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									Attention-Deficit/Hyperactivity Disorder and Substance
Use Disorders in Adolescents
http:// www.ps ychi atricti mes.com/showArticle.jhtml?articleId=177101046

By Timothy Wilens, M.D.

Psychiatric Times January 2006 Vo l. XXV Issue 1




The overlap between attention-deficit/ hyperactivity disorder and alcohol or drug abuse or
dependence (referred to here as substance use disorders [SUDs]) in adolescents has been
an area of increasing clinical, research and public health interest. Appearing in early
childhood, ADHD affects from 6% to 9% of children and adolescents worldwide
(Anderson et al., 1987) and up to 5% of adults (Kessler, in press). Longitudinal data
suggest that childhood ADHD persists into adolescence in 75% of cases and into
adulthood in approximately one-half of cases (for review, see Weiss, 1992). Substance use
disorders usually appear in adolescence or early adulthood and affect between 10% to 30%
of U.S. adults and a less defined, but sizable, number of juveniles (Kessler, 2004). The
study of comorbidity between SUDs and ADHD is relevant to both research and clinical
practice in developmental pediatrics, psychology and psychiatry with implications for
diagnosis, prognosis, treatment and health care delivery.

Overlap Between ADHD and SUD

Structured psychiatric diagnostic interviews assessing ADHD and other disorders in
substance-abusing groups have indicated that from one-third to one- half of adolescents
with SUDs have ADHD (DeMilio, 1989; Milin et al., 1991). For example, aggregate data
from government-funded studies of mainly cannabis-abusing youth indicate that ADHD is
the second most common comorbidity with from 40% to 50% of both girls and boys
manifesting full criteria for ADHD. Data largely ascertained from adult groups with SUDs
also show an earlier onset and more severe course of SUD associated with ADHD (Carroll
and Rounsaville, 1993; Levin and Evans, 2001).

ADHD as a Risk Factor or Precursor for SUD

The association of ADHD and SUDs is particularly compelling from a developmental
perspective as ADHD appears to manifest itself earlier than the SUD; therefore, the SUD
is an unlikely risk factor for ADHD. Thus, it is important to evaluate to what extent
ADHD is a precursor of SUDs. Prospective studies of children with ADHD have provided
evidence that the group with conduct or bipolar disorders co-occurring with ADHD have
the poorest outcome with respect to developing SUDs and major morbidity (Biederman et
al., 1997; Mannuzza et al., 1993). As part of an ongoing prospective study of ADHD, it
was found that differences in the risk for SUDs in adolescents with ADHD (mean age=15)
compared to controls without ADHD were accounted for by comorbid conduct or bipolar
disorders (Biederman et al., 1997). However, it also has been shown that the age of risk for

                                                     1
SUD onset in adolescents without comorbid ADHD is approximately 17 years in girls and
19 years in boys (Biederman et al., in press-a; Milberger et al., 1997b). These findings
were confirmed by Katusic and associates (2005) and Molina and Pelham (2003), who
have shown elevated risk of SUDs in adolescents with ADHD.

ADHD treatment and SUD. Clarification of the critical influence of ADHD treatment in
youth on later SUDs remains hampered by methodological issues. Since prospective
studies in youth with ADHD are naturalistic, and hence not randomized for treatment,
attempts to disentangle positive or deleterious effects of treatment from the severity of the
underlying condition(s) are hampered by serious confounds. Whereas concerns of the
abuse liability and potential kindling of specific types of abuse (e.g., cocaine) secondary to
early stimulant exposure in children with ADHD have been raised (Drug Enforcement
Administration, 1995; Vitiello, 2001), the preponderance of clinical data do not appear to
support such a contention.

To reconcile findings in this important area, my group completed a meta-analysis of the
literature (Faraone and Wilens, 2003; Wilens et al., 2003). We included studies examining
the later risk of SUDs in children exposed to stimulant pharmacotherapy, identifying two
studies into adolescence and five studies into adulthood. We found that stimulant
pharmacotherapy did not increase the risk for later SUDs. In fact, we found that stimulant
pharmacotherapy protected against later SUDs (odds ratio of 1.9) and that the effect was
stronger in adolescents relative to adults (Wilens et al., 2003). It is notable that the
magnitude of risk reduction (e.g., 50% reduction in risk) indicated that the ultimate risk of
SUDs in treated individuals with ADHD may approximate the level of risk in individuals
without ADHD (general population).

