Section Free - Video Lectures

08. Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities

Published on December 1, 2021 Expired on April 1, 2025

Andrew Saxon, M.D.

Professor, Department of Psychiatry and Behavioral Sciences - University of Washington School of Medicine

Key Points

Topiramate shows some benefit for cocaine use disorder alone and in combination with MAS.
Individuals with cocaine use disorder and co-occurring ADHD appear to have a response to methylphenidate and MAS.
Individuals with cocaine use disorder but without ADHD do not seem to respond to stimulant replacement.

Free Downloads for Offline Access

Free Download Audio File (MP3)
Free Download Video (MP4)
Free Download Presentation File (PPTX)

Slides and Transcript

Slide 1 of 18

Now, we're going to move on to talking about some other medications that might have benefit for cocaine use disorder.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 1 of 18

Slide 2 of 18

The first one is topiramate. So topiramate is approved for seizure disorders and also for migraine headaches, and it really has a different mechanism of action than most of the medications we've talked about. Topiramate works on the glutamate system and the GABA system. We believe that it may have some effects for cocaine use disorder by inhibiting the effects of dopamine when people do use stimulants so that they don't get the effect that they're looking for and thereby stop using stimulants.

References:

Johnson, B. A., Ait-Daoud, N., Wang, X., Penberthy, J. K., Javors, M. A., Seneviratne, C., & Liu, L. (2013). Topiramate for the treatment of cocaine addiction. JAMA Psychiatry, 70(12), 1338.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 2 of 18

Free downloads for "Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities"

Success!

Check your inbox, we sent you all the materials there.

Slide 3 of 18

This study was another randomized, double-blind, controlled trial for cocaine use disorder. They got placebo versus topiramate. The target dose was 300 mg per day. Probably, the average dose ended up being 200 mg per day because many people cannot tolerate the 300 mg.

References:

Johnson, B. A., Ait-Daoud, N., Wang, X., Penberthy, J. K., Javors, M. A., Seneviratne, C., & Liu, L. (2013). Topiramate for the treatment of cocaine addiction. JAMA Psychiatry, 70(12), 1338.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 3 of 18

Slide 4 of 18

We're looking at the weekly mean proportion of cocaine non-use days. After about week 5, we see the group start to separate with the topiramate group represented in the filled circles demonstrating more days of cocaine non-use than the placebo group, and the separation even increases over time.

References:

Johnson, B. A., Ait-Daoud, N., Wang, X., Penberthy, J. K., Javors, M. A., Seneviratne, C., & Liu, L. (2013). Topiramate for the treatment of cocaine addiction. JAMA Psychiatry, 70(12), 1338.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 4 of 18

Free downloads for "Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities"

Success!

Check your inbox, we sent you all the materials there.

Slide 5 of 18

Now, topiramate does have some cognitive effects, primarily effects on concentration and word finding. So that needs to be taken into consideration but the data looked really good for topiramate and so that's a medication to consider when treating cocaine use disorder.

References:

Johnson, B. A., Ait-Daoud, N., Wang, X., Penberthy, J. K., Javors, M. A., Seneviratne, C., & Liu, L. (2013). Topiramate for the treatment of cocaine addiction. JAMA Psychiatry, 70(12), 1338.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 5 of 18

Slide 6 of 18

In this study the participants had both cocaine and alcohol use disorders, and they got placebo versus topiramate. Again, the goal was 300 mg per day.

References:

Kampman, K. M., Pettinati, H. M., Lynch, K. G., Spratt, K., Wierzbicki, M. R., & O’Brien, C. P. (2013). A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence. Drug and Alcohol Dependence, 133(1), 94-99.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 6 of 18

Free downloads for "Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities"

Success!

Check your inbox, we sent you all the materials there.

Slide 7 of 18

Topiramate was better in keeping people in treatment and getting cocaine abstinence in the last three weeks. And it worked better in patients who had a high severity of cocaine withdrawal symptoms. So again, not a perfect medication but topiramate should be given some consideration for people with co-occurring cocaine and alcohol use disorders.

