Bipolar DisorderPhase 2NCT00001483
Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression
A Phase 2 study testing buproprion (Wellbutrin), sertraline (Zoloft) and venlafaxine (Effexor) in people with Bipolar Disorder and Depressive Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Bipolar Disorder, Depressive Disorder
- What is being tested?
- buproprion (Wellbutrin), sertraline (Zoloft) and venlafaxine (Effexor)
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 1995to May 2002
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Mental Health (NIMH)
Bethesda, Maryland, 20892
About this study
Official title: Acute Efficacy of Bupropion, Sertraline, and Venlafaxine as Adjuvant Treatment to Mood Stabilizers in Bipolar Depression: A Randomized, Double-Blind, Comparative Study
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.
Read more
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;
- Inventory for Depressive Symptoms - Clinicians form (IDS-C)
- Clinical Global Impression scale(CGI-BP)
- 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.
Read the 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.
- Conditions
- Bipolar Disorder, Depressive Disorder
- Being tested
- buproprion (Wellbutrin), sertraline (Zoloft), venlafaxine (Effexor)
- Keywords
- Manic-Depressive Disorder, Antidepressants, Re-Randomization, Continuation, Ratings, Bipolar Illness, Depression, Bupropion, Sertraline
- Medical subject headings
- Bipolar Disorder, Depressive Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
buproprion (Wellbutrin)Drug
sertraline (Zoloft)Drug
venlafaxine (Effexor)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startJun 1995
- Study completionMay 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 75 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001483
- Sponsor's protocol ID
- 950129
- Other IDs
- 95-M-0129
- Status last verified
- May 2002
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Davidson J. Seizures and bupropion: a review. J Clin Psychiatry. 1989 Jul;50(7):256-61.
PubMed 2500425Sachs GS, Lafer B, Stoll AL, Banov M, Thibault AB, Tohen M, Rosenbaum JF. A double-blind trial of bupropion versus desipramine for bipolar depression. J Clin Psychiatry. 1994 Sep;55(9):391-3.
PubMed 7929019Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994 Jan;51(1):8-19. doi: 10.1001/archpsyc.1994.03950010008002.
PubMed 8279933
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Efficacy of Bupropion, Sertraline, and Venlafaxine as Adjuvant Treatment to Mood Stabilizers in Bipolar Depression: A Randomized, Double-Blind, Comparative Study
- ClinicalTrials.gov ID
- NCT00001483
- Acronym / sponsor ID
- 950129
- Conditions
- Bipolar Disorder, Depressive Disorder
- Keywords
- Manic-Depressive Disorder, Antidepressants, Re-Randomization, Continuation, Ratings, Bipolar Illness, Depression, Bupropion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Jun 1995
- Study completion
- May 2002
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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;
- Inventory for Depressive Symptoms - Clinicians form (IDS-C)
- Clinical Global Impression scale(CGI-BP)
- 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.
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| buproprion (Wellbutrin) | Drug | – |
| sertraline (Zoloft) | Drug | – |
| venlafaxine (Effexor) | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 2500425Davidson J. Seizures and bupropion: a review. J Clin Psychiatry. 1989 Jul;50(7):256-61.
- Background: PubMed 7929019Sachs GS, Lafer B, Stoll AL, Banov M, Thibault AB, Tohen M, Rosenbaum JF. A double-blind trial of bupropion versus desipramine for bipolar depression. J Clin Psychiatry. 1994 Sep;55(9):391-3.
- Background: PubMed 8279933Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994 Jan;51(1):8-19. doi: 10.1001/archpsyc.1994.03950010008002.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing buproprion (Wellbutrin), sertraline (Zoloft) and venlafaxine (Effexor) in people with Bipolar Disorder and Depressive Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001483, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.