SUD Pathways Associated With ADHD

An increasing body of literature shows an intriguing association between ADHD and
cigarette smoking. It has been previously reported that ADHD is a significant predictor for
early initiation of cigarette smoking (before age 15) and that conduct and mood disorders
comorbid with ADHD put youth at particularly high risk for early-onset smoking
(Milberger et al., 1997a) (Figure). Data also suggest that one-half of smokers with ADHD
go on to later SUDs (Biederman et al., in press-b). This is not surprising given that not
only does smoking lead to peer group pressures and availability of illicit substances, but
that nicotine exposure may make the brain more susceptible to later behavioral disorders
and SUDs (Trauth et al., 2000). Furthermore, nicotinic- modulating agents are increasingly
being evaluated for the treatment of ADHD (Wilens et al., in press-b). Of interest,
prospective data funded by the National Institute on Drug Abuse suggest that stimulant
treatment of ADHD reduces not only the time to onset but also the incidence of cigarette
smoking (Monuteaux, 2004).

The precise mechanism(s) mediating the expression of SUDs in ADHD remains to be
seen. The self- medication hypothesis is compelling in ADHD considering that the disorder
is chronic and often associated with demoralization and failure, factors frequently
associated with SUDs in adolescents. Moreover, it has been found that among substance-
abusing adolescents with and without ADHD, adolescents with ADHD reported using


                                                 2
substances more frequently to attenuate their mood and to help them sleep. No evidence of
differences in types of substances has emerged between substance-abusing teen-agers with
or without ADHD (Biederman et al., 1997). In addition, the potential importance of se lf-
medication needs to be tempered against more systematic data showing the strongest
association between ADHD and SUDs is comorbidity and familial contributions, such as
exposure to parental SUDs during vulnerable developmental phases.

Diagnosis and Treatment Guidelines

Evaluation and treatment of comorbid ADHD and SUDs should be part of a plan in which
consideration is given to all aspects of the teen-ager's life. Any intervention in this group
should follow a careful evaluation of the adolescent including psychiatric, addiction,
social, cognitive, educational and family evaluations. A thorough history of substance use
should be obtained that includes past and current usage and treatments. Although no
specific guidelines exist for evaluating the patient with an active SUD, in my experience at
least one month of abstinence is useful in accurately and reliably assessing for ADHD
symptoms. Semi-structured psychiatric interviews or validated rating scales of ADHD are
invaluable aids for the systematic diagnostic assessments of this group.

The treatment needs of individuals with SUDs and ADHD need to be considered
simultaneously; however, the SUD needs to be addressed initially (Riggs, 1998). If the
SUD is active, immediate attention needs to be paid to stabilization of the addiction(s).
Depending on the severity and duration of the SUD, adolescents may require inpatient
treatment. Self- help groups offer a helpful treatment modality for many with SUDs. In
tandem with addiction treatment, adolescents with co-occurring SUDs and ADHD require
intervention(s) for the ADHD as well as other co-occurring psychiatric disorders.

Medication serves an important role in reducing the symptoms of ADHD and other
concurrent psychiatric disorders. Effective agents for adolescents with ADHD include the
stimulants, noradrenergic agents and catecholaminergic antidepressants (Wilens et al.,
2002). Findings from a meta-analysis of 10 studies of open and controlled trials suggest
that medications used in adolescents and adults with ADHD plus SUDs have only a
meager effect on the ADHD, but have little effect on substance use or cravings (Riggs et
al., 2004; Schubiner et al., 2002; Wilens et al., 2005). Of interest, no evidence exists that
treating ADHD pharmacologically through an active SUD exacerbates the SUD. This is
consistent with the work of Grabowski et al. (2004), who used stimulants to block cocaine
and amphetamine abuse. Also consistent with these findings, earlier work by Volkow et al.
(1998) demonstrated significant differences between binding at the dopamine transporter
between methylphenidate and cocaine, suggesting a much smaller abuse risk for
methylphenidate in contrast to cocaine.

In ADHD adults with SUDs, the nonstimulant agents (atomoxetine [Strattera]),
antidepressants (bupropion [Wellbutrin]), and extended-release or longer-acting stimulants
with lower abuse liability and diversion potential are preferable (Riggs, 1998). While of
particular interest because of the drug's broad spectrum of activity in ADHD and lack of
abuse liability (Heil et al., 2002), results from ongoing trials of atomoxetine in SUDs are
not yet available. In individuals with SUDs and ADHD, frequent monitoring of


                                                3
pharmacotherapy should be undertaken--including evaluation of compliance with
treatment, use of questionnaires (Gignac et al., 2005), random toxicology screens as
indicated, and coordination of care with addiction counselors and other caregivers.

Issues of diversion. Surprisingly, limited information is available on the inappropriate use
of stimulants in terms of the magnitude of the problem and the characteristics of misuse in
individuals for whom they are prescribed. Musser et al. (1998) surveyed 161 children with
ADHD responding to methylphenidate in order to assess diversion. The authors reported
that 16% of children had been approached to sell or give away their prescribed medication;
however, the actual rates of diversion were not reported. Marsh et al. (2000), using a
retrospective review of the medical charts of 240 adolescents with ADHD, reported that
12% had misused their methylphenidate, although the characteristics of those youth were
not reported. Poulin (2001) surveyed 13,549 students in grades 7 through 12 and found
that 8.5% had used nonprescribed stimulants in the year prior to the survey. Of those
students who were receiving prescribed stimulants, 14.7% had given their medications and
7.3% had sold their medication to other students. Similar to other studies, those to whom
the stimulants were diverted misused the stimulants in context with other substances of
abuse.

Similarly, we recently found that 11% of adolescents and young adults with ADHD
diverted (sold) and 22% had misused their stimulants (e.g., escalated dose, used with other
substances, became euphoric) (Wilens et al., in press-a). We also found that ADHD
individuals with conduct disorder or SUDs accounted for the misuse and diversion and
that there appeared to be more misuse and diversion of immediate-release compared to
extended-release stimulants (Wilens et al., in press-a).

Summary

There is a strong literature supporting a relationship between ADHD and SUDs. Both
family/genetic and self- medication influences may be operational in the development and
continuation of SUDs in ADHD. Adolescents with ADHD and SUDs require mult imodal
interventions incorporating addiction and mental health treatment. Pharmacotherapy in
individuals with ADHD and SUDs needs to take into consideration timing, misuse and
diversion liability, potential drug interactions, and compliance concerns.

While the existing literature has provided important information on the relationship of
ADHD and SUDs, it also points to a number of areas in need of further study. The
mechanism by which untreated ADHD leads to SUDs, as well as the risk reduction of
ADHD treatment on cigarette smoking and SUDs, needs to be better understood. Given
the prevalence and major morbidity and impairment caused by SUDs and ADHD,
prevention and treatment strategies for these adolescents need to be further developed and
evaluated.

Acknowledge ments

This research was supported by National Institutes of Health grants R01 DA14419 and
K24 DA016264 to Dr. Wilens. Dr. Wilens is director of Substance Abuse Services at


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Massachusetts General Hospital's Pediatric Psychopharmacology Clinic and associate
professor of psychiatry at Harvard Medical School.

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     use disorders. Findings from a longitudinal study of high-risk siblings of ADHD children. Am J Addict 6(4):318-329.
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     school administrators and longitudinally followed children. J Dev Behav Pediatr 19(3):187-192.
     Poulin C (2001), Medical and nonmedical stimulant use among adolescents: from sanctioned to unsanctioned use.
     CMAJ 165(8):1039-1044 [see comment].




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          Riggs PD (1998), Clinical approach to treatment of ADHD in adolescents with substance use disorders and conduct
          disorder. J Am Acad Child Adolesc Psychiatry 37(3):331-332.
          Riggs PD, Hall SK, Mikulich-Gilbertson SK et al. (2004), A randomized controlled trial of pemoline for attention-
          deficit/hyperactiv ity disorder in substance-abusing adolescents. J Am Acad Child Adolesc Psychiatry 43(4):420-429.
          Schubiner H, Saules KK, Arfken CL et al. (2002), Double-blind placebo-controlled trial of methylphenidate in the
          treatment of adult ADHD patients w ith comorbid cocaine dependence. Exp Clin Psychopharmacol 10(3):286-294.
          Trauth JA, Seidler FJ, Slotkin TA (2000), Persistent and delayed behavioral changes after nicotine treatment in
          adolescent rats. Brain Res 880(1-2):167-172.
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          attention defic it hyperactiv ity disorder. J Child Adolesc Psychopharmacol 11(1):25-34.
          Volkow ND, Wang GJ, Fow ler JS et al. (1998), Dopamine transporter occupancies in the human brain induced by
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          Philadelphia: W.B. Saunders Company.
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          Med 53:113-131.
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          divert or misuse their prescribed medications. J Am Acad Child Adolesc Psychiatry.
          Wilens TE, Monuteaux MC, Snyder LE, Moore H (2005), The clinical dilemma of using medications in substance
          abusing adolescents and adults w ith ADHD: w hat does the literature tell us? J Child Adolesc Psychopharmacol
          15(5):787-798.
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          treatment of ADHD in adults: results of a pilot study. Biol Psychiatry.


