Psychotropic Medications for Patients With Bipolar Disorder in the United States: Polytherapy and Adherence

Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Psychiatric services (Washington, D.C.) (Impact Factor: 1.99). 10/2008; 59(10):1175-83. DOI: 10.1176/
Source: PubMed

ABSTRACT Because treatments for bipolar disorder include a growing number of psychotropic agents, the authors evaluated psychotropic polytherapy and adherence to treatment among U.S. patients with bipolar disorder.
National health plan claims data (2000-2004) were used to identify patients diagnosed as having bipolar disorder who had continuous benefits and had not been prescribed medication for bipolar disorder for six months or more. The study compared drugs dispensed to these patients initially and at one year and characterized patients who were adherent to mood-stabilizers.
A total of 7,406 patients had a bipolar disorder: bipolar I (55%), bipolar II (15%), or bipolar disorder not otherwise specified (30%). Women represented 57% of the sample; mean+/-SD age was 35.4+/-12.4 years. Initial prescription fills involved one psychotropic agent in 67% of patients, and two or more psychotropics (polytherapy) in 33%. Initial prescription drug selections involved: antidepressants > anticonvulsants >or= antipsychotics > sedatives > lithium; initial mood stabilizer use ranked: valproate > lithium > carbamazepine or oxcarbazepine > lamotrigine; antipsychotics ranked: olanzapine > quetiapine >or= risperidone > ziprasidone > aripiprazole > clozapine. Rankings were similar at one year, when only 31% of patients received monotherapy (a 2.2-fold decline), 32% received polytherapy, and 37% received no psychotropics. Initially patients received 1.42 psychotropic drugs per person; at one year, patients received 175, and at both times polytherapy was less likely with lithium than with anticonvulsants. In multivariate modeling, one-year mood stabilizer use was greater with the following: older age, type of mood stabilizer (lamotrigine > valproate > carbamazepine or oxcarbazepine > lithium) and was associated with more psychiatric office and emergency visits, clinician type (more common with psychiatrists than with primary care physicians), and nonuse of off-label anticonvulsants.
Polytherapy was used by one-third of patients initially and at one year, antidepressant use was highly prevalent initially and later, but lack of treatment was prevalent at one year. Plausible clinical and treatment factors were associated with sustained mood stabilizer adherence.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Treating pregnant women with bipolar disorder is among the most challenging clinical endeavors. Patients and clinicians are faced with difficult choices at every turn, and no approach is without risk. Stopping effective pharmacotherapy during pregnancy exposes the patient and her baby to potential harms related to bipolar relapses and residual mood symptom-related dysfunction. Continuing effective pharmacotherapy during pregnancy may prevent these occurrences for many; however, some of the most effective pharmacotherapies (such as valproate) have been associated with the occurrence of congenital malformations or other adverse neonatal effects in offspring. Very little is known about the reproductive safety profile and clinical effectiveness of atypical antipsychotic drugs when used to treat bipolar disorder during pregnancy. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated or undertreated maternal bipolar disorder during pregnancy, the effectiveness of interventions for bipolar disorder management during pregnancy, and potential obstetric, fetal, and neonatal risks associated with core foundational pharmacotherapies for bipolar disorder.
    Drug, Healthcare and Patient Safety 01/2015; 7:7-29. DOI:10.2147/DHPS.S50556
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Drug-effect phenotypes in human lymphoblastoid cell lines recently allowed to identify CHL1 (cell adhesion molecule with homology to L1CAM), GAP43 (growth-associated protein 43) and ITGB3 (integrin beta 3) as new candidates for involvement in the antidepressant effect. CHL1 and ITGB3 code for adhesion molecules, while GAP43 codes for a neuron-specific cytosolic protein expressed in neuronal growth cones; all the three gene products are involved in synaptic plasticity. Sixteen polymorphisms in these genes were genotyped in two samples (n=369 and 90) with diagnosis of major depressive episode who were treated with antidepressants in a naturalistic setting. Phenotypes were response, remission and treatment-resistant depression. Logistic regression including appropriate covariates was performed. Genes associated with outcomes were investigated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) genome-wide study (n=1861) as both individual genes and through a pathway analysis (Reactome and String databases). Gene-based analysis suggested CHL1 rs4003413, GAP43 rs283393 and rs9860828, ITGB3 rs3809865 as the top candidates due to their replication across the largest original sample and the STAR*D cohort. GAP43 molecular pathway was associated with both response and remission in the STAR*D, with ELAVL4 representing the gene with the highest percentage of single nucleotide polymorphisms (SNPs) associated with outcomes. Other promising genes emerging from the pathway analysis were ITGB1 and NRP1. The present study was the first to analyze cell adhesion genes and their molecular pathways in antidepressant response. Genes and biomarkers involved in neuronal adhesion should be considered by further studies aimed to identify predictors of antidepressant response.The Pharmacogenomics Journal advance online publication, 7 April 2015; doi:10.1038/tpj.2015.15.
    The Pharmacogenomics Journal 04/2015; DOI:10.1038/tpj.2015.15 · 5.51 Impact Factor
  • Source
    03/2015; 13(1):102-112. DOI:10.1176/appi.focus.130119