Double-blind fluoxetine trial in comorbid MDD–CUD youth and young adults

Abstract

Objective This study compared the acute phase (12-week) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the cannabis use of adolescents and young adults with comorbid major depression (MDD) and an cannabis use disorder (CUD)(cannabis dependence or cannabis abuse). We hypothesized that fluoxetine would demonstrate efficacy versus placebo for the treatment of the depressive symptoms and the cannabis use of adolescents and young adults with comorbid MDD/CUD. Methods We conducted the first double-blind placebo-controlled study of fluoxetine in adolescents and young adults with comorbid MDD/CUD. All participants in both treatment groups also received manual-based cognitive behavioral therapy (CBT) and motivation enhancement therapy (MET) during the 12-week course of the study. Results Fluoxetine was well tolerated in this treatment population. No significant group-by-time interactions were noted for any depression-related or cannabis-use related outcome variable over the 12-week study. Subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in depressive symptoms and in number of DSM diagnostic criteria for a CUD. Large magnitude decreases in depressive symptoms were noted in both treatment groups, and end-of-study levels of depressive symptoms were low in both treatment groups. Conclusions Fluoxetine did not demonstrate greater efficacy than placebo for treating either the depressive symptoms or the cannabis-related symptoms of our study sample of comorbid adolescents and young adults. The lack of a significant between-group difference in these symptoms may reflect limited medication efficacy, or may result from efficacy of the CBT/MET psychotherapy or from limited sample size.

Pharmacotherapies for cannabis dependence

“…This limited the extent of analysis that was possible.The medications investigated, grouped according to type and mechanism of action, were: preparations containing THC, dronabinol (Levin 2011) and nabiximols (Allsop 2014);selective serotonin reuptake inhibitor (SSRI) antidepressants fluoxetine (Cornelius 2010), escitalopram (Weinstein 2014);mixed action antidepressants (noradrenergic and serotonergic effects), nefazodone (Carpenter 2009), mirtazapine (Frewen 2007), venlafaxine (Levin 2013);anticonvulsant and mood stabilisers divalproex sodium (Levin 2004), gabapentin (Mason 2012), lithium (Johnston 2012);atypical antidepressant (dopamine reuptake inhibitor and weak norepinephrine reuptake inhibitor) bupropion (Carpenter 2009; Penetar 2012);anxiolytic (serotonin 5-HT 1A partial agonist) buspirone (McRae-Clark 2009);selective norepinephrine reuptake inhibitor atomoxetine (McRae-Clark 2010);a supplement promoting glutamate release and modulating N-methyl-D-aspartate (NMDA) receptor, N-acetylcysteine (Gray 2012). …”

“…selective serotonin reuptake inhibitor (SSRI) antidepressants fluoxetine (Cornelius 2010), escitalopram (Weinstein 2014);…”

“…Two studies (Cornelius 2010; Penetar 2012) included participants with cannabis use disorders as well as cannabis dependence, but the majority of participants met diagnostic criteria for cannabis dependence. In the other studies all participants were cannabis dependent.…”

“…The target population for the remaining two studies (Cornelius 2010; Gray 2012) was adolescents and young adults. The average age of participants in these studies was 21.1 and 18.9 years, respectively.…”

Pharmacologic management of comorbid post-traumatic stress disorder and addictions

“…50 In an earlier open label pilot study of adolescents and young adults with comorbid major depressive disorder (MDD) and SUD, Cornelius et al reported that fluoxetine was able to decrease symptoms of depression as well as drinking and cannabis use; however, in a later double-blind study, fluoxetine did not significantly reduce number of days of cannabis use or cannabis related symptoms. 51 In addition, medications such as lithium and lofexidine have shown some efficacy in controlled laboratory studies and small open-label clinical studies, but additional study is necessary to determine their potential benefits. 52 Of the aforementioned medications, fluoxetine (as well as other SSRI medications) and buspirone are cornerstone components in the pharmacologic management of PTSD, and thus worth consideration in treatment of comorbid PTSD and CUD, given their potential to decrease cannabis use.…”