Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

Based on the following article: Williams et al. American Journal on Addictions 2004;13:381-9

Reviewed by:

Samuel Y. Chang, MD, FRCPC

Medical Director Addiction Centre Adolescent Program Foothills Medical Centre Calgary, Alberta

Clinical Associate Professor Department of Psychiatry University of Calgary Calgary, Alberta

Attention-deficit hyperactivity disorder (ADHD) is a heritable neurobehavioural disorder, most prominent in childhood but often continuing into the adult years. Its principal clinical features—attention dysfunction, impulsivity and hyperactivity—vary in degree but generally are observed to interfere with daily functioning. The disorder appears to spring from abnormalities in neurotransmission, chiefly of dopamine and norepinephrine. The brain regions affected are believed to be the brain stem, striatum, cerebellum and frontocortical areas (Greydanus et al. Dis Mon 2007;53:70-131, Wilens T. J Clin Psychiatry 2006;67(suppl 8):32-7).

The prevalence of ADHD in Canada is 4.8% to 10%, with a higher frequency observed in boys than girls (Szatmari et al. J Child Psychol Psychiatry 1989;30(2):205-17, Waddell et al. Can J Psychiatry 2005;50:226-33, Poulin C. Addiction 2007;102(5):740-51). Absolute numbers are likely rising with the growing population.

Treatment Strategies

A wide range of therapies may be employed for ADHD. Among nonpharmaceutical options are psychotherapy or cognitive-behaviour therapy, support groups and specialized educational and social skills strategies. The list of pharmacotherapies includes the psychostimulants methylphenidate, dextroamphetamine and mixed amphetamine (dextroamphetamine/levoamphetamine) salts. The nonstimulant atomoxetine is also indicated for ADHD treatment. Other agents may be employed, including tricyclic antidepressants, alpha-agonists, modafinil and nicotinic acids (Wilens 2006).

The role of pharmacologic treatment was solidified by the Collaborative Multi-Site Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder Combined Type, or MTA (Arch Gen Psychiatry 1999;56(12):1073-86). This landmark 14-month study compared 579 children aged 7 to 10 years in four treatment arms. Its key finding was that patients receiving intensive medical therapy (medication given three times daily at doses titrated to symptom normalization or until side effects occurred, with rigorous follow-ups) achieved the best outcomes, as measured by scales for hyperactivity, impulsivity, inattention and aggression. Routine community care (typically, a prescription for methylphenidate to be taken twice daily, with occasional follow-up by a nonspecialist physician) produced the worst outcomes. The addition of psychosocial support including intensive social skills training improved the success of the intensive medication group by approximately 10%. Psychosocial treatment alone was no more successful at reducing hyperactivity and impulsivity than routine community care. Moreover, medical therapy was less expensive than psychosocial intervention.

Despite these instructive data, only a small proportion of children with ADHD are treated with medication. According to a recent survey of 12,990 children in Atlantic Canada, 9.2% of those with a positive ADHD screening test reported the use of methylphenidate or amphetamine (Poulin 2007). In the US, the prevalence of drug therapy among patients with a diagnosis of ADHD is 12.5% (Janssen et al. J Am Acad Child Adolesc Psychiatry 1999;38:797-804). Continued compliance with ADHD therapy is problematic, as the one-year drop-off rate may be as high as 80% to 90%.

Potential Risks of Misuse or Abuse

There has been periodic expression of alarm, both in the lay media and in healthcare circles, about overprescribing of medications for ADHD. Also cited is the potential for stimulant misuse and abuse, either by patients or through diversion of the agents to other individuals. Examples of misuse include overconsumption of the medication by the patient, casual experimentation, or the use of stimulants to suppress appetite or fatigue or to heighten the capacity to work or study. Abuse is characterized by the aim of intoxication. It may involve high-dose oral consumption but more often involves grinding of tablets into a powder that can be taken intranasally or dissolved and injected. A third concern is the possibility that young individuals who use stimulants, prescribed or not, may be prone to later illicit substance abuse (McCabe et al. J Am Coll Health 2006;54(5):269-78‚ Wilens T. Pediatrics 2003;111(1):179-85).

Several recent articles have reported that nonmedical use of stimulants among students in high schools and post-secondary institutions has increased; some have noted this rise has occurred concurrently with increased prescribing of stimulants for ADHD (Poulin C. CMAJ 2001;165(8):1039-44, McCabe et al. J Psychoactive Drugs 2006;38(1):43-56, McCabe et al. Subst Use Misuse 2004;39(70):1095-116). One Canadian author indicated that more than 20% of high school students prescribed stimulants have voluntarily given or sold some of their medication and another 7% have had it stolen or taken from them. Students in a class in which at least one student had diverted stimulant medication were 50% more likely to misuse methylphenidate than students where this activity had not occurred (Poulin 2001, 2007).

While these findings are of concern, it is inappropriate to conclude there is an epidemic of overuse, misuse or abuse of ADHD medications. It may be argued that reluctance to treat individuals with ADHD medically, arising from qualms about drug misuse or abuse, may actually promote the development of substance use disorders. In addition, expanded use of ADHD medication in patients who could benefit from it has the potential to reduce misuse of stimulants and substance use disorders.

Untreated ADHD is an important risk factor for substance or alcohol abuse, while adequate treatment reduces the risk. According to a meta-analysis of six studies of at least four years’ duration (Wilens et al. 2003), a 15-year-old with treated vs. untreated ADHD is 5.8 times less likely to have a substance abuse disorder (Figure 1); half of substance-abusing adolescents had ADHD. Studies that followed patients into adulthood showed that in those who received stimulant therapy, the risk of substance abuse was 40% lower than in those who had not received stimulant therapy.