Bipolar Disorder – Comobidity
http://www.brainexplorer.org/bipolar_disorder/Bipolar_Disorder_% 20comorbidity.shtml

Substance Abuse

Approximately 60% of people with bipolar disorder have a substance abuse problem (NIMH, 2000),
and a recent study by the National Institute of Mental Health (NIMH) found that 46% of patients
with bipolar disorder are dependent on alcohol and about 40% exhibit drug abuse or dependency
(Evans, 2000). Substance abuse can make bipolar disorder more severe and worsen the course of the
disease by exacerbating symptoms or precipitating episodes (Evans, 2000). The factors which may
increase the risk of comorbid substance abuse are family history of substance use, an early age of
onset of bipolar disorder and the presence of mixed episodes (NIMH, 2000).

Psychiatric Conditions

The Stanley Foundation Bipolar Network reports a high percentage of concomitant psychiatric
conditions with bipolar disorder. One of the most common comorbid conditions is anxiety disorder,
including panic disorder and social phobia. Symptoms of anxiety and panic followed by hypomaina
may complicate the course of bipolar disorder (Suppes et al, 2000).

Other psychiatric conditions that can occur with bipolar disorder include post-traumatic stress
disorder (PTSD), obsessive compulsive disorder (OCD) and impulse control disorders (e.g.
pathologic gambling, kleptomania) (NIMH, 2000; Suppes et al, 2000). The NIMH recently reported
a high incidence of PTSD and OCD in patients with bipolar disorder, with 43% of patients

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exhibiting symptoms for PTSD. However, only 2% had the symptoms of PTSD listed on their
charts, suggesting that improved diagnosis of this concomitant condition may lead to better
treatment of bipolar disorder (NIMH, 2000). This may be especially relevant in the case of OCD as
the course of the OCD and mood disorders often alter in line with each other.

Attention Deficit Hyperactivity Disorder (ADHD)

Bipolar disorder that develops in early childhood may be more commonly associated with
disruptive behavioural conditions, such as ADHD or conduct disorder (CD), than with bipolar
disorders onsetting later in life. A study by Wozniak et al, 1995, found that 11% of 301 children
under the age of 12 with bipolar disorder also met criteria for ADHD. In contrast, those patients that
develop bipolar disorder later in adolescence or as adults do not tend to have high rates of
concomitant ADHD or CD (Evans, 2000; NIMH, 2000).

Other Problems to be Considered:
From http://www.emedicine.com/ped/topic240.htm

On presentation to health care services, youths with bipolar disorder exhibit behaviors that mimic
and overlap other diagnoses. The overlap of bipolar symptoms with symptoms of ADHD and
conduct disorder (CD) is significant. Specifically, as with patients with bipolar disorder, activity is
increased and self-esteem may be inflated in the early stages of ADHD and CD. Societal and
educational responses to the behaviors of ADHD and CD ultimately may result in reduced self-
esteem in these patients compared to those with bipolar disorder. Many other features of bipolar
disorder compared to ADHD and CD are further described in Table 2, which may help to compare
and contrast the clinical features of these 3 important disorders that impact young individuals.




