How should ADHD be treated in persons with stimulant (including cocaine) use disorder?

Question from a Member:

I have a question regarding the use of a stimulant for ADHD with a past cocaine addiction. The patient has depression along with ADHD. Difficulty keeping employment and not currently working but interviewing intensively. Cocaine has not been used for the past 11 yrs, with 10 yrs use in the past.

Tried Adderall IR [mixed amphetamine salts] in 2014 and 2019 by another provider and was helpful for ADHD but was too activating and increased HR. In 2019, he felt a strong urge to use cocaine after a couple of doses.

I recently trialed Straterra [atomoxetine] but he reported painful ejaculation, stopped and retrialed Straterra [atomoxetine] again, and had the same unwanted effect. Recently increased his Wellbutrin [bupropion] to 450 mg daily to see if this would help with ADHD symptoms and it was tolerated but no real help with attention/focus.

I wonder if an extended-release stimulant may help without the activating and worrisome effect of urges for cocaine. Any suggestions would be appreciated.

DISCLAIMER: We cannot give medical advice about a particular patient. The information on this website and in our daily emails are for general educational purposes only. We provide psychopharmacology knowledge and tips, but our clinician readers are the ones who have to decide how to apply the knowledge and tips to their patients.

Note: Cocaine and other stimulants are subsumed under stimulant use disorder, so, on this page, we’ll consider the treatment of ADHD with comorbid use of either cocaine or other stimulants like amphetamines, methylphenidate, etc.

Note: On this page, we are only talking about the treatment of ADHD in persons with a stimulant use disorder and not about the treatment of stimulant use disorder per se.

Why this is so important

There is an increased prevalence of ADHD in persons with a substance use disorder and the presence of ADHD is associated with worse outcomes of treatment of the substance use disorder (Carpentier and Levin, 2017). So, it is important that ADHD be treated in these patients both to reduce symptoms of ADHD and to improve the outcomes of treatment for the substance use disorder (Carpentier and Levin, 2017). Treating ADHD can help with the substance use disorder by improving cognitive control, reducing impulsivity, etc.(Carpentier and Levin, 2017). In the case of stimulant use disorder, ADHD medications can also act as “substitution therapy”

Fortunately, there are at least a few published randomized, placebo-controlled clinical trials that have addressed the question of treating ADHD in a person with stimulant use disorder.

Methylphenidate?

A small randomized, placebo-controlled clinical trial in patients with ADHD along with cocaine dependence found methylphenidate to reduce ADHD symptoms (on some measures only) but not cocaine use (Schubinger et al., 2002). But, we should note that in this study the mean dose of methylphenidate was only 26 mg/day.

The next randomized, placebo-controlled clinical trial of methylphenidate in patients with ADHD and comorbid cocaine dependence found that methylphenidate treatment was associated with a reduction in cocaine use but, surprisingly, not with improvement in ADHD symptoms (Levin et al., 2007). Reduction in cocaine use was more likely in ADHD responders than in non-responders.

In a small randomized, placebo-controlled clinical trial in prisoners who had been dependent on amphetamines and were being released from prison, treatment with high doses of methylphenidate, up to 180 mg/day, was been found to both reduce ADHD symptoms AND reduce the use of amphetamines and other substances (Konstenius et al., 2014).

Amphetamines?

A randomized, placebo-controlled clinical trial found extended-release mixed amphetamine salts (brand name Adderall XR) 60 mg/day and 80 mg/day in persons with ADHD and cocaine dependence to reduce both ADHD symptoms and cocaine use (Levin et al., 2015).

Further analysis of this study (Levin et al., 2015) led to the conclusion that “When treating co-occurring ADHD and cocaine dependence with stimulant medication, abstinence is most likely preceded by improvement in ADHD, which tends to occur early with medication treatment (Levin et al., 2018).

Worsening of substance use?

Our Member’s case above raises an important question—could giving stimulant medication to a person with ADHD who has comorbid cocaine or other stimulant dependence lead to worsening (“kindling”) of the substance use disorder?

The clinical trials discussed above did not find worsening of the stimulant use disorder in patients with ADHD treated with stimulant medication. Other studies of stimulants for the treatment of stimulant use disorder also did not find such worsening; it can occur in isolated cases but is believed to be uncommon (Schubiner et al., 2002). So, in individual patients, we should be cautious and watch for this possibility.

In the case described above, the patient felt a strong urge to use cocaine after a couple of doses of immediate-release mixed amphetamine salts prescribed by someone other than our Member. But, as our Member implies, using immediate-release preparations should be avoided in patients with a history of substance use or who are, for any other reason, at risk of misusing the medication. Also, as we will note below, clinical experience suggests that in a person who has been abstinent for a while, titrating the medication up more slowly than usual may reduce the risk of triggering cravings.

What should we do?

