Fluoxetine for MDD/Cannabis Disorder in Young People

描述(由申请人提供)：本提案是对RFA-DA-04-014，“大麻相关疾病的药物开发”的回应。 美国食品和药物管理局(FDA)最近(2003年1月3日)批准氟西汀用于治疗青少年和儿童中的严重抑郁症，这是基于两项急性期双盲安慰剂对照研究的结果(Emsle等人，1997；2002)。因此，氟西汀成为第一个获得FDA批准的治疗青少年和儿童严重抑郁障碍(MDD)的抗抑郁药物。目前尚不清楚这些结果在多大程度上适用于患有MDD和药物使用障碍(SUD)的青少年，如滥用大麻或依赖，因为患有SUD的青少年被排除在该研究之外。然而，我们自己的初步工作表明，氟西汀对于治疗抑郁症、大麻相关障碍以及青少年和年轻人共病饮酒是安全和有效的(Cornelius等人，1999；2001；2004)。 在这项研究中，将进行第一项大规模前瞻性、双盲、安慰剂对照研究，以评估SSRI药物氟西汀与安慰剂在治疗患有严重抑郁障碍和大麻相关障碍(MDD/CRD)的青少年中的疗效。两个治疗组的所有受试者在急性期试验期间也将接受照常治疗(TAU)，该试验将包括动机增强疗法(MET)和认知行为疗法(CBT)。本研究的目标是：1)比较SSRI药物加氟西汀和安慰剂加TAU治疗大麻使用和抑郁症状的急性期(12周)疗效；2)比较合并有CRD(大麻依赖或大麻滥用)和MDD的青少年和青壮年(12-25岁)的急性期(12周)疗效；3)对氟西汀在这一合并人群中的长期疗效进行初步评估。

DESCRIPTION (provided by applicant): This proposal is in response to RFA-DA-04-014, "Medications Development for Cannabis-Related Disorder." The Food and Drug Administration (FDA) recently (January 3, 2003) approved fluoxetine for the treatment of major depression among adolescents and children, based on the results of two acute phase double-blind, placebo-controlled studies (Emslie et al., 1997; 2002). Fluoxetine thus became the first antidepressant medication to receive FDA approval for treatment of major depressive disorder (MDD) among adolescents and children. It is unclear to what extent those results apply to adolescents with comorbid MDD and a substance use disorder (SUD) such as cannabis abuse or dependence, since adolescents with SUDs were excluded from participation in that study. However, our own preliminary work suggests that fluoxetine is safe and effective for treating the depression, the cannabis related disorder, and the drinking of comorbid adolescents and young adults (Cornelius et al, 1999; 2001; 2004). In this study, a first large scale prospective double-blind, placebo-controlled study will be conducted to assess the efficacy of the SSRI medication fluoxetine vs. placebo in the treatment of adolescents with comorbid major depressive disorder and a cannabis related disorder (MDD/CRD). All subjects in both treatment groups will also receive Treatment As Usual (TAU) during the acute phase trial, which will consist of motivation enhancement therapy (MET) and Cognitive Behavioral Therapy (CBT). The goals of this study are: 1) to compare the acute phase (12 week) efficacy of the SSRI medication fluoxetine plus TAU vs. placebo plus TAU for the treatment of the cannabis use and the depressive symptoms of an adolescent and young adult (ages 12-25) sample of subjects with comorbid diagnoses of a CRD (cannabis dependence or cannabis abuse) plus MDD; 2) to assess specific predictors of medication response; 3) to perform a preliminary evaluation of the longer-term efficacy of fluoxetine in this comorbid population.