When Frances R. Levin, MD, began her clinical psychiatry career in the mid-1990s, she spent a lot of time educating colleagues about the validity of an ADHD diagnosis in adults.
Dr. Frances R. Levin
“That’s no longer an issue,” Dr. Levin, the Kennedy-Leavy Professor of Psychiatry at Columbia University, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “But at the time, we often thought, ‘ADHD is something that’s specific to people who are stimulant users.’ In fact, what we found over the years was that these rates are elevated in a range of substance use populations.”
According to National Comorbidity Survey, a nontreatment sample of more than 3,000 adults, individuals who have SUD have two to three times the risk of having ADHD, while individuals who have ADHD have about three times the rate of having an SUD, compared with those who don’t (Am J Psychiatry. 2006;163[4]:716-23). “When you move to treatment samples, the rates also remain quite high,” said Dr. Levin, who is also chief of the division of substance use disorders at the medical center.
“In the general population, the rates of ADHD are 2%-4%. When we look at people who are coming in specifically for treatment of their SUD, the rates are substantially higher, ranging from 10% to 24%.”
According to a 2014 review of medical literature, potential reasons for the association between ADHD and SUD vary and include underlying biologic deficits, such as parental SUDs and genetics; conduct disorder symptoms, such as defiance, rule breaking, and delinquency; poor performance in school, such as low grades, grade retention, or drop-out; and social difficulties, such as rejection from conventional groups or few quality friendships (Annu Rev Clin Psychol. 2014;10:607-39). Other potential pathways include neurocognitive deficits, stress-negative affect models, impulsive anger, and other underlying traits.
One key reason to treat ADHD in patients with SUDs is that they tend to develop the SUD earlier when the ADHD is present, Dr. Levin said. They’re also less likely to be retained in treatment and have a reduced likelihood of going into remission if dependence develops. “Even when they do achieve remission, it seems to take longer for people to reach remission,” she said. “They have more treatment exposure yet do less well in treatment. This can make it more challenging to treat this population.”
One common assumption from clinicians regarding patients with ADHD and a concomitant SUD is that standard treatments for ADHD do not work in active substance users. Another is that, even if treatments work for ADHD, they do not affect the substance use disorder. “Understandably, there is also concern that active substance abusers will misuse and divert their medications,” she said. “Finally, there are often additional psychiatric comorbidities that may make it harder to effectively treat individuals with ADHD and SUD.”
Since 2002, 15 double-blind outpatient studies using stimulants/atomoxetine to treat substance abusers with ADHD have appeared in the medical literature, Dr. Levin said. Only three have included adolescents. “That’s surprising, because up to 40% of kids who come in for treatment, often for cannabis use disorder, will have ADHD, yet there is very little guidance from empirical studies as to how to best treat them,” she said. “There have been several studies looking at atomoxetine to treat substance abusers with ADHD, but results have been mixed. In the cannabis use populations, atomoxetine has not been shown to be effective in treating the substance use disorder, and results are mixed regarding superiority in reducing ADHD symptoms. There is one study showing that ADHD is more likely to be improved in adults with alcohol use disorders with mixed results regarding the alcohol use.”
Overall, most of the outpatient and inpatient studies conducted in this population have demonstrated some signal in terms of reducing ADHD, she said, while a minority of the outpatient studies suggest some benefit in terms of substance use. “What’s interesting is that when you see a response in terms of the ADHD, you often see an improvement in the substance use as well,” Dr. Levin said. “This potentially suggests that patients may be self-medicating their ADHD symptoms or that if the ADHD responds to treatment, then the patient may benefit from the psychosocial interventions that targets the SUD.”
A separate meta-analysis involving more than 1,000 patients found mixed results from pharmacologic interventions and concluded that, while they modestly improved ADHD symptoms, no beneficial effect was seen on drug abstinence or on treatment discontinuation (J Psychopharmacol. 2015 Jan;29[1]:15-23). “I would argue that you don’t need to be as nihilistic about this as the meta-analysis might suggest, because the devil’s in the details,” said Dr. Levin, whose own research was included in the work.
“First of all, many of the studies had high drop-out rates. The outcome measures were variable, and some of the studies used formulations with poor bioavailability. Also, trials that evaluated atomoxetine or stimulants were combined, which may be problematic given the different mechanisms of action. Further, the meta-analysis did not include two recent placebo-controlled trials in adults with stimulant-use disorders that both found that higher dosing of a long-acting stimulant resulted in greater improvements in ADHD symptoms and stimulant use” (Addict. 2014;109[3]:440-9 and JAMA Psychiatry. 2015;72[6]:593-602).
Dr. Levin went on to note that there are few empirical data to guide treatment for those who have multiple psychiatric disorders, let alone treatment for ADHD and SUDs without additional psychiatric disorders. The challenge is what to treat first and/or how to treat the concomitant conditions safely.
“Generally, if possible, treat what is most clinically impairing first,” she said. “Overall, both stimulants and atomoxetine may work for ADHD even in the presence of additional depression, anxiety disorders, and substance use disorders.”
She cautioned against treating a patient with ADHD medication if there is a preexisting psychosis or bipolar illness. “If you start a stimulant or atomoxetine and psychosis or mania occurs, you clearly want to stop the medication and reassess,” she said. Researchers found that the risk of precipitating mania with a stimulant is uncommon if you alleviate symptoms first with a mood stabilizer. “This is a situation where you probably want to treat the bipolar illness first, but it does not preclude the treatment of ADHD once the mood stabilization has occurred,” she said.
In patients with ADHD and anxiety, she often treats the ADHD first, “because oftentimes the anxiety is driven by the procrastination and the inability to get things done,” she explained. “It’s important to determine whether the anxiety is an independent disorder rather than symptoms of ADHD. Inner restlessness can be described as anxiety.”
When there are concerns that preclude the use of a controlled medication, there are medications, in addition to atomoxetine, that might be considered. While bupropion is not Food and Drug Administration approved for ADHD, it might be useful in comorbid mood disorders for nicotine dependence. Other off-label medications that may help include guanfacine, modafinil, and tricyclic antidepressants.
“To date, robust dosing of long-acting amphetamine or methylphenidate formulations have been shown to be effective for patients with stimulant-use disorder, but as mentioned earlier, the data only come from two studies,” she said.
In order to determine whether stimulant treatment is yielding a benefit in a patient with co-occurring ADHD and SUD, she recommends carrying out a structured assessment of ADHD symptoms. Monitoring for functional improvement is also key.
“If there is no improvement in social, occupational, or academic settings and the patient is still actively using drugs, then there is no reason to keep prescribing,” she said. Close monitoring for cardiovascular or other psychiatric symptoms are key as well. Further, for those individuals with both ADHD and a substance-use disorder, it is critical that both are targeted for treatment.
Dr. Levin reported that she has received research, training, or salary support from the National Institute on Drug Abuse, New York state, and the Substance Abuse and Mental Health Services Administration. She has also received or currently receives industry support from Indivior and U.S. World Meds and for medication and from Major League Baseball. In addition, Dr. Levin has been an unpaid scientific advisory board member for Alkermes, Indivior, and Novartis.