Figure 1. Substance Abuse Potential

According to the Canadian survey mentioned earlier (Poulin 2007), the prevalence of nonmedical use of methylphenidate and amphetamine was 6.6%% and 8.7%, respectively. A positive ADHD screening test was predictive of both medical and nonmedical use. In other words, the nonmedical use of these drugs was primarily self-medication by patients with ADHD, not abuse for the sake of intoxication.

In 2004, Williams and colleagues reported in a study (in which I participated) that among 450 patients aged 12 to 18 attending our substance abuse program, 23% had misused methylphenidate or dextroamphetamine at least once (Williams et al. Am J Addict 2004;13:381-9). Only 6% were abusers of these medications (Figure 2). In 77% of cases, the agents had been diverted from medical users. A subsequent expanded analysis of these data (unpublished) confirmed the findings of Wilens et al. that untreated ADHD increases the likelihood of substance abuse. In the Williams et al. study population, misuse or abuse of methylphenidate or dextroamphetamine medications did not occur in isolation but rather was part of a pattern of abuse of multiple substances, often taken in combination to enhance their psychoactive effects. It is germane to this discussion that misuse or abuse of ADHD medications involved their short-acting formulations. For an abuser, the goal is to get enough medication into the bloodstream and the brain as fast as possible. Therefore, the rate at which the concentration of a stimulant rises in the brain determines the euphorigenic effect (Volkow ND, Swanson JM. Am J Psychiatry 2003;160:1909-18). Immediate-release methylphenidate and dextro-amphetamine are more likely to be sought by abusers because they allow a “high” to be achieved relatively more rapidly and easily as compared with extended-release formulations.

Figure 2. Substance Us
le of 450 Adolescents

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Avoiding Misuse and Abuse of ADHD Medications

The following suggestions and recommendations may assist physicians in their decisions on the need for and prescription of ADHD medication.

Physicians should be on the lookout for symptoms of ADHD in young children, given that early intervention can help avoid many of the complications and comorbidities that may arise as the patient enters adolescence. According to a 2004 report, patients who initiate treatment before the age of 8 rather than after age 10 are more likely to persist with treatment (Miller et al. Can J Psychiatry 2004;49(11):761-8). Underdiagnosis and/or reluctance to accept ADHD as a treatable disorder constitute a disservice to the children affected.

Of course, it is necessary to ensure the diagnosis of ADHD is correct and justified. Appropriate resources include the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and guidelines issued by the Canadian Paediatric Society (www.cps.ca), Canadian ADHD Resource Alliance (www.caddra.ca) and Collège des médecins du Québec (www.cmq.org) which offer information on assessment, differential diagnosis, interventions and follow-up.

A recent editorial in a primary care journal (McLennan JD. Can Fam Phys 2006;52(8):940-1) suggests that positive answers to these three questions can assist clinical judgments on the use of medication: 1. Is the child functionally impaired? 2. Do the ADHD symptoms cause the functional impairment? 3. Is a trial of medication indicated, based on the severity of the functional impairment?

Once drug treatment is initiated, it should be titrated so that optimal effects are achieved—in other words, that the patient is experiencing as few ADHD symptoms as possible. Regular checking and comparison of symptom rating scales—a step too frequently neglected in primary care—can assist in this regard (McLennan 2006). The family should make use of appropriate psychosocial support, such as educational resources and social skills training and courses aimed at improving the parents’ ability to deal with a difficult child. Parents require education on the need to supervise and control the dispensing of stimulant medications. Regular follow-up is also key to ensuring adherence to treatment and addressing the risk of diversion.

Patients at Risk

Any interview of an adolescent patient should include detailed questions about substance use. A patient who admits to experimentation with many substances is a higher risk for misuse or abuse of an ADHD medication than a patient who has used only alcohol and/or cannabis. Such high-risk patients should undergo substance abuse treatment before a trial of ADHD medication is considered. (Some substance abuse physicians insist the patient should be completely “clean” for a defined period, such as six months, before ADHD treatment is begun. Others, including myself, feel that many patients find it difficult to remain free of substance abuse without concurrent ADHD treatment.) Keeping in mind that ADHD is a heritable disorder, substance abuse by the patient’s parents should also be investigated, and treatment initiated if necessary, before the child’s ADHD treatment is initiated. About half of the patients seen at our program have a first-degree relative who also is a substance abuser. Patients with ADHD and a comorbid condition such as a mood or conduct disorder are also at higher risk.

Drug selection may also take into account the potential for misuse or abuse by the patient or others around him or her. A nonstimulant medication may be employed. If a stimulant is required, both methylphenidate and amphetamine salts are available in an extended-release formulation. This offers longer symptom control, for example, up to 12 hours with MAS XR vs. six to eight hours with dextroamphetamine (Canadian ADHD Practice Guidelines, CADDRA 2006). In addition, this formulation considerably diminishes their potential and appeal for abuse, even if several capsules or tablets are taken at once. Taken orally, these extended-release formulations exhibit smoother pharmacokinetics (slower uptake and rise in concentration and no “peaks/valley” effect) and hence do not induce the “buzz” craved by addicts. Due to their complex composition, extended-release formulations are difficult to crush or dissolve for intranasal or intravenous administration, and consequently may be a better choice when medication abuse, misuse or diversion is a possibility.

Summary

As is the case with other chronic disorders, therapeutic success of ADHD involves its early identification, optimal treatment and persistence with therapies shown to be useful for a given patient. As untreated ADHD is an important risk factor for substance abuse, early effective treatment can help ensure problems with medication and substance misuse/abuse are minimized. Current data confirm that some misuse/abuse of ADHD medication occurs, but is far less likely than abuse of other substances such as alcohol or cannabis. The potential for misuse or abuse can be addressed with identification of patients at risk, medication selection and follow-up. Underutilization of ADHD medications may be a greater issue than misuse or abuse.