Substance Use Disorder and ADHD

Abstract

Objective: To assess the pattern of substance use disorder (SUD) in adolescents with and without history of attention - deficit / hyperactivity disorder (ADHD) using an Iranian sample in the context of a cultural background and drug availability is differing from Western countries. Method: In this case- control study, the participants were interviewed by a child psychiatrist and the measures included: kiddie Schedule for Affective Disorder and Schizophrenia for school age children (K-SADS), Opium Treatment Index (OTI) and Global Assessment Functioning (GAF). Data were analyzed with chi square test and T test and fisher exact test by EPI.6 soft ware. Results: Adolescents with ADHD were younger at the time of starting cigarette smoking, substance use, abuse and dependency (p = 0.0001), a shorter period between their first-time substance use and substance dependence or abuse (p = 0.0001), more severe substance use (for cannabis, heroine, cigarette and drugs such as benzodiazepines p < 0.05) and more functional impairment (p = 0.0007). Average number of co morbid disorders were higher in ADHD group. (p = 0.03) Conclusion: Although the pattern and type of substance use may be different in Iranian culture, our findings about the relationship between ADHD and SUD are similar to other western and non western countries. The presence of ADHD may over-ride cultural barriers and lower availability of drugs to the development of SUD in Iranian adolescents. Early diagnosis and treatment of ADHD may propose with better prognosis of SUD and subsequent decrease in the prevalence of SUD and the costs of SUD-related pathology in this population.

Keywords

ADHD substance use disorder adolescents

ADHD is characterized by the triad of inattention, hyperactivity, and impulsivity, one of the most common neuropsychiatric disorders in child and adolescent psychiatry (Wilens, Faraone, Biederman, & Gunawarden, 2003). Prevalence of ADHD is estimated to be up to 12% (Spetie & Arnold, 2007) with its estimated persistence rate into adulthood of 50% to 60%. The prevalence of adult ADHD is estimated to be around 5% (Adler & Cohen, 2004). However, substance use disorder (SUD) is a major public health problem in adolescents. This comorbidity between SUD and ADHD is relevant to research and clinical practice in developmental pediatrics, psychology, and psychiatry. This has implications for diagnosis, prognosis, treatment, and health care delivery. Identification of specific risk factors of SUD comorbid with ADHD may permit more targeted treatments for both disorders at earlier stages of their expression. This may potentially dampen the morbidity, disability, and poor long-term prognosis of adolescents and adults with this comorbidity (Clure et al., 1999; Riggs, 1998; Wilens, 2004).

Children with ADHD are believed to be at greater risk for drug use/abuse (Barkley, Fischer, Smallish, & Fletcher, 2004). ADHD may also worsen prognosis of SUD and antisocial behaviors into adulthood (Barkley et al., 2004; King, Brooner, Kidorf, Stoller, & Mirsky, 1999; Riggs, 1998; Riggs, Hall, Mikulich-Gilbertson, Lohman, & Kayser, 2004). Although ADHD simplex appears to be a risk factor for late adolescent to young adult onset SUD (Wilens, 2004; Wilens, Biederman, Mick, Faraone, & Spencer, 1997), compared with the normal population, the risk of SUDs appears to be twice as high among people with ADHD and four times as high among people with ADHD with comorbid conduct disorder (CD; Ercan, Coskunol, Varan, & Toksoz, 2003). In 1996, Thompson, Riggs, Mikulich, and Crowley concluded that the age of initial substance use did not differ between ADHD and non-ADHD participants, whereas age of regular substance use tended to be younger for ADHD participants and diagnosis of substance dependency. In addition, the results of Biederman et al.’s (1997) study revealed that adolescent ADHD sample shows no elevated risk for SUD in early adolescence. However, he found an association between SUD, conduct disorder, and bipolar mood disorder (BMD) in this age group. He found no differences between ADHD participants and non-ADHD comparison group with regard to the onset of substance use, although adolescents with ADHD had a significantly shorter transition time from abuse to dependence (Biederman et al., 1997). Their results suggest that conduct disorder and juvenile onset bipolar disorder are risk factors for early adolescent onset SUD, whereas ADHD simplex appears to be a risk factor for late adolescent to young adult SUD (Wilens et al., 1997).

Some studies showed that marijuana seems to be the preferred drug of abuse in ADHD participants (Biederman et al., 1995). Others, however, found no differences between ADHD participants and non-ADHD comparison adolescents for the preferred drugs of abuse (Biederman et al., 1997; Clure et al., 1999; Thompson et al., 1996). In addition, an increasing body of literature shows an interesting association between ADHD and cigarette smoking, although ADHD is a significant predictor for early initiation of cigarette use after adjusting for potential confounding variables (Ercan et al., 2003; Modestine, Matutat, & Wurmle, 2001; Riggs, Mikulick, Whitmore, & Crowley, 1999; Wilens, 2004).

Family, genetic, twin, and adoption studies provide consistent evidence suggestive of genetic contribution to ADHD and SUD (Biederman et al., 1997; Qian et al., 2003). A number of studies imply that individuals with the combined and inattentive subtypes of ADHD are significantly more likely to meet criteria for ADHD as adults compared with those with the hyperactive/impulsive subtype of ADHD, and the former groups have higher risk for SUD (Clure et al., 1999). The combined and inattentive types do not differ in their use of alcohol and marijuana (Murphy, Barkley, & Busht, 2002). Many researchers have studied the impact of treatment of ADHD on SUD and concluded that stimulant therapy in childhood is associated with a reduction in the risk for subsequent drug and alcohol use disorder (Wilens, 2004; Wilens et al., 2003). A number of studies indicated the psychiatric comorbidity between SUD and anxiety disorders, mood disorders, eating disorders as well as disruptive behavior disorders (King et al., 1999; Weinberg, Rahdert, Colliver, & Glantz, 1998).

The association between ADHD and SUD was shown in many studies; however, nearly all of them were conducted in North America and in adults with history of ADHD. Moreover, there is clear evidence that cultural and social variables affect the pattern of substance use (Johnson & Muffler, 2000). General population surveys in the U.S. adolescents show that approximately one in four older adolescents meets criteria for abuse for at least one substance, and one in five meets the criteria for dependency. Nearly one in three adolescents reports daily smoking (Hopfer & Riggs, 2007). According to documented data, prevalence of smoking and substance use in the Iranian general population of adolescents is in low grade (Ahmadi, Alishahi, & Alavi, 2004; Mohtasham-Amiri, Cirus Bakht, & Nikravesh-Rad, 2008; Moosavi, 2000; Poorasl, Vahidi, Fakhari, Rostami, & Dastghiri, 2007; Ziai, Hatamizadeh, & Vameghi, 2001). One study among Iranian 12th graders reports that 7.2% of boys started smoking at the average age of 14.3 years (Ziai et al., 2001). Based on a study conducted among 1,400 male high school students, Mohtasham-Amiri et al. (2008) found that 28.2% reported ever smoking and only 15% stated they were currently smoking. In addition, they found the mean age for starting smoking was 12.8 years (Mohtasham-Amiri et al., 2008). One study among 1,785 10th-grade male students in 2007 showed that 12.7% had ever used alcohol and 2.0% used drugs (Poorasl et al., 2007). Another study showed that 14% of boys reported currently using tobacco and 5.7% using other substance (Moosavi, 2000). Ahmadi et al. (2004) found that substance dependency rate was 8.3% among Iranian secondary school students and their mean age was 13.4 years. They concluded that Iranian drug abuse policies state that people would be arrested and may be imprisoned for possession and use of illicit substance. This may be noted for a low reported rate of substance use in Iran (Ahmadi et al., 2004). The purpose of this study was to evaluate the impact of ADHD on the pattern of SUD among Iranian adolescents.

The question is as follows: Is ADHD a specific risk factor for changing the pattern of substance use in Iranian adolescents?

Method

Participants

Participants who met the criteria of SUDs—based on Diagnostic and Statistical Manual of Mental Disorders (4th ed., text revision; DSM-IV-TR; American Psychiatric Association, 2000)—were consecutively recruited from referrals to Roozbeh Hospital (a psychiatric hospital affiliated with Tehran University of Medical Sciences, which is also a referral center for child and adolescent psychiatric patients) or Correction Center for Juvenile Offenders (CCJO; a correction center for delinquent persons below 18 years of age).

The inclusion criteria were as follows: (a) age range of 11 to 18 years, (b) use of drugs in the preceding month, and (c) fulfillment of criteria for substance dependency or abuse. The exclusion criteria were the following: (a) experiential use, (b) use of drugs limited to cigarette and alcohol, and (c) psychosis.

Participants were divided into two groups: one with histories of ADHD (n = 33) and one without histories of ADHD (n = 33).

To control for the confounding effect of gender, we recruited a male-only sample.

Measures

Kiddie Schedule for Affective Disorder and Schizophrenia for School-Age Children (K-SADS)

It is a semistructured diagnostic interview tool to assess current, past, and lifetime diagnostic status in children and adolescents (6-8 years; Ambrosini, 2000). This instrument ascertains the diagnosis of ADHD and other psychiatric comorbidity based on DSM-IV criteria.

Opiate treatment index (OTI)

This measure assesses the pattern of psychoactive substance use in the past month, including cigarette, alcohol, marijuana, opium, diphenoxylate, amphetamines, cocaine, hallucinogens, and inhalants. This instrument also ascertains information on intravenous addiction behaviors, sexual behaviors, delinquency and medical health status, and onset of cigarette smoking, drug use, dependency, and abuse (Darke, Ward, Heather, & Wodak, 1991). All the items measured in OTI were measures expressed as a continuous score, and the final score is an index of severity of substance use.

First usage is according to the age they began to smoke cigarette or onset of substance use as experimentation and dependency, or abuse defined according to DSM-IV criteria and the time from substance use onset to dependency or abuse assessed on month.

Global Assessment Functioning (GAF)

It assesses adolescents’ functioning in the preceding year. This scale considers psychological, social, and occupational functioning on a hypothetical continuum of mental health/illness; it does not assess impairment of function due to physical or environmental limitations.

Design and Procedures

This case-control study was conducted from 2004 to 2005. Patients were interviewed by a child and adolescent psychiatrist and recruited into the study according to predetermined inclusion and exclusion criteria. The children and their parents signed the informed consent.

Data Analyses

The data were analyzed with chi-square test and t test. Where cell size falls below 5, we used Fisher’s exact test. For two-group comparison of means—including age, age of starting cigarette smoking, scores on substance use and substance abuse or dependency, severity of smoking and substance use, and also score of GAF—t test was used. Chi-square was used to compare individual status in education, employment, and prevalence rate for subtypes of substance use and psychiatric comorbidities.

Results

Ten out of 33 (30%) ADHD adolescents were from Roozbeh Hospital and 23 (70%) were from the CCJO. In non-ADHD group, there were 12 (36%) and 21 (64%) participants, respectively, from these centers who were not significantly different (p = .794, χ² = 0.2851). The two groups were matched on all relevant variables.

All participants were male. There was no difference for the age and occupation of the two groups, but educational level of ADHD group was significantly lower compared with that of non-ADHD group (χ² = 274.737, p = .0000, df = 2; Table 1).

Table 1.

Demographic Characteristics of Sample

	ADHD+ (n = 33)		ADHD− (n = 33)
	M	SD	M	SD	p value
Age (year)	16.9	0.8	17.1	1.1	ns
	n	%	n	%	p value
Education
Elementary notary school	20	61	8	25	.001
High school	9	27	22	65	.003
No education	4	12	3	10	ns
Employment
Worker	8	24	9	27	ns
Student	3	9	1	3	ns
Self-employment	20	61	19	58	ns
No employment	2	6	4	12	ns

In the ADHD group (n = 33), 1 patient had inattentive type, 8 patients had hyperactive/impulsive type, and 24 patients had combined type. For all the participants, ADHD had continued into adolescence.

Based on Table 2, adolescents with ADHD had earlier age of onset for cigarette smoking (t = 5.4, Fisher’s exact test = 29.2, p = .0001, df = 1), substance use (t = 8.1, Fisher’s exact test = 66.4, p = .0001, df = 1), substance abuse and dependence (t = 9.02, Fisher’s exact test = 81.5, p = .0001, df = 1), more severe use of substances (cannabis: t = 2.4, Fisher’s exact test = 5.6, p = .028, df = 1; heroin: t = 3.2, Fisher’s exact test = 10.3, p = .002, df = 1; cigarette: t = 2.6, Fisher’s exact test = 69, p = .01, df = 1; other drugs: t = 2.3, Fisher’s exact test = 5.2, p = .02, df = 1), and more functional impairment (t = 3.6, Fisher’s exact test = 12.76, p = .0007, df = 1). Drugs use (especially benzodiazepines) was more prevalent in this group (χ² = 7, p = .008, df = 1). Table 3 shows the prevalence of psychiatric comorbidities in ADHD and non-ADHD groups.

Table 2.

Characteristics of SUD in Groups With and Without ADHD

	ADHD+ (n = 33)		ADHD− (n = 33)
	M	SD	M	SD	p value
Age of cigarette smoking (year)	11.4	1.7	13.7	2.2	.0001
Age of substance use onset (year)	12.6	1.2	15	1.1	.0001
Age of substance dependency or abuse (year)	13.2	1.3	15.9	1.1	.0001
Time from substance use onset to dependency or abuse (month)	6	7	13.5	7	.0001
	n	%	n	%	p value
Prevalence for type of substance use
Opium	25	75	28	84	ns
Cannabis	26	78	20	60	ns
Heroin	18	54	12	36	ns
Alcohol	21	63	17	51	ns
Cigarette	33	100	30	95	ns
Drugs	12	36	3	9	.008
	M	SD	M	SD	p value
Severity of SUD^a
Opium	1.9	1.4	2.2	1.3	ns
Cannabis	1.7	1.3	1.1	1	.028
Heroin	1.9	1.8	0.6	1.3	.002
Alcohol	0.93	0.8	0.6	0.7	ns
Cigarette	3.8	0.5	3.2	1.2	.004
Drugs	0.5	0.8	0.1	0.4	.02
Mean GAF (past year)	45	5	55	5	.001

Note: SUD = substance use disorder; GAF = Global Assessment Functioning; OTI = opium treatment index.

According to OTI measure.

Table 3.

The Prevalence of Comorbid Disorders in Groups With and Without ADHD

	ADHD+ (n = 33)		ADHD− (n = 33)
Type of comorbid disorder	n	%	n	%	p value
Conduct disorder	12	36	7	21	ns
Major depression disorder	11	33	16	48	ns
Bipolar mood disorder	10	30	3	12	ns
Oppositional defiant disorder	10	30	5	15	ns
Tic disorder	8	24	3	9	ns
Phobia	5	15	4	12	ns
Obsessive compulsive disorder	4	12	2	6	ns
Generalize anxiety disorder	1	3	3	9	ns
Enuresis	1	3	0	0	ns
Posttraumatic stress disorder	0	0	1	3	ns

We detected a trend of higher rates of comorbidities between ADHD participants and oppositional defiant disorder (ODD), obsessive compulsive disorder (OCD), CD, BMD, and tic disorders. But no statistically significant association was found. Overall, the average number of comorbid disorders was higher in ADHD group (1.9 compared with 1.3 disorders in non-ADHD group; χ² = 10.73, p = .03, df = 4).

The characteristics of substance use in ADHD patients with and without conduct disorder were summarized in Table 4. As seen, the results revealed no significant difference between the two groups.

Table 4.

Characteristics of Substance Use in ADHD Patients With and Without CD

	CD+ (n = 12)		CD− (n = 21)
	M	SD	M	SD	p value
Age of cigarette smoking (year)	12	2	12.3	1.5	ns
Age of substance use onset (year)	13.5	1.1	13.7	1.4	ns
Age of substance dependency or abuse (year)	13.9	1.1	14.4	1.2	ns
Time from substance use onset to dependency or abuse (month)	4.5	5	7.5	10	ns
	n	%	n	%	p value
Prevalence for type of substance use
Opium	10	83	16	71	ns
Cannabis	9	75	16	71	ns
Heroin	8	66	10	47	ns
Alcohol	9	75	12	57	ns
Cigarette	12	100	21	100	ns
Drugs	5	41	8	38	ns
	M	SD	M	SD	p value
Severity of substance use disorder^a
Opium	21	1.3	2	1.5	ns
Cannabis	1.6	1.3	1.7	1.3	ns
Heroin	2	1.9	1.7	1.8	ns
Alcohol	0.8	0.3	1	1	ns
Cigarette	3.4	0.3	3.8	0.6	ns
Drugs	0.5	0.8	0.5	0.9	ns
Mean GAF (past year)	35	5	45	5	.001

Note: CD = comorbid conduct disorder; GAF = Global Assessment Functioning; OTI = opium treatment index.

According to OTI measure.

In Table 5, we compared the prevalence of psychiatric comorbidities in groups of ADHD adolescents with and without CD. Although there was no significant difference between the two groups, the average number of comorbid disorders was higher in ADHD patients who had CD (2.5 vs. 1.5; χ² = 290, p = .0000, df = 4).

Table 5.

The Prevalence of Comorbid Disorders in ADHD Adolescents With and Without CD

	CD+ (n = 12)		CD− (n = 21)
Type of comorbid disorder	n	%	n	%	p value
Oppositional defiant disorder	6	50	4	19	ns
Major depression disorder	5	41	6	28	ns
Bipolar mood disorder	3	25	7	33	ns
Tic disorder	3	25	5	33	ns
Obsessive compulsive disorder	0	0	4	19	ns
Phobia	0	0	1	5	ns
Generalized anxiety disorder	0	0	1	5	ns

Note: CD = comorbid conduct disorder.

Discussion

Our study examined the patterns of SUD among Iranian adolescents with ADHD. We found an earlier onset of cigarette smoking and substance use, a shorter interval between the starting of substance use and meeting the criteria for SUD, and a pattern of greater severity of substance use and functional impairment.

The early onset of substance use in adolescents with ADHD is consistent with the results of previous studies (King et al., 1999; Riggs, 1998; Wilens, 2004). Although Thompson et al. (1996) found no difference between the onset of substance use in adolescents with or without ADHD, their sample consisted of adolescents who had CD. Given that CD even without ADHD is associated with early onset of substance use, the specificity of ADHD effect could not be identified with precision.

In addition, Biederman et al. (1997) and Wilens et al. (1997) showed that there was no association between ADHD itself and the onset of substance use in early adolescence, but presence of BMD or CD with ADHD was associated with earlier substance use. In our study, 66% of the ADHD group had comorbid BMD or CD, whereas only 33% of the control group had these disorders. This difference may explain the significant earlier onset of substance use in the ADHD group.

Consistent with previous studies, even in this study we found an earlier age of onset of substance use in ADHD group (Biederman et al., 1997; Thompson et al., 1996; Wilens, 2004; Wilens et al., 1997) as well as greater severity in usage and functional impairments (Modestine et al., 2001; Riggs et al., 1999; Riggs et al., 2004; Wilens, 2004).

In our study, the mean age of cigarette smoking in ADHD group was 11.4 years and the mean age of substance use beginning was 12.6 years. This was lower compared with general population of students in the same culture (Ahmadi et al., 2004; Mohtasham-Amiri et al., 2008; Ziai et al., 2001). We postulate that characteristics intrinsic to ADHD—such as impulsivity, novelty seeking, and high preference for small, immediate rewards over larger delayed rewards in ADHD patients—embody the risks leading to the development of SUD. In our study, these risks appear to override cultural barriers and lower availability of drugs to the development of SUD. The association of ADHD with substance use may rely on risk factors shared by the two behaviors. In recent years, a growing number of studies have focused on the dopamine D4 receptor gene (DRD4) as mediating the susceptibility to ADHD (El-Faddagh, Laucht, Maras, Vohringer, & Schmidt, 2004). However, the involvement of dopamine in drug reinforcement is well recognized (Volkow, Fowler, Wang, & Swanson, 2004).

A number of hypotheses derived from candidate genes studies suggest plausible biological mechanisms for the association between ADHD and SUD. Some studies have reported an association between the presence of the seven-repeat allele of the DRD4 and novelty-seeking behavior, ADHD, and substance abuse (Comings et al., 1999).

Reduced central serotonin (5-HT) activity has been associated with impulsive choice behavior (Liu, Wilkinson, & Robbins, 2004) as both the serotonin and dopamine neuromodulator systems are implicated in impulsivity. There is some evidence that limbic cortical and striatal structures are abnormal in animal models of ADHD, and damage to these systems can cause impulsivity (Cardinal, Winstanley, Robbins, & Everitt, 2004).

In addition, catechol-o-methyl transferese (COMT) polymorphism, which affects enzyme activity, and DRD4 have been associated with personality characteristics and disease, such as novelty-seeking personality and substance abuse (Comings et al., 1999; Qian et al., 2003). Our study does not include genotype data and cannot examine the role of candidate genes in the detected associations.

Two distinct subtypes showed up in our results. They included those who dropped out during elementary school as well those who completed higher education. Our statistical analysis showed no differences in the pathway to SUD between them.

Our study did not detect significant differences in comorbid psychiatric disorders in the two groups studied. This could be due to the small sample size, lacking sufficient statistical power to detect statistical significance despite the detected trend. However, similar to other studies (King et al., 1999), the average number of comorbid disorders was higher in the ADHD group. The prevalence of mood disorders in ADHD patients without CD (41% had major depressive disorder and 25% had BMD) is an important finding of our study. The presence of BMD is an important factor affecting the pattern of SUDs in adolescents (Biederman et al., 1997; Wilens, 2004).

The most important limitation of this study was the small sample size because of the low number of the adolescents who was referred to the hospital for substance use. In addition, interviewing the parents of some adolescents in CCJO was not possible. Our all-male sample control was confounded due to gender, as we were limited by the lack of female participants. Although the pattern and type of substance use in Iranian culture may be different, the relationship between ADHD and SUD was similar to the rest of the world.

An important implication of our results is the fact that the management of ADHD as a treatable disorder might be associated with better prognosis of SUDs in adolescents, to diminish the diverse negative complications of SUD and decrease the social and financial consequences of this problem. Considering the adverse consequences of SUDs in adolescents and adults, the high prevalence of ADHD in community, and the effects of treatment of ADHD on decreasing substance use, the importance of early diagnosis and treatment of ADHD seem quite reasonable and encouraging. However, longitudinal studies are required to evaluate the effects of screening, early diagnosis, and treatment of ADHD in children and adolescents in lowering the negative consequences of SUD.

Footnotes

The authors declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

The authors received no financial support for the research and/or authorship of this article.

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