Ravi Srivastava, MD, one of the peer-reviewers for this article, summarizes the situation as follows:

“Treating ADHD adequately may decrease the chances of street stimulant use in these patients. The follow-up visits should focus on both addiction and ADHD-related issues.

It is important to keep in mind what the target symptoms are for ADHD and why is it necessary to treat them in this particular case. Is the patient performing poorly due to ADHD or due to addiction-related behaviors? Just because someone has ADHD does not mean that they need to be treated with medications only.

Having said that, there is evidence that harm reduction of substitution therapy with stimulants can be helpful in keeping these patients out of trouble. Similar to prescribing buprenorphine or methadone in opiate use disorder.”

Next, we’ll discuss a series of specific issues about how to treat ADHD in persons with a history of stimulant use disorder.

Is medication for ADHD essential?

I have a lot of clinical experience treating adults with ADHD and I think that their main problem is not paying attention but being impulsive and disorganized, that is, “executive dysfunction”. So, adults with ADHD benefit not only from medication but equally from executive function skills training, which has different names—ADHD coaching, meta-cognitive therapy, or cognitive-behavior therapy.

Which medications?

1. An international consensus statement on the treatment of substance use disorders with comorbid ADHD (Crunelle et al., 2018) notes:

Long-acting methylphenidate, extended-release amphetamines, and atomoxetine are effective in the treatment of comorbid ADHD and SUD, and up-titration to higher dosages may be considered in some patients.

2. The same guideline also states (Crunelle et al., 2018):

The abuse potential is limited with long-acting agents.

So, definitely, only long-acting preparations should be used.

3. I think there are good reasons to believe that lisdexamfetamine, in particular, has a lower risk of abuse. For more on this, please see the following article on this website: Does lisdexamfetamine really have lower abuse potential?

Higher doses?

We should at least consider that the patient with comorbid ADHD and stimulant use disorder may benefit from higher doses. Anecdotally, it has been suggested that persons with ADHD and comorbid substance use disorder need higher doses of the stimulant, for example, methylphenidate >1 mg/kg/day (Carpentier and Levin, 2017). Also, we should note that in the clinical trials described above methylphenidate was used up to 180 mg/day and mixed amphetamine salts was used at 60 to 80 mg/day.

How can the risks be reduced?

1. If the person has been abstinent for a while, titrating the dose up more slowly than usual may reduce the risk of triggering cravings.

2. When prescribing stimulant medications to these patients, we should, of course, take measures to reduce the risk of abuse of the medication. In another article on this website, we provided tips for reducing this risk. Please do read that article and follow the eight recommendations made there, which can be remembered using the mnemonic L.A.M.E.D.U.C.K.

3. In patients with a history of stimulant use disorder, it is probably wise to get an ECG before prescribing a stimulant (Özgen et al., 2020).

4. Careful monitoring of the patient is, of course, essential. This includes frequent urine drug screens at random intervals.

Simple and Practical Medical Education thanks (alphabetically) Jonathan Beatty, MD, Marina Goldman, MD, and Ravi Srivastava, MD, for peer-reviewing and approving this article in October 2020. Drs. Beatty, Goldman, and Srivastava are board-certified addiction psychiatrists with extensive clinical experience in treating patients with substance use disorders.

Tips for managing abuse potential of medications for ADHD

Does lisdexamfetamine really have lower abuse potential?

References

Practice guidelines

Crunelle CL, van den Brink W, Moggi F, Konstenius M, Franck J, Levin FR, van de Glind G, Demetrovics Z, Coetzee C, Luderer M, Schellekens A; ICASA consensus group, Matthys F. International Consensus Statement on Screening, Diagnosis and Treatment of Substance Use Disorder Patients with Comorbid Attention Deficit/Hyperactivity Disorder. Eur Addict Res. 2018;24(1):43-51. doi: 10.1159/000487767. Epub 2018 Mar 6. PMID: 29510390; PMCID: PMC5986068.

Özgen H, Spijkerman R, Noack M, Holtmann M, Schellekens ASA, van de Glind G, Banaschewski T, Barta C, Begeman A, Casas M, Crunelle CL, Daigre Blanco C, Dalsgaard S, Demetrovics Z, den Boer J, Dom G, Eapen V, Faraone SV, Franck J, González RA, Grau-López L, Groenman AP, Hemphälä M, Icick R, Johnson B, Kaess M, Kapitány-Fövény M, Kasinathan JG, Kaye SS, Kiefer F, Konstenius M, Levin FR, Luderer M, Martinotti G, Matthys FIA, Meszaros G, Moggi F, Munasur-Naidoo AP, Post M, Rabinovitz S, Ramos-Quiroga JA, Sala R, Shafi A, Slobodin O, Staal WG, Thomasius R, Truter I, van Kernebeek MW, Velez-Pastrana MC, Vollstädt-Klein S, Vorspan F, Young JT, Yule A, van den Brink W, Hendriks V. International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder. Eur Addict Res. 2020;26(4-5):223-232. doi: 10.1159/000508385. Epub 2020 Jul 7. PMID: 32634814.

