Lack of relationship between plasma levels of escitalopram and QTc-interval length.

Despite safety concerns raised by the European Medicines Agency (EMA), evidence supporting QT-lengthening effects of escitalopram is far to be conclusive. We aimed to evaluate the relationship between escitalopram plasma levels (Escit-PL) and corrected QT-interval length (QTc-length) in 91 outpatients recruited from a hospital setting. Fifteen patients had an abnormally prolonged QTc-interval, and 3 had QTc-intervals ≥500 ms. No correlation between Escit-PL and QTc-length was found (r = 0.08; p = 0.45). Linear/logistic regression analyses were also conducted taking into account potential confounders such as age, gender, personal history of heart disease, medication load and concomitant use of antipsychotic/tricyclic antidepressants. Escit-PL did not predict either QTc-length or abnormally prolonged QTc-interval. Only antipsychotics/tricyclics use (adjusted ß = 0.26, SE = 9.1; p = 0.01) was an independent predictor of QTc-length (R 2 = 0.096, F = 4.68, df = 2,88; p = 0.01). Only antipsychotics/tricyclics use (OR 3.56 [95% CI 1.01-12.52]; p < 0.05) and medication load (OR 1.32 [95% CI 1.06-1.64]; p < 0.01) were significantly associated with an increased risk of abnormally prolonged QTc-interval (Omnibus test χ 2 = 9.5, df = 2; p < 0.01). Our study did not find a significant relationship between Escit-PL and QTc-length even when recognized modulating factors of the QT-interval were controlled for. Concomitant use of other potentially arrhythmogenic agents may help to explain the apparent link between escitalopram and QT prolongation previously suggested. The advisability of maintaining the EMA warning is once again called into question.

Neuropsychological effects of maintenance treatment with Clozapine in Treatment-Resistant Psychotic Disorder.

INTRODUCTION: Clozapine is a second-generation antipsychotic drug that is mainly prescribed for treatment-resistant psychotic disorder. It is known to have several undesirable side effects, including cognitive functional complaints, such as memory or attention. The aim of this work is to study if reduction of the dosage within the therapeutic margins could improve cognitive performance of Clozapine treated patients. To do so, a study was made of the relationship between Clozapine plasma levels and neuropsychological performance in patients undergoing Clozapine monotherapy. MATERIAL AND METHODS: This is a single-blind design study of the correlation between Clozapine plasma levels and neuropsychological testing in a sample of 19 patients with treatment-resistant psychotic disorder in whom Clozapine was the only psychotropic drug. Spearman correlations were carried out between neuropsychological variables and Clozapine plasma levels. Additionally, the sample was divided into two groups between patients with high Clozapine plasma drug levels (Clz pl≥300µg/L) and low ones (Clz pl<300 µg/L). MANOVA was performed to determine neuropsychological differences between the two groups. Subsequently, a linear regression model was carried out to predict neuropsychological performance. RESULTS: There was no significant Spearman correlation between neuropsychological scores and Clozapine plasma levels (p>0.1). MANOVA showed no significant differences between the two groups in any of the tests administered, although there was a trend towards significance in the number on attempts of the Card Sorting Test (WCST), where subjects with high levels of Clozapine showed worse performance (F=3.86; df=1.17; p=0.07). The linear regression model showed that only plasma levels significantly predicted executive performance, explaining 31% of the variance (F=3.62; df=2.16; p=0.05). CONCLUSION: No relationship between plasma levels of Clozapine and cognitive performance has been found. This result suggests that it is not desirable to reduce a relevant dose of Clozapine in patients with cognitive complaints.

Efectos neuropsicológicos del tratamiento de mantenimiento con Clozapina en el Trastorno Psicótico Resistente / Neuropsychological effects of maintenance treatment with Clozapine in Treatment-Resistant Psychotic Disorder

Introducción. La Clozapina es un antipsicótico de segunda generación, indicado en casos de trastorno psicótico resistente al tratamiento convencional. Presenta varios efectos secundarios, entre ellos, las quejas sobre la función cognitiva como la memoria o la atención. El objetivo es estudiar si la reducción de la dosis dentro de los márgenes terapéuticos podría mejorar el rendimiento cognitivo de los pacientes tratados con clozapina. Para ello se estudia la relación entre la concentración plasmática de Clozapina y el rendimiento cognitivo en pacientes en monoterapia con Clozapina. Material y Métodos. El estudio es un diseño simple ciego de correlación entre niveles plasmáticos de Clozapina y rendimiento neuropsicológico en una muestra de 19 pacientes con trastorno psicótico resistente en monoterapia con Clozapina. Se realizaron correlaciones de Spearman entre variables neuropsicológicas y niveles plasmáticos. Adicionalmente, la muestra se dividió entre pacientes con niveles plasmáticos altos (Clz pl≥300μg/L) y bajos (Clz pl<300μg/L) de Clozapina. Se llevó a cabo una MANOVA para determinar diferencias entre grupos. Se realizó un análisis de regresión lineal para predecir el rendimiento neuropsicológico. Resultados. No se halló ninguna correlación significativa entre las pruebas neuropsicológicas y los niveles plasmáticos de Clozapina (p>0.1). La MANOVA no mostró diferencias significativas entre los dos grupos en ninguna de las pruebas administradas, aunque sí se observó una tendencia a la significación en los análisis univariantes donde en el número de intentos del Test de Clasificación de Tarjetas (WCST)los sujetos con niveles altos de Clozapina mostraron un peor rendimiento (F=3.86; gl=1.17; p=0.07). El modelo de regresión lineal mostró que el único factor significativo fueronlos niveles plasmáticos, explicando un 31% de la varianza (F=3.62; gl=2.16; p=0.05). Conclusiones. No se evidencia relación entre los niveles plasmáticos de Clozapina y el rendimiento cognitivo. Este resultado sugiere que no es conveniente reducir de forma relevante la dosis de Clozapina en pacientes que se quejan de disfunciones cognitivas

Introduction. Clozapine is a second-generation antipsychotic drug that is mainly prescribed for treatment-resistant psychotic disorder. It is known to have several undesirable side effects, including cognitive functional complaints, such as memory or attention. The aim of this work is to study if reduction of the dosage within the therapeutic margins could improve cognitive performance of Clozapine treated patients. To do so, a study was made of the relationship between Clozapine plasma levels and neuropsychological performance in patients undergoing Clozapine monotherapy. Material and Methods. This is a single-blind design study of the correlation between Clozapine plasma levels and neuropsychological testing in a sample of 19 patients with treatment-resistant psychotic disorder in whom Clozapine was the only psychotropic drug. Spearman correlations were carried out between neuropsychological variables and Clozapine plasma levels. Additionally, the sample was divided into two groups between patients with high Clozapine plasma drug levels (Clz pl.300ƒÊg/L) and low ones (Clz pl<300ƒÊg/L). MANOVA was performed to determine neuropsychological differences between the two groups. Subsequently, a linear regression model was carried out to predict neuropsychological performance. Results. There was no significant Spearman correlation between neuropsychological scores and Clozapine plasma levels (p>0.1). MANOVA showed no significant differences between the two groups in any of the tests administered, although there was a trend towards significance in the number on attempts of the Card Sorting Test (WCST), where subjects with high levels of Clozapine showed worse performance (F=3.86; df=1.17; p=0.07). The linear regression model showed that only plasma levels significantly predicted executive performance, explaining 31% of the variance (F=3.62; df=2.16; p=0.05). Conclusion. No relationship between plasma levels of Clozapine and cognitive performance has been found. This result suggests that it is not desirable to reduce a relevant dose of Clozapine in patients with cognitive complaints