Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DS...Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DSM-IV bipolar disorder with divalproex sodium extended release (ER) monotherapy. Severity of mania was assessed weekly with the Young Mania Rating Scale (YMRS). Results: The sample was 8.9 ± 2.0 years of age and predominantly male (83%). At study entry the mean YMRS score was 26.3 ± 4.5. Of the 18 subjects enrolled, 7 (39%) completed the 8 week course. We failed to find a clinically or statistically significant improvement with divalproex sodium ER. Pre-post comparisons at endpoint (LOCF) indicated an average response reduction of 6.1 ± 2.6 in the YMRS to a mean of 20.3 ± 8.1. Weight increased by 1.36 ± 0.7 kg (p = 0.08) from baseline to endpoint. Conclusion. Divalproex sodium ER monotherapy was associated with poor tolerability, was associated with clinically concerning weight gain but had modest therapeutic benefits in the management of symptoms of mania and depression in children with pediatric bipolar disorder.展开更多
Typical antipsychotics, potent D2 dopamine receptor antagonists, are the most commonly used drugs in the treatment of bipolar disorders. In the central nervous system, the discovery of antagonistic interactions betwee...Typical antipsychotics, potent D2 dopamine receptor antagonists, are the most commonly used drugs in the treatment of bipolar disorders. In the central nervous system, the discovery of antagonistic interactions between A2A adenosine receptors and D2 dopamine receptors suggests that the adenosine system may be involved in the pathogenesis of different psychiatric disorders and in the therapeutic effectiveness of antipsychotic drugs. Previously, we have demonstrated an increase in A2A receptor expression and agonist affinity in platelets from psychotic patients treated with haloperidol. This result suggests that there is also a structural and functional interaction between A2A and D2 receptors in peripheral cells. In this work, we investigated the effect of different doses of typical drugs on A2A adenosine receptor binding and correlated these parameters with the severity of symptoms. We demonstrated, for the first time, that there was a strong correlation between A2A receptor affinity constant values (Kd) and drug doses in psychotic patients with a moderate severity of illness and moderate psychotic symptoms. The correlation was completely lost in patients with severe illness and severe psychotic symptoms. These results demonstrated that in platelets of patients affected by psychosis, typical antipsychotics modulated A2A receptor binding parameters;this regulation is dependent on the degree of D2 receptor occupancy in relation to the severity of psychotic symptoms, suggesting A2A receptors are a peripheral marker for individual therapy effectiveness.展开更多
文摘Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DSM-IV bipolar disorder with divalproex sodium extended release (ER) monotherapy. Severity of mania was assessed weekly with the Young Mania Rating Scale (YMRS). Results: The sample was 8.9 ± 2.0 years of age and predominantly male (83%). At study entry the mean YMRS score was 26.3 ± 4.5. Of the 18 subjects enrolled, 7 (39%) completed the 8 week course. We failed to find a clinically or statistically significant improvement with divalproex sodium ER. Pre-post comparisons at endpoint (LOCF) indicated an average response reduction of 6.1 ± 2.6 in the YMRS to a mean of 20.3 ± 8.1. Weight increased by 1.36 ± 0.7 kg (p = 0.08) from baseline to endpoint. Conclusion. Divalproex sodium ER monotherapy was associated with poor tolerability, was associated with clinically concerning weight gain but had modest therapeutic benefits in the management of symptoms of mania and depression in children with pediatric bipolar disorder.
文摘Typical antipsychotics, potent D2 dopamine receptor antagonists, are the most commonly used drugs in the treatment of bipolar disorders. In the central nervous system, the discovery of antagonistic interactions between A2A adenosine receptors and D2 dopamine receptors suggests that the adenosine system may be involved in the pathogenesis of different psychiatric disorders and in the therapeutic effectiveness of antipsychotic drugs. Previously, we have demonstrated an increase in A2A receptor expression and agonist affinity in platelets from psychotic patients treated with haloperidol. This result suggests that there is also a structural and functional interaction between A2A and D2 receptors in peripheral cells. In this work, we investigated the effect of different doses of typical drugs on A2A adenosine receptor binding and correlated these parameters with the severity of symptoms. We demonstrated, for the first time, that there was a strong correlation between A2A receptor affinity constant values (Kd) and drug doses in psychotic patients with a moderate severity of illness and moderate psychotic symptoms. The correlation was completely lost in patients with severe illness and severe psychotic symptoms. These results demonstrated that in platelets of patients affected by psychosis, typical antipsychotics modulated A2A receptor binding parameters;this regulation is dependent on the degree of D2 receptor occupancy in relation to the severity of psychotic symptoms, suggesting A2A receptors are a peripheral marker for individual therapy effectiveness.
