Trajectories of craving in the course of pharmacotherapy trials for methamphetamine use disorder

Aims The aim of this study was to measure trajectories of craving for methamphetamine during the course of pharmacotherapy trials for methamphetamine use disorder. Design, setting and participants Craving trajectories were identified using Group‐Based Trajectory Modeling. The association of craving trajectories with drug use trajectories was examined using a dual trajectory model. Association of craving trajectories with other health and social outcomes was also examined. The study used pooled data from five randomized controlled pharmacotherapy trials for methamphetamine use disorder. A total of 866 adults with methamphetamine use disorder participated in randomized controlled pharmacotherapy trials. Measurement Craving was assessed weekly using the Brief Substance Craving Scale. Drug use was assessed using urine toxicology. Alcohol‐ and drug‐related problems, as well as psychiatric, medical, legal, employment and relationship problems, were measured using the Addiction Severity Index. Findings A three‐trajectory model with high, medium and low craving trajectories was selected as the most parsimonious model. Craving trajectories were associated with methamphetamine use trajectories in the course of trial; 88.4% of those in the high craving trajectory group had a consistently high frequency of methamphetamine use compared with 18.7% of those in the low craving group. High craving was also associated with less improvement in most other outcomes and higher rate of dropout from treatment. In turn, low craving was associated with a rapidly decreasing frequency of methamphetamine use, greater improvement in most other outcomes and a lower rate of dropout. Participants on modafinil daily and ondansetron 1 mg twice daily were less likely to be in the high craving group compared with those on placebo. Conclusions Trajectories of methamphetamine craving in the course of clinical trials for methamphetamine use disorder appear to be both highly variable and strongly associated with greater frequency of drug use, other drug‐related outcomes and dropout from trials. Two medications, modafinil daily and ondansetron at a dose of 1 mg two times daily, appear to be associated with greater reduction in craving in the course of treatment compared with placebo. A decrease in methamphetamine craving shows promise as an early indicator of recovery from methamphetamine use disorder.