This application, entitled """"""""Treatment of Bipolar Type II Major Depression,"""""""" is a competing continuation grant that is predicated upon findings from our prior NIMH-funded study entitled """"""""Relapse-Prevention of Bipolar Type II Disorder"""""""" (R01 MH060353). Bipolar type II (BP II) major depressive episode (MDE), the subject of this proposal, affects 2.5% of the US adult population and results in an estimated healthcare cost of $40 billion annually. BP II disorder is a distinct clinical entity that differs from BP I disorder, and is characterized by a preponderance of MDEs that result in particularly high morbidity and mortality rates. The treatment of BP II MDE remains a challenge for clinicians. Concerns over antidepressant drug (AD) induced manic switch episodes have led current practice guidelines to recommend treating BP II MDE with mood stabilizer (MS) monotherapy and to avoid AD monotherapy. To date, there are no controlled clinical trials to test the validity of these empirical guidelines. Results from our preliminary BP II MDE studies have shown that fluoxetine or venlafaxine monotherapy may be a safe and effective initial treatment of BP II MDE with a low manic switch rate. Based upon these observations, we now ask (Specific aim #1): """"""""What is the relative safety and efficacy of initial AD monotherapy vs. MS monotherapy of BP II MDE?"""""""" and """"""""What is the relative manic switch rate of initial AD vs. MS monotherapy ofBP II MDE?"""""""" To answer these questions, patients with BP II MDE will be treated in a 12-week, randomized, parallel group comparison of venlafaxine monotherapy vs. lithium monotherapy. We hypothesize that AD monotherapy will have superior efficacy vs. MS monotherapy, and that there will be a similar manic switch rate among both treatment conditions. We will also ask (Specific Aim #2): """"""""What is the efficacy of continuation AD vs. MS monotherapy in BP II patients who have recovered from their MDE?"""""""" and """"""""What is the manic switch rate during continuation AD vs. MS monotherapy for 6 months in recovered BP II MDE patients?"""""""" To answer this question, patients who have responded during initial therapy will receive 6-month continuation treatment of venlafaxine vs. lithium monotherapy. We hypothesize that AD monotherapy will have superior efficacy vs. MS monotherapy, and that there will be a similar manic switch rate among both treatment conditions. If our hypotheses are correct, we believe that these results may have an important public health impact on the current practice guidelines for treating BP II MDE.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060353-10
Application #
8089357
Study Section
Interventions Committee for Adult Mood and Anxiety Disorders (ITMA)
Program Officer
Pearson, Jane L
Project Start
2001-02-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2011
Total Cost
$350,831
Indirect Cost
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Amsterdam, Jay D; Lorenzo-Luaces, Lorenzo; DeRubeis, Robert J (2017) Comparison of treatment outcome using two definitions of rapid cycling in subjects with bipolar II disorder. Bipolar Disord 19:6-12
Amsterdam, Jay D; Lorenzo-Luaces, Lorenzo; DeRubeis, Robert J (2016) Step-wise loss of antidepressant effectiveness with repeated antidepressant trials in bipolar II depression. Bipolar Disord 18:563-570
Lorenzo-Luaces, L; Amsterdam, J D; Soeller, I et al. (2016) Rapid versus non-rapid cycling bipolar II depression: response to venlafaxine and lithium and hypomanic risk. Acta Psychiatr Scand 133:459-69
Amsterdam, Jay D; Lorenzo-Luaces, Lorenzo; Soeller, Irene et al. (2016) Short-term venlafaxine v. lithium monotherapy for bipolar type II major depressive episodes: effectiveness and mood conversion rate. Br J Psychiatry 208:359-65
Amsterdam, Jay D; Lorenzo-Luaces, Lorenzo; Soeller, Irene et al. (2015) Safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for relapse-prevention of bipolar II depression: A randomized, double-blind, parallel-group, prospective study. J Affect Disord 185:31-7
Fournier, Jay C; DeRubeis, Robert J; Amsterdam, Jay et al. (2015) Gains in employment status following antidepressant medication or cognitive therapy for depression. Br J Psychiatry 206:332-8
Lorenzo-Luaces, Lorenzo; German, Ramaris E; DeRubeis, Robert J (2015) It's complicated: The relation between cognitive change procedures, cognitive change, and symptom change in cognitive therapy for depression. Clin Psychol Rev 41:3-15
Amsterdam, Jay D; Luo, Lola; Shults, Justine (2013) Effectiveness and mood conversion rate of short-term fluoxetine monotherapy in patients with rapid cycling bipolar II depression versus patients with nonrapid cycling bipolar II depression. J Clin Psychopharmacol 33:420-4
Amsterdam, Jay D; Newberg, Andrew B; Newman, Cory F et al. (2013) Change over time in brain serotonin transporter binding in major depression: effects of therapy measured with [(123) I]-ADAM SPECT. J Neuroimaging 23:469-76
Amsterdam, Jay D; Luo, Lola; Shults, Justine (2013) Efficacy and mood conversion rate during long-term fluoxetine v. lithium monotherapy in rapid- and non-rapid-cycling bipolar II disorder. Br J Psychiatry 202:301-6

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