Phenotypic spectra of bipolar disorder in responders to lithium versus lamotrigine

Passmore, Michael J.; Garnham, Julie; Duffy, Anne; MacDougall, Marsha; Munro, Allana; Slaney, Claire; Teehan, Andrew; Alda, Martin

doi:10.1034/j.1399-5618.2003.00026.x

Cited by 97 publications

(91 citation statements)

References 24 publications

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“…132 In studies of three independent populations, we found that lithium responders were a more homogeneous subgroup of BD, characterized by a stronger genetic loading for BD, and with a familial transmission compatible with a major-gene effect. 102,103,133,134 Similar support for a major-gene effect was found in other study of lithium responders 131 and in typical BD. 135 Nonaffective psychiatric disorders among relatives of lithium responders are uncommon.…”

Section: Response To Long-term Treatmentsupporting

confidence: 83%

“…102 Such traits, on the other hand, are common among responders to the anticonvulsant lamotrigine. 103 Substance abuse also occurs at high rates in BD. This association could arise from a shared genetic basis, but substance use can also be a consequence of psychiatric symptoms (impulsivity, disinhibition) or response to them-'self-medication'.…”

Section: Psychiatric Comorbiditymentioning

confidence: 99%

“…135 Nonaffective psychiatric disorders among relatives of lithium responders are uncommon. [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.…”

Section: Response To Long-term Treatmentmentioning

confidence: 99%

“…[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%

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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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Section: Response To Long-term Treatmentsupporting

confidence: 83%

Section: Psychiatric Comorbiditymentioning

confidence: 99%

Section: Response To Long-term Treatmentmentioning

confidence: 99%

Section: Response To Long-term Treatmentmentioning

confidence: 99%

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The phenotypes of bipolar disorder: relevance for genetic investigations

2005

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“…Responders to lamotrigine have a predominantly depressive polarity as well as comorbid anxiety 420, 421. Lamotrigine monotherapy is not appropriate for patients with frequent manic episodes, as it has limited efficacy in preventing mania.…”

Section: Maintenance Therapy For Bipolar Disordermentioning

confidence: 99%

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

et al. 2018

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The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

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Meta-analytic Evidence for Familial Coaggregation of Schizophrenia and Bipolar Disorder

Snellenberg¹,

Candia²

2009

Arch Gen Psychiatry

144

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Phenotypic spectra of bipolar disorder in responders to lithium versus lamotrigine

Abstract: These findings suggest that lithium- and lamotrigine-responsive patients differ with respect to course of illness, comorbidity and family history and may represent distinct subtypes of bipolar disorder.

Cited by 97 publications

References 24 publications

The phenotypes of bipolar disorder: relevance for genetic investigations

The phenotypes of bipolar disorder: relevance for genetic investigations

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

Meta-analytic Evidence for Familial Coaggregation of Schizophrenia and Bipolar Disorder

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