References:

Kampman, K. M., Pettinati, H. M., Lynch, K. G., Spratt, K., Wierzbicki, M. R., & O’Brien, C. P. (2013). A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence. Drug and Alcohol Dependence, 133(1), 94-99.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 7 of 18

Slide 8 of 18

Now, we're going to get back into the notion of stimulant replacement. And in this study, they looked at methylphenidate, in this case for cocaine use disorder co-occurring with ADHD. The methylphenidate dose was up to 60 mg per day.

References:

Levin, F. R., Evans, S. M., Brooks, D. J., & Garawi, F. (2007). Treatment of cocaine dependent treatment seekers with adult ADHD: Double-blind comparison of methylphenidate and placebo. Drug and Alcohol Dependence, 87(1), 20-29.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 8 of 18

Free downloads for "Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities"

Success!

Check your inbox, we sent you all the materials there.

Slide 9 of 18

And some very interesting findings here. They divided them into four groups. They were placebo and methylphenidate groups and there were those whose ADHD symptoms did respond to the methylphenidate and those who didn’t. We're looking at likelihood of cocaine-positive urine specimen. You can see there are three groups that really don't change much over time or, if anything, they get worse during the course of the study. But one group is getting better and that was the group that had an improvement in their ADHD symptoms due to the methylphenidate.

References:

Levin, F. R., Evans, S. M., Brooks, D. J., & Garawi, F. (2007). Treatment of cocaine dependent treatment seekers with adult ADHD: Double-blind comparison of methylphenidate and placebo. Drug and Alcohol Dependence, 87(1), 20-29.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 9 of 18

Slide 10 of 18

So, what this does suggest is for patients with cocaine use disorder who have clear ADHD, methylphenidate might be worth trying certainly to manage their ADHD symptoms at least and then if they get a response to that in terms of their ADHD they are likely to also reduce their cocaine use.

References:

Levin, F. R., Evans, S. M., Brooks, D. J., & Garawi, F. (2007). Treatment of cocaine dependent treatment seekers with adult ADHD: Double-blind comparison of methylphenidate and placebo. Drug and Alcohol Dependence, 87(1), 20-29.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 10 of 18

Free downloads for "Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities"

Success!

Check your inbox, we sent you all the materials there.

Slide 11 of 18

We've seen previously that combining two medications with different mechanisms of action might have some efficacy. In this study, they looked at also a strategy for stimulant replacement but combined that with topiramate. In this study for cocaine use disorder they're using mixed amphetamine salts up to 60 mg titrated up over the first two weeks comparing the combination to placebo.

References:

Mariani, J. J., Pavlicova, M., Bisaga, A., Nunes, E. V., Brooks, D. J., & Levin, F. R. (2012). Extended-release mixed amphetamine salts and Topiramate for cocaine dependence: A randomized controlled trial. Biological Psychiatry, 72(11), 950-956.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 11 of 18

Slide 12 of 18

And the way they presented the data was looking at the baseline severity of cocaine use disorder. So they have three groups. They have the low severity who had zero to eight days of cocaine use in the prior month, the middle group had nine to 15 days, and the higher group had 16 or more days in the prior month

References:

Mariani, J. J., Pavlicova, M., Bisaga, A., Nunes, E. V., Brooks, D. J., & Levin, F. R. (2012). Extended-release mixed amphetamine salts and Topiramate for cocaine dependence: A randomized controlled trial. Biological Psychiatry, 72(11), 950-956.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 12 of 18

Free downloads for "Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities"

Success!

Check your inbox, we sent you all the materials there.

Slide 13 of 18

So, what you can see is this combination and we're looking at a proportion of patients with three weeks of cocaine abstinence. Among the lower severity group, there really wasn't much difference between placebo and active medication. But as we get into the higher severity groups, we show a real difference with the mixed amphetamine salts plus topiramate, represented by the light gray bars, really outperformed placebo.

References:

Mariani, J. J., Pavlicova, M., Bisaga, A., Nunes, E. V., Brooks, D. J., & Levin, F. R. (2012). Extended-release mixed amphetamine salts and Topiramate for cocaine dependence: A randomized controlled trial. Biological Psychiatry, 72(11), 950-956.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 13 of 18

Slide 14 of 18

This same group also pursued just the mixed amphetamine salts alone compared to placebo for co-occurring cocaine use disorder in ADHD. And they tried two different doses of mixed amphetamine salts, 60 mg was the lower dose, 80 mg per day was the higher dose compared to placebo. And both of these dosage forms outperformed placebo with the higher dose doing a little better.

