Efficacy of Olanzapine in Combination With Valproate or Lithium in the Treatment of Mania in Patients Partially Nonresponsive to Valproate or Lithium Monotherapy

Tohen, Mauricio; Chengappa, K. N. Roy; Suppes, Trisha; Zarate, Carlos A.; Calabrese, Joseph R.; Bowden, Charles L.; Sachs, Gary S.; Kupfer, David J.; Baker, Robert W.; Risser, Richard C.; Keeter, Elisabeth L.; Feldman, Peter D.; Tollefson, Gary D.; Breier, Alan

doi:10.1001/archpsyc.59.1.62

Cited by 398 publications

(237 citation statements)

References 20 publications

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“…Nine participants met criteria for a current manic episode (Young Mania Rating Scale score X20) and seven were classified as hypomanic (Young Mania Rating Scale score ¼ 12-15;Tohen et al, 2002). The majority of patients were taking mood stabilizers and/or atypical antipsychotics with the most common medication being valproate and lithium or risperidone, respectively.…”

Section: Participantsmentioning

confidence: 99%

Reduced Dopamine Transporter Functioning Induces High-Reward Risk-Preference Consistent with Bipolar Disorder

Enkhuizen

Henry

Minassian

et al. 2014

Neuropsychopharmacol

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Individuals with bipolar disorder (BD) exhibit deleterious decision making, negatively impacting their lives. Such aberrant decision making can be quantified using the Iowa Gambling Task (IGT), which requires choosing between advantageous and disadvantageous options based on different reward/punishment schedules. The mechanisms underlying this behavioral deficit are unknown, but may include the reduced dopamine transporter (DAT) functioning reported in BD patients. Using both human and mouse IGTs, we tested whether reduced DAT functioning would recreate patterns of deficient decision making of BD patients. We assessed the IGT performance of 16 BD subjects (7 female) and 17 healthy control (HC) subjects (12 female). We recorded standard IGT performance measures and novel post-reward and post-punishment decision-making strategies. We characterized a novel single-session mouse IGT using C57BL/6J mice (n ¼ 44). The BD and HC IGT performances were compared with the effects of chronic (genetic knockdown (KD; n ¼ 31) and wild-type (n ¼ 28) mice) and acute (C57BL/6J mice (n ¼ 89) treated with the DAT inhibitor GBR12909) reductions of DAT functioning in mice performing this novel IGT. BD patients exhibited impaired decision making compared with HC subjects. Both the good-performing DAT KD and GBR12909-treated mice exhibited poor decision making in the mouse IGT. The deficit of each population was driven by highreward sensitivity. The single-session mouse IGT measures dynamic risk-based decision making similar to humans. Chronic and acute reductions of DAT functioning in mice impaired decision-making consistent with poor IGT performance of BD patients. Hyperdopaminergia caused by reduced DAT may impact poor decision making in BD patients, which should be confirmed in future studies.

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Section: Participantsmentioning

confidence: 99%

Reduced Dopamine Transporter Functioning Induces High-Reward Risk-Preference Consistent with Bipolar Disorder

Enkhuizen

Henry

Minassian

et al. 2014

Neuropsychopharmacol

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“…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. 140,141 Finally, genetic research may benefit from growing knowledge of the mechanisms of action of moodstabilizing drugs. This includes the possibility of biochemical endophenotypes as well as informed selection of candidate genes.…”

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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“…There is little data regarding the efficacy of atypical antipsychotic medications in aged BP patients. Although newer agents such as aripiprazole may have particular advantages in elders, the broadest experience for mixed-age BP patients relates to risperidone and olanzapine as adjunct therapy [98,99] or as monotherapy [100]. Risperidone, olanzapine, quetiapine, aripiprazole, and ziprasidone have US Food and Drug Administration-approved indications for use in BP disorder.…”

Section: Pharmacodynamic Drug-drug Interactionsmentioning

confidence: 99%

Evidence-Based Pharmacological Treatment of Geriatric Bipolar Disorder

Young

2005

Psychiatric Clinics of North America

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Efficacy of Olanzapine in Combination With Valproate or Lithium in the Treatment of Mania in Patients Partially Nonresponsive to Valproate or Lithium Monotherapy

Cited by 398 publications

References 20 publications

Reduced Dopamine Transporter Functioning Induces High-Reward Risk-Preference Consistent with Bipolar Disorder

Reduced Dopamine Transporter Functioning Induces High-Reward Risk-Preference Consistent with Bipolar Disorder

The phenotypes of bipolar disorder: relevance for genetic investigations

Evidence-Based Pharmacological Treatment of Geriatric Bipolar Disorder

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