Outcome of Bipolar Disorder on Long-Term Treatment with Lithium

O’Connell, Ralph A.; Mayo, Julia A.; Flatow, Leslie; Cuthbertson, Beverly Ann; O'Brien, Barbara E.

doi:10.1192/bjp.159.1.123

Cited by 312 publications

(174 citation statements)

References 34 publications

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“…This finding suggests that control (or lack of control) of mania may affect the depressive side of bipolar disorder. Supportive of this finding, others have observed that, during lithium treatment, a greater lifetime number of affective episodes (Gelenberg et al, 1989;Harrow et al, 1990;Gitlin et al, 1995;Tohen et al, 1990) or hospitalizations (O'Connell et al, 1991;Harrow et al, 1990) predicts more affective symptoms (O'Connell et al, 1991) or higher rate of affective relapse (Prien et al, 1974;Gelenberg et al, 1989;Harrow et al, 1990;Keller et al, 1992;Aagaard and Vestergaard, 1990). However, predictors for the prophylaxis of depressive morbidity in controlled maintenance studies have not been previously reported.…”

Section: Discussionmentioning

confidence: 87%

“…Double-blind, placebo-controlled studies conducted during the 1970s demonstrated that lithium was more effective than placebo at preventing recurrences of bipolar depression (Prien et al, 1973a;Fieve et al, 1976;Goodwin and Jamison, 1990). A later, naturalistic study revealed that approximately 30% of lithium-treated bipolar patients experienced depressive relapse yearly (O'Connell et al, 1991). Lithium has been found to be more effective in the maintenance treatment of 'classical' rather than 'nonclassical' bipolar disorder (Greil et al, 1998), and less effective in rapid cycling, for which several anticonvulsants appear to be more effective (Dunner and Fieve, 1974;Bauer et al, 1994;Calabrese et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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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: 87%

Section: Introductionmentioning

confidence: 99%

Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression

Gyulai

Bowden

McElroy

et al. 2003

Neuropsychopharmacol

145

View full text Add to dashboard Cite

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“…Some studies report a positive association between clinical course, measured as number of prior admissions 108,109 or past episodes, 110 and interepisode level of functioning. Others have failed to find such relations.…”

Section: Clinical Course and Outcomementioning

confidence: 99%

The phenotypes of bipolar disorder: relevance for genetic investigations

2005

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The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-term course, comorbid conditions, and response to prophylactic treatment may define groups associated with more or less specific loci. One such group is characterized by symptoms of psychosis and linkage to 13q and 22q. A second group includes mainly bipolar II patients with comorbid panic disorder, rapid mood switching, and evidence of chromosome 18 linkage. A third group comprises typical BD with an episodic course and favourable response to lithium prophylaxis. Reproducibility of cognitive deficits across studies raises the possibility of using cognitive profiles as endophenotypes of BD, with deficits in verbal explicit memory and executive function commonly reported. Brain imaging provides a more ambiguous data set consistent with heterogeneity of the illness. Keywords: bipolar disorder; genetics; endophenotype; neurocognitive function; brain imaging Bipolar disorder (BD) has a genetic basis with heritability of at least 80%. 1 A number of studies have attempted to map the susceptibility loci giving evidence of linkage in multiple genomic regions. In particular, findings in 4p, 4q, 8q, 10p, 12q24, 13q, 18p, 18q, 21q, and 22q have been supported by more than one study. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] However, these studies have not identified any specific genes, and a recent metaanalysis of available genome scans showed no regions with a conclusive evidence of linkage. 20 The relatively slow progress of gene-mapping efforts is often explained by the 'complex' nature of the illness and of the genotype-phenotype relation. The complexity most likely includes heterogeneity, interactions of multiple loci, incomplete penetrance, as well as phenotypes resulting from environmental effects-either alone or in interaction with the genetic predisposition. The goal of psychiatric genetic research is identification of (heritable) variations in DNA sequence or function that influence behaviour or give rise to mental illness. By definition, in complex (multifactorial) traits, this link is not unique and specific. That is, a particular change in gene sequence does not necessarily lead to a specific behaviour, and similar behaviours (symptoms) may be due to distinct (sets of) genes. Moreover, we must consider the possibility that the path between the genotype and behaviour is not unidirectional. Emerging examples point not only to general effects of environment, for instance stress, on behaviour, but also to specific behaviours influencing gene function that can be transmitted onto the next generation. 21 No single method is considered clearly superior in identifying susceptibility genes for complex traits such as BD. Most researchers agree that a combination of strategies is most lik...

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“…Clinical predictors account for less than half of the variance, [1][2][3][4][5][6][7][8] and there are evidences suggesting that genetic factors play a substantial role in lithium prophylaxis effectiveness. [9][10][11][12][13][14][15][16][17][18][19][20] A large number of studies reported an association between prophylactic lithium response and a family history of bipolar disorder, 10,[12][13][14]17 although not unequivocally confirmed.…”

Section: Introductionmentioning

confidence: 99%

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders

et al. 2004

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We previously reported an association between the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR) and the prophylactic efficacy of lithium in a sample of 201 Italian subjects affected by Mood disorders. The aim of the present study was to replicate analyses on an independent sample. In total, 83 subjects affected by Bipolar disorder were recruited in the Mood Disorders Clinic of the Eginition Hospital of the Athens University, Medical School Department of Psychiatry. All patients were administered with lithium as prophylactic therapy and they were prospectively observed for at least 3 years. Subjects were typed for their SERTPR variant using polymerase chain reaction techniques. SERTPR variants were associated with lithium outcome among those subjects who had few manic episodes before lithium treatment and, as a trend, among subjects who received a high daily dose of lithium (X1200 mg/die). In both cases, subjects with the l/l variant showed a higher probability to develop an illness episode within 3 years of prophylactic treatment with lithium. The present study confirmed our previous observation of a better response of SERTPR*l/s carriers, but could not confirm a poor efficacy in subjects with the SERTPR*s/s genotype. Notwithstanding the conflicting results, SERTPR variants are a possible liability factor for lithium long-term efficacy in mood disorders. Further studies on independent and large samples are required to determine the reliability and direction of the possible association between SERTPR variants and lithium outcome. INTRODUCTIONLithium is an effective prophylactic agent in mood disorders but not all patients equally respond to lithium therapy. Clinical predictors account for less than half of the variance, 1-8 and there are evidences suggesting that genetic factors play a substantial role in lithium prophylaxis effectiveness. [9][10][11][12][13][14][15][16][17][18][19][20] A large number of studies reported an association between prophylactic lithium response and a family history of bipolar disorder, 10,[12][13][14]17 although not unequivocally confirmed. [21][22][23][24][25] Recently, Grof et al 26 reported that lithium response in a sample of relatives of responder probands was 67% compared to 30% in the comparison group.

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Outcome of Bipolar Disorder on Long-Term Treatment with Lithium

Cited by 312 publications

References 34 publications

Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression

Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression

The phenotypes of bipolar disorder: relevance for genetic investigations

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders

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