Randomized clinical trials

Kollins SH, Youcha S, Lasser R, Thase ME. Lisdexamfetamine dimesylate for the treatment of attention deficit hyperactivity disorder in adults with a history of depression or history of substance use disorder. Innov Clin Neurosci. 2011 Feb;8(2):28-32. PMID: 21468295; PMCID: PMC3071091. Post-hoc analysis, only 17 participants with a history of substance use.

Konstenius M, Jayaram-Lindström N, Guterstam J, Beck O, Philips B, Franck J. Methylphenidate for attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence: a 24-week randomized placebo-controlled trial. Addiction. 2014 Mar;109(3):440-9. doi: 10.1111/add.12369. Epub 2013 Dec 1. PMID: 24118269; PMCID: PMC4226329.

Levin FR, Choi CJ, Pavlicova M, Mariani JJ, Mahony A, Brooks DJ, Nunes EV, Grabowski J. How treatment improvement in ADHD and cocaine dependence are related to one another: A secondary analysis. Drug Alcohol Depend. 2018 Jul 1;188:135-140. doi: 10.1016/j.drugalcdep.2018.03.043. Epub 2018 May 1. PMID: 29775957; PMCID: PMC6158788.

Levin FR, Evans SM, Brooks DJ, Garawi F. Treatment of cocaine dependent treatment seekers with adult ADHD: double-blind comparison of methylphenidate and placebo. Drug Alcohol Depend. 2007 Feb 23;87(1):20-9. doi: 10.1016/j.drugalcdep.2006.07.004. Epub 2006 Aug 22. PMID: 16930863.

Levin FR, Mariani JJ, Specker S, Mooney M, Mahony A, Brooks DJ, Babb D, Bai Y, Eberly LE, Nunes EV, Grabowski J. Extended-Release Mixed Amphetamine Salts vs Placebo for Comorbid Adult Attention-Deficit/Hyperactivity Disorder and Cocaine Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2015 Jun;72(6):593-602. doi: 10.1001/jamapsychiatry.2015.41. PMID: 25887096; PMCID: PMC4456227.

Mooney ME, Herin DV, Specker S, Babb D, Levin FR, Grabowski J. Pilot study of the effects of lisdexamfetamine on cocaine use: A randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend. 2015 Aug 1;153:94-103. doi: 10.1016/j.drugalcdep.2015.05.042. Epub 2015 Jun 19. PMID: 26116930; PMCID: PMC4509923. No comorbid ADHD. Small sample size (n=43).

Schubiner H, Saules KK, Arfken CL, Johanson CE, Schuster CR, Lockhart N, Edwards A, Donlin J, Pihlgren E. Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence. Exp Clin Psychopharmacol. 2002 Aug;10(3):286-94. doi: 10.1037//1064-1297.10.3.286. PMID: 12233989.

Other references

Carpentier PJ, Levin FR. Pharmacological Treatment of ADHD in Addicted Patients: What Does the Literature Tell Us? Harv Rev Psychiatry. 2017 Mar/Apr;25(2):50-64. doi: 10.1097/HRP.0000000000000122. PMID: 28272130; PMCID: PMC5518741.

Klassen LJ, Bilkey TS, Katzman MA, Chokka P. Comorbid attention deficit/hyperactivity disorder and substance use disorder: treatment considerations. Curr Drug Abuse Rev. 2012 Sep;5(3):190-8. doi: 10.2174/1874473711205030190. PMID: 22571450.

Manni C, Cipollone G, Pallucchini A, Maremmani AGI, Perugi G, Maremmani I. Remarkable Reduction of Cocaine Use in Dual Disorder (Adult Attention Deficit Hyperactive Disorder/Cocaine Use Disorder) Patients Treated with Medications for ADHD. Int J Environ Res Public Health. 2019 Oct 15;16(20):3911. doi: 10.3390/ijerph16203911. PMID: 31618876; PMCID: PMC6843793. Very small sample size, retrospective, no control group.

Mariani JJ, Levin FR. Psychostimulant treatment of cocaine dependence. Psychiatr Clin North Am. 2012 Jun;35(2):425-39. doi: 10.1016/j.psc.2012.03.012. Epub 2012 Apr 26. PMID: 22640764; PMCID: PMC3417072.

Rush CR, Baker RW. Behavioral pharmacological similarities between methylphenidate and cocaine in cocaine abusers. Exp Clin Psychopharmacol. 2001 Feb;9(1):59-73. doi: 10.1037/1064-1297.9.1.59. PMID: 11519636.

Simon N, Rolland B, Karila L. Methylphenidate in Adults with Attention Deficit Hyperactivity Disorder and Substance Use Disorders. Curr Pharm Des. 2015;21(23):3359-66. doi: 10.2174/1381612821666150619093254. PMID: 26088112.

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