Lithium versus carbamazepine in the maintenance treatment of bipolar disorders – a randomised study

Greil, Waldemar; Ludwig‐Mayerhofer, Wolfgang; Erazo, Natalia; Schöchlin, C.; Schmidt, Sandy; Engel, Rolf R.; Czernik, Adelheid; Giedke, H.; Müller‐Oerlinghausen, B.; Osterheider, Michael; Rudolf, G. A. E.; Sauer, Heinrich; Tegeler, J.; Wetterling, Tilman

doi:10.1016/s0165-0327(96)01427-9

Cited by 248 publications

(191 citation statements)

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“…After screening, 226 publications were identified through the combined search strategies, and we identified 21 trials, with a combined total of 5364 participants that fulfilled the inclusion criteria (Bowden et al 2000bCalabrese et al 2000Calabrese et al , 2003Calabrese et al , 2005Greil et al 1997 ;Hartong et al 2003 ;Keck et al 2007 ;Macfadden et al 2009 ;McElroy et al 2008 ;Quiroz et al 2010 ;Suppes et al 2009 ;Tohen et al 2003Tohen et al , 2004Tohen et al , 2005Tohen et al , 2006Vieta et al 2008a, b ;Young et al 2008 ;Zarate & Tohen, 2004). Table 1 shows details of all trials included in the analysis.…”

Section: Resultsmentioning

confidence: 99%

“…We identified : one trial each for aripiprazole (Keck et al 2007), olanzapine+mood stabilizer , oxcarbazepine+lithium (Vieta et al 2008a), perphenazine+mood stabilizer (Zarate & Tohen, 2004), risperidone long-acting injectable monotherapy (Quiroz et al 2010), risperidone long-acting injectable+mood stabilizer (Macfadden et al 2009) and ziprasidone+mood stabilizer ; two trials for carbamazepine (Greil et al 1997 ;Hartong et al 2003) and quetiapine+mood stabilizer (Suppes et al 2009 ;Vieta et al 2008 b) and quetiapine monotherapy Young et al 2008) ; three trials each for divalproex (Bowden et al 2000a, b ;Greil et al 1997 ;Tohen et al 2003), lamotrigine Calabrese et al 2000Calabrese et al , 2003 and olanzapine (Tohen et al 2003(Tohen et al , 2005(Tohen et al , 2006 ; and eight trials for lithium (Bowden et al 2000(Bowden et al b, 2003Calabrese et al 2003Calabrese et al , 2005Greil et al 1997 ;Hartong et al 2003 ;Tohen et al 2005 ;Vieta et al 2008a). BPRS, Brief Psychiatric Rating Scale ; CGI-S, Clinical Global Impression -Severity ; CGI-C, Clinical Global Impression -Change ; CI, confidence interval ; GAF, global assessment of functioning ; HAMD, Hamilton Rating Scale for Depression ; IR, insufficient response ; MADRS, Montgomery-Å sberg Depression Rating Scale ; MRS, Mania Rating Scale ; TEM, treatment-emergent mania ; YMRS, Young Mania Rating Scale.…”

Section: Resultsmentioning

confidence: 99%

“…The length of follow-up was 26 wk in three studies Calabrese et al 2000 ;Zarate & Tohen, 2004), between 47 and 52 wk in eight studies (Bowden et al 2000b ;Macfadden et al 2009 ;McElroy et al 2008 ;Tohen et al 2003Tohen et al , 2005Tohen et al , 2006Vieta et al 2008a ;Young et al 2008), between 72 and 80 wk in four studies Calabrese et al 2003Calabrese et al , 2005Tohen et al 2004) and between 100 and 130 wk in six studies (Greil et al 1997 ;Hartong et al 2003 ;Keck et al 2007 ;Quiroz et al 2010 ;Suppes et al 2009 ;Vieta et al 2008b). Median follow-up among the 21 studies was 52 wk, and mean follow-up was 68 wk.…”

Section: Resultsmentioning

confidence: 99%

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Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials

Vieta

Günther²,

Locklear

et al. 2011

Int. J. Neuropsychopharm.

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The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of o6 months' duration with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combination treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of relapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical antipsychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials

Vieta

Günther²,

Locklear

et al. 2011

Int. J. Neuropsychopharm.

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“…[101][102][103] Treatment outcome findings in BD also define lithium responders as a distinct, more uniform subgroup. Responders to lithium differ from responders to other mood stabilizers and the treatment response appears to be specific; 103,[136][137][138][139] the antimanic responses to valproate and lithium are present in different patient groups. 137 In the MAP Study, Greil et al 138 found that in contrast to lithium responders, patients who benefited from long-term treatment with carbamazepine had atypical clinical features.…”

Section: Response To Long-term Treatmentmentioning

confidence: 99%

“…Responders to lithium differ from responders to other mood stabilizers and the treatment response appears to be specific; 103,[136][137][138][139] the antimanic responses to valproate and lithium are present in different patient groups. 137 In the MAP Study, Greil et al 138 found that in contrast to lithium responders, patients who benefited from long-term treatment with carbamazepine had atypical clinical features. As well, a study comparing responders to lithium and lamotrigine identified robust differences with respect to clinical course, comorbid conditions, and family history; 103 and patients nonresponsive to lithium may respond well to olanzapine.…”

Section: Response To Long-term Treatmentmentioning

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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Does Lithium Treatment Still Work?

Baldessarini

Tondo²

2000

Arch Gen Psychiatry

145

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To evaluate whether lithium treatment has been overvalued and may be no longer as effective as formerly, we reviewed published reports on long-term lithium treatment (1970-1996) as well as analyzing its clinical effects on 360 patients with DSM-IV bipolar disorder who entered into lithium maintenance monotherapy after 1970. Neither reported recurrence rates nor average proportions of time ill nor patient improvement of 50% or more during lithium maintenance therapy in a stable clinic setting has changed significantly since the 1970s. Unfavorable results in some settings may reflect accumulation over time of patients with complex, less treatment-responsive illnesses. Lithium is unmatched in research support for long-term clinical effectiveness against morbidity and mortality associated with depression or mania in bipolar I and II disorders. Data evaluated herein did not support suggestions that benefits of lithium have been exaggerated in the past or have been lost recently.

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Lithium versus carbamazepine in the maintenance treatment of bipolar disorders – a randomised study

Cited by 248 publications

References 24 publications

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials

The phenotypes of bipolar disorder: relevance for genetic investigations

Does Lithium Treatment Still Work?

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