02. ADHD in Substance Use Disorders: Choosing a Medication, Handling Dose Requests, and Planning an Exit

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Choosing the Right Medication

Flavio Guzman, M.D.: When a patient has a substance use disorder, how do you actually choose the ADHD medication?

Cleo Crunelle, M.D., Ph.D.: A history of substance use does not automatically mean that stimulants are contraindicated.

I am part of a very large consortium called ICASA, the International Collaboration on ADHD and Substance Abuse. We work with researchers and psychiatrists around the world who treat ADHD and substance use, and we share information.

We did a very large naturalistic study, and we see this difference there as well. For some of our American colleagues, stimulants are not first-line in patients with ADHD and substance use disorder, while in Europe we do give them first-line.¹

When we use stimulants, we always prefer a long-acting formulation rather than an immediate-release preparation. Compared with short-acting formulations, the slower onset and more stable exposure reduce the potential for misuse.²,³

So we do prescribe stimulants, but we always make sure they are long-acting formulations.

I would not use a simple stimulant versus non-stimulant rule. Instead, I would look at:

• The patient’s current substance use
• Their previous response to ADHD medication
• Their risk of misuse
• The overall clinical picture

Agents with a positive randomized trial in adults with ADHD plus a substance use disorder

The three trials were run in different substance populations and have never been compared with one another, so the rows are not a ranking.

When to Use Non-Stimulants

Flavio Guzman, M.D.: What about non-stimulants? When would you reach for one first?

Cleo Crunelle, M.D., Ph.D.: I would reach for a non-stimulant in a few situations:

• Concerns about abuse or diversion. For example, when I am not convinced that the treatment request is really only about ADHD.
• Significant side effects from stimulants. Most of these patients have tried stimulant medication once or twice in their lifetime and know what works for them and what doesn’t.
• A significant risk of paranoia or psychotic symptoms. This applies particularly when a patient is still using substantial amounts of non-prescribed stimulants.

In that last situation, adding a prescribed stimulant may not be the safest starting point. I would generally start with a non-stimulant and reassess as the substance use stabilizes.

Side Effects in Patients Who Use Substances

Flavio Guzman, M.D.: Some say side effects can look different in someone who uses substances. How do you handle sleep and appetite problems?

Cleo Crunelle, M.D., Ph.D.: It is true that sleep and appetite can be affected by intoxication, by withdrawal, or by the lifestyle associated with substance use. For sleep problems, I look at the formulation and the time of day the patient takes the medication.

What I see a lot is that the lifestyle associated with substance use shifts the patient’s day. They wake up much later, and sometimes they don’t have a daily routine.

When they wake up at ten or eleven in the morning and take their medication then, a long-acting formulation can cause sleep problems at night. If you start by looking at the formulation you are prescribing and the timing of the dose, I think you can already resolve many issues.

What we usually see in patients with ADHD and substance use disorder is that their routine improves on stimulants. That includes their daytime routine, their sleep routine, and their sleep itself, which actually improves rather than worsens.

That is part of the response to stimulants. I think it is a somewhat indirect effect of managing things better during the day, having fewer unresolved issues before nighttime, and maintaining a better daily routine.

So sleep problems are not a central issue in the patients I treat.

Appetite suppression is another side effect. We usually manage it by monitoring weight and encouraging adequate food intake, particularly when the patient already has an irregular eating pattern.

So it is all context-based. Of course, if the side effects are too prominent, we change formulations.

Rethinking Medication Choice

Flavio Guzman, M.D.: What would make you step back and rethink the medication?

Cleo Crunelle, M.D., Ph.D.: The things that would make me rethink the medication include:

• Significant cardiovascular effects
• Severe, persistent insomnia
• Substantial weight loss
• A clear worsening of anxiety or agitation
• An increase in substance-related behaviors

And of course, if there are signs of misuse, diversion, or loss of control over medication intake, I would reassess the treatment strategy.

Dosing Beyond Standard Ranges

Flavio Guzman, M.D.: When standard doses aren’t enough for these patients, how do you titrate?

Cleo Crunelle, M.D., Ph.D.: I do see in clinical practice that standard doses can sometimes be insufficient in this population. But that does not mean we should assume a higher dose is always needed.

Response is very individual. There are also studies showing that doses higher than the usual ranges can be effective in some patients with ADHD and substance use.⁴,⁵

I titrate according to clinical response and to what the patient tolerates well. I do not automatically stop at the standard dose if the patient has only a partial response.²

At the same time, the dose does not need to keep increasing once symptoms are adequately controlled. The goal is to find the lowest effective dose for that individual patient.

So I titrate gradually, even above the limits, if we can put it that way. I also reassess frequently.

When someone suddenly loses response or needs further dose escalation, I always check for factors that might explain it:

• Adherence
• Ongoing substance use
• Other contributing factors

Overall, in this population, I would say: don’t undertreat the ADHD because of the patient’s substance use history, or because you are already at the limit of the usual dosing range.

Handling Requests for a Higher Dose

Flavio Guzman, M.D.: Sometimes a patient asks for a higher dose because they expect more benefit. How do you tell whether that’s undertreatment, tolerance, or misuse?

Cleo Crunelle, M.D., Ph.D.: For me, a request for a higher dose is not automatically a sign of misuse. I first ask about the patient’s experience.

I think it is very important to ask whether the medication is actually improving functioning, not just whether symptom scores have changed. From there, a few patterns can help:

• Clear ongoing impairment, with some benefit that has plateaued. That may simply be undertreatment, and I would consider a dose adjustment, even above the standard ranges if needed.
• A good initial response that is now fading despite consistent use. I would think about tolerance, but I would also reassess the current context before simply increasing the dose. That means looking again at the diagnosis, the formulation, adherence, and ongoing substance use.

What I often see in clinical practice is that when the effect goes down, something in the context has changed. It does not always require a dose adjustment as such.

I also see small dose adjustments in women around their menstrual cycle. Some need a slightly higher dose for the week before their menses.⁶

For example, a woman who is stable on methylphenidate (Concerta) 36 mg might need 54 mg for one week each month to get the same effect. There is a very important hormonal component that we often forget, but it is very present.

When you have a patient with a substance use disorder in front of you, you might falsely assume that they simply want more medication. That is not always the case.

I think misuse is more concerning when the request is disconnected from functional benefit. Examples include:

• Using the medication to feel euphoric
• Using it to stay awake
• Using it to counteract other substances
• Repeated early refill requests
• Inconsistent medication use

In those situations, it’s another story. I think the response depends on what we find:

• Undertreatment may call for titration.
• Suspected tolerance calls for reassessment.
• Suspected misuse may mean switching to a non-stimulant, increasing monitoring, or both.
• Excessive substance use at a particular point in time may also be addressed through residential treatment.

Sorting out a request for a higher dose

Combining ADHD and Addiction Medications

Flavio Guzman, M.D.: Many of these patients are also on medication for their addiction. Can you safely combine that with ADHD medication?

Cleo Crunelle, M.D., Ph.D.: There is no general rule that ADHD medication and addiction medication cannot be combined. In practice, I commonly treat both conditions in parallel, so I often combine ADHD medication with medication for substance use disorder.

That does not depend on whether the ADHD medication is a stimulant or a non-stimulant.

When you combine treatment for ADHD and for substance use disorder, it is important to check for drug-drug interactions. That is a very specific safety issue.

For example, I would be very cautious with bupropion in patients with an increased seizure risk. This is particularly true when they use other substances or medications that can further lower the seizure threshold.

So that combination is something we use less. I am also not sure whether bupropion is prescribed much in the States.

Here in Belgium, we do use bupropion off-label for the treatment of ADHD. We look at the individual patient, and when a patient has both depressive symptoms and ADHD symptoms, we sometimes use bupropion to address the psychiatric comorbidity together with the ADHD symptoms.

So rather than thinking in terms of combinations that should never be used, I would say: treat both disorders when they are indicated. What actually limits combined prescribing is the risk of drug interactions, seizures, and cardiovascular effects.

Exit Plans, Stopping Treatment, and Relapse

Flavio Guzman, M.D.: Sometimes we hear that every medication needs an exit plan. So when would you actually stop a stimulant in these patients?

Cleo Crunelle, M.D., Ph.D.: I think the idea of an exit plan only really makes sense if the underlying disorder itself has an exit. ADHD doesn’t.

ADHD is a disorder with onset in childhood. When it persists into adulthood, which it often does, it doesn’t just disappear after a few months of treatment, or even after a few years.

Chronic conditions need chronic treatment. That is really the starting point for how I think about it.

So when do I actually stop treatment? For me, it comes down to only two things:

• Signs of misuse
• Drug-drug interactions that make continuing the medication truly unsafe

That’s it. What I don’t do is base the decision on the comorbid condition.

I look at functioning and I look at effect. Is this medication still doing its job for the patient’s attention, impulse control, and ability to function?

I think that is the question, not whether the addiction treatment is going well or badly this month.

I want to come back to relapse, because I think this is where people get it most wrong. A relapse is not a reason to discontinue ADHD treatment.

If anything, it’s the opposite. These patients need treatment most precisely when they are most vulnerable.

That is when they need tools to take their lives back into their own hands. Pulling treatment away at exactly the moment someone is struggling the most really doesn’t protect them.

I think it takes away one of the things that could actually help them recover.

Take-Home Messages

Flavio Guzman, M.D.: For our last question, what do you think our listeners should change in their practice tomorrow?

Cleo Crunelle, M.D., Ph.D.: I would have two take-home messages:

1. Screen for ADHD as a standard part of intake. It should not be an afterthought.
2. Don’t wait for abstinence to start the conversation about treating ADHD.²

I must say that a lot of countries have already implemented this.

References

1. Brynte, C., Schellekens, A., Barta, C., et al. Treatments and Treatment Predictors in Patients With Substance Use Disorders and Comorbid Attention-Deficit/Hyperactivity Disorder: First Results From the International Naturalistic Cohort Study of ADHD and SUD (INCAS). The Journal of Clinical Psychiatry. 2024;86(1):24m15494.
2. Crunelle, C.L., van den Brink, W., Moggi, F., et al. International Consensus Statement on Screening, Diagnosis and Treatment of Substance Use Disorder Patients with Comorbid Attention Deficit/Hyperactivity Disorder. European Addiction Research. 2018;24(1):43-51.
3. Cassidy, T.A., McNaughton, E.C., Varughese, S., et al. Nonmedical use of prescription ADHD stimulant medications among adults in a substance abuse treatment population: early findings from the NAVIPPRO surveillance system. Journal of Attention Disorders. 2015;19(4):275-283.
4. Konstenius, M., Jayaram-Lindström, N., Guterstam, J., et al. Methylphenidate for attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence: a 24-week randomized placebo-controlled trial. Addiction. 2014;109(3):440-449.
5. Levin, F.R., Mariani, J.J., Specker, S., et al. 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;72(6):593-602.
6. de Jong, M., Wynchank, D.S.M.R., van Andel, E., et al. Female-specific pharmacotherapy in ADHD: premenstrual adjustment of psychostimulant dosage. Frontiers in Psychiatry. 2023;14:1306194.