Substance misuse to psychiatric disorders for cannabis an early assertive pharmacotherapy intervention pilot study

Abstract

<p>Introduction: Anxiety and depressed mood are common upon cannabis withdrawal, and a reduction in anxiety has been associated with reductions in cannabis use. Lifetime prevalence for major depressive disorder and anxiety disorders in cannabis users were as high as 20.9% and 30.5%, respectively. Synthetic cannabinoid agonist has been shown to decrease both pre- and post-synaptic serotonin 5-HT_1A receptor activities. Vortioxetine, a potent 5HT_1A agonistic antidepressant with little or no abuse potential, might thus be a medication candidate for treating cannabis use disorder. Aim: this single (rater) blined study compared the changes in severity of cannabis use disorder, co-morbid depressive and anxiety symptoms, and cognitive and functional outcomes between subjects taking vortioxetine and treatment-as-usual controls. Methods: Cannabis users with depressive and/or anxiety symptoms were recruited. Consented subjects were randomized to receive either vortioxetine (C1 group) or treatment-as-usual management (C2 group) for 6 months. They were followed-up prospectively with outcomes assessed by raters on changes in severity of DSM-5 defined cannabius use disorder, Severity of Dependence Scale (SDS), Stages of Change Readiness and Treatment Eagerness Scale-Drug (SOCRATES-D), Clinical Global Impression-Severity of Illness (CGI-S), Hamilton Anxiety and Depression Rating Scales (HAM-D and HAM-D), Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB), and Addiction Severity Index-Lite (ASI-Lite). Independet t-tests were used for investigating differences on demographics, whereas generalized estimating equations were used to compare the treatment outcomes between these two treatment groups. All outcome models were fitted into the auto-regressive working correlation for robutness in study design with repeated measures. Results: 37 subjects participated and randomized but 7 of them only completed the baseline assessment. Thus, 30 subjects with 11 subjects in the C1 vortioxetine group and 19 subjects in the C2 treatment-as-usual group were included in the analysis. Twenty subjects were males and the mean age of all subjects was 30.13 (SD = 10.60). No significant differences on gender, age, and cannabis use history between the two treatment groups, including age of first use, duration and frequency of cannabis use, and THC contents of cannabis used were noted. There was a significant difference between the two treatment groups in CGI-S (B = 0.68, SE = 0.34, χ2 = 4.02, p = .045). Pairwise comparisons revealed that the mean scores of CGI-S from the C1 vortioxetine group decreased significantly from the baseline (M = 4.00) to the 3-month follow-up (M = 2.78, p = .010) and the 6-month follow-up (M = 2.51, p < .001) under Bonferroni correction. No significant change in CGI-S was observed over time for the C2 treatment-as-usual group. Although no significant between-group differences were observed for SDS, mean SDS scores of the C1 vortioxetine group appeared to be on a downward trend over the 6-month study duration (M= -1.36), whereas those of the C2 treatment-as-usual group appeared to be on a rising trend (M= 1.5). Otherwise, no significant between-group differences had been demonstrated for other outcomes. Conclusion: vortioxetine might reduce the severity of illness in cannabis users with depressive and anxiety symptoms. ​​​​​​​</p>