This is a resubmission of a Mentored Patient-Oriented Career Development (K23) Award application to enhance the applicant's expertise in the study of innovative therapies for treatment-resistant major depression. The research component of this application includes a randomized, double-blind, placebo controlled trial of adjunctive pramipexole, a dopamine receptor agonist, for treatment-resistant depression. Subjects who improve with randomized treatment will also enter a continuation-phase pilot study. The application utilizes an innovative therapy and a simple, rigorous design to address an understudied disorder with major impact on public health. Preliminary studies suggest augmentation with dopamine receptor agonists such as pramipexole may be efficacious in these patients, though the optimum dose has not been established. The primary aim of this study will be to determine the efficacy of flexibly-dosed pramipexole compared to placebo. Secondary analyses will include clinical predictors of response. During the final two years of the award period, the candidate will develop a larger study building on this data and drawing on his formal training. The proposed study will be conducted at Massachusetts General Hospital in the Depression Clinical and Research Program, under the mentorship of Andrew Nierenberg, M.D. and co-mentorship of Maurizio Fava, M.D., A. John Rush, M.D., and Michael Thase, M.D., with consultation from a panel of local and national experts. The application also includes a rich didactic component combining formal coursework at the Harvard School of Public Health with tutorials in study design, assessment and management of treatment resistance, biostatistics, and bioethics. As the co-mentors are co-principal investigator or principal investigator in two large NIMH-funded effectiveness studies in mood disorders, the candidate will also participate in statistical review and ongoing analysis of both studies, applying skills developed in his coursework and tutorials. The proposed investigation and training program will provide critical skills, experience and data to aid the candidate in writing an R01 and becoming an independent investigator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH067060-02
Application #
6767839
Study Section
Special Emphasis Panel (ZMH1-NRB-G (13))
Program Officer
Chavez, Mark
Project Start
2003-07-01
Project End
2008-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$165,818
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Cusin, Cristina; Iovieno, Nadia; Iosifescu, Dan V et al. (2013) A randomized, double-blind, placebo-controlled trial of pramipexole augmentation in treatment-resistant major depressive disorder. J Clin Psychiatry 74:e636-41
Laje, Gonzalo; Perlis, Roy H; Rush, A John et al. (2009) Pharmacogenetics studies in STAR*D: strengths, limitations, and results. Psychiatr Serv 60:1446-57
Perlis, R H; Fava, M; Trivedi, M H et al. (2009) Irritability is associated with anxiety and greater severity, but not bipolar spectrum features, in major depressive disorder. Acta Psychiatr Scand 119:282-9
Perlis, Roy H; Patrick, Amanda; Smoller, Jordan W et al. (2009) When is pharmacogenetic testing for antidepressant response ready for the clinic? A cost-effectiveness analysis based on data from the STAR*D study. Neuropsychopharmacology 34:2227-36
Perlis, Roy H; Dennehy, Ellen B; Miklowitz, David J et al. (2009) Retrospective age at onset of bipolar disorder and outcome during two-year follow-up: results from the STEP-BD study. Bipolar Disord 11:391-400
Perlis, Roy H; Purcell, Shaun; Fagerness, Jesen et al. (2008) Family-based association study of lithium-related and other candidate genes in bipolar disorder. Arch Gen Psychiatry 65:53-61
Perlis, Roy H; Purcell, Shaun; Fava, Maurizio et al. (2007) Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study. Arch Gen Psychiatry 64:689-97
Perlis, Roy H; Beasley Jr, Charles M; Wines Jr, James D et al. (2007) Treatment-associated suicidal ideation and adverse effects in an open, multicenter trial of fluoxetine for major depressive episodes. Psychother Psychosom 76:40-6
Cusin, Cristina; Fava, Maurizio; Amsterdam, Jay D et al. (2007) Early symptomatic worsening during treatment with fluoxetine in major depressive disorder: prevalence and implications. J Clin Psychiatry 68:52-7
Perlis, Roy H; Ostacher, Michael J; Patel, Jayendra K et al. (2006) Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry 163:217-24

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