Placebo-Controlled Trial of Lithium Augmentation of Fluoxetine and Lofepramine

Katona, Cornelius; Abou‐Saleh, Mohammed T.; Harrison, D.; Nairac, Bertrand A.; Edwards, David I.; Lock, Toni; Burns, Robert; Robertson, Mary M.

doi:10.1192/bjp.166.1.80

Cited by 148 publications

(89 citation statements)

References 13 publications

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“…The efficacy of lithium augmentation has been well documented in placebo-controlled acute (Joffe et al 1993;Katona et al 1995;Baumann et al 1996) and continuation treatment trials (Bauer et al 2000;Bschor et al 2002) using different classes of antidepressants. A recent meta-analysis confirmed the evidence that lithium augmentation is superior to placebo augmentation for the treatment of unipolar major depression, with a median response rate of 50% across double-blind studies (Bauer and Döpfmer 1999).…”

Section: On the Next Day) Twenty-four Patients Were Reassessed Aftmentioning

confidence: 99%

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

Bschor

Adli

Baethge

et al. 2002

Neuropsychopharmacology

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Lithium augmentation is a well established strategy for treatment-resistant depression. The exact mode of its action is unknown, but an enhancement of serotonergic transmission is hypothesized. The authors investigated changes in the hypothalamic-pituitary-adrenocortical (HPA) system during lithium augmentation and their correlation to clinical response by means of the combined dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major depressive episodes (DSM IV) who had not responded to an adequate trial with an antidepressantwere assessed on the day before lithium augmentation (baseline) with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P . M . and CRH stimulation at 3 P . M . on the next day). Twenty-four patients were reassessed after response was determined or, in cases of nonresponse, four weeks after initiation of lithium augmentation. Response to lithium augmentation was measured by weekly ratings on the Hamilton DepressionRating Scale Regardless of the initial choice of antidepressant, about 30 to 40% of patients with major depressive disorder will not respond sufficiently (Thase and Rush 1995 Among the various treatment options that have been proposed for non-responding depressed patients, lithium augmentation has been recommended as a first-line strategy . The efficacy of lithium augmentation has been well documented in placebo-controlled acute (Joffe et al. 1993;Katona et al. 1995;Baumann et al. 1996) and continuation treatment trials (Bauer et al. 2000;Bschor et al. 2002) using different classes of antidepressants. A recent meta-analysis confirmed the evidence that lithium augmentation is superior to placebo augmentation for the treatment of unipolar major depression, with a median response rate of 50% across double-blind studies (Bauer and Döpfmer 1999). Severity of depression was recently identified as a clinical predictor of response to lithium augmentation (Bschor et al. 2001). Better knowledge of the neurobiological mechanisms of lithium augmentation would help to identify patients who will respond favorably to this treatment intervention. However, to date, the mode of action of lithium augmentation is unknown. Shortly after the initial report on its efficacy (de Montigny et al. 1981), it was postulated by de Montigny et al. (1983) that a pharmacodynamic action mediated via the serotonergic systems might account for the synergistic effect of lithium when added to a tricyclic antidepressant.Another system potentially involved in its mechanism of action is the hypothalamic-pituitary-adrenocortical (HPA) system, putatively the best studied biological system in affective disorders (Dinan 1997). The most sensitive challenge test of the HPA system is the combined dexamethasone/CRH test (DEX/CRH test) (Heuser 1998). A dysfunction in the regulation of the HPA system, especially an overstimulation of ACTH and cortisol in the DEX/CRH test, was repeatedly shown in depressed patients (for a review see Steckler et al. 1999;Holsboer 2000). In treatment studies with ...

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Section: On the Next Day) Twenty-four Patients Were Reassessed Aftmentioning

confidence: 99%

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

Bschor

Adli

Baethge

et al. 2002

Neuropsychopharmacology

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“…However, few studies were conducted on SSRI nonresponders. Most of those studies were open label, and the results confirmed that augmentation with lithium was effective in TRD (Table 2) [20][21][22][23][24][25][26][27][28][29][30].…”

Section: Level 1: Lithiummentioning

confidence: 97%

Evidence for the Benefits of Nonantipsychotic Pharmacological Augmentation in the Treatment of Depression

Chang

Sato²,

Han

2013

CNS Drugs

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Failure to achieve an adequate response after initial antidepressant treatment in patients with depression is common and remains a clinical challenge. In recent years, some atypical antipsychotic agents have been approved by the US Food and Drug Administration for use in an augmentation strategy for major depressive disorder, and other agents are already in common use in clinical practice. We conducted a search of MEDLINE for relevant studies of augmentation strategies using randomized controlled trials and meta-analyses, and we summarize and discuss the various agents other than atypical antipsychotics. Lithium and thyroid hormone augmentation may improve the response of tricyclic antidepressants but not that of selective serotonin reuptake inhibitors. The efficacy of augmentation with modafinil, buspirone, methylphenidate, folic acid, pindolol and lamotrigine is limited or equivocal. Most of the studies have not focused on treatment-resistant depression (TRD). More trials are needed to help develop evidence-based options for augmentation in TRD.

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“…Entre os estudos, 14 utilizaram tricíclicos, seis utilizaram inibidores seletivos da recaptação da serotonina (ISRS), dois utilizaram inibidores da monoamina oxidase (IMAO) e dois utilizaram outras classes de antidepressivos. Dos 14 trabalhos envolvendo tricíclicos, nove utilizaram apenas esses fármacos (De Montigny et al, 1983;Cournoyer et al, 1984;Kantor et al, 1986;Dinan e Barry 1989;Browne et al, 1990;Stein e Bernardt 1993;Joffe et al, 1993;Hoencamp et al, 1994;Nierenberg et al, 2003) e cinco envolveram dois ou mais antidepressivos (Heninger et al, 1983;Zusky et al, 1988;Schopf et al, 1989;Katona et al, 1995;Rybakowski et al, 1999). Os IMAO foram utilizados em apenas dois ensaios, provavelmente devido ao fato de em geral serem empregados em etapas mais tardias da resistência ao tratamento e, também, devido aos riscos inerentes aos mesmos (Tabela 1).…”

Section: Lítiounclassified

“…Apesar da controvérsia, recomenda-se a utilização do lítio em níveis terapêuticos (Rouillon e Gorwood, 1998). Quanto ao tempo de latência, embora haja relato de melhora significativa em apenas 48h após adição de lítio (De Montigny et al, 1983), observou-se que a maioria dos pacientes apresentou melhora após a primeira (Heninger et al, 1983;Stein e Bernardt, 1993;Joffe et al, 1993;Baumann et al, 1996), a segunda ou a sexta semana de potencialização (Katona et al, 1995). Portanto, tendo em vista essas variações no tempo de resposta, sugeriu-se o emprego do lítio por, no mínimo, três (Rouillon e Gorwood, 1998) a seis semanas (Katona et al, 1995).…”

Section: Lítiounclassified

“…A maioria dos ensaios utilizou amostras pequenas (De Montigny et al, 1983;Heninger et al, 1983;Cournoyer et al, 1984;Kantor et al, 1986;Zusky et al, 1988;Schopf et al, 1989;Kramlinger e Post, 1989;Dinan e Barry, 1989;Browne et al, 1990, Stein e Bernardt, 1993Baumann et al, 1996;, alguns incluíram pacientes que não fizeram uso do antidepressivo pelo período de tempo mínimo preconizado (Heninger et al, 1983;Montigny et al, 1981;De Montigny et al, 1983;Kantor et al, 1986), outros não foram controlados com placebo (Hoencamp et al, 1994;Fava et al, 1994Fava et al, e 2002 e vários incluíram e analisaram em conjunto pacientes com história de episódio(s) de mania ou hipomania (Heninger et al, 1983;Dinan e Barry, 1989;Schopf et al, 1989;Hoencamp et al, 1994;Katona et al, 1995;Baumann et al, 1996;Stein e Bernardt, 1993).…”

Section: Lítiounclassified

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

Santos¹,

Hara

Stumpf³

et al. 2006

J. bras. psiquiatr.

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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...

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Placebo-Controlled Trial of Lithium Augmentation of Fluoxetine and Lofepramine

Cited by 148 publications

References 13 publications

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

Evidence for the Benefits of Nonantipsychotic Pharmacological Augmentation in the Treatment of Depression

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

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