Lamotrigine Alone Compared to Lamotrigine Plus Antidepressant for the Treatment of Bipolar II Depression

NCT00475137 | Completed Phase 2

• 1 other identifier: H06-03732
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Depression is a medical condition characterized by feeling sad even when good things happen, having low energy and motivation, and sometimes even experiencing suicidal thoughts. Bipolar II Disorder is an illness in which periods of depression alternate with periods of abnormally elevated mood, energy and activity, referred to as hypomania. After Major Depressive Disorder, Bipolar II Disorder is the most common cause of depression. Unfortunately, antidepressant medications, used alone, do not work as well in treating Bipolar depression as they do in treating other kinds of depression. Lamotrigine is a medication which studies show is effective in treating Bipolar depression. The investigators will determine if lamotrigine works best to treat Bipolar II depression if it is used alone, or if it is taken with an antidepressant. In the first part of our investigation, people with Bipolar II depression who have not responded to an antidepressant will either add lamotrigine to their antidepressant, or will stop the antidepressant and take lamotrigine alone. They will see the study doctor for 6 visits over 8 weeks, and will answer questions about their depressive symptoms and their overall health. The purpose of this study phase is to determine which treatment works best to treat active Bipolar depression. In the second part of the study, people who have responded to their assigned treatment may continue to receive it for another 44 weeks. They will see the study doctor monthly, and will answer similar questions about their health. Participants will also receive a physical examination and get a blood test three times during the study. The purpose of the second phase is to ascertain which treatment is best at preventing relapses of depression. The investigators hypothesize that people who take Lamotrigine plus an antidepressant will recover from their depression more completely, have a longer period of wellness, and have better quality of life compared to those taking Lamotrigine alone.

Conditions

Bipolar II Disorder, Most Recent Episode Major Depressive

Keywords

Bipolar II Disorder; depression; Lamotrigine; Add On antidepressant; randomized; single blind; parallel group

Outcome Measures

Primary Outcomes (1)

• Efficacy of Lamotrigine monotherapy versus Lamotrigine plus antidepressant in the acute and maintenance treatment of Bipolar II depression as evidence by decrease in Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline to endpoint.

  8 weeks

Secondary Outcomes (1)

• Rates of response to treatment and remission in both treatment arms maintenance efficacy of treatments as evidenced by relapse rates. Rates of treatment associated mania or hypomania as evidenced by increased score on the Young Mania Rating Scale (YMRS).

  44 weeks

Study Arms (2)

Lamotrigine Plus Antidepressant

EXPERIMENTAL

Subjects will be randomized to one of two study arms at baseline. Those in the first treatment arm will be prescribed lamotrigine in addition to the antidepressant medication they were prescribed prior to study entry.

Drug: Lamotrigine

2. Lamotrigine Monotherapy

ACTIVE COMPARATOR

Subjects in the second treatment arm will discontinue their antidepressants and will be prescribed lamotrigine monotherapy. Lamotrigine will be initiated at 25mg daily for two weeks, then increased to 50mg daily for one week, and then increased to 100 mg daily. The dose may then be adjusted upward or downward by 50-100mg weekly, at the investigator's discretion, provided that it remains within the protocol defined range of 100mg - 400mg daily.

Drug: Lamotrigine

Interventions

Lamotrigine DRUG

Lamotrigine will be initiated at 25mg daily for two weeks, then increased to 50mg daily for one week, and then increased to 100 mg daily. The dose may then be adjusted upward or downward by 50-100mg weekly, at the investigator's discretion, provided that it remains within the protocol defined range of 100mg - 400mg daily. For subjects in this combination therapy arm, antidepressant dose will remain constant throughout the study.

Also known as: Lamictal

Lamotrigine Plus Antidepressant

Eligibility Criteria

• Age: 17 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who meet all of the following criteria are eligible to participate in this trial:
• Males or females, inpatients or outpatients, aged 17 to 70 years inclusive.
• Diagnosis of Bipolar II Disorder, current episode depressed, without psychotic features. Specifically, patients must have experienced at least one previous episode of hypomania lasting at least 2 days, and no previous manic episodes.
• The current episode of depression has a duration of at least 6 weeks.
• Montgomery-Asberg Depression Rating Scale score of at least 18.
• If female and of child-bearing age, must be using a reliable method of birth control. Reliable methods of birth control include: oral contraceptive pill or patch or surgically implanted device; intra-uterine device (IUD); tubal ligation; barrier device such as diaphragm or condom plus spermicidal jelly or foam; or abstinence.

You may not qualify if:

• Subjects meeting any of the following criteria are not eligible to participate in the trial:
• Manic or hypomanic symptoms, defined as a YMRS score of 16 or greater.
• Treatment with ECT or a depot antipsychotic medication within eight weeks prior to enrolment; or treatment with an experimental drug within 30 days prior to enrolment.
• Known lack of response to, or intolerance for, Lamotrigine. Lack of response is defined as failure of depressive symptoms to improve after a trial of an acceptable dose of medication, ie. 100 mg daily or greater of Lamotrigine for at least four weeks.
• Depressive symptoms secondary to substance use or a general medical condition, in the opinion of the investigator.
• Diagnosis of an anxiety disorder, including Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, Obsessive Compulsive Disorder, Specific Phobia, Post-Traumatic Stress Disorder, or Acute Stress Disorder, which was the primary focus of clinical attention in the year preceding enrolment.
• Diagnosis of Schizophrenia, Schizoaffective Disorder, or Delusional Disorder.
• Substance dependence within one month of enrolment, except for dependence in full remission, and except for caffeine or nicotine dependence, as defined by the DSM-IV-TR.
• Diagnosis of Borderline Personality Disorder, Narcissistic Personality Disorder, Histrionic Personality Disorder, or Antisocial Personality Disorder, which was the primary focus of clinical attention in the year preceding enrolment.
• Significant risk of harm to self or others, in the opinion of the investigator.
• Use of any cytochrome P450 inducer or inhibitor within five half-lives prior to enrolment.
• Pregnancy or lactation in female subjects.
• Unstable or inadequately treated medical illness, as judged by the investigator.
• Liver function tests (AST and ALT) three times the upper limit of normal.
• Glomerular Filtration Rate (GFR) of less than 60 mL/min per 1.73m2

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia Mood Disorders Centre

Vancouver, British Columbia, Canada

Location

MeSH Terms

Conditions

Bipolar Disorder; Depression

Interventions

Lamotrigine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David Bond, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Lakshmi Yatham, MD

  University of British Columbia

  STUDY DIRECTOR

• Edwin Tam, MD

  University of British Columbia

  STUDY DIRECTOR

• Mauricio Kunz, Dr.

  University of British Columbia

  STUDY DIRECTOR

• Kyooseob Ha, Dr.

  Seoul National University Bundang Hospital

  STUDY DIRECTOR

• Wetid Pratoomsri, Dr.

  Chachoengsao Hospital Thailand

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2007
• First Posted: May 17, 2007
• Study Start: December 1, 2007
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 4, 2015

Record last verified: 2015-06

Locations

CA (1)