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The “Law of the Few” and ADHD & Psychostimulants (Adderall, Ritalin, Concerta)

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Stanley Milgram and Our “Small-World”• The Law of the Few: Certain people are critical to social epidemics.

Question: How are human beings connected?

“Small-World” research experiment

(e.g., from Omaha, Nebraska to a stockbroker in Massachusetts)

• Connectors: a very small number of special people—who thrive at making innumerable “weak tie” acquaintances—and through whom the rest of us are all linked (measure: # of Facebook friends?)

5 or 6 steps = “Six Degrees of Separation” because not all degrees

are equal

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Background & SignificanceSo what? What is the significance of ADHD and psychostimulants?

– ADHD is the most commonly diagnosed behavioral disorder in children, making up more than 50% of all child psychiatric diagnoses

– 75-85% of children diagnosed with ADHD are prescribed psychostimulant drugs (e.g., Ritalin, Adderall, Concerta, Dexedrine)

– the U.S. population consumes 90% of the world’s production of psychostimulants

– school-age children in the U.S. consume 4 times more psychiatric medication than children in the rest of the world combined

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Background & SignificanceSo what? What is the significance of ADHD and psychostimulants? cont’d . . .

– an estimated 3-5% of school-age children have the disorder (NIH Consensus Statement, 1998); other estimates 4-12% (Vanderbilt, MUSC);

(1.5-to-6 million kids, 1-to-3 students in every classroom in the U.S.)

– ADHD prevalence estimates from actual community samples range from as low as 1.7% (Calif. Bay Area) to as high as 26% (military bases near Virginia Beach)

– rates of psychostimulant use vary as much as 3-fold between states and 10-fold within them (Rappley et al., 1995; Wennberg & Wennberg, 2000; Zito et al., 1997)

– At the peak age for psychostimulant use, 11, almost 1 in every 9 boys in the U.S. uses these drugs (Cox et al., Journal of Pediatrics, February 2003).

– big $$: approximately $3 billion spent in 2005 on ADHD related drugs (new potential growth markets: pre-schoolers and adults)

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DSM-IV Diagnostic Criteria for ADHDDiagnostic and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric Association)

Either (1) or (2)

(1). 6 (or more) of the following 9 symptoms of inattention have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:

Inattention (a) often fails to give close attention to details or makes careless mistakes in schoolwork,

work, or other activities (b) often has difficulty sustaining attention in tasks or play activities (c) often does not seem to listen when spoken to directly (d) often does not follow through on instructions and fails to finish schoolwork, chores, or

duties in the workplace (not due to oppositional behavior or failure to understand instructions) (e) often has difficulty organizing tasks and activities (f) often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort

(such as schoolwork or homework). (g) often loses things necessary for tasks or activities (e.g. toys, school assignments, pencils,

books, or tools) (h) is often easily distracted by extraneous stimuli (i) is often forgetful in daily activities

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DSM-IV Diagnostic Criteria for ADHDDiagnostic and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric Association)

(2). 6 (or more) of the following 9 symptoms of hyperactivity-impulsivity have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:

Hyperactivity (a) often fidgets with hands or feet or squirms in seat (b) often leaves seat in classroom or in other situations in which remaining seated is expected (c) often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness) (d) often has difficulty playing or engaging in leisure activities quietly (e) is often "on the go" or often acts as if "driven by a motor" (f) often talks excessively

Impulsivity (g) often blurts out answers before questions have been completed (h) often has difficulty awaiting turn (i) often interrupts or intrudes on others (e.g. butts into conversations or games)

ADHD’s inherent subjectivity lends itself to criticisms of being a convenient social construct (for “medicalizing” and medicating annoying behavior) and fuels the controversy over the disorder.

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Four Aspects to the Controversy Over ADHD/Stimulants

1. Allegation: ADHD is not a real disorder and could be part of a larger feminist conspiracy to make little boys more like little girls. etiology (its cause) is unknown and no independent medical test for diagnosing ADHD;

biology/nature vs. environment/nurture debate

2. Allegation: ADHD is a conspiracy on the part of public schools to warehouse kids instead of effectively teaching and disciplining them. initial identification of ADHD is often by teachers or other school personnel in academic settings

3. Allegation: Ritalin is really “kiddie cocaine” and parents who give their kids these kinds of drugs are simply doping up their problem children. psychostimulants are powerful, potentially addictive drugs susceptible to personal abuse and illegal diversion

(classified as Schedule II drugs by the DEA, along with Oxycontin and morphine)

4. Allegation: ADHD is over-diagnosed and psychostimulants are over-prescribed across the country. number of ADHD diagnoses and psychostimulants Rx’s increased dramatically in the 1990s

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Ritalin/ADHD’s Tipping Point (early 1990s)

• 400-500% increase in ADHD diagnoses in the 1990s

– 1991: 800,000 to 950,000 children diagnosed with ADHD

– 2001: 4 to 4.75 million children diagnosed with ADHD

• 800-900% increase in psychostimulant use in the 1990s

– 1991: 2 million psychostimulant prescriptions

– 2001: 21 million psychostimulant prescriptions

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Per Capita Ritalin Use Over Time (1981-1996)

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Ritalin/ADHD’s Tipping Point

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Increased Public Awareness During Clinton Years “As many of you know, the Journal of the American Medical Association recently

reported that the number of preschoolers, ages 2-4 who are taking psychotropic drugs increased dramatically from 1991 to 1995 [200,000-300,000 or 1.5% of the total]. We know that the increase for Ritalin alone was 150 percent, and the use of anti-depressants increased over 200 percent. Now I am no doctor, as is obvious, but I am a parent and I have been a longtime children’s advocate. And these findings concern me. I know they concern Dr. Hyman [Director, NIMH], Secretary [Donna] Shalala and countless other experts.”

The White House -- March 20, 2000

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Public Policy Implications & Questions

• Over-diagnosis of ADHD (Are we “pathologizing” childhood?)Does the U.S. have a monopoly of wisdom on diagnosing and treating ADHD? TYPE II error

• Over-use of psychostimulants (public health issue)waste of limited resources; Society for Neuroscience findings, 2001

--------------------------------------------------------------------• Under-diagnosis of ADHD (public health/education issues)

Children with unmet mental health needs are more likely to suffer academically and developmentally.

TYPE I error

• Under-use of psychostimulants (public health/education issues)Studies show that untreated ADHD can lead to increased self-medication and drug addiction.

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Research Question

What explains the enormous variation

in psychostimulant consumption across the U.S.?

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0 to 1,600 Low (4.6%)1,600 to 3,150 Below Average (25.5%)3,150 to 5,150 Average (43.5%)5,150 to 6,750 Above Average (19.6%)6,750 to 8,350 High (4.9%)

grams/per 100,000 Individuals

8,350 to 11,000 Extremely High (1.8%)

Methylphenidate and Amphetamine Distribution, 2005 (DEA data)(average = 4,150 grams/100,000 individuals)

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National Profile of Psychostimulant Use Data Set: DEA’s Automation of Reports & Consolidated Orders System (ARCOS)

- access via Freedom of Information Act (chocolates and flowers helped expedite an otherwise extraordinarily tedious and time-consuming process)

- not a sample: tracks every ounce of psychostimulant distribution in the U.S. from its point of manufacture through commercial distribution channels to points of sale at the dispensing/retail level: hospitals, pharmacies, practitioners and academic medical centers

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Characteristics of Counties with High and Low Use of Psychostimulants, DEA ARCOS data

* difference in means significant at the .10 level, ** at the .05 level, *** at the .01 level

Variable

Mean for all U.S. Counties (Standard Error)

Low Consumption

n=1,015 counties (Standard Error)

High Consumption n=1,015 counties

(Standard Error)

Distribution Rate (Grams of Psychostimulant/per 100K)***

3,359 grams (37.31)

1,796 grams (20.72)

4,923 grams (43.50)

Total Population***

89,327 (52.22)

65,680 (86.25)

114,000 (59.34)

Per Capita Income***

$21,397 (130.8)

$20,118 (159.2)

$22,760 (204.6)

Unemployment Rate***

4.9% (0.049)

5.4% (0.079)

4.4% (0.055)

% of Pop. With Some Form of Health Insurance***

82.9% (0.10)

82.1% (0.137)

83.7% (0.131)

White Population as Percentage of Total Population**

87.9% (0.290)

87.1% (0.455)

88.6% (0.362)

Black Population as Percentage of Total Population

9.7% (0.280)

10.2% (0.438)

9.4% (0.352)

Asian Population as Percentage of the Total Population

2.45% (0.280)

2.5% (0.441)

2.4% (0.358)

State has Schedule II Rx Monitoring Program***

30.7% (0.008)

34.3% (0.012)

27.0% (0.012)

Soci

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hara

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istic

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Children/Adolescents as a % of the Population***

29.0% (0.061)

29.2% (0.10)

28.8% (0.075)

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Characteristics of Counties with High and Low Use of Psychostimulants, DEA ARCOS data

* difference in means significant at the .10 level, ** at the .05 level, *** at the .01 level

Variable

Mean for all U.S. Counties (Standard Error)

Low Consumption

n=1,015 counties (Standard Error)

High Consumption n=1,015 counties

(Standard Error)

Students--to--Teacher Ratio***

14.6 (0.048)

14.3 (0.070)

14.8 (0.066)

Private Students--to--Public Students Ratio***

.058 (0.001)

.043 (0.0018)

.069 (0.002)

Private Coed--to--Private Non-Coed Students***

58.0 (8.609)

38.0 (8.092)

68.3 (12.33)

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ract

eris

tics

Private Sectarian--to--Private Non-Sectarian Students***

23.8 (2.755)

14.5 (2.072)

28.5 (3.990)

HMO Penetration (% of Individuals Enrolled in HMOs)***

12.1% (0.248)

10.2% (0.322)

14.1% (0.374)

Number of HMOs Operating in a County***

3.9 (0.069)

3.4 (0.092)

4.5 (0.101)

MDs/per 100,000 Individuals***

112 (2.690)

86 (3.50)

139 (4.00)

Child Psychiatrists as Percentage of Total MDs***

0.4% (0.026)

0.3% (0.038)

0.5% (0.036)

Psychiatrists as Percentage of Total MDs***

3.0% (0.099)

2.5% (0.149)

3.4% (0.119)

GPs, FPs as Percentage of Total MDs***

41.1% (0.515)

47.7% (0.757)

34.7% (0.662)

Pediatricians as Percentage of Total MDs***

5.5% (0.129)

4.9% (0.200)

6.1% (0.166)

Neurologists as Percentage of Total MDs***

0.9% (0.046)

0.7% (0.085)

1.1% (0.039)

Female MDs--to--Male MDs Ratio

.210 (0.004)

.210 (0.006)

.210 (0.004)

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Sys

tem

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isti

cs

Young MDs(<55)--to--Senior MDs(>55) Ratio***

1.8 (0.023)

1.6 (0.035)

1.9 (0.030)

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Main Limitation of Existing Studies: Generalizability

Most of what we know about ADHD is based on local community studies of children with the disorder.

Thus, to date we have relied primarily on massive meta-analyses and the NIH funded Multimodal Treatment Study of ADHD (MTA) to cobble together a national profile of the child population diagnosed with ADHD.

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A National Profile of Children Diagnosed with ADHDData Set: National Health Interview Survey (NHIS)

- nationally representative, cross-sectional health survey conducted jointly by the National Center for Health Statistics (NCHS) and the Centers for Disease Control & Prevention (CDC)

- sample size: 37,573 households; 97,059 persons in 38,171 families

- child component: 12,910 children less than 18 years old; response rate, 91%

- survey question: “Has a doctor or a health professional ever told you that [child’s name] has ADHD?”

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Characteristics of Children Diagnosed with ADHD* difference in means significant at the .10 level, ** at the .05 level, *** at the .01 level

Variable

Overall Mean (S.E.)

ADHD? Yes (n=590, 5%)^

ADHD? No (n=10,728, 95%)^

Demographic Male*** .512

(.005) .767 (.020)

.498 (.006)

Female***

.488 (.005)

.233 (.020)

.502 (.006)

Age (mean)***

9.52 (.056)

11.7 (.150)

9.39 (.052)

Birth Weight (mean in ounces)** 118.4 (.227)

116.1 (1.06)

118.7 (.253)

White*** .766 (.006)

.838 (.017)

.764 (.006)

Black** .153 (.005)

.117 (.015)

.156 (.005)

Asian***

.081 (.003)

.045 (.009)

.080 (.003)

Geographic Region Northeast** .184

(.005) .147 (.019)

.186 (.006)

Midwest .251 (.007)

.273 (.021)

.250 (.007)

South*** .352 (.007)

.423 (.026)

.348 (.007)

West*** .212 (.006)

.157 (.018)

.215 (.006)

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Characteristics of Children Diagnosed with ADHD * difference in means significant at the .10 level, ** at the .05 level, *** at the .01 level

Variable

Overall Mean (S.E.)

ADHD? Yes (n=590, 5%)^

ADHD? No (n=10,728, 95%)^

Family # of persons in the family (mean)***

4.43 (.019)

4.12 (.061)

4.46 (.021)

Relationship with Parents Mother: biological*** .965

(.002) .900 (.015)

.965 (.002)

Mother: step, adoptive, foster, none***

.035 (.002)

.100 (.015)

.034 (.002)

Parents Present Mother and Father*** .706

(.006) .604 (.024)

.709 (.006)

Mother, no Father*** .226 (.005)

.286 (.022)

.225 (.005)

Father, no Mother .041 (.002)

.060 (.011)

.040 (.002)

Neither Mother nor Father*

.027 (.002)

.050 (.010)

.026 (.002)

Parents’ Marital Status Married*** .754

(.005) .640 (.025)

.758 (.006)

Divorced/Separated/Never Married/Widowed***

.246 (.005)

.360 (.025)

.242 (.006)

Mother’s Highest Level of Education Less Than College .768

(.005) .830 (.020)

.768 (.005)

College Degree or More***

.232 (.004)

.170 (.020)

.232 (.005)

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Mayes, Bokhari, Scheffler, 2005 Conditional Probability of a Child Being Diagnosed with ADHD

0.0000

0.0500

0.1000

0.1500

0.2000

2 3 4 5 6 7 8

Family Size

White Male ChildMale Child w/o Bio MomMale Child w/o Dad in HouseWhite Male Child w/o Bio MomWhite Male Child w/o Bio Mom & w/o Dad In House