Lithium Versus Paroxetine in Patients With Major Depression Who Have a Family History of Bipolar Disorder or Suicide

Summary

This study is being done to look at how well people respond to two very different drug treatments for depression. Clinically, people with depression can respond differently to drug treatments for reasons which are not always clear. Some of our own recent research suggests that people with depression who have a family history of bipolar disorder or completed suicide, may react differently to standard antidepressant medications than those without such a family history. Our data shows that family history of completed suicide, as well as the known predictor of family history of bipolar disorder, may help identify a pre-bipolar high risk group i.e. they currently have depression but at some future date will declare a bipolar illness (manic-depression) by virtue of development of a manic episode also. Our research suggests that treatment- emergent symptoms in response to a trial of antidepressant, such as agitation may be strong predictors of future bipolarity and inherently dangerous particularly as they are not ascribed to the antidepressant treatment. Finally, it is possible that this subgroup of those with depressive illness may respond better and more safely to lithium, a mood stabiliser used in known bipolar depression. The objective of this proposal is to investigate response to acute lithium treatment in subjects who meet the diagnostic criteria for major depression, but who are potentially at risk for bipolar disorder, by virtue of family history of bipolarity or completed suicide.

Timeline

Start

2007-06

Primary completion

2013-01

Completion

2013-01

Publications

• Background Judd LL, Akiskal HS. The prevalence and disability of bipolar spectrum disorders in the US population: re-analysis of the ECA database taking into account subthreshold cases. J Affect Disord. 2003 Jan;73(1-2):123-31. doi: 10.1016/s0165-0327(02)00332-4.
• Background Perugi G, Micheli C, Akiskal HS, Madaro D, Socci C, Quilici C, Musetti L. Polarity of the first episode, clinical characteristics, and course of manic depressive illness: a systematic retrospective investigation of 320 bipolar I patients. Compr Psychiatry. 2000 Jan-Feb;41(1):13-8. doi: 10.1016/s0010-440x(00)90125-1.
• Background Roy-Byrne P, Post RM, Uhde TW, Porcu T, Davis D. The longitudinal course of recurrent affective illness: life chart data from research patients at the NIMH. Acta Psychiatr Scand Suppl. 1985;317:1-34. doi: 10.1111/j.1600-0447.1985.tb10510.x.
• Background Yatham LN, Kennedy SH, O'Donovan C, Parikh S, MacQueen G, McIntyre R, Sharma V, Silverstone P, Alda M, Baruch P, Beaulieu S, Daigneault A, Milev R, Young LT, Ravindran A, Schaffer A, Connolly M, Gorman CP; Canadian Network for Mood and Anxiety Treatments. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies. Bipolar Disord. 2005;7 Suppl 3:5-69. doi: 10.1111/j.1399-5618.2005.00219.x.
• Background Ghaemi SN, Rosenquist KJ, Ko JY, Baldassano CF, Kontos NJ, Baldessarini RJ. Antidepressant treatment in bipolar versus unipolar depression. Am J Psychiatry. 2004 Jan;161(1):163-5. doi: 10.1176/appi.ajp.161.1.163.
• Background Blacker D, Lavori PW, Faraone SV, Tsuang MT. Unipolar relatives in bipolar pedigrees: a search for indicators of underlying bipolarity. Am J Med Genet. 1993 Dec 15;48(4):192-9. doi: 10.1002/ajmg.1320480405.
• Background Bowden CL. A different depression: clinical distinctions between bipolar and unipolar depression. J Affect Disord. 2005 Feb;84(2-3):117-25. doi: 10.1016/S0165-0327(03)00194-0.
• Background Strober M, Carlson G. Bipolar illness in adolescents with major depression: clinical, genetic, and psychopharmacologic predictors in a three- to four-year prospective follow-up investigation. Arch Gen Psychiatry. 1982 May;39(5):549-55. doi: 10.1001/archpsyc.1982.04290050029007.
• Background Hirschfeld RM, Cass AR, Holt DC, Carlson CA. Screening for bipolar disorder in patients treated for depression in a family medicine clinic. J Am Board Fam Pract. 2005 Jul-Aug;18(4):233-9. doi: 10.3122/jabfm.18.4.233.
• Background Koukopoulos A, Faedda G, Proietti R, D'Amico S, de Pisa E, Simonetto C. [Mixed depressive syndrome]. Encephale. 1992 Jan;18 Spec No 1:19-21. French.
• Background Berk M, Dodd S. Are treatment emergent suicidality and decreased response to antidepressants in younger patients due to bipolar disorder being misdiagnosed as unipolar depression? Med Hypotheses. 2005;65(1):39-43. doi: 10.1016/j.mehy.2005.02.010.

Drugs

Indications