El papel histórico de los barbitúricos en las "curas de sueño" de los trastornos psicóticos y maníacos / The historical role of barbiturates in "sleep cures" for psychotic and manic disorders

La introducción clínica de los barbitúricos en 1904, gracias a los trabajos de Von Mering y Fischer, supuso el inicio de una nueva era en el abordaje farmacológico de diferentes trastornos psiquiátricos. En el presente trabajo, se analiza el empleo de estos fármacos durante el primer tercio del siglo XX en pacientes esquizofrénicos y maníacos, en el marco de las denominadas "curas de sueño", auténtico precedente de las grandes terapias biológicas en psiquiatría. Estas terapias de sueño prolongado consistían en la inducción de un estado de narcolepsia continua durante más de 20 h diarias y 2 semanas consecutivas. Su introducción clínica, mediante el uso de barbitúricos, está asociada históricamente a Jakob Klaesi y a la Clínica Psiquiátrica Universitaria de Zurich (Burghölzli, Suiza), donde se aplicaron por primera vez en 1920. En este trabajo se describen los métodos de aplicación de estas técnicas (Dauerschlaf, Dauernarkose) y la experiencia acumulada por distintos autores en Burghölzli (Klaesi, Cloetta, Maier, Boss, Monnier) y en otros centros, tanto con Somnifen® (1920), una mezcla de ácido dietil y dipropenilbarbitúrico y dietilamina comercializada por la firma suiza Hoffmann-La Roche, como con Cloettal® (1934), un preparado que incluía, entre otras sustancias, ácido isopropilalilbarbitúrico. Las curas de sueño fueron los únicos tratamientos de cierta eficacia terapéutica disponibles en esa época para el abordaje de los trastornos psiquiátricos agudos, aunque a finales de la década de los treinta su uso comenzó a declinar, debido a problemas de seguridad, con una considerable tasa de mortalidad, al conocimiento de los fenómenos de dependencia de los barbitúricos y a la paulatina introducción clínica de otras nuevas terapias biológicas para el tratamiento de la esquizofrenia (AU)

[A century of barbiturates in neurology]. / Un siglo de barbitúricos en neurologia.

INTRODUCTION AND AIMS: Until the early 20th century, pharmacological treatments for neurological disorders were scarce and inefficient; only bromides stood out as sedating and antiepileptic agents. DEVELOPMENT: The introduction of barbiturates for clinical use in 1904 heralded the beginning of a new age in the pharmacological management of certain neurological pathologies. In this study, we analyse the historical process of the discovery and use of barbiturates in the field of neurology, from the moment it was started by von Baeyer in 1864, with the synthesis of malonylurea, up to the period of the decline of barbiturate therapy in the 1960s. In 1903, von Mering and Fischer discovered the hypnotic properties of barbital and later synthesised phenobarbital (1911). In the years that followed a number of barbiturates, such as butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, and so on, were gradually incorporated into the therapeutic arsenal. During this period, the different therapeutic uses of barbiturates in neurology were analysed, from their traditional use as hypnotic agents (von Husen) to the discovery of the anticonvulsant properties of phenobarbital (Hauptmann) and its use in the treatment of epilepsy. CONCLUSIONS: The barbiturates were one of the first pharmacological tools that proved to be really effective in the management of some neurological disorders. Nevertheless, problems associated with their safety (dependence phenomena and deaths from overdoses), together with the introduction of numerous psychopharmacological agents in the 1950s, ended up eclipsing the use of barbiturates, except for a few very specific cases in which they are still indicated.

