Clinical trial NCT02989727: Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine
Official title: Melancholic Symptoms in Bipolar Depression and Responsiveness to Lamotrigine: Results From an 8-week, Multicenter, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Bipolar Disorder
Bipolar Depression
Melancholia
Lamotrigine
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2016-12-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if patients with melancholic bipolar II depression are more responsive to lamotrigine than patients with non-melancholic bipolar II depression. To do this, the investigators will re-analyze a previous clinical trial that evaluated lamotrigine as a treatment for bipolar II depression (GSK-SCA100223; NCT00274677).

Detailed description: Patients suffering from depression with melancholic symptoms (i.e., anhedonia, flat affect, diurnal mood variation, terminal insomnia, psychomotor disturbances, decreased weight/appetite, and excessive guilt) respond better to certain antidepressants. Melancholic symptoms also occur in bipolar depression, although they have received less research. Lamotrigine has been shown to alter some of the biological processes that are known to occur in melancholic depression. The purpose of this study is to determine if patients with melancholic bipolar II depression are more responsive to lamotrigine than patients with non-melancholic bipolar II depression.

This study will re-analyze data from a previous 8-week, randomized, placebo-controlled trial that evaluated lamotrigine as a treatment for bipolar II depression (GSK-SCA100223; NCT00274677). The original study data was made available by GlaxoSmithKline as part of an initiative to make clinical trials data available for research use. Access was applied for via https://www.clinicalstudydatarequest.com.

The analysis strategy will be comparable to the original study, although the investigators will first classify participants as suffering from either melancholic or non-melancholic depression. The diagnosis of melancholic depression was established according to baseline responses to the Hamilton Depression Rating Scale (HAMD-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS), according to the DSM-IV-TR diagnostic criteria. HAMD-17 and MADRS change scores will be compared between the treatment and placebo groups using Analysis of Variance (ANOVA). Both ANOVA models will include a test for an interaction between treatment group (lamotrigine vs. placebo) and melancholic depression (melancholic depression vs. non-melancholic depression). To handle missing data, each ANOVA model will be computed with only complete-case data first and subsequently using inverse probability weights that account for the probability of drop out. Inverse probability weights will be created based on covariates that predict missing responses. HAMD-17 and MADRS response rates between the treatment and placebo groups will be evaluated with a Cox proportional hazard regression analysis. There will be two separate analyses, one including participants with melancholic depression, and one including participants with non-melancholic depression. Statistical models will also adjust for baseline depression severity, if participants with melancholic depression are found to have more severe depressive symptoms at baseline.

Given the delay between antidepressant initiation and response, trial-and-error prescribing is an inevitably lengthy process. The investigators hope the results of this study will enable more timely and effective treatment for patients with bipolar depression.

Eligibility criteria: Inclusion Criteria:

1. Patients must provide written and informed consent.
2. Diagnosis of Bipolar II Disorder and currently depressed for minimum of the last 8 weeks, with a HAMD-17 score of at least 18 with scores of 3 or more on Items 1 or 7.
3. For females, be of non-childbearing potential, or of childbearing potential with a negative pregnancy test at screening and agrees to one of (a) abstinence from sex two weeks prior and five days after drug continuation/discontinuation, (b) personal or partner sterilization, (c) one method of hormonal contraception, or (d) two barrier methods of contraception.
4. Acceptable results (within two times the normal limit) on laboratory screening tests (e.g., thyroid function).

Exclusion Criteria:

1. Active suicidality.
2. History of non-response to antidepressant treatment, or any previous treatment with lamotrigine.
3. History of substance dependence in the past year, or abuse within the 4 weeks prior to study entry.
4. Rapid cycling bipolar disorder.
5. Receiving additional psychoactive medication (not including lorazepam for agitation), or has started a new course of psychotherapy within the last month.
6. Received treatment for an anxiety or eating disorder within the last 12 months.
7. Investigational drug use within the last month.
8. History of epilepsy.

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Change Scores
timeFrame: Eight weeks
measure: Hamilton Depression Rating Scale (HAMD-17) Change Scores
timeFrame: Eight weeks
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Eight weeks
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Seven weeks
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Six weeks
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Five weeks
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Four weeks
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Three weeks
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Two weeks
measure: Number of Participants With 50% Reduction in the Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: One week
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
timeFrame: Eight weeks
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
timeFrame: Seven weeks
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
timeFrame: Six weeks
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
timeFrame: Five weeks
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
timeFrame: Four weeks
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
timeFrame: Three weeks
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
timeFrame: Two weeks
measure: Number of Participants With 50% Reduction in the Hamilton Depression Rating Scale (HAMD-17)
timeFrame: One week
Secondary outcomes:
Other outcomes:
Locations:
city: Saskatoon
country: Canada
facility: Department of Psychiatry, Royal University Hospital
state: Saskatchewan
Study officials:
affiliation: University of Saskatchewan
name: Rudy C Bowen, FRCPC
role: STUDY_DIRECTOR
References: