Sarah M. Bowman

PSY 414, Psychopharmacology

Dr. Anya Hillery

Saint Louis Univeristy Madrid

December 17th, 2013

Stimulant Pharmacotherapy Of Attention-deficit/Hyperactivity Disorder Reduction of

Risk For Substance Use Disorders

Abstract

Research has demonstrated a strong correlation between Attention Deficit/ Hyperactive Disorder

(ADHD) and Substance Use Disorders (SUD). Further research should be undertaken to

distinguish specifically which SUD has a higher correlation with ADHD. Possible preventative

measures that can be taken in order to decrease likelihood for later development of SUDs include

early initiation of ADHD patient into stimulant care. Additional research should be conducted in

pairing early stimulant care with intensive behavioral therapy.

Introduction:

Attention Deficit/ Hyperactive Disorder, or ADHD, is one of the most common

neuropsychiatric disorders affecting 3% to 6% of children and almost 5% of adults (Salman et

al., 2012). Given the high prevalence of ADHD in the population, it is desirable to be able to

predict negative consequences that may arise in the long-term for those who are diagnosed. In

this paper, analysis of the available research demonstrating a strong correlation between ADHD

and substance use disorders (SUD) is described. In addition, possible preventative and

protective measures are explained in order to decrease the number of SUDs in individuals

diagnosed with ADHD.

Literature Review:

Though ADHD has been established as a clinical entity for a substantial amount of time,

researchers have been unable to pinpoint the exact cause of the disorder (Thapar, Cooper, Eyre,

Langley, 2013). It is generally agreed that ADHD has a genetic component, meaning the

disorder often runs in the family (Thapar et al., 2013). Despite the lack of conclusive data on its

cause, the clinical diagnosis and symptoms that accompany the disorder are recognized

universally (Thapar et al., 2013). Clinical diagnosis of ADHD rests on a triad of symptoms:

inattention, hyperactivity, and impulsivity (Maisto, Galizio, & Connors, 2010). Inattention could

show itself in the inability to sustain attention on tasks or activities (Maisto et al., 2010).

Hyperactivity could show itself in an excessive degree of fidgeting or squirming when seated

(Maisto et al., 2010). Finally, impulsivity could show itself in impatience. In other words,

ADHD is a disorder with features including greater-than-normal activity, restlessness, difficulty

concentrating or sustaining attention, and impulsivity (Maisto et al., 2010).

Due to this triad, many children with ADHD experience learning and developmental

difficulties later in life (Thapar et al., 2013). Research affirms that 50-75% of children with

ADHD continue to suffer from symptoms into adolescence and adulthood (Glass & Flory, 2011).

In addition to the difficulties created by ADHD itself, the condition has been associated with

other disorders, notably Substance Use Disorder (SUD), which has been shown in multiple

studies to have a strong correlation with ADHD (Salman et al., 2012). Due to the nature of

ADHD, individuals with ADHD may try to modulate their disorders with substances of abuse.

Fifty-two percent of patients with ADHD have been shown to exhibit life-long symptoms of

SUD (Salman et al., 2012).

Substance Abuse disorders are associated with psychiatric disorders and with low

educational levels, unemployment, and risky sexual behavior (Brook et al., 2010). Given the

negative consequences of SUD, it is important to identify predictors, such as ADHD (Brook et

al., 2010). Strong evidence exists establishing ADHD as a predictor of SUD. In an article using

a comparative meta-analysis, thirteen different studies were examined that analyzed the

relationship between ADHD and SUD (Charach, Yeung, Climans, &Lillie, 2011). The study

examined the estimated long-term risk for development of alcohol, cannabis, combined alcohol

and psychoactive SUDs, combined SUDs (non-alcohol), and nicotine use disorders in individuals

diagnosed in childhood with ADHD (Charach et al., 2011). By calculating the OR and

confidence interval of these separate studies, Charach et al. (2011) found that Childhood ADHD

was associated with alcohol use disorder by young adulthood (OR = 1.35, 95% confidence

interval = 1.11-1.64) and with nicotine use by middle adolescence (OR = 2.36, 95% confidence

interval = 1.71-3.27) (Charach et al., 2011). In this way, the meta-analysis supports the

hypothesis that childhood ADHD is associated with later drug and alcohol use disorders. In

particular, Charach, et al. found that, for persons with ADHD, alcohol and drug use disorders

become prevalent in adulthood and nicotine becomes more prevalent in adolescence (Charach et

al., 2011).

Conversely, ADHD has been reported in 40-75% of clinically referred groups of

substance-abusing adolescents and 15-25% of substance-abusing adults (Wilens et al., 2007). In

a study performed at a large multi-site outpatient Cannabis Youth Treatment, ADHD was found

in 38% of adolescents of both sexes diagnosed with a marijuana use disorder (Wilens et al.,

2007). In a more recent study, Salman et al. (2012) examined a sample of adults admitted into a

psychiatry ward seeking detoxification treatment for heroin, THC, opium, alcohol, and poly-drug

dependency. Post admission, the patients were examined to determine whether they suffered

from ADHD in childhood (Salman et al., 2012). The study also looked at whether the ADHD

disorder persisted into adulthood (Salman et al., 2012). In order to determine the prevalence of

ADHD in childhood, Salman et al. (2012) conducted retrospective interviews with each patient

and identified four different characteristics that separated the ADHD patients from the non-

ADHD patients: Inattention and memory problems, hyperactivity and restlessness, impulsivity

and emotional liability, and problems with self-concept. These four factors were found in both

the retrospective childhood and the adult assessment in the corresponding instruments (Salman et

al., 2012). The results of this study confirmed that a high percentage of drug and alcohol-

dependent patients admitted into psychiatric treatment for SUD fulfilled the diagnostic criteria

for the presence of ADHD, thus supporting the proposition that an ADHD patient with persisting

symptoms of ADHD is a marked risk for the development of different types of substance

dependence (Salman et al., 2012).

As demonstrated, the correlation between SUD and ADHD has been sufficiently

established for it to become a serious public health concern. However, the type of SUDs for

which ADHD may serve as a precursor are not as well established. For example, the

comparative meta-analysis article by Charach et al. (2011) considers the evidence regarding

whether childhood ADHD is a risk factor for development of alcohol, cannabis, combined

alcohol and psychoactive SUDs, combined SUDs (non-alcohol), and nicotine use disorders later

in life. However, only alcohol and nicotine were shown to have a correlation. In contrast,

Salman et al. (2012) examined the relationship between ADHD and THC, opium, alcohol, and

poly drug dependency. Salman et al. (2012) found a correlation between ADHD and alcohol

abuse, but also found an additional correlation between ADHD and the development of heroin

dependence. These differing results may be due to differing experimental methods. However,

similar inconsistencies appear in other studies regarding the correlation between ADHD and

SUD (Beiderman, Wilens, Mick, Spencer, Faranoe, 1999; Glass & Flory, 2012). Further research

must be done in order to establish a more concise link between ADHD and SUD.

Though the specific details regarding the correlation between ADHD and SUD may not

be consistent, the data is sufficiently strong to give rise to serious concern about the probability

of developing SUDs for individuals diagnosed with ADHD. Additional investigation into the

reasons for the correlation between ADHD and SUDs is needed, and is important as a matter of

public health. In the past, there has been some question about whether or not the treatment of

ADHD with amphetamines can lead to a SUD due to their well-documented abuse potential

(Biederman, Wilens, Mick, Spencer, Faraone, 1999). Biederman et al. (1999) assessed the risk

of SUD when associated with previous exposure to psychotropic medication in a longitudinal

follow-up of psychiatrically referred boys. The cumulative incidence of SUD throughout

adolescence was compared to fifty-six medicated individuals with ADHD, nineteen medicated

individuals with ADHD, and 137 non-ADHD control individuals (Biederman et al., 1999).

Somewhat counter-intuitively, given the addictive quality of amphetamines, the study concluded

that individuals with ADHD who did not receive pharmacological treatment were at a

significantly increased risk for SUD in comparison to those who were treated pharmacologically

for ADHD (Biederman et al., 1999). The results suggest that rather than inducing SUD in youth

with ADHD, pharmacotherapy for ADHD may protect children with ADHD from SUD

(Beiderman et al., 1999). However, there were several limitations to this study including the

absence of females and non-white participants (Beiderman et al., 1999).

Due to the limitations of the Beiderman et al. (1999) study, further research has been

conducted concerning the relationship of future SUD and pharmacological treatment for ADHD.

Dalsgaard, Mortensen, Fryenberg, and Thomsen (2013) produced results similar to those of

Beiderman et al. (1999), suggesting early methamphetamine treatment as a preventative SUD

measure for individuals with ADHD. In addition to studying the relationship between

pharmacological treatment for ADHD and SUD, the study investigated how age of initiation into

treatment was related to SUD (Dalsgaard et al., 2013). The subjects included 208 subjects with

ADHD in their youth, 183 boys and 25 girls (Dalsgaard et al., 2013). Males suffering from

ADHD in youth were found to be six times more likely to develop SUD later in life than non-

ADHD individuals (Dalsgaard et al., 2013). However, females who suffered from ADHD in

youth were thirty-eight times more likely to develop alcohol abuse later in life when compared to

non-ADHD individuals (Dalsgaard et al., 2013). In addition, the researchers found that the

earlier an individual was initiated into treatment of methamphetamines, the less likely it was that

SUD would later develop (Dalsgaard et al., 2013). Therefore, this study reinforces the

suggestion that untreated ADHD is a significant risk factor for SUD.

There are some studies that refute the claim that pharmacological treatment can act as a

protective measure in individuals with ADHD, Lambert and Hartsough (1998) conducted a

prospective study examining tobacco smoking and substance dependencies among samples of

ADHD and non-ADHD participants (Lambert & Hartsough, 1998). This study consisted of a 10-

year follow-up to adulthood of 93 children with ADHD who received stimulant medication and

81 who did not receive stimulant medication (Lambert & Hartsough, 1998). Lambert and

Hartsough (1998) found that ADHD smokers began smoking earlier; on average, they began

smoking regularly shortly after 15 years of age in comparison to the age-mate control smokers

who began regularly smoking around age 17. In addition, the study found that at the age of 17,

46% of the ADHD group smoked cigarettes daily in comparison to the age-mate control

smokers, 24% of who smoked cigarettes daily. The lifetime dependency rate of smoking was

40% in the ADHD group and 19% in age-mate control group (Lambert & Hartsough, 1998).

There was also a possible link found between stimulant medication and treatments and rates of

adult smoking, adult cocaine use, and tobacco dependency (Lambert & Hartsough, 1998). The

implications of these findings are that stimulant treatment may predispose an individual with

ADHD to SUD later in life. However, this study did not control for severity of ADHD

symptoms in the medication treated and untreated hyperactive groups, which may in fact have

been responsible for increase in substance use reported (Lambert & Hartsough, 1998).

A review study performed by Schubiner (2005) further debunks Lambert and

Hartsough’s (1998) claim by explaining why ADHD medication treatments as a precursor to

future cocaine use it not valid. A hypothesis widely accepted concerning substance abuse is that

there is a strong connection between substance abuse and the mesolimbic dopamine reward

pathways, resulting in a powerful reinforcing effect (Schubiner, 2005). Cocaine,

methylphenidate, and amphetamines all act by binding to presynaptic dopamine receptors, thus

increasing dopamine activity in the brain synapses (Schubiner, 2005). This finding is concerning

in regards to usage of ADHD medication especially when taking into account that

methylphenidate produces similar effects as cocaine on both healthy and substance-abuse

individuals (Schubiner, 2005). However, in studies reviewed by Schubiner (2005), results have

shown that routes of administration and rates of onset play important roles in differing risks of

substance dependency. Cocaine has a very rapid rate of onset in the brain when it is

administered by intravenous or nasal routes (Schubiner, 2005). In contrast, due to administration

of methylphenidates via oral routes, onset is much more delayed (Schubiner, 2005). Thus,

subjects who administered medication through the oral route do not report similar euphoric

effects that are reported by cocaine using subjects (Schubiner, 2005). These findings further

explain why the vast majority of physicians providing care for ADHD patients rarely see abuse

of stimulants (Schubiner, 2005).

Discussion:

A sufficient link has been established between individuals with ADHD and SUDs. When

examined through several different lenses, ADHD can be seen as a precursor for SUD through

examining individuals seeking treatment for ADHD and through individuals seeking treatment

for SUDs. In other words, for individuals seeking treatment for ADHD, prevalence of substance

abuse is often found. In addition, for individuals seeking treatment for substance abuse

disorders, there is often comorbidity present with symptoms equitable to ADHD symptoms.

Though the type of SUD may vary, the correlation between the two disorders is well established.

Further research should be undergone in order to better understand specifically what SUD is

more likely to develop when considering ADHD patients.

In the past, the usage of stimulant medication has been held accountable for this

correlation. However, through examining research this hypothesis conflicts significantly with

results examining the relationship between stimulant medication and SUD onset. Instead of a

precursor for SUDs, stimulant medication has been found to act as a protective measure against

SUDs. Further, the earlier an individual with ADHD starts stimulant treatment, the less likely he

will develop SUDs in the future. These findings have major implications towards drug

prevention strategies and educational information for parents of children with ADHD.

Decreased apprehension toward appropriate pharmacotherapy may lead to earlier

intervention for affected youth with its attendant benefits of avoiding the academic psychiatric

and interpersonal complications of ADHD. These implications would be valuable to the families

of patients who are seeking the best possible route of treatment. Additional research should be

conducted in regards to pairing these findings with intensive behavioral treatment in order to

equip patients with behavioral strategies to manage their disorder in addition to taking

medication that will limit the symptoms. In this way, children diagnosed with ADHD will be

less likely to develop learning and developmental difficulties later in life, thus, decreasing

likelihood for later development of SUDs.

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