Unipolar DepressionNCT00901407
Lamotrigine Augmentation in Resistant Depression
A study testing lamotrigine and paroxetine in people with Unipolar Depression, run by Louisiana State University Health Sciences Center in New Orleans at 1 site in United States.
Trial summary
This study is intended to evaluate the efficacy and safety of lamotrigine as an antidepressant augmentation agent in a sample of individuals with major depression and a history of both prior non-response and prospective failure to respond to at least one adequate trial of an antidepressant (for a total of two failed… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Unipolar Depression
- What is being tested?
- lamotrigine and paroxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 138 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2003to Apr 2007
- Phase
- Interventional
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects, age 18-65
- A current primary diagnosis of unipolar major depression based on certain criteria
- Have a score of > 18 on the 17-item Hamilton Depression scale
- A history of prior failure of at least one adequate trial of an FDA-approved antidepressant. The antidepressant failure must have occurred within the current episode of major depression
- Females of childbearing potential will be allowed as long as they are taking adequate contraceptive precautions
Who cannot join
- A primary Axis I diagnosis other than primary unipolar major depression
- A history suggestive of hypomania or mania during the current episode or during the person's lifetime
- A history of psychosis, dementia, organic affective disorders or alcohol and/or substance abuse in the previous six months
- Individuals with a current or past diagnosis of schizoid, schizotypal, borderline or antisocial or any other current or past severe personality disorder
- Individuals with a current or past diagnosis of schizophrenia or schizoaffective disorder
- A history of failure to respond to electroconvulsive therapy during the current or any prior lifetime episode of major depression
Show all 27Show fewer
- A history of failure of a prior adequate trial of paroxetine or paroxetine-CR for the treatment of Major Depression
- Significant, coexisting medical conditions that might make it unsafe to take either of the study medications, or in which any average reasonable clinician would assume that the medical condition may, in fact, be exacerbating the current episode of depression or impede the person's ability to recover fully from their depressive illness
- Presence of significant medical abnormalities on baseline laboratory values or physical examination, including vital signs
- Individuals with any significant abnormalities of thyroid function
- Subjects on thyroid supplementation must have been on a stable dose for six months prior to the screening visit
- Individuals who will require concomitant psychotropic medications, including benzodiazepines
- Subjects with severe insomnia will be allowed to take a maximum of 10 mg of zolpidem on two nights weekly at the investigator's discretion.
- Zolpidem may not be taken on the night before the study visit.
- Each dose of zolpidem should be listed on the concurrent medication case report form
- Medications likely to cause significant effects on mood and anxiety are also excluded
- Individuals with a positive urine drug screen for drugs of abuse at the screening visit
- Use during the time of the study of any medications known to affect the metabolism of lamotrigine
- Individuals on valproate and carbamazepine will be specifically excluded
- Investigators should be aware that oral contraceptives have been reported to lower the levels of lamotrigine, but any change in dosing is left to the judgment of the investigator
- Subjects who have taken other psychoactive drugs within certain time frames of the screening visit
- The presence of significant risk of suicide
- Pregnant females or those who are breastfeeding infants
- A history of hypersensitivity or intolerance to either of the study medications, lamotrigine or paroxetine or paroxetine-CR
- Subjects initiating or terminating psychotherapy within 12 weeks of the screening visit
- Individuals who are currently on disability for a psychiatric disorder, or who are in any other way likely to experience considerable secondary gain from the persistence of their psychiatric illness, such as pending legal litigation of any type
- Individuals who in the opinion of the investigator would not be able to understand or comply with the study requirements
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Lamotrigine as an Antidepressant Augmentation Agent in Treatment Refractory Unipolar Depression
This study is intended to evaluate the efficacy and safety of lamotrigine as an antidepressant augmentation agent in a sample of individuals with major depression and a history of both prior non-response and prospective failure to respond to at least one adequate trial of an antidepressant (for a total of two failed trials).
Read the detailed description
The study will consist of four phases: screening, open-label, double-blind and discontinuation phases. After screening to ensure that subjects meet the study criteria, individuals will enter an open-label (flexible-dose) trial of paroxetine-CR given in dosages up to 62.5 mg for a period of eight weeks. Paroxetine may be substituted for paroxetine-CR in dosages up to 50 mg. Subjects may be switched from paroxetine-CR to the bioequivalent dose of paroxetine due to drug supply disruption but should not be switched back to paroxetine-CR. Subjects are not allowed to switch from paroxetine to paroxetine-CR. Subjects who start on paroxetine at the first visit must remain on paroxetine for the duration of the study. At the discretion of the investigator, additional monitoring or interim visits may be needed for subjects who require a switch from paroxetine-CR to paroxetine. Those individuals who fail to respond adequately will then continue into the second phase (double-blind portion) of the study, in which participants will continue on either paroxetine-CR or paroxetine, and will be randomized to either placebo or lamotrigine in a flexible-dose design up to 400mg for a 10-week period. Subjects will remain on the same dose of paroxetine-CR or paroxetine that they were taking at the final visit in the first phase of the study (Visit 5/Week 8). The study medications will be discontinued following the final study visit (Visit 11/Week 18 or the early termination visit). Paroxetine-CR or paroxetine may be continued in the dosages used during the study after completion of the protocol if, in the judgment of the investigator, the subject has shown a partial response to treatment with the drug. The lamotrigine (or placebo) dose will be decreased by half for one week and then discontinued. Subjects will return two weeks post-study and four weeks post study for follow up visits consisting of safety evaluations. In addition, a MADRS and CGI should be performed at the two-week post study follow up visit. The visit at four weeks post study may be omitted if the 3rd and 4th week of taper are not needed. The decision to restart lamotrigine at that time would also be up to the investigator, but the dosage of lamotrigine would have to be titrated in the first month per the manufacturer's clinical trial program. This is necessary since all subjects will be discontinuing from the drug following Visit 11/Week 18 or the early termination visit in order to maintain the blind at the conclusion of each subject's participation in the study. Subjects who are discontinued from paroxetine-CR at dosages of 25 mg/day or higher should undergo a gradual dose reduction of 12.5 mg per week rather than abrupt cessation. Subjects who are discontinued from paroxetine at dosages of 20 mg/day or higher should undergo a gradual dose reduction of 10 mg per week rather than abrupt cessation.
- Conditions
- Unipolar Depression
- Being tested
- lamotrigine, placebo, paroxetine
- Keywords
- augmentation, depression, resistance
- Medical subject headings
- Depressive Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lamotrigineDrug
Also called Lamictal
lamotrigine augmentation 25 to 100 mg tablets, 25 to 200 mg bid,10 weeks
placeboDrug
placebo: 1-2 tablets bid; 10 weeks
paroxetineDrug
Also called paxil
open label paroxetine 10 to 50 mg, at bedtime for 18 weeks (8 weeks prior to randomization and 10 weeks after)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | lamotrigine Receives: Drug: lamotrigine; Drug: paroxetine |
| 2 | Placebo comparator | placebo Receives: Drug: placebo; Drug: paroxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
MADRS score
Measured: weeks 0 (randomization); 8, 9, 10, 12, 14, 16, 18, and 20
Secondary outcomes (2)
Ham-D score
Measured: weeks 0 (randomization); 2, 4, 6, 8, 9, 10, 12, 14, 16, and 18
CGI-S and CGI-I
Measured: weeks 0 (randomization); 8, 9, 10, 12, 14, 16, 18 and 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2009 (estimated)
- Study startDec 2003
- Primary completionJul 2006
- Study completionApr 2007
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 Unipolar DepressionStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 138 participants (actual)
Sponsor and investigators
- Lead sponsor
- Louisiana State University Health Sciences Center in New Orleans
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Investigators
- James G. Barbee, MD, Principal investigator, Louisiana State University Health Sciences Center in New Orleans
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00901407
- Sponsor's protocol ID
- LMC-R93
- Status last verified
- May 2009
- First submitted
- 11 May 2009
- Last updated
- 13 May 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Barbee, J.G., Jamhour, N,J., Stewart, J.W., Shelton, R.C., Reimherr, F.W., Thompson, P.M., Conrad, E.J. &Thompson, T.R. (2007, May). Lamotrigine as an antidepressant augmentation in treatment refractory unipolar depression. Poster session presented at the annual meeting of the American Psychiatric Association, San Diego, CA.
Barbee, J.G., Jamhour, N,J. & Conrad, E.J. (2007, June). Predictors of response to lamotrigine augmentation in treatment refractory unipolar depression. Poster session presented at the annual meeting of the New Clinical Drug Evaluation Unit, Boca Raton, FL.
Barbee JG, Thompson TR, Jamhour NJ, Stewart JW, Conrad EJ, Reimherr FW, Thompson PM, Shelton RC. A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression. J Clin Psychiatry. 2011 Oct;72(10):1405-12. doi: 10.4088/JCP.09m05355gre.
PubMed 21367355
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lamotrigine as an Antidepressant Augmentation Agent in Treatment Refractory Unipolar Depression
- ClinicalTrials.gov ID
- NCT00901407
- Acronym / sponsor ID
- LMC-R93
- Conditions
- Unipolar Depression
- Keywords
- augmentation, depression, resistance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 138 participants (actual)
- Lead sponsor
- Louisiana State University Health Sciences Center in New OrleansUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Dec 2003
- Primary completion
- Jul 2006 (actual)
- Study completion
- Apr 2007 (actual)
- First posted
- 13 May 2009 (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 is intended to evaluate the efficacy and safety of lamotrigine as an antidepressant augmentation agent in a sample of individuals with major depression and a history of both prior non-response and prospective failure to respond to at least one adequate trial of an antidepressant (for a total of two failed trials).
Detailed description
The study will consist of four phases: screening, open-label, double-blind and discontinuation phases. After screening to ensure that subjects meet the study criteria, individuals will enter an open-label (flexible-dose) trial of paroxetine-CR given in dosages up to 62.5 mg for a period of eight weeks. Paroxetine may be substituted for paroxetine-CR in dosages up to 50 mg. Subjects may be switched from paroxetine-CR to the bioequivalent dose of paroxetine due to drug supply disruption but should not be switched back to paroxetine-CR. Subjects are not allowed to switch from paroxetine to paroxetine-CR. Subjects who start on paroxetine at the first visit must remain on paroxetine for the duration of the study. At the discretion of the investigator, additional monitoring or interim visits may be needed for subjects who require a switch from paroxetine-CR to paroxetine. Those individuals who fail to respond adequately will then continue into the second phase (double-blind portion) of the study, in which participants will continue on either paroxetine-CR or paroxetine, and will be randomized to either placebo or lamotrigine in a flexible-dose design up to 400mg for a 10-week period. Subjects will remain on the same dose of paroxetine-CR or paroxetine that they were taking at the final visit in the first phase of the study (Visit 5/Week 8). The study medications will be discontinued following the final study visit (Visit 11/Week 18 or the early termination visit). Paroxetine-CR or paroxetine may be continued in the dosages used during the study after completion of the protocol if, in the judgment of the investigator, the subject has shown a partial response to treatment with the drug. The lamotrigine (or placebo) dose will be decreased by half for one week and then discontinued. Subjects will return two weeks post-study and four weeks post study for follow up visits consisting of safety evaluations. In addition, a MADRS and CGI should be performed at the two-week post study follow up visit. The visit at four weeks post study may be omitted if the 3rd and 4th week of taper are not needed. The decision to restart lamotrigine at that time would also be up to the investigator, but the dosage of lamotrigine would have to be titrated in the first month per the manufacturer's clinical trial program. This is necessary since all subjects will be discontinuing from the drug following Visit 11/Week 18 or the early termination visit in order to maintain the blind at the conclusion of each subject's participation in the study. Subjects who are discontinued from paroxetine-CR at dosages of 25 mg/day or higher should undergo a gradual dose reduction of 12.5 mg per week rather than abrupt cessation. Subjects who are discontinued from paroxetine at dosages of 20 mg/day or higher should undergo a gradual dose reduction of 10 mg per week rather than abrupt cessation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: lamotrigine, Drug: paroxetinelamotrigine |
| 2 | Placebo comparator | Drug: placebo, Drug: paroxetineplacebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female subjects, age 18-65
- A current primary diagnosis of unipolar major depression based on certain criteria
- Have a score of > 18 on the 17-item Hamilton Depression scale
- A history of prior failure of at least one adequate trial of an FDA-approved antidepressant. The antidepressant failure must have occurred within the current episode of major depression
- Females of childbearing potential will be allowed as long as they are taking adequate contraceptive precautions
Key exclusion criteria (27 listed)
- A primary Axis I diagnosis other than primary unipolar major depression
- A history suggestive of hypomania or mania during the current episode or during the person's lifetime
- A history of psychosis, dementia, organic affective disorders or alcohol and/or substance abuse in the previous six months
- A history of failure to respond to electroconvulsive therapy during the current or any prior lifetime episode of major depression
- A history of failure of a prior adequate trial of paroxetine or paroxetine-CR for the treatment of Major Depression
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 |
|---|---|---|
| lamotrigineAlso: Lamictallamotrigine augmentation 25 to 100 mg tablets, 25 to 200 mg bid,10 weeks | Drug | 1 |
| placeboplacebo: 1-2 tablets bid; 10 weeks | Drug | 2 |
| paroxetineAlso: paxilopen label paroxetine 10 to 50 mg, at bedtime for 18 weeks (8 weeks prior to randomization and 10 weeks after) | Drug | 1, 2 |
Primary outcome
MADRS score
Time frame: weeks 0 (randomization); 8, 9, 10, 12, 14, 16, 18, and 20
2 secondary outcomes
Ham-D score
Time frame: weeks 0 (randomization); 2, 4, 6, 8, 9, 10, 12, 14, 16, and 18
CGI-S and CGI-I
Time frame: weeks 0 (randomization); 8, 9, 10, 12, 14, 16, 18 and 20
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 13 May 2009.
- Results publicationBarbee, J.G., Jamhour, N,J., Stewart, J.W., Shelton, R.C., Reimherr, F.W., Thompson, P.M., Conrad, E.J. &Thompson, T.R. (2007, May). Lamotrigine as an antidepressant augmentation in treatment refractory unipolar depression. Poster session presented at the annual meeting of the American Psychiatric Association, San Diego, CA.
- Results publicationBarbee, J.G., Jamhour, N,J. & Conrad, E.J. (2007, June). Predictors of response to lamotrigine augmentation in treatment refractory unipolar depression. Poster session presented at the annual meeting of the New Clinical Drug Evaluation Unit, Boca Raton, FL.
- Derived from this study: PubMed 21367355Barbee JG, Thompson TR, Jamhour NJ, Stewart JW, Conrad EJ, Reimherr FW, Thompson PM, Shelton RC. A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression. J Clin Psychiatry. 2011 Oct;72(10):1405-12. doi: 10.4088/JCP.09m05355gre.
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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.
James G. Barbee, MD principal investigator
Louisiana State University Health Sciences Center in New Orleans
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing lamotrigine and paroxetine in people with Unipolar Depression, run by Louisiana State University Health Sciences Center in New Orleans at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2009. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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.
What does the primary outcome measure?
MADRS score (time frame: weeks 0 (randomization); 8, 9, 10, 12, 14, 16, 18, and 20). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00901407, 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 13 May 2009.