Trazodona, un antidepresivo atípico con propiedades ansiolíticas y sedantes

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Artículo de revisión RESUMEN La trazodona es un antidepresivo atípico de segunda generación. Ejerce acciones inhibidoras selectivas sobre el transporte de serotonina (5-HT), pero con menor potencia que los antidepresivos selectivos de la recaptura de 5-HT. El efecto farmacológico más potente es su acción antagonista sobre los receptores 5-HT 2A y 5-HT 2C ; bloqueando los receptores α 1 -α 2 adrenérgicos y receptores histaminérgicos tipo H1. Resulta eficaz para el tratamiento de depresión, insomnio y algunos trastornos de ansiedad, en monoterapia o en combinación con otros fármacos. También es utilizada como terapia coadyuvante en algunos casos de manía, síndrome de Tourette, enfermedad de Alzheimer y esquizofrenia, aunque su eficacia en estos desórdenes es debatida. Por sus acciones bloqueadoras a los α-adrenorreceptores, se ha utilizado para tratar la disfunción eréctil, pero su uso es controversial por algunos reportes de priapismo. La trazodona tiene interacciones farmacológicas con otros antidepresivos, algunos neurolépticos, antimi-cóticos, antirretrovirales y antibióticos, entre otros. El propósito de esta revisión es describir la farmacología de la trazodona, usos clínicos y efectos secun-darios. ABSTRACT Trazodone is a second generation, atypical antidepre-ssant. It exerts selective inhibitory actions on the transport of serotonin (5-HT), in a lesser amount than the selective serotonin reuptake inhibitors. The most striking pharmacological effect is as a 5-HT 2A and 5-HT 2C antagonist. It also blocks the α 1 -α 2 adrenergic and histamine-1 receptors. It is effective for depression, insomnia treatment and some anxiety disorders, either as monotherapy or in combination with other drugs. Albeit non-conclusive, it is also used as adjunctive therapy in some cases of mania, Tourette syndrome, Alzheimer's disease and schizophrenia. Trazodone has tried in the erectile dysfunction treatment given its blocking actions on the α-adrenoceptors, but its use is controversial from some reports of priapism. Trazodone has drug interactions with other antidepressants, and some neuroleptics, antimycotics and antiretroviral drugs, among others. The aim of this review is to describe the pharmacology of trazodone and its clinical uses and side effects.
  • [Show abstract] [Hide abstract] ABSTRACT: Eight healthy subjects were administered trazodone-HCl orally (100 mg) with and without food and by infusion in a three way cross-over study. Unchanged trazodone was determined in serum and urine by high performance liquid chromatography after an alkaline extraction. Absorption of trazodone was irregular in fasting subjects and improved after food intake. Food intake significantly decreased the maximum serum concentrations of trazodone from 1.88 +/- 0.42 to 1.47 +/- 0.16 micrograms/ml, and increased the time for reaching maximum concentration from 1.3 +/- 0.8 hr to 2.0 +/- 1.5 hr. No differences were observed in the total amount of trazodone absorbed with or without food with bioavailability values of 65 +/- 6 and 63 +/- 4 per cent, respectively. The apparent volume of distribution and total body clearance for trazodone were estimated to 0.84 +/- 0.16 l/kg and 5.3 +/- 0.9 l/hr, respectively. The terminal elimination half-life of 7.3 +/- 0.8 hr showed no significant differences between the different ways of administration. Urinary excretion of unchanged trazodone during 26 hr was less than 0.13 per cent of the administered dose, suggesting a high degree of trazodone metabolism. Earlier statements of enterohepatic circulation of trazodone and pharmacokinetic differences between males and females were not confirmed by the present study. Due to the irregular absorption in fasting subjects, trazodone should preferably be administered after food.
    Article · Sep 1992
  • [Show abstract] [Hide abstract] ABSTRACT: The aim of the present study was to prove that substantial amounts of mCPP are formed in the brain after oral administration of trazodone. To obtain preliminary information on the significance of mCPP formation for the effects of trazodone, brain levels of mCPP in rats treated with trazodone were compared with those found after pharmacologically and biochemically effective doses of mCPP. These results confirm the suggestion that mCPP may play an important role in the 5-HT-agonistic effects of relatively high doses of trazodone in the rat. Whether this is also true for the anti-5-HT effects found after low doses of trazodone remains to be clarified.
    Article · Aug 1981
  • [Show abstract] [Hide abstract] ABSTRACT: To clarify the involvement of cytochrome P4502D6 (CYP2D6) in the metabolism of trazodone, the effects of coadministration of thioridazine, which is an inhibitor of this isozyme, on plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were studied. The subjects were 11 depressed patients receiving trazodone at bedtime for 1-18 weeks. The dose was 150 mg in 10 patients and 300 mg in one. Thioridazine 40 mg/day was coadministered for 1 week, and blood samplings were performed before and after the coadministration. Thioridazine significantly (p < 0.001) increased plasma concentrations of both trazodone (713 +/- 252 vs. 969 +/- 370 ng/ml) and m-CPP (61 +/- 22 vs. 94 +/- 34 ng/ml). The present study thus suggests that CYP2D6 is involved in the metabolism of trazodone.
    Article · Aug 1995
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