Editorial, J Addict Behav Ther Rehabil Vol: 0 Issue: 0
Running Over the Same Old Ground: What�s Missing in Cocaine Clinical Pharmacotherapy Trials?
|Jennifer G. Plebani*|
|University of Pennsylvania, USA|
|Corresponding author : Jennifer G. Plebani, PhD
Research Assistant Professor of Psychology in Psychiatry, University of Pennsylvania, 3900 Chestnut Street, Philadelphia, PA 19104, USA
Tel: +1-215-222-3200; Fax: +1- 215-386-5106
E-mail: [email protected]
|Received: June 17, 2012 Accepted: June 19, 2012 Published: June 21, 2012|
|Citation: Melvin A (2012) Running Over the Same Old Ground: What’s Missing in Cocaine Clinical Pharmacotherapy Trials?. J Addict Behav Ther Rehabil 1:1. doi:10.4172/2324-9005.1000e102|
Running Over the Same Old Ground: What’s Missing in Cocaine Clinical Pharmacotherapy Trials?
In over two decades of cocaine treatment research, countless pharmacotherapies have been tested, without a single medication approved for the treatment of cocaine dependence. A short and entirely incomplete list of tested medications includes: olanzapine, valproate, coenzyme Q10, L-carnitine, cabergoline, reserpine, tiagabine, amantadine, propranolol, selegiline, modafinil, sertraline, disulfiram, baclofen, and citicoline. Setting aside the very real possibility that none of the medications tested to date is actually efficacious for treating cocaine dependence, there are three main issues that appear to have potentially hindered accurate findings in such studies.
|In over two decades of cocaine treatment research, countless pharmacotherapies have been tested, without a single medication approved for the treatment of cocaine dependence. A short and entirely incomplete list of tested medications includes: olanzapine, valproate, coenzyme Q10, L-carnitine, cabergoline, reserpine, tiagabine, amantadine, propranolol, selegiline, modafinil, sertraline, disulfiram, baclofen, and citicoline. Setting aside the very real possibility that none of the medications tested to date is actually efficacious for treating cocaine dependence, there are three main issues that appear to have potentially hindered accurate findings in such studies.|
|The first is medication adherence, or lack thereof. Study participants are expected to take medications as prescribed. Although efforts are made to ensure compliance (e.g. pill counts, riboflavin tracers, MEMS caps), the onus is on the participant. It is somewhat ironic that we biochemically verify the same participants drug use as we do not trust their self-report regarding use, but we essentially put complete faith in the evidence they provide regarding medication compliance.|
|The other two issues, attendance and attrition are related, results in both are less than complete data collection. Infrequent attendance or missed visits leave researchers wondering about what happened while the participant was not attending visits. Missing data can be ignored, it can be interpolated, or it can be set to missing equals drug positive. The problem with any of the three is that it’s still missing.|
|Similarly, attrition, where participants drop out of the trial, provides no data after the point at which they drop out also results in large amounts of missing data. Participants may leave a trial because they see no change in their cocaine use, which they may attribute to a lack of medication effect, to placebo assignment, or to some other unknown factor. Conversely, participants may leave a trial because they stop using cocaine and no longer want or need treatment. Regardless of use during the trial, participants may also drop out due to factors unrelated to cocaine use, including family obligations, employment issues, and legal system involvement. Perhaps the most critical issue in attrition is differential drop out, where placeboassigned and medication-assigned participants leave the study at different times, in different proportions, or both. Differential drop may indicate medication side effect problems, but again, having no data after drop out, this cannot be known.|
|As in the problem of Schoedinger’s cat, until you “open” the box and know for sure one way or the other, we can’t ever truly know what has happened. In the same way the cat is neither alive nor dead until you open the box, the participant is neither cocaine positive nor cocaine negative until you test the urine for benzoylecgonine. Those missing urine results, due to missed visits or attrition, which can be over 40%, may leave too much information in the box to allow for efficacy determination in cocaine pharmacotherapy trials.|
|Efforts are underway to improve medication compliance through observed dosing, which is both low cost and low tech. This is in contrast to improved compliance efforts such as MEMS (Medication Monitoring Event System) caps, which record each opening of a medication bottle, or the addition of tracers to medication capsules, or testing plasma levels of medications, all of which add to the cost of trials. Efforts are also underway to improve attendance and retention using low cost incentives for attendance, delivered on a variable interval, variable ratio schedule, which engenders steady high rates of the target behavior (visit attendance). These efforts will likely improve data collection efforts in future cocaine clinical pharmacotherapy trials. Going forward, we should be able to establish the efficacy of potential medications for cocaine dependence that are tested in the future. What is still left unknown is the true efficacy of the medications that have “failed” in the past. Perhaps we need to open some of those old boxes to see what they hold.|