Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001483
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: May 2002
  Purpose

This study will compare the effectiveness of relatively new antidepressants which have different mechanisms of action.

Buproprion (Wellbutrin) works on dopamine and the dopaminergic pathway.

Sertraline (Zoloft) works as a selective serotonin reuptake inhibitor (SSRI).

Venlafaxine (Effexor) works as a mixed serotonin, norepinephrine, and dopamine reuptake inhibitor.

Subjects enrolled in this study will be patients diagnosed with a bipolar disorder who are presently taking medication to prevent the symptoms of the disease (prophylactic treatment), but have had breakthrough episodes of depression despite taking their medication.

Patients will receive any one of the three antidepressant medications as noted above plus a placebo inactive sugar pill, in order to mask which antidepressant is being prescribed) in addition to their regular medication for bipolar disorder. All of the doses will be calculated as effective for the treatment of a unipolar major depressive disorder. The patient will continue receiving the medication for ten weeks.

The effectiveness of the drug treatment will be measured by using three different scales;

  1. Inventory for Depressive Symptoms - Clinicians form (IDS-C)
  2. Clinical Global Impression scale(CGI-BP)
  3. Life Charting Methodology (LCM)

Patients who do not respond to their medication within ten weeks from the beginning of the study will be considered as non-responders and be offered the opportunity to start the study again, taking one of the two remaining medications. For example, if a patient was assigned to take Wellbutrin but it was ineffective, he/she could re-enter the study and be given either Zoloft or Effexor.

Patients that do respond in the first ten weeks of the study will be eligible to continue taking the medication for one year to assess the long term effectiveness of the drug on preventing episodes of depression and to assess for any possible differential induction of mania.


Condition Intervention Phase
Bipolar Disorder
Depressive Disorder
Drug: buproprion (Wellbutrin)
Drug: sertraline (Zoloft)
Drug: venlafaxine (Effexor)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: Acute Efficacy of Bupropion, Sertraline, and Venlafaxine as Adjuvant Treatment to Mood Stabilizers in Bipolar Depression: A Randomized, Double-Blind, Comparative Study

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 75
Study Start Date: June 1995
Estimated Study Completion Date: May 2002
Detailed Description:

This NIMH-Stanley Foundation Bipolar Network (the "Network") study will be the first systematic assessment in bipolar depression of the comparative efficacy of bupropion (Wellbutrin), sertraline (Zoloft), and venlafaxine (Effexor), three newer antidepressants which have very different mechanisms of action. Bupropion is largely dopaminergic while sertraline is a serotonin selective reuptake inhibitor (SSRI) and venlafaxine is a mixed serotonin, norepinephrine, and to a lesser extent dopamine reuptake inhibitor. Subjects enrolled in this study will be bipolar patients on prophylactic treatment who experience a breakthrough major depressive episode. Subjects will be assigned in a double-blind manner using a three-arm forced randomization procedure to antidepressant therapy with either bupropion, sertraline, or venlafaxine for a ten-week acute response trial. The study medications will be assigned as adjuvant treatment to mood stabilizing medication(s) which have proven unsatisfactorily effective within therapeutic range(s) or at maximum tolerated dose(s). All subjects will receive active drug at dosages established as clinically relevant for unipolar major depressive disorder. Subjects and research personnel conducting cross-sectional and longitudinal rating assessments of mood and functioning will be blinded to treatment group assignment. The primary outcome measures will be the Inventory for Depressive Symptoms - Clinician form (IDS-C), the Clinical Global Impression (CGI-BP) scale, and the Life Charting Methodology (LCM). Subjects who worsen from baseline to week four of treatment will be considered non-responders to the initially assigned medication, and will be offered re-randomization to either of the two drugs to which the subject was not originally randomized (e.g., for bupropion non-response, to either sertraline or venlafaxine) for an additional ten-week acute response trial. Responders to the acute trial enter a 12 month trial of continuation therapy to assess long term effects on prophylaxis of depression and possible induction of mania or cycle acceleration. We also wish to explore possible clinical and biological correlates of acute and long term response to these antidepressants which have received almost no systematic study in bipolar illness. One hypothesis of this study is that the acute efficacy for the three antidepressants would be the same. Another hypothesis is that because of the potent noradrenergic (NE) effects, venlafaxine would have a higher rate of inducing mania compared with bupropion or sertraline.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Subjects fulfill DSM-IV criteria for Bipolar I disorder (BPI), Bipolar II disorder (BPII), Bipolar disorder not otherwise specified (BPNOS), or schizoaffective disorder bipolar type.

Subjects must be competent to comprehend the purpose of the study and provide informed consent.

Subjects must undergo complete psychiatric diagnostic interview (SCID--DSM-IV), medical, neurological, and Laboratory examinations (including EKG, renal and liver function tests, serum electrolytes, urinalysis, HIV, hepatitis B, pregnancy testing, and urine drug screen for the presence of psychoactive drugs and drugs of abuse).

At least 18 years old.

Subjects must have a depression of sufficient severity to rate greater than or equal to 16 on the Inventory of Depressive Symptomatology -Clinician (IDS-C) comparable to greater than or equal to 12 on the Hamilton Depression Rating Scale) or the clinician must decide that there is a need to treat with an antidepressant. In addition, patients must be on at least one mood stabilizer.

Subjects should have no general medical illness that is causing the mood disorder.

Subjects should not have liver, renal, hematological, or neurological disease.

Women participants of childbearing potential must be nongravid, nonnursing, and using an acceptable method of birth control.

Patients must not have alcohol or substance use or dependence of sufficient magnitude to require independent, concurrent treatment intervention (excluding self-help groups), i.e., hospitalization, day treatment programs, or counselor visits.

No patients taking concomitant medications that would contraindicate the medications under study, such as chemotherapy.

No history of bulimia or seizure disorder.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001483

Locations
United States, Maryland
National Institute of Mental Health (NIMH)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001483     History of Changes
Other Study ID Numbers: 950129, 95-M-0129
Study First Received: November 3, 1999
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Manic-Depressive Disorder
Antidepressants
Re-Randomization
Continuation
Ratings
Bipolar Illness
Depression
Bupropion
Sertraline

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Sertraline
Venlafaxine
Bupropion
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Dopamine Uptake Inhibitors
Dopamine Agents

ClinicalTrials.gov processed this record on July 22, 2014