This R01 application, based at New York State Psychiatric Institute (NYPSI) requests five years of support for a prospective, parallel group, double blind, random assignment treatment study of high-risk (previous suicide attempters) patients with Bipolar Disorder, who are in a mixed or depressed phase. This study will compare the effects of acute and maintenance treatment with lithium and valproate in the prevention of suicidal behavior in these subjects. Subjects (N=280) will be well characterized in terms of Axis I and II diagnosis, psychopathology (measures of suicidal behavior including ideation and acts) and aggression and impulsivity. This study will have three distinct phases: an acute stabilization phase, a treatment continuation phase and a treatment maintenance phase. Upon study entry, subjects will be randomized to lithium or valproate. Depressed patients will be stabilized using paroxetine (or two other alternative antidepressants) and patients with psychosis or in a mixed state will receive olanzapine (or two other antipsychotics). Up to six months will be devoted to an acute stabilization phase. In the continuation phase subjects will be maintained on lithium or valproate and an antidepressant or antipsychotic for up to 6 months. The acute phase ends when patients have achieved at least two weeks of euthymia. During the 18 months maintenance phase, most subjects will be maintained on mood stabilizer alone. They have operationalized rescue procedures that will be available for patients with a recurrence of an episode. Over the course of the study, patients will be assessed for changes in psychopathology, mood symptoms, suicidal behavior, aggressive behavior and substance abuse. They predict that subjects on lithium will have less suicidal behavior, including completion, attempt or hospitalization for suicidal ideation than subjects on valproate and that this effect will be independent of mood stabilization. The project will test the following hypotheses: (1) Lithium treatment will be superior to valproate in the prevention of suicidal behavior (suicidal acts or episodes of suicidal ideation with a plan that would require a change in treatment such as addition of a rescue medication or hospitalization). (2) The two treatment groups will not differ in terms of the total number of episodes of, or total duration in, a major depression or mixed mood states requiring commencement of a rescue medication over 18 months of the maintenance phase. (3) Lithium treatment will be superior to valproate in decreasing aggression.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1-ITV-D (01))
Program Officer
Pearson, Jane L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York State Psychiatric Institute
New York
United States
Zip Code
Abreu, L N; Oquendo, M A; Galfavy, H et al. (2018) Are comorbid anxiety disorders a risk factor for suicide attempts in patients with mood disorders? A two-year prospective study. Eur Psychiatry 47:19-24
Dervic, K; Garcia-Amador, M; Sudol, K et al. (2015) Bipolar I and II versus unipolar depression: clinical differences and impulsivity/aggression traits. Eur Psychiatry 30:106-13
Sher, Leo; Grunebaum, Michael F; Sullivan, Gregory M et al. (2014) Association of testosterone levels and future suicide attempts in females with bipolar disorder. J Affect Disord 166:98-102
Keilp, John G; Wyatt, Gwinne; Gorlyn, Marianne et al. (2014) Intact alternation performance in high lethality suicide attempters. Psychiatry Res 219:129-36
MacGregor, Erica K; Grunebaum, Michael F; Galfalvy, Hanga C et al. (2014) Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal family study. J Clin Psychiatry 75:879-85
Oquendo, M A; Perez-Rodriguez, M M; Poh, E et al. (2014) Life events: a complex role in the timing of suicidal behavior among depressed patients. Mol Psychiatry 19:902-9
Gorlyn, Marianne; Keilp, John G; Oquendo, Maria A et al. (2013) Iowa gambling task performance in currently depressed suicide attempters. Psychiatry Res 207:150-7
Keilp, J G; Gorlyn, M; Russell, M et al. (2013) Neuropsychological function and suicidal behavior: attention control, memory and executive dysfunction in suicide attempt. Psychol Med 43:539-51
Oquendo, Maria A; Ellis, Steven P; Chesin, Megan S et al. (2013) Familial transmission of parental mood disorders: unipolar and bipolar disorders in offspring. Bipolar Disord 15:764-73
Deo, Anthony J; Huang, Yung-yu; Hodgkinson, Colin A et al. (2013) A large-scale candidate gene analysis of mood disorders: evidence of neurotrophic tyrosine kinase receptor and opioid receptor signaling dysfunction. Psychiatr Genet 23:47-55

Showing the most recent 10 out of 37 publications