References:

Levin, F. R., Mariani, J. J., Specker, S., Mooney, M., Mahony, A., Brooks, D. J., Babb, D., Bai, Y., Eberly, L. E., Nunes, E. V., & Grabowski, J. (2015). Extended-release mixed amphetamine salts vs placebo for comorbid adult attention-deficit/Hyperactivity disorder and cocaine use disorder. JAMA Psychiatry, 72(6), 593.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 14 of 18

Free downloads for "Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities"

Success!

Check your inbox, we sent you all the materials there.

Slide 15 of 18

There does seem to be a dose response effect and we really don't know the ceiling dose if we're going to use mixed amphetamine salts to treat cocaine use disorder, what the highest optimal dose would be. So that's something we need to think about for the future. But again, if you were to treat someone with cocaine use disorder and ADHD it's very worthwhile to consider mixed amphetamine salts as a treatment. It wouldn't even be off-label use because you'd be directly treating their ADHD.

References:

Levin, F. R., Mariani, J. J., Specker, S., Mooney, M., Mahony, A., Brooks, D. J., Babb, D., Bai, Y., Eberly, L. E., Nunes, E. V., & Grabowski, J. (2015). Extended-release mixed amphetamine salts vs placebo for comorbid adult attention-deficit/Hyperactivity disorder and cocaine use disorder. JAMA Psychiatry, 72(6), 593.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 15 of 18

Slide 16 of 18

To summarize, topiramate shows some benefit for cocaine use disorder alone and in combination with mixed amphetamine salts. Individuals with cocaine use disorder and co-occurring ADHD appeared to have some response to stimulant replacement either with methylphenidate or with mixed amphetamine salts.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 16 of 18

Free downloads for "Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities"

Success!

Check your inbox, we sent you all the materials there.

Slide 17 of 18

Whereas, individuals with cocaine use disorder but without ADHD do not seem to have much of a response to stimulant replacement.

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 17 of 18

Slide 18 of 18

Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities Slide 18 of 18

Free downloads for "Topiramate and Methylphenidate for Cocaine Use Disorder and Its Comorbidities"

Success!

Check your inbox, we sent you all the materials there.

Next Section

09. Modafinil, Buprenorphine, and Ketamine Infusion for Cocaine Use Disorder

Learning Objectives:

After completing this activity, the learner will be able to:

Review the pathophysiology and clinical course of stimulant use disorder.
Discuss the appropriate use of psychotropic medications for the management of stimulant use disorder.
Cite specific strategies in the management of specific stimulant use disorders, such as methamphetamine and cocaine use disorders.

Original Release Date: 12/01/2021

Review and Re-release Date: 03/01/2024

Expiration Date: 04/01/2025

Expert: Andrew Saxon, M.D.

Medical Editor: Melissa Mariano, M.D

Relevant Financial Disclosures:

The following planners, faculty, and reviewers have the following relevant financial relationships with commercial interests to disclose:

Dr. Saxon has disclosed the following relationships:

Indivior, Inc.: Advisory board
UpToDate, Inc.: Section Editor
Indivior, Inc.: Advisory board
UpToDate, Inc.: Editor

All of the relevant financial relationships listed for these individuals have been mitigated.

Contact Information: For questions regarding the content or access to this activity, contact us at support@psychopharmacologyinstitute.com

Instructions for Participation and Credit:

Participants must complete the activity online during the valid credit period that is noted above.

Follow these steps to earn CME credit:

View the required educational content provided on this course page.
Complete the Post Activity Evaluation for providing the necessary feedback for continuing accreditation purposes and for the development of future activities. NOTE: Completing the Post Activity Evaluation after the quiz is required to receive the earned credit.
Download your certificate.

Accreditation Statement

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education through the joint providership of Medical Academy LLC and the Psychopharmacology Institute. Medical Academy is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation Statement

Medical Academy designates this enduring activity for a maximum of 1 AMA PRA Category 1 credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.