Un siglo de barbitúricos en neurología / A century of barbiturates in neurology

Introducción y objetivos. Hasta principios del siglo XX, los tratamientos farmacológicos de los trastornos neurológicos eran escasos y poco eficaces; únicamente destacaban los bromuros como agentes sedantes y antiepilépticos. Desarrollo. Con la introducción clínica de los barbitúricos en 1904, se inicia una nueva era en el abordaje farmacológico de ciertas patologías neurológicas. En este trabajo, se analiza el proceso histórico del descubrimiento y del empleo de los barbitúricos en el ámbito de la neurología, que inició von Baeyer en 1864, con la síntesis de la malonilurea, hasta el período de declive de la terapéutica barbitúrica en la década de los años sesenta. En 1903, von Mering y Fischer descubrieron las propiedades hipnóticas del barbital y posteriormente sintetizaron el fenobarbital (1911). En los años sucesivos fueron incorporándose al arsenal terapéutico, de forma paulatina, numerosos barbitúricos (butobarbital, amobarbital, secobarbital, pentobarbital, tiopental, etc.). Analizamos los diferentes usos terapéuticos de los barbitúricos en neurología durante este período, desde su tradicional empleo como agentes hipnóticos (von Husen) al descubrimiento de las propiedades anticomiciales del fenobarbital (Hauptmann) y su empleo en el tratamiento de la epilepsia. Conclusiones. Los barbitúricos constituyeron las primeras herramientas farmacológicas realmente eficaces en el manejo de algunos trastornos neurológicos. Sin embargo, sus problemas de seguridad (fenómenos de dependencia y muertes por sobredosis), junto a la introducción de una pléyade de psicofármacos en la década de los cincuenta, acabaron por eclipsar el uso de los barbitúricos, salvo en algunas indicaciones puntuales (AU)

Introduction and aims. Until the early 20th century, pharmacological treatments for neurological disorders were scarce and inefficient; only bromides stood out as sedating and antiepileptic agents. Development. The introduction of barbiturates for clinical use in 1904 heralded the beginning of a new age in the pharmacological management of certain neurological pathologies. In this study, we analyse the historical process of the discovery and use of barbiturates in the field of neurology, from the moment it was started by von Baeyer in 1864, with the synthesis of malonylurea, up to the period of the decline of barbiturate therapy in the 1960s. In 1903, von Mering and Fischer discovered the hypnotic properties of barbital and later synthesised phenobarbital (1911). In the years that followed a number of barbiturates, such as butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, and so on, were gradually incorporated into the therapeutic arsenal. During this period, the different therapeutic uses of barbiturates in neurology were analysed, from their traditional use as hypnotic agents (von Husen) to the discovery of the anticonvulsant properties of phenobarbital (Hauptmann) and its use in the treatment of epilepsy. Conclusions. The barbiturates were one of the first pharmacological tools that proved to be really effective in the management of some neurological disorders. Nevertheless, problems associated with their safety (dependence phenomena and deaths from overdoses), together with the introduction of numerous psychopharmacological agents in the 1950s, ended up eclipsing the use of barbiturates, except for a few very specific cases in which they are still indicated (AU)

Double-blind comparison of moclobemide, imipramine and placebo in depressive patients.

In a prospective, randomized double-blind study, moclobemide was compared with imipramine and placebo in the treatment of depressed outpatients. Three parallel groups of 24 patients each received capsules containing 100 mg moclobemide, 33 mg imipramine or placebo for 6 weeks; the maximum daily dose was 6 capsules. The only concomitant psychotropic medication allowed was diazepam for severe agitation or insomnia, and continuation of established lithium prophylaxis; no tyramine restrictions were imposed. Both moclobemide and imipramine were clearly superior to placebo in reducing depressive symptoms, moclobemide showing a somewhat faster response on the Hamilton Rating Scale for Depression than imipramine; the mean final improvement in total score compared with baseline was 48.3% for moclobemide, 50.2% for imipramine and 18.6% for placebo. The difference between moclobemide and imipramine was not significant. Placebo was clearly better tolerated than either active drug, and moclobemide slightly but not significantly better than imipramine. A 52-week assessment in 22 of the patients receiving moclobemide showed that the clinical response was maintained and the long-term treatment was well tolerated. It is concluded that both moclobemide and imipramine were superior to placebo in treatment of major depressive episodes in outpatients. There was a slight tendency to earlier response with moclobemide, probably because it can be given in the full dose from the start of treatment.