Lamotrigine in Treatment Resistant Depression in Adolescents

Tracking Information
First Submitted Date ICMJE	January 30, 2006
First Posted Date ICMJE	February 1, 2006
Last Update Posted Date	May 17, 2017
Actual Study Start Date ICMJE	January 2006
Actual Primary Completion Date	February 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE	Not Provided
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00284791 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Lamotrigine in Treatment Resistant Depression in Adolescents
Official Title ICMJE	Lamotrigine Use in Treatment Refractory Depression in Adolescents
Brief Summary	The primary hypothesis of this study is that in fluoxetine (Prozac)-resistant adolescents with Major Depressive Disorder (MDD), Lamotrigine plus fluoxetine will be safe and as effective as sertraline (Zoloft). Our Primary Aim is to determine the efficacy and safety of Lamotrigine-augmentation of fluoxetine for treatment-resistant depression in adolescents. Our Secondary Aims are to characterize the factors associated with treatment-resistance for adolescents with major depression. Also to assess the relationships in the families of adolescents with major depression as they enter treatment, and to track the differences in family relationships for adolescents who respond or do not respond. We postulate that tense, frustrated, irritable, and over-involved relationships constitute a risk factor for attenuated improvement or relapse.
Detailed Description	Mood disorders in youth, which include Major Depressive Disorder (MDD) and Bipolar Disorder (BPD), are highly prevalent, and are associated with significant mortality and morbidity. Many youths with major depression fail first-line treatments with psychotherapy and psychotropic medications. Lamotrigine (Lamictal®) recently gained approval by the FDA for maintenance treatment of bipolar disorder in adults. A few pilot studies have also shown promising results for lamotrigine (LTG) in treatment refractory mood disorders in both youth and adults, especially for depressive symptoms (Carandang et al., 2003; Frye et al., 2000). For this proposed study, the modified design begins with adolescents with major depressive disorder who have not responded to a trial of a selective serotonin reuptake inhibitor antidepressant (SSRI), fluoxetine, of adequate dose and duration, and randomizes them either to a second SSRI or to fluoxetine augmented by lamotrigine. Non-responders to 8 weeks of fluoxetine, on at least 40 mg/day, who have not had to discontinue fluoxetine because of adverse effects, would be randomized to: (A) continue fluoxetine with lamotrigine augmentation, for 8 weeks, as in the active arm of the original Stage 2, or (B) discontinue fluoxetine and begin a second SSRI, for 8 weeks. We will use sertraline as the second SSRI, because of the data supporting efficacy from the randomized placebo-controlled trial by Wagner, et.al. (JAMA, '03). Citalopram is also a possibility (Wagner et.al, Am J. Psychiatry '04), but it has been in use for a shorter period of time than sertraline. To maintain the blind, the B group will receive placebo augmentation. The assessments and outcome measures would be the same as in the original study. We will consult with primary care offices to coach them through doing the initial, Stage 1, fluoxetine trial in their offices, and we will monitor the progress of adolescents started on fluoxetine in our clinic. Consent will be discussed only with those who are not responding, and treatment in the study will involve only the post-randomization treatment. Background Mood disorders in youth are common and debilitating. Early-onset of mood disorders often indicates a severe illness, with high likelihood of recurrence into adulthood. For prepubertal children, point prevalence of MDD is 2%, and 6% in adolescents, while the lifetime prevalence for MDD in adolescents is 20% (Birmaher et al., 2002). The duration of a Major Depressive Episode in youth ranges from 3 to 9 months, with 10% lasting more than 2 years, 60-70% recurring in adulthood, and 20-40% developing Bipolar Disorder within 5 years (Weller and Weller, 2000). The prevalence of prepubertal bipolar disorder is estimated at 0.5%. Prevalence of bipolar disorder in adolescents is 1% (Lewinshon et al., 1995). Suicide is the third leading cause of death in the 15 - 24 year old age group (10.1 per 100,000) and the fifth leading cause in the 5 - 14 year old group (0.7 per 100,00), and is highly correlated with MDD and BPD (Pfeffer, 2002). In addition, mood disorders in youth can impair functioning, often characterized by poor school performance, impaired relationships, delinquent behavior, and substance abuse.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
Condition ICMJE	Adolescent Depression
Intervention ICMJE	Drug: Lamotrigine (drug); Drug: Fluoxetine (drug); Drug: sertraline (drug)
Study Arms	Not Provided
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Enrollment ICMJE; (submitted: January 30, 2006)	50
Original Enrollment ICMJE	Same as current
Actual Study Completion Date	February 2007
Actual Primary Completion Date	February 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Adolescents (13-17) diagnosed with a major depressive episode (MDE) (DSM-IV criteria) from either major depressive disorder (MDD) or bipolar disorder (BPD). BPD can present as a major depressive episode, with previous or subsequent cycling into a hypomanic, manic, or mixed episode. By definition, major depressive disorder MDD requires the presence of a major depressive episode, without cycling into a hypomanic, manic, or mixed episode.; CDRS (Children's Depression Rating Scale) > 40.; CGAS (Children's Global Assessment Scale) < 60. Exclusion Criteria: Adolescents who meet the following criteria will be excluded from the study: Prior medically serious suicide attempt, within 3 months of enrollment into study or a score of 3 on suicide questions within KSADS at initial visit or the side effect checklist on follow up visits regarding current state.; Known or suspected mental retardation. For patients with known mental retardation, full scale IQ below 70 should be documented.; Current significant physical illnesses (e.g. diabetes mellitus, asthma, cystic fibrosis, congenital heart defects, genetic disorders). Patients with seizure disorders taking anticonvulsants will be excluded (no concomitant anticonvulsants).; Current drug or alcohol abuse. No active abuse will be permitted within two weeks of beginning the study trial (confirmed by urine testing in all cases of suspected abuse).; Females who are sexually active and are unwilling or considered unable to use appropriate contraception.; Use of benzodiazepines and other anxiolytics, antipsychotic medications, other antidepressants, stimulant medication, other mood stabilizers (e.g., lithium, valproate), and other sedative-hypnotics will not be permitted
Sex/Gender	Sexes Eligible for Study: All
Ages	13 Years to 18 Years (Child, Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00284791
Other Study ID Numbers ICMJE	MMC-2571
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Not Provided
Study Sponsor ICMJE	Maine Medical Center
Collaborators ICMJE	GlaxoSmithKline
Investigators ICMJE	Principal Investigator: Douglas R Robbins, MD Maine Medical Center Psychiatry Department Study Director: William McFarlane, MD Maine Medical Center, Center for Psychiatric Research
PRS Account	Maine Medical Center
Verification Date	May 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP