A Randomized, Single-Blind Comparison of Lamotrigine Add-on Versus Switch to Lamotrigine Monotherapy in the Treatment of Bipolar II Depression Unresponsive to Antidepressant Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
PURPOSE: To evaluate the efficacy and safety of lamotrigine when added to antidepressant medication, versus lamotrigine monotherapy, in the treatment and prevention of major depression in patients with Bipolar II Disorder which has not responded to antidepressant treatment alone.
HYPOTHESIS: Our primary hypothesis is that depressed patients with Bipolar II Disorder using lamotrigine plus antidepressant, as compared to those using lamotrigine monotherapy, will experience a greater decrease in their score on the Montgomery-Asberg Depression Rating Scale, a standard measure of severity of depression. The investigators also hypothesize that patients using lamotrigine in combination with antidepressant will have a greater survival time without experiencing depressed, manic, or hypomanic episodes during maintenance therapy, and an improved quality of life, compared to those receiving lamotrigine monotherapy.
JUSTIFICATION: Bipolar Disorder is a severe and recurrent psychiatric illness which is associated with high rates of mental health service utilization and functional disability. 15% - 20% of patients will complete suicide, the greatest rate of any psychiatric illness. With a lifetime prevalence of 3% - 5%, over one million Canadians suffer from this potentially disabling condition.
Bipolar I Disorder is characterized by one or more manic or mixed episodes, frequently in combination with episodes of depression. It has been well studied, and effective treatments are available for the depressed, manic, and maintenance phases of this condition. Bipolar II Disorder consists of periods of depression, plus one or more hypomanic (mild manic) episodes. The depressed phase of Bipolar II illness is overwhelmingly responsible for its substantial burden. Long-term follow-up studies demonstrate that patients experience depressive symptoms almost 40 times more often than symptoms of hypomania, and that even mild depressive symptoms are associated with significant functional impairment. Hypomanic episodes, conversely, are generally short, infrequent, and do not significantly impair functioning.
Bipolar II Disorder has been under-recognized, primarily due to its frequent misdiagnosis as Major Depressive Disorder. However, it is becoming increasingly clear that it is the most common Bipolar phenotype, affecting up to 80% of people with Bipolar illness. Underestimation of its prevalence has led to it being understudied. To date, no large randomized controlled trials exclusively involving Bipolar II patients have been published. Clinical decisions regarding the treatment of Bipolar II Disorder must therefore be extrapolated from research on Bipolar I patients, or based on the results of small open label studies. Clinical trials in Bipolar I samples show conclusively that mood stabilizing medications such as Lithium are the optimal treatment, and that antidepressant therapy may potentiate a switch into mania, or the development a rapid cycling course of illness. Several lines of evidence, however, including genetic, family, and long-term follow-up studies, suggest that Bipolar II Disorder is a distinct illness from Bipolar I Disorder. Making treatment decisions based on data from Bipolar I patients may therefore be inappropriate. While some open-label studies support the efficacy of mood stabilizing medications in Bipolar II Disorder, others suggest that Bipolar II patients may respond to antidepressant monotherapy. Antidepressants may be less effective in treating Bipolar II Disorder than Major Depressive Disorder, however, and Bipolar patients are over-represented in the treatment refractory population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 17 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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
- •A history of significant cardiac conduction abnormalities, as determined by the investigator.
研究组 & 干预措施
Lamotrigine Plus Antidepressant
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.
干预措施: Lamotrigine (Drug)
2. Lamotrigine Monotherapy
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.
干预措施: Lamotrigine (Drug)
结局指标
主要结局
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.
时间窗: 8 weeks
次要结局
- 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)