Placebo-group responders in methamphetamine pharmacotherapy trials: The role of immediate establishment of abstinence.

Abstract

Objective Treatment responses of placebo groups in addiction medicine trials have important implications for research methodology and clinical practice, however, studies examining placebo group responses in addiction medicine is scarce. Extant data suggests the importance of early treatment responsiveness for long-term outcomes. Among methamphetamine (MA) dependent individuals randomized to placebo pill plus behavioral support conditions in pharmacotherapy development trials, we hypothesized that immediate abstinence would be a necessary but insufficient predictor for end-of-trial (EOT) abstinence. Methods The study is a secondary analysis of participants (N=184; 36% female) in the placebo condition of three randomized, placebo-controlled methamphetamine dependence pharmacotherapy trials. Receiver operating characteristic (ROC) curve analyses assessed the predictive power of initial abstinence, assessed by thrice weekly urine samples, for EOT abstinence. Results Sixty percent of individuals with complete abstinence in the first two weeks of treatment were abstinent at EOT while 18% of people who failed to meet this standard were abstinent at EOT. Early response was related to retention at EOT and 12 month follow-up. Findings suggested that the inability to achieve at least three MA negative screenings in the first two weeks is associated with greater than 90% likelihood of treatment failure. A third week of screening added minimally to the prediction of EOT outcomes. The prediction of treatment failure was more precise than the prediction of treatment success. Conclusion The absence of a clinical response in the first two weeks of treatment among participants in the placebo group signals high risk of treatment failure. The vast majority of information regarding response in the placebo group from a12-week trial is obtained in early in the trial.

Contingent Vs. Non-Contingent Rewards: Time-Based Intervention Response Patterns Among Stimulant-Using Men Who Have Sex With Men

“…That temporal responders were more likely to be observed among those who presented a stimulant metabolite-free urine sample at intake is consistent with prior analyses of outcomes in trials of methamphetamine treatments that show strong correlations between start-of-intervention drug use status and intervention response (Brensilver et al, 2012; Cochran, Stitzer, Nunes, Hu, & Campbell, 2014). Patterns of intervention response observed in this study also are consistent with findings from early studies of CM used in methadone maintenance clinics (Morral et al, 1997), though the identification of a single positive responder pattern is unique to this study.…”

Clinically relevant characteristics associated with early treatment drug use versus abstinence

“…Prominent among these individual differences are the drug(s) endorsed as the primary problem, and reason for treatment entry, and the current drug use status of the individuals entering treatment. In clinical trials with stimulant abusers, it repeatedly has been shown that a substantial proportion has already achieved abstinence prior to treatment entry or does so rapidly upon treatment entry, and that early drug abstinence is strongly associated with better treatment prognosis [ 1 - 16 ]. Studies among alcohol users receiving treatment similarly have described divergent pre-treatment drinking patterns, including pre-treatment abstinence, and have demonstrated their association with treatment outcomes [ 17 , 18 ].…”

Dropout in clinical trials of pharmacological treatment for methamphetamine dependence: the role of initial abstinence

“…Several reports have shown a relationship between early treatment response and positive outcomes in clinical trials of substance use treatments [14][15][16][17][18]. Early abstinence is associated with better retention in out-patient behavioral and pharmacological treatment programs for opiate use [19][20][21].…”