Modafinil for the treatment of cocaine dependence

Abstract

Aim Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo. Methods This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, having a diagnosis of cocaine dependence; 72 participants were randomized to placebo, 69 to modafinil 200 mg, and 69 to modafinil 400 mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy weekly. The primary outcome measure was the weekly percentage of cocaine non-use days. Results The GEE regression analysis showed that for the total sample, there was no significant difference between either modafinil group and placebo in the change in average weekly percent of cocaine non-use days over the 12-week treatment period (p > 0.79). However, two secondary outcomes showed significant effects by modafinil 200 mg: the maximum number of consecutive non-use days for cocaine (p = 0.02), and a reduction in craving (p = 0.04). Also, a post hoc analysis showed a significant effect of modafinil that increased the weekly percentage of non-use days in the subgroup of those cocaine patients who did not have a history of alcohol dependence (p < 0.02). Conclusions These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing cocaine craving.

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

“…It is this potentiation of neurotransmission that is understood to be responsible for cocaine's psychomotor stimulant effects (e.g., Johanson and Fischman, 1989). Brain dopamine transporters have been implicated in these effects to a (2) Mansbach and Balster, 1993 (+) Rush et al, 2010 (+) Grabowski et al, 2001 (+) Negus, 2003 (+) Shearer et al, 2003 (+) Negus and Mello, 2003a (+) Schmitz et al, 2012 (+) Negus and Mello, 2003b (+) Levin et al, 2015 (2) Barrett et al, 2004 (+) Chiodo et al, 2008 (+) Czoty et al, 2010 (+) Czoty et al, 2011 (+) Banks et al, 2013 (2) Thomsen et al, 2013 (acute) (+) Thomsen et al, 2013 (chronic) (+) Banks et al, 2015 Methylphenidate (2) Hiranita et al, 2009 (+) Collins et al, 2006 (2) Grabowski et al, 1997 (2) Czoty et al, 2013 (+) Schubiner et al, 2002 (2) Levin et al, 2007 Modafinil (+) Newman et al, 2010 (+) Hart et al, 2008 (+) Dackis et al, 2005 (2) Verrico et al, 2014 (2) Anderson et al, 2009 (2) Dackis et al, 2012 (2) Schmitz et al, 2012 (2) Schmitz et al, 2014 (+) Kampman et al, 2015 (2) Karila et al, 2016 Desipramine (2) Mello et al, 1990a (2) Fischman et al, 1990 (+) Gawin et al, 1989 (2) Campbell et...…”

“…Seven double-blind, placebo-controlled, randomized clinical trials have investigated modafinil for managing cocaine dependence (Dackis et al, 2005(Dackis et al, , 2012Anderson et al, 2009;Schmitz et al, 2012Schmitz et al, , 2014Kampman et al, 2015;Karila et al, 2016). In the earliest trial (Dackis et al, 2005), cocaine-dependent subjects were randomly assigned to receive 400 mg modafinil per day (n = 30) or placebo (n = 32) for 8 weeks.…”

Acute Modafinil Effects on Attention and Inhibitory Control in Methamphetamine-Dependent Humans

“…Results from these trials have sometimes shown a positive effect of modafi nil on stimulant abstinence, but the results have been variable (see Anderson et al, 2009;Heinzerling et al, 2010;McGaugh et al, 2009;Shearer et al, 2009). In particular, moderator variables may play a role in the success of treatment.…”

Medication Development for the Treatment of Cocaine Addiction – Progress at Preclinical and Clinical Levels

“…No significant adverse effects were noted. The therapeutic effects of modafinil in cocaine users have been supported by a recently completed multi-site, placebo-controlled clinical trial involving 210 cocaine-dependent outpatients (Anderson et al, 2009). Currently, more than 10 additional clinical trials are under way to further evaluate the efficacy of modafinil treatment for cocaine addiction ( Table 1).…”