Antonio Luque

Validación de las versiones en español de la Montgomery-Asberg Depression Rating Scale y la Hamilton Anxiety Rating Scale para la evaluación de la depresión y de la ansiedad

Fundamento Los trastornos del estado de animo (TEA) y los trastornos de ansiedad (TA) constituyenlas alteraciones psiquiatricas mas comunes en la poblacion general. En este estudio se han evaluado,por primera vez, las propiedades psicometricas de las versiones en espanol de la Montgomery-AsbergDepression Rating Scale (MADRS) y la Hamilton Anxiety Rating Scale (HARS), ampliamente utilizadasen la practica asistencial y en investigacion clinica. Pacientes y metodo Se diseno un estudio de cohortes, observacional, prospectivo y multicentrico enpacientes con TEA o TA, clinicamente estables o inestables. Las escalas se administraron en la visitade inclusion en el estudio y en una segunda visita realizada a la semana .en el caso de pacientes estables.o dos meses despues –en pacientes inestables–. Se evaluaron la estructura factorial, la validez(convergente y discriminante), la fiabilidad (consistencia interna, estabilidad temporal y entre observadores)y la sensibilidad al cambio de ambas escalas. Resultados Se incluyo a 108 pacientes con TEA y a 106 pacientes con TA en 10 centros de asistenciapsiquiatrica con amplia distribucion geografica. Ambas escalas presentaron una adecuada: a) validezdiscriminante (MADRS/HARS-Impresion Clinica Global de Gravedad: p < 0,001); b) validez convergente(MADRS-Hamilton Depression Rating Scale: p < 0,05 y 0,01, respectivamente;MADRS/HARS-EuroQoL 5D: p < 0,05; HARS-State Trait Anxiety Inventory: p < 0,05); c) consistenciainterna (α de Cronbach: MADRS = 0,88; HARS = 0,89); d) fiabilidad test-retest y entre observadores(coeficiente de correlacion intraclase: MADRS = 0,94 y 0,98, respectivamente; HARS = 0,92 y0,92), y e) sensibilidad al cambio (tamano del efecto: MADRS = 2,05; HARS = 1,36). Conclusiones Las versiones en espanol de la MADRS y de la HARS presentan buenas propiedades psicometricas,similares a las de las escalas originales, por lo que resultan apropiadas para su uso en lapractica asistencial y en investigacion clinica en Espana.

Evaluación psicométrica comparativa de las versiones en español de 6, 17 y 21 ítems de la Escala de valoración de Hamilton para la evaluación de la depresión

Fundamento y objetivo Los estudios espanoles previos de la Hamilton Depression Rating Scale(HDRS) se han centrado en su version de 17 items y se han realizado fundamentalmente enpoblaciones hospitalizadas. En el presente estudio se ha llevado a cabo una evaluacion psicometricacomparativa de las versiones en espanol de la HDRS de 6, 17 y 21 items en pacientescon depresion en tratamiento ambulatorio. Pacientes y metodo Estudio multicentrico, observacional y prospectivo en pacientes con depresion,clinicamente estables o inestables. Se evaluaron la validez discriminante, la fiabilidad(consistencia interna, estabilidad temporal y entre observadores) y la sensibilidad al cambio dela HDRS con 6, 17 y 21 items. Resultados Se incluyo a 168 pacientes de 15 centros de asistencia psiquiatrica. Las versionesde 6, 17 y 21 items de la HDRS presentaron una adecuada validez discriminante (HDRS-ImpresionClinica Global de Gravedad, p Conclusiones Las versiones en espanol de la HDRS con 6, 17 y 21 items presentan similarespropiedades psicometricas. El buen rendimiento de HDRS-6 justifica su utilizacion en mediosambulatorios y en atencion primaria.

Sleep Laboratory Study on Single and Repeated Dose Effects of Paroxetine, Alprazolam and Their Combination in Healthy Young Volunteers

Aims: To evaluate the potential interaction of 20 mg paroxetine and 1 mg alprazolam (early morning once-daily administration) on polysomnographic (PSG) sleep and subjective sleep and awakening quality, both after a single intake and after reaching a steady-state concentration. Methods: Twenty-two (11 for the PSG) healthy young volunteers of both sexes with no history of sleep disturbances (Pittsburgh Sleep Quality Index <5) participated in a double-blind, double-dummy, placebo-controlled, repeated-dose, 4-period, cross-over study. All volunteers received all 4 treatment sequences: paroxetine–alprazolam placebo (PAP); paroxetine placebo–alprazolam (PPA); paroxetine–alprazolam (PA), and paroxetine placebo–alprazolam placebo (PLA), in a randomized order. Each treatment was administered over 15 consecutive days, with a treatment-free interval of 7 days prior to the subsequent study period. In each experimental period, one PSG sleep study was performed on the 1st night (single-dose effects) and another study was performed on the 15th night (repeated-dose effects). Additionally, two other PSG studies were assessed: an adaptation recording, and a control night recording. All-night PSG recordings were obtained following standard procedures. Each 30-second period was scored according to the criteria of Rechtschaffen and Kales by means of an automatic sleep analysis system: Somnolyzer 24x7TM. A self-rating scale for sleep and awakening quality and early morning behavior was completed no later than 15 min after awakening over the 15 days of each experimental intervention. General lineal models (treatment/time) were applied separately to each variable. Results: (1) No significant effects were observed in any sleep variables when control nights were compared with the 1st night with PLA. (2) Sleep continuity: After PAP a clear awakening effect was seen both in the first and second evaluations, mainly in wake time, movement time, number of awakenings and stage-1 duration. After PPA an evident hypnotic effect was observed on night 1. This effect was mainly observed in maintenance variables and slightly in sleep initiation variables; it had decreased by night 15. After PA an intermediate behavior in the variables related to sleep continuity was seen, highlighting the absence of the tolerance phenomenon observed when PPA was administered alone. (3) Sleep architecture: The most important effects in REM sleep were observed after PAP; an increase in REM latency and decreases in REM sleep. PAP also induced decreases in the number of non-REM and REM periods and increases in the average duration of non-REM periods and sleep cycles. PA presented a similar pattern to PAP, and PPA similar to PLA. In relation to non-REM sleep, PA showed more stage-2 and less slow-wave sleep (SWS). (4) Subjective perception: No significant differences were observed between treatments while they were being taken, but impairments in subjective sleep quality, awaking quality, latency and efficiency were seen, mainly after PA but also after PPA discontinuations. Conclusion: The combination of PAP and PPA presented an intermediate pattern in relation to sleep continuity, with less awaking effect than PAP alone and less hypnotic effect than PPA alone, and without developing tolerance. The PAP and PPA combination also showed a similar effect to PAP on REM sleep and was the treatment with the longest stage 2 and shortest SWS. No subjective sleep and awakening effects were seen during drug intake but subjective withdrawal reports were seen after abrupt interruption. The high agreement rate for the epoch-by-epoch comparison between automatic and human scoring confirms the validity of the Somnolyzer 24x7 and thus facilitates sleep studies in neuropsychopharmacological research.

Lack of pharmacologic interaction between paroxetine and alprazolam at steady state in healthy volunteers.

Abstract: This investigation aimed to provide evidence on the lack of pharmacokinetic interaction of paroxetine (20 mg/d) and alprazolam (1 mg/d) in combined therapy. In addition, the central effects of both drugs when administered alone and in combination were assessed to rule out any relevant synergistic depressant central effect. Twenty-five healthy young adult volunteers participated in a double-blind, double-dummy, placebo-controlled, repeated dose (15 days), 4-period crossover study. Each subject received each of 4 treatment sequences (ie, paroxetine-alprazolam placebo, alprazolam-paroxetine placebo, paroxetine-alprazolam, and paroxetine placebo-alprazolam placebo) in randomized order. The ratios for area under the curve within a dosing interval and maximum plasma concentration of the paroxetine plus alprazolam sequence to single agent paroxetine were 1.07 (90% confidence interval = 0.99 to 1.16) and 1.05 (90% confidence interval = 0.97 to 1.13), respectively, with no statistically significant differences between the 2 treatments. Similarly, for alprazolam, ratios for the combined to the single treatment sequence were 0.99 (90% confidence interval = 0.93 to 1.05) and 1.00 (90% confidence interval = 0.94 to 1.07) for area under the curve within a dosing interval and maximum plasma concentration, respectively, showing no evidence for interaction. Comparative pharmacodynamics on the combination was assessed using 6 Psychomotor Performance Tests and 5 Visual Analogue Scales focused on mood variables. Alprazolam and paroxetine plus alprazolam induced similar and significant performance impairment and sedation after both single and repeated dose administration, being less evident on day 15. After dosing, paroxetine plus alprazolam showed a lower recovery pattern than alprazolam alone, especially on day 15. No treatment sequence showed cumulative effects after repeated dose administration. Psychomotor Performance Tests and Visual Analogue Scales data suggested lack of pharmacodynamic interactions. Accordingly, study results showed no evidence for pharmacologic interactions between paroxetine and alprazolam at steady state. The most commonly reported adverse event was drowsiness, with a higher incidence under both single and combined alprazolam treatments.

Validación de las versiones en español de la Clinical Anxiety Scale y del Physician Questionnaire para la evaluación de los trastornos de ansiedad

Fundamento y objetivo Validar las versiones espanolas de la Clinical Anxiety Scale (CAS) y delPhysician Questionnaire (PQ) para valorar la gravedad sintomatica presente en pacientes condiagnostico de trastornos de ansiedad (TA) y tratados ambulatoriamente. Pacientes y metodo Estudio observacional, prospectivo y multicentrico (15 centros de asistenciapsiquiatrica) con periodos de seguimiento de 1 a 6 semanas en pacientes con TA clinicamenteestables o inestables. Se evaluaron la validez convergente, frente a la Hamilton Anxiety RatingScale; la validez discriminante, frente a la Impresion Clinica Global, asi como la fiabilidad (coherenciainterna, estabilidad temporal y entre observadores) y sensibilidad al cambio. Resultados Se incluyo a 161 pacientes con TA (48 pacientes estables y 113 inestables). Ambasescalas presentaron valores adecuados de validez convergente (r ≥ 0,70) y discriminante (p. 0,001), coherencia interna (α de Cronbach > 0,75), estabilidad temporal (coeficiente de correlacionintraclase [CCI] > 0,90), fiabilidad entre observadores (CCI > 0,90) y sensibilidad alcambio (p Conclusiones Las versiones en espanol de la CAS y del PQ presentan valores adecuados de validezy fiabilidad para valorar la gravedad y evolucion sintomatica en pacientes ambulatoriosdiagnosticados de TA.