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Titolo:
Augmentation of fluoxetine's antidepressant action by pindolol: Analysis of clinical, pharmacokinetic, and methodologic factors
Autore:
Perez, V; Puigdemont, D; Gilaberte, I; Alvarez, E; Artigas, F;
Indirizzi:
CSIC, IIBB, IDIBAPS, Dept Neurochem, Barcelona 08036, Spain CSIC Barcelona Spain 08036 IBAPS, Dept Neurochem, Barcelona 08036, Spain Hosp Santa Creu & Sant Pau, Dept Psychiat, Barcelona, Spain Hosp Santa Creu & Sant Pau Barcelona Spain t Psychiat, Barcelona, Spain Lilly SA, Madrid, Spain Lilly SA Madrid SpainLilly SA, Madrid, Spain
Titolo Testata:
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
fascicolo: 1, volume: 21, anno: 2001,
pagine: 36 - 45
SICI:
0271-0749(200102)21:1<36:AOFAAB>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; POSTSYNAPTIC 5-HT1A RECEPTORS; SPONTANEOUS FIRING RATE; MAJOR DEPRESSION; DOUBLE-BLIND; IN-VIVO; EXTRACELLULAR 5-HYDROXYTRYPTAMINE; AUTORECEPTOR BLOCKADE; PLASMA-CONCENTRATIONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Artigas, F CSIC, IIBB, IDIBAPS, Dept Neurochem, Rossello 161, Barcelona 08036, Spain CSIC Rossello 161 Barcelona Spain 08036 Barcelona 08036, Spain
Citazione:
V. Perez et al., "Augmentation of fluoxetine's antidepressant action by pindolol: Analysis of clinical, pharmacokinetic, and methodologic factors", J CL PSYCH, 21(1), 2001, pp. 36-45

Abstract

In a controlled trial, the beta -adrenoceptor/5-hydroxytryptamine-1A (5-HT1A) receptor antagonist pindolol accelerated and enhanced the antidepressant effect of fluoxetine. The median times to sustained response (greater than or equal to 50% reduction of baseline severity maintained until endpoint)were 19 days for fluoxetine plus pindolol (N = 55) and 29 days for fluoxetine plus placebo (N = 56) (p = 0.01). The response rate at endpoint was 16%greater in patients treated with the combination. The plasma concentrationof pindolol remained stable between 3 days (first blood sampling) and 6 weeks. Mean values were similar to 26 nM, a concentration higher than the K-iof (-)pindolol for human 5-HT1A autoreceptors (11 nM). Plasma. fluoxetine and norfluoxetine concentrations increased steadily until the fourth week of treatment. Fluoxetine concentrations were lower in patients receiving thecombination (p = 0.043), but there was no significant relationship to the clinical response in either group. A reanalysis of the data using a survival analysis revealed that significant differences in the time to sustained response between both groups would have also been detected (1) in a 2-week trial, (2) without a placebo lead-in phase, and (3) with less frequent visits. However, the use of "response" instead of "sustained response" as measure of clinically relevant change would have greatly diminished the difference between treatment arms (p = 0.08 instead of p = 0.01). This emphasizes the need of using stringent outcome criteria in antidepressant drug trials. Acomparison of the data. of all sustained responders (N = 27) in the fluoxetine-plus-placebo group with the first 27 responders in the fluoxetine-plus-pindolol group (of a total of 38) revealed a highly significant differencein the time to sustained response (18 and 10 days, respectively; p = 0.0002). This indicates that the faster response in the fluoxetine-plus-pindololgroup is not a result of the greater proportion of responders.

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Documento generato il 20/01/20 alle ore 04:52:55