Risks and Mechanism of Action of Stimulants
Peter R. Breggin, M.D.

 

NIH Consensus Development Conference
on Diagnosis and Treatment
of Attention Deficit Hyperactivity Disorder

November 16–18, 1998
National Institutes of Health

The following is an abstract of the presentation of Peter R. Breggin, M.D. on risks and mechanism of action of stimulants. The abstract is designed for the use of panelists and participants in the conference and as a reference document for anyone interested in the conference deliberations. We are grateful to the author, who has summarized his materials and made them available in a timely fashion.
It is intended that this be a text-only version. Much of the information in the original is in tables which are not reproduced here. E-mail me if you need the tables sent to you. (I can send them as a Microsoft Word 6.0 document.) (A page using both tables and graphics is also available.)

Book by Peter R. Breggin, M.D.: Talking Back to Ritalin

Webmaster's note: This presentation was made before the announcement of results at Stanford showing the efficacy of Ritalin and the brain differences in boys with ADHD - both in function and in the way the brain responds to Ritalin. Breggin's views are considered controversial by many who have studied and worked with ADHD patients.

Risks and Mechanism of Action of Stimulants
Peter R. Breggin, M.D.

Table 1 summarizes the adverse drug reactions caused by methylphenidate and amphetamine stimulant drugs. Table 2 provides estimated frequencies of these reactions and adds those to pemoline. Younger children are especially vulnerable to these harmful effects (Dulcan, Popper, 1991; Schleifer, Weiss, