Efectos terapéuticos de medicamentos antidepresivos para la depresión clínica en mujeres peri y posmenopáusicas

¿Cuáles son los efectos terapéuticos de los antidepresivos sobre MDE en mujeres perimenopáusicas y posmenopáusicas?

Dos grandes ensayos clínicos aleatorios, doble ciego, controlados con placebo, examinaron la eficacia de la desvenlafaxina para el TDM en las mujeres perimenopáusicas y posmenopáusicas y definieron el uso de Criterios de STRAW.93,94

El tratamiento a corto plazo con dosis de 50 mg y 100-200 mg de desvenlafaxina condujo a significativas mejoras en los síntomas depresivos en comparación con placebo.93,94

Análisis post hoc de datos agrupados de estos ensayos mostraron una mejoría significativa con desvenlafaxina en los subgrupos de perimenopáusicas y posmenopáusicas, incluyendo una menor carga de síntomas y unas mayores tasas de remisión.95,96

Hasta la fecha, no se han estudiado otros antidepresivos en grandes ensayos aleatorios controlados con placebo de mujeres perimenopáusicas y posmenopáusicas bien definidos con TDM.

Ha habido una serie de pequeños estudios abiertos de otros antidepresivos, incluyendo inhibidores selectivos de la recaptación de serotonina (ISRS; citalopram, escitalopram, vortioxetina), inhibidores de la recaptación de serotonina y norepinefrina (IRSN; venlafaxina, duloxetina) y mirtazapina para tratar el TDM en la perimenopausia y mujeres posmenopáusicas, que han demostrado un efecto positivo en el estado de ánimo, así como SVM, sueño, ansiedad y dolor.97-99,100-103

Bupropión, un inhibidor de la recaptación norepinefrina-dopamina (NDRI), a veces se prescribe solo o en combinación con un SSRI/SNRI para mujeres perimenopáusicas porque no produce tanto aumento de peso, disfunción sexual o somnolencia como ISRS/ISRS104.

Sin embargo, no hay ECAs de bupropión en la mujer perimenopáusica.

¿Existen Diferencias en la Eficacia entre los Tipos de Antidepresivos en el Tratamiento de Mujeres Peri o Posmenopáusicas con TDM?

Un gran ensayo aleatorizado doble ciego comparó el SNRI desvenlafaxina y el SSRI escitalopram en MDD en mujeres posmenopáusicas definidas utilizando criterios de STRAW; no se observó diferencia significativa en la eficacia después de 8 semanas de tratamiento de fase aguda, ni después de 6 meses de fase de tratamiento de continuación.105

Estos hallazgos estuvieron en contraste con un análisis previo de un gran conjunto de datos agrupados por sexo y edad (usando un límite de 50) comparando las tasas de remisión con venlafaxina, ISRS o placebo que encontró una ventaja significativa en tasas de remisión que favorecen la venlafaxina SNRI sobre los SSRI en mujeres mayores.106

Otros análisis post hoc de datos de ensayo clínico sobre el estado de la menopausia definida por edad no mostraron diferencias en la eficacia de la SNR venlafaxina frente a la ISRS fluoxetina en mujeres más jóvenes o mayores.107

Del mismo modo, un conjunto de análisis de ensayos de etiqueta abierta no mostró diferencias en tasas de res puesta a la reboxetina, sertralina o venlafaxina en mujeres mayores y jóvenes.108

Algunos estudios han observado un efecto superior de un ISRS sobre un inhibidor de la captación (NRI) tricíclico o norepinefrínico en mujeres premenopáusicas, pero no se encontraron diferencias en mujeres posmenopáusicas en estos estudios109-111.

¿Existen Respuestas Clínicas a los Antidepresivos según el Estado de la Menopausia?

Los estudios han examinado si existen diferencias en la respuesta de los antidepresivos en mujeres premenopáusicas frente a posmenopáusicas, y todos utilizan la edad como un variable proxy para el estado de la menopausia.

En el análisis combinado de los ensayos clínicos de venlafaxina, ISRS y placebos discutidos anteriormente, se observó una respuesta más pobre a los ISRS en la posmenopausia en comparación con las mujeres premenopáusicas, mientras que la respuesta a venlafaxina no difirió según el estado de la menopausia106.

Otro análisis agrupado no mostró diferencias en la respuesta antidepresiva a ningún bupropión o ISRS por estado de menopausia,112 ni tampoco una gran estudio de venlafaxina y fluoxetina.107

Al igual que en el estudio Thase 2005106, varios estudios abiertos han demostrado una resistencia relativa a los ISRS y otros antidepresivos en mujeres posmenopáusicas versus premenopáusicas; otros113-115 no encontraron una diferencia por estado de menopausia.111,116-118

Solo un estudio examinó el estado de la menopausia como un predictor de la recurrencia de la depresión durante el tratamiento con antidepresivos; las tasas de recurrencia de la TDM durante el tratamiento con venlafaxina o fluoxetina no difirieron en mujeres premenopáusicas versus posmenopáusicas107.

¿El tratamiento con Estrógenos mejora la Respuesta Antidepresiva en Mujeres Peri Menopáusicas o Posmenopáusicas?

Dos análisis post hoc de estudios aleatorizados controlados con placebo de ISRS en mujeres mayores con MDD encontraron una intervención entre el uso de la terapia concomitante de estrógeno y el efecto del tratamiento antidepresivo, lo que sugiere que el estrógeno puede aumentar la respuesta antidepresiva a los ISRS en mujeres deprimidas posmenopáusicas. 119,120

Dos ensayos pequeños de etiqueta abierta mostraron una respuesta mayor o acelerada a los ISRS en mujeres posmenopáusicas que también tomaron estrógeno,121,122 mientras los otros estudios no mostraron diferencias en las tasas de respuesta o remisión en mujeres con depresión peri o posmenopáusicas tratadas con ISRS que tomaron versus no tomaron estrógeno123,124.

En el análisis del gran conjunto de datos de los ensayos de venlafaxina, ISRS y placebo que se discutió anteriormente, el uso concomitante de TH en mujeres posmenopáusicas eliminó la disparidad en las tasas de respuesta a los ISRS en las mujeres pre vs. posmenopáusicas; la TH no afectó las respuestas a la venlafaxina.106

En un pequeño estudio ciego controlado con estrógeno, el aumento de estrógenos mejoró la respuesta antidepresiva en mujeres perimenopáusicas con TDM en remisión parcial.125

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Otras Reseñas

• 115. Pae CU, Mandelli L, Kim TS, et al. Effectiveness of antidepressant treatments in pre-menopausal versus post-menopausal women: a pilot study on differential effects of sex hormones on antidepressant effects. Biomed Pharmacother 2009;63:228-35. Maki et al. 16 Menopause, 2018;25(10). The North American Menopause Society Copyright 2018. The North American Menopause Society. Unauthorized reproduction of this article is prohibited.
• 116. Quitkin FM, Stewart JW, McGrath PJ, et al. Are there differences between women’s and men’s antidepressant responses? Am J Psychiatry 2002;159:1848-54.
• 117. Parker G, Parker K, Austin MP, Mitchell P, Brotchie H. Gender differences in response to differing antidepressant drug classes: two negative studies. Psychol Med 2003;33:1473-7.
• 118. Cassano P, Soares CN, Cusin C, Mascarini A, Cohen LS, Fava M. Antidepressant response and well-being in pre-, peri- and postmenopausal women with major depressive disorder treated with fluoxetine. Psychother Psychosom 2005;74:362-5.
• 119. Schneider LS, Small GW, Hamilton SH, Bystritsky A, Nemeroff CB, Meyers BS. Estrogen replacement and response to fluoxetine in a multicenter geriatric depression trial. Fluoxetine Collaborative Study Group. Am J Geriatr Psychiatry 1997;5:97-106.
• 120. Schneider LS, Small GW, Clary CM. Estrogen replacement therapy and antidepressant response to sertraline in older depressed women. Am J Geriatr Psychiatry 2001;9:393-9.
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Relación

• 123. Amsterdam J, Garcia-Espana F, Fawcett J, et al. Fluoxetine efficacy in menopausal women with and without estrogen replacement. J Affect Disord 1999;55:11-7.
• 124. Kornstein SG, Toups M, Rush AJ, et al. Do Menopausal Status and Use of Hormone Therapy Affect Antidepressant Treatment Response? Findings from the Sequenced Treatment Alternatives to Relieve Depression (STAR_D) Study. J Womens Health (Larchmt) 2013;22:121-31.
• 125. Morgan ML, Cook IA, Rapkin AJ, Leuchter AF. Estrogen augmentation of antidepressants in perimenopausal depression: a pilot study. J Clin Psychiatry 2005;66:774-80.