                                                   7
Table 2. Differential Diagnosis Considerations

  Behavior            Bipolar Disorder                   ADHD                        CD

Self-esteem                Inflated               Inflated/deflated           Inflated/deflated

                                                                           Pleasure in violating
                    Euphoric in mania
                                                 Often dysphoric or          societal norms,
Pleasure           Dysphoric in mixed or
                                                     euthymic             especially if not caught
                     depressed state

Attention                Distractible                  Distractible          Normal to vigilant

Hyperactivity           Goal directed                 Unproductive              Goal directed

                   Episodic disturbances                                      Not known to be
                                                 Chronic poor sleep;
Sleep               such as decreased                                      disrupted except with
                                                 often late bedtimes
                      need in mania                                          substance abuse

                    Pressured or rapid in
                                                 Often rapid; may be
Speech                 mania; slow in                                       May be normal rate
                                                      pressured
                        depression

                      Externally driven;                                  May have predatory or
Impulsivity                                        Internally driven
                         reactionary                                        reactionary acts

Social                   Often good                    Often poor                Often poor

                                                          Often
Academic                 Often good                                              Often poor
                                                          poor

                    Agitated in mania or
Psychomotor
                   mixed states; retarded        Chronically agitated          Easily agitated
activity
                    in depressed states




Additional consideration must be given to the possibility of the existence of schizophrenia or
schizoaffective disorder, posttraumatic stress disorder (PTSD), substance abuse, or anxiety states
(eg, generalized anxiety disorder, social anxiety disorder) because any of these disorders may
transiently mimic bipolar disorder. Rarely is dementia an issue in youths, but this may need to be
excluded in some patients (particularly after head trauma).

Comorbidity

Biederman et al (Biederman, Arch Gen Psychiatry, 1996) noted that the combination of CD and
major depression in adolescence could be predictive of bipolar disorder in a 4-year follow-up
assessment of those patients. An estimated 10-15% of adolescents who present with recurrent


                                                  8
episodes of major depression later are given the diagnosis of bipolar disorder. Also, children with
ADHD who later develop bipolar disorder have increased rates of other psychiatric conditions,
including opposition defiant disorder (ODD). Overall, the combined symptoms of severe ADHD,
unstable affect, and aggression may be predictive of bipolar disorder later in life for children in
whom ADHD is already diagnosed.

Biederman reports that an important predictor of bipolar disorder in youth involved in his study is
the presence of disruptive behavior disorder (DBD). Specifically, his research suggests that the
combination of ADHD with ODD, as compared to ADHD alone, correlates to future onset of
bipolar symptoms at rates of 7% and 5%, respectively. However, when ADHD with ODD is present
but later ODD progresses to CD, the rate of occurrence of bipolar disorder dramatically increases to
44%. Obviously, this means that approximately 55% of adolescents who have a diagnosis of
comorbid ADHD, ODD, and CD do not experience onset of bipolar symptoms. Nonetheless, one
potential complication to note in youths who have comorbid ADHD and ODD is the development
of bipolar features, including depression and psychosis. Also, the combination of ADHD and ODD
increases the risk of involvement in legal activities and incarceration. Thus, bipolar symptoms
already exist or may develop in some incarcerated youths.

Kovacs and Polack (1995) performed a prospective study of 26 prepubertal youths with onset of
bipolar disorder and CD when aged 8-13 years. In a 12-year follow- up evaluation, they discovered
that the lifetime comorbidity for these 2 disorders was 69%. Additional review of the pattern of
psychiatric pathology revealed that, of those who had onset of both disorders when younger than 13
years, CD had been diagnosed first in 42%, whereas bipolar disorder had been diagnosed first in
27%.

Because clinicians often are concerned that CD carries an increased risk of development of
antisocial personality disorder, the data suggest that careful screening and monitoring for the
comorbid conditions of bipolar disorder and CD may be necessary in youth who present with either
of these disorders. Such screening may help to identify and treat these youths so they may avoid the
risk of incarceration and perhaps erroneous labeling as antisocial adults rather than individuals with
coexisting bipolar disorder and CD. Another commonly observed co morbid diagnosis in youths
with bipolar disorder is ADHD. Among prepubertal youths presenting with bipolar symptoms,
nearly 90% have a diagnosis of ADHD; among adolescents, about 30% have ADHD (Geller, 1997).
In summary, sustained symptoms of conduct and impulse control problems may be warning signs of
prepubertal onset of bipolar disorder.

Incarcerated youths have a disproportionately higher prevalence of bipolar disorders compared to
youths in the general population. Recent studies by Steiner (2000) estimate that 2% of incarcerated
juveniles have bipolar I disorder, whereas 4% have bipolar II disorder.




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