo la necesidad de una rama de placebo y, preferiblemente, otra rama con un comparador activo, han permitido evaluar nuevos fármacos, fundamentalmente antipsicóticos atípicos y antiepilépticos de tercera generación, respecto a su eficacia y seguridad en el trastorno bipolar. Los problemas éticos y metodológicos que plantea el placebo, principalmente en estudios a largo plazo, constituye un tema polémico de plena actualidad. Sin el placebo, sin embargo, resulta actualmente imposible evaluar la sensibilidad intraensayo y, en último término, la eficacia real del fármaco en estudio (AU)

Lack of clinical relevance of routine chest radiography in acute psychiatric admissions.

To make clinically relevant recommendations for chest X-ray testing in acute psychiatric admissions, this study examined the current practice of this screening test in patients admitted to a University Hospital. The records of the 332 first consecutive admissions to the psychiatric ward were assessed. In 200 patients (60%) a chest X-ray was requested. The X-ray film was normal in 81.5% of patients. The remaining subjects presented abnormalities: nonrelevant in twenty-seven (13.5% of the total), and relevant in eleven (5.5%). Since all these relevant abnormalities were already known, in no cases was the test followed by changes in therapy or by additional diagnostic procedures. In almost all cases this screening test was of no practical value. Our findings challenge the systematic indication of chest X-ray in acute psychiatric patients, and suggest that the number of tests performed and the cost of medical care could be reduced by a more efficient use of past medical history and physical examination criteria, without compromising the quality of patient care.

Intervención familiar de tipo psicoeducativo en el trastorno bipolar / Family psychoeducation in bipolar disorder

Aunque los factores genéticos y biológicos juegan un papel fundamental en la fisiopatología del trastorno bipolar, la importancia de factores psicosociales como desencadenantes o protectores de las recaídas justifica la incorporación de intervenciones psicoterapéuticas que complementen y faciliten el tratamiento farmacológico. Algunos estudios han asociado determinadas actitudes familiares a un peor curso del trastorno bipolar. La importancia del estrés ambiental en la evolución del trastorno, la carga experimentada por los familiares que conviven con el paciente y la demanda de las familias de recibir más información sobre el trastorno bipolar y las estrategias de afrontamiento son algunas de las razones que dan soporte a la introducción de intervenciones familiares de tipo psicoeducativo. Los estudios realizados con familias de pacientes bipolares sugieren que la intervención familiar acompañada de tratamiento farmacológico permite la reducción del número de recaídas y hospitalizaciones, mejorando el funcionamiento familiar, ocupacional y social del paciente. Sin embargo, los estudios controlados son escasos y la mayoría adolecen de múltiples déficit metodológicos. Futuros estudios deberían solventar, en la medida de lo posible, dichas limitaciones y delimitar de forma más precisa el papel de la intervención familiar en el tratamiento del trastorno bipolar. (AU)