Lithium Maintenance Treatment of Depression and Mania in Bipolar I and Bipolar II Disorders

Tondo, Leonardo; Baldessarini, Ross J.; Hennen, John; Floris, Gianfranco

doi:10.1176/ajp.155.5.638

Cited by 156 publications

(135 citation statements)

References 43 publications

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“…Negative findings regarding the efficacy of lithium vs placebo must be viewed cautiously, especially in the light of the relatively low relapse rate on placebo in this study and continued evidence of maintenance efficacy of lithium in bipolar disorder (Gelenberg et al, 1989;Berghofer et al, 1996;Tondo et al, 1998;Bowden et al, 2003). Furthermore, clinical variables such as episode sequence (Kokopolus et al, 1980;Maj et al, 1989), frequency of mood cycling (Dunner and Fieve, 1974;Bowden 1995;Denicoff et al, 1997), presence of mood-congruent or -incongruent psychotic features of the index episode (Greil et al, 1998;Tohen et al, 1992), comorbid conditions (especially anxiety disorders) (Greil et al, 1998;Feske et al, 2000), and family history (Grof et al, 1994) may provide further explanation of the differential response to lithium and divalproex.…”

Section: Discussionmentioning

confidence: 89%

Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression

Gyulai

Bowden

McElroy

et al. 2003

Neuropsychopharmacol

145

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Breakthrough depression is a common problem in the treatment of bipolar disorder. Only one, recently published, double-blind, placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients. This report describes, in further detail, the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder. A randomized, double-blind, parallel-group, multicenter study was conducted over a 52-week maintenance period. Bipolar I patients, who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode, were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2 : 1 : 1 ratio. Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase. Outcome measures were the rate of early discontinuation for depression, time to depressive relapse, proportion of patients with depressive relapse, mean change in Depressive Syndrome Scale score, proportion of patients receiving antidepressants, and time in the study. Among patients taking an antidepressant, a higher percentage of patients on placebo than divalproex discontinued early for depression. Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period. Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance. Indices of severity of prestudy illness course predicted worse outcome in all treatment groups. Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder, particularly in patients who had responded to divalproex when manic, and among patients with a more severe course of illness.

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Section: Discussionmentioning

confidence: 89%

Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression

Gyulai

Bowden

McElroy

et al. 2003

Neuropsychopharmacol

145

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“…6 The clinical efficacy of lithium in preventing recurrent affective episodes requires a lag period for onset and is reversed upon discontinuation of treatment only after weeks or months. [7][8][9] By virtue of its prophylactic properties, lithium is thought to target the underlying pathophysiology of the disease, yet the precise molecular mechanism for this therapeutic action remains elusive. Evidence from both in vitro and in vivo studies has demonstrated that lithium exerts multiple effects on neurotransmitter/receptor-mediated signaling, ion transport, signal transduction cascades, hormonal and circadian regulation, and profoundly alters gene expression patterns (see reviews Lenox and Hahn, 3 Lenox et al, 10 Manji and Lenox, 11 Jope, 12 Williams and Harwood, 13 and Manji and Lenox 14 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks

2003

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The clinical efficacy of lithium in the prophylaxis of recurrent affective episodes in bipolar disorder is characterized by a lag in onset and remains for weeks to months after discontinuation. Thus, the long-term therapeutic effect of lithium likely requires reprogramming of gene expression. Protein kinase C and glycogen synthase kinase-3 signal transduction pathways are perturbed by chronic lithium at therapeutically relevant concentrations and have been implicated in modulating synaptic function in nerve terminals. These signaling pathways offer an opportunity to model critical signals for altering gene expression programs that underlie adaptive responses of neurons to long-term lithium exposure. While the precise physiological events critical for the clinical efficacy of lithium remain unknown, we propose that linking lithium-responsive genes as a regulatory network will provide a strategy to identify signature gene expression patterns that distinguish between therapeutic and nontherapeutic actions of lithium.

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“…Sua freqüência variaria de acordo com os critérios clínicos utilizados, havendo aumento de prevalência em mulheres à medida que tais critérios são mais rígidos (Tondo et al, 1998).…”

Section: Ciclagem Rápidaunclassified

Transtorno bipolar do humor e gênero

Dias¹,

Kerr-Corrêa²,

Torresan³

et al. 2006

Rev. psiquiatr. clín.

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ResumoEmbora o transtorno bipolar (TB) ocorra quase igualmente em ambos os sexos, a fenomenologia e o curso da doença diferem no homem e na mulher. No entanto, há evidências de que mulheres bipolares, mais que os homens, apresentariam início mais tardio (em especial na quinta década de vida), ciclagem rápida, mais episódios depressivos, mais mania disfó-rica que eufórica, estados mistos e evolução do tipo bipolar II, ainda que os achados nem sempre sejam consistentes. Embora o risco de comorbidades no TB inclua, para ambos os gêneros, abuso de álcool e drogas, homens bipolares teriam maior probabilidade de ser alcoolistas, não procurar tratamento e de se suicidar. Hipóteses sugeridas para explicar tais diferenças variam daquelas centradas em aspectos culturais ou psicológicos para as que focalizam os sistemas hormonais, como os esteróides gonadais ou o eixo tireoidiano, e até mesmo a anatomia cerebral. A influência do ciclo reprodutivo (ciclo menstrual, gravidez e menopausa) sobre as opções terapêuticas no tratamento do TB é apresentada na última parte desta revisão.Palavras-chave: Transtorno bipolar, gênero, tratamento, epidemiologia, evolução. AbstractAlthough the bipolar disorder (BD) occurs almost with the same frequency in both genders, the phenomenology and the outcome of the illness differ between them. Nevertheless, there is evidence that women with BD show, more than men, delayed beginning, especially in their fifth decade, more rapid cycling outcome, more depressive episodes, more dysphoric mania, more mixed states and more BD type II. Even so, the findings are not always consistent. Although the risk of comorbidities in BD includes, for both the sorts, excessive alcoholic consumption and drugs, bipolar men would have greater probability of being alcohol dependent, of not seeking treatment and of committing suicide. Suggested hypotheses to explain such Bipolar affective disorder and gender

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Lithium Maintenance Treatment of Depression and Mania in Bipolar I and Bipolar II Disorders

Abstract: Lithium maintenance yielded striking long-term reductions of depressive as well as manic morbidity in both bipolar disorder subtypes, with greater overall benefits in type II patients and with earlier treatment.

Cited by 156 publications

References 43 publications

Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression

Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression

Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks

Transtorno bipolar do humor e gênero

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