The Benefit of Lithium Carbonate Adjunct in Refractory Depression — Fact or Fiction?

Abstract

Our group attempted to validate previous claims of rapid success with lithium carbonate adjunct therapy in antidepressant-resistant depression. Seven depressed patients volunteered for a study of placebo controlled, double-blind design. During their treatment on general hospital psychiatric wards, these patients received antidepressant medication for a period of at least 21 days. While continuing to receive antidepressant medication after the 21 day period, four of the patients then received lithium carbonate, and three received placebo. This combination pharmacological therapy continued for a 48 hour period. After this time, six of the seven patients showed no significant improvement. The remaining patient, who had received lithium carbonate, improved markedly over the 48 hour period. However, this patient relapsed within one week. A review of the two most extensive studies claiming significant results with the lithium carbonate adjunct therapy was performed. We feel that they, as presented, leave serious doubt as to the validity of their conclusions. We conclude that on the basis of our work up to this point in time and the analysis of previous reports claiming otherwise, no valid evidence exists for a consistent therapeutic effect of lithium carbonate adjunct in antidepressant-resistant depression. It was also found that methodologic contamination necessitated the exclusion of an additional six patients from the double-blind trial. We conclude that in order to objectively examine the rapidly expanding field of biological psychiatry, teaching of clinical staff in basic research procedure should be stressed as a part of routine ward orientation.

Lithium or an atypical antipsychotic drug in the management of treatment-resistant depression: a systematic review and economic evaluation

“…67-82 a 4-week minimum duration of treatment; [74][75][76][77][78][79][80]81 or two or more failures of antidepressant therapy in the current episode of depression [67][68][69][70][71][72][73] (it is unclear how many trials in Crossley et al 60 are affected by this criterion). The results of both the Crossley et al 60 meta-analysis evaluating lithium compared with placebo augmentation and the Nelson et al…”

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

“…Os estudos sobre DRT apresentaram problemas metodológicos importantes: utilização de diferentes definições de DRT; não-explicitação do critério de definição de resistência utilizado em ensaios (Goodwin et al, 1982;Kramlinger e Post, 1989); utilização de amostras insuficientes (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;Nierenberg et al, 2003;Maes et al, 1996;Moreno et al, 1997;Maes et al, 1999;Sokolski et al, 2004;Barbosa et al, 2003); realização de estudos não-controlados com placebo (Hoencamp, 1994;Fava et al, 1994Fava et al, e 2002Maes et al, 1999;Rybakowski et al, 1999;Corya et al, 2006); não-explicitação de inclusão (Maes et al, 1996;Maes et al, 1999;Sokolski et al, 2004), ou inclusão e análise em conjunto, de pacientes com história de episódio(s) de mania ou de 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;Normann et al, 2002;Barbosa et al, 2003;Dubé et al, 2002a;…”

“…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).…”

“…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).…”

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

“…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].…”