Pindolol Augmentation of Treatment-Resistant Depressed Patients

Moreno, Francisco; Gelenberg, Alan J.; Bachar, Karen J.; Delgado, Pedro L.

doi:10.4088/jcp.v58n1005

Cited by 91 publications

(51 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At the clinical level, the ␤ -adrenoceptor/ 5-HT 1A receptor antagonist pindolol accelerates the antidepressant effects of SSRIs in open-label and placebocontrolled trials Blier and Bergeron 1995;Pérez et al 1997;Zanardi et al 1997Zanardi et al , 1998Bordet et al 1998). However, its effectiveness to potentiate antidepressant response in chronically ill or treatmentresistant patients is still controversial (Maes et al 1996(Maes et al , 1999Berman et al 1997;Moreno et al 1997;Pérez et al 1999). Based on this rationale, selective 5-HT 1A receptor antagonists (for use with SSRIs; add-on strategy) and dual action compounds (5-HT reuptake inhibitor ϩ 5-HT 1A antagonist) are being developed for use in the treatment of major depression.…”

mentioning

confidence: 99%

Desensitization of 5-HT1A Autoreceptors by a Low Chronic Fluoxetine Dose Effect of the Concurrent Administration of WAY-100635

Hervás

2001

Neuropsychopharmacology

100

View full text Add to dashboard Cite

Using microdialysis, receptor autoradiography and in situ hybridization, we examined the effects of fluoxetine alone or with WAY-100635 on: (a) extracellular 5-HT in frontal cortex; and (b) density and sensitivity of 5-HT 1A autoreceptors in rat brain. WAY-100635 (0.3 mg/kg, s.c.) doubled the increase in extracellular 5-HT produced by fluoxetine (3 mg/kg, i.p.) (SSRI) Selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs) are extensively used in the treatment of major depression. The increase in forebrain extracellular 5-HT elicited by SSRIs is limited by a negative feed-back involving raphe autoreceptors . The prevention of this inhibitory mechanism with 5-HT 1A receptor antagonists augments the neurochemical and behavioral effects of SSRIs (Gartside et al. 1995;Artigas et al. 1996;Hashimoto et al. 1997;Mitchell and Redfern 1997;Grignaschi et al. 1998;Trillat et al. 1998). At the clinical level, the ␤ -adrenoceptor/ 5-HT 1A receptor antagonist pindolol accelerates the antidepressant effects of SSRIs in open-label and placebocontrolled trials Blier and Bergeron 1995;Pérez et al. 1997;Zanardi et al. 1997Zanardi et al. , 1998Bordet et al. 1998). However, its effectiveness to potentiate antidepressant response in chronically ill or treatmentresistant patients is still controversial (Maes et al. 1996(Maes et al. , 1999Berman et al. 1997;Moreno et al. 1997;Pérez et al. 1999). Based on this rationale, selective 5-HT 1A receptor antagonists (for use with SSRIs; add-on strategy) and dual action compounds (5-HT reuptake inhibitor ϩ 5-HT 1A antagonist) are being developed for use in the treatment of major depression. The prolonged administration of SSRIs has been reported to desensitize raphe 5-HT 1A autoreceptors, as assessed by single unit recordings and brain microdialysis (Blier and de Montigny 1994;Invernizzi et al. 1994;Arborelius et al. 1995;Le Poul et al. 1995). This reduces the efficacy of the above negative feedback and increases extracellular 5-HT (Bel and Artigas 1993;Invernizzi et al. 1994;Rutter et al. 1994;Arborelius et al. 1996). Other studies, however, have failed to observe such effects even using large doses of SSRIs (Hjorth and Auerbach 1994a;Bosker et al. 1995;Invernizzi et al. 1995).To our knowledge, there are no published reports on the effects of prolonged treatments with combinations of SSRIs and 5-HT 1A receptor antagonists on these experimental paradigms, except in abstract form (Dawson et al. 1998). As with pindolol, future selective 5-HT 1A receptor antagonists would be administered for a limited period of time. Should prolonged blockade of 5-HT 1A receptor result in receptor sensitization, the withdrawal of the antagonist would increase the efficacy of the above negative feed-back and reduce the ability of the SSRI to increase extracellular 5-HT, thus increasing the possibility of a clinical relapse. Since this is crucial for the success of this therapeutic strategy, we examined the effects of two-week treatments with fluoxetine, WAY-100635 and their combination...

show abstract

mentioning

confidence: 99%

Desensitization of 5-HT1A Autoreceptors by a Low Chronic Fluoxetine Dose Effect of the Concurrent Administration of WAY-100635

Hervás

2001

Neuropsychopharmacology

100

View full text Add to dashboard Cite

show abstract

“…Um dos ensaios avaliou o emprego do pindolol na potencialização da trazodona (Maes et al, 1996); três na potencialização de ISRS (Maes et al, 1999;Sokolski et al, 2004;Perry et al, 2004) e dois na potencialização de ISRS e tricíclicos (Moreno et al, 1997;Perez et al, 1999;Perry et al, 2004). Em três estudos (Maes et al, 1996;Maes et al, 1999;Sokolski et al, 2004) foi encontrada diferença significativa entre associação de pindolol a antidepressivos versus placebo, e em três (Moreno et al, 1997;Perez et al, 1999;Perry et al, 2004) não foi evidenciada tal diferença. Como não existem estudos comparando diretamente a eficácia do pindolol em potencializar diferentes classes de antidepressivos, não é possível afirmar se há diferença na potencialização das diversas classes (Tabela 3).…”

Section: Pindololunclassified

“…Em alguns dos ensaios duplo-cegos observou-se celeração na resposta aos ISRSs na primeira e na segunda semana (Moreno et al, 1997;Perez et al, 1999;Maes et al, 1999). A duração do tratamento não foi estudada.…”

Section: Pindololunclassified

“…As principais falhas encontradas nos estudos duplo-cegos sobre o uso do pindolol na potencialização de antidepressivos foram o uso de amostras pequenas (Maes et al, 1996;Moreno et al, 1997;Maes et al, 1999;Sokolski et al, 2004) e a não-explicitação sobre inclusão ou não de pacientes com história de bipolaridade (Maes et al, 1996;Maes et al, 1999;Sokolski et al, 2004).…”

Section: Pindololunclassified

“…Foi realizada metanálise sobre o emprego do pindolol na potencialização de antidepressivos (Stimpson et al, 2002), incluindo três estudos duplo-cegos (Maes et al, 1996;Moreno et al, 1997;Perez et al, 1999). Nesse trabalho o pindolol não se mostrou eficaz.…”

Section: Pindololunclassified

See 2 more Smart Citations

Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos

Santos¹,

Hara

Stumpf³

et al. 2006

J. bras. psiquiatr.

View full text Add to dashboard Cite

ResumoObjetivo: Fazer uma revisão sobre oito estratégias farmacológicas de potencialização de antidepressivos na DRT. Métodos: Fez-se um levantamento bibliográfico de 1990 até janeiro de 2006, nas bases eletrônicas de busca Medline, LILACS e da Biblioteca Cochrane, utilizando-se os termos de busca treatment, resistant, refractory e depression e os descritores depression, drug resistance e augmentation, incluindo apenas ensaios controlados duplo-cegos. Foi consultada a referência dos artigos para obtenção de ensaios realizados em data anterior a 1990 e artigos originais de valor histórico. Resultados: Foram encontrados 17 estudos duplo-cegos com o lítio, seis com o hormônio tireoidiano, dois com a buspirona, seis com o pindolol, um com a carbamazepina, dois com a lamotrigina e quatro com a olanzapina. Foram favoráveis à potencialização 41,2% dos ensaios com lítio; 60% daqueles com hormônio tireoidiano e antidepressivos tricíclicos e nenhum com hormônio tireoidiano e inibidores seletivos da recaptação da serotonina (ISRS); 50% dos com pindolol; 100% dos ensaios com carbamazepina e 40% daqueles com olanzapina. Nenhum dos estudos com a buspirona foi favorável. No único estudo com lamotrigina não houve eficácia de tratamento na avaliação pelo critério principal, mas superioridade ao placebo em critérios secundários. Conclusão: Na DRT há evidência de eficácia apenas em relação ao lítio na potencialização de várias classes de antidepressivos e ao hormônio tireoidiano na potencialização de tricíclicos. A olanzapina foi razoavelmente estudada e sua eficácia não foi estabelecida. Os poucos estudos realizados com a buspirona e o pindolol não comprovaram sua eficácia. A carbamazepina foi muito pouco estudada, e a lamotrigina ainda não foi adequadamente avaliada. Palavras-chave: depressão, resistência a drogas, potencialização. AbstractObjective: The aim of this study is to review eight pharmacologic antidepressant augmentation strategies in TRD. Methods: Database search on Medline, LILACS and Cochrane Library, from 1990 to June 2006 using the words treatment, resistant, refractory, depression and the medical subject headings depression, drug resistance and augmentation. Double-blind controlled trials and reviews were included. We also consulted reference of the articles in order to obtain studies and original articles of historical value from before 1990. Results: There were 17 double-blind trials with lithium, six with thyroid hormone, two with buspirone, six with pindolol one with carbamazepine, two with lamotrigine and four with olanzapine. Forty-one percent of the trials with lithium, 60% of those with thyroid hormone and tricyclics, 0% of the ones with thyroid hormone and selective serotonin reuptake inhibitors (SSRI), 50% of those with pindolol, 100% of those with carbamazepine and 40% of the ones with olanzapine were favorable. No trials with buspirone were favorable. The only trial with lamotrigine did not show efficacy using the main outcome measures. Otherwise, there was superiority over placebo on secondary measu...

show abstract

A Double-blind, Randomized, Placebo-Controlled Trial of Pindolol Augmentation in Depressive Patients Resistant to Serotonin Reuptake Inhibitors

Pérez¹

1999

Arch Gen Psychiatry

142

View full text Add to dashboard Cite

show abstract

Pindolol Augmentation of Treatment-Resistant Depressed Patients

Cited by 91 publications

References 0 publications

Desensitization of 5-HT1A Autoreceptors by a Low Chronic Fluoxetine Dose Effect of the Concurrent Administration of WAY-100635

Desensitization of 5-HT1A Autoreceptors by a Low Chronic Fluoxetine Dose Effect of the Concurrent Administration of WAY-100635

Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos

A Double-blind, Randomized, Placebo-Controlled Trial of Pindolol Augmentation in Depressive Patients Resistant to Serotonin Reuptake Inhibitors

Contact Info

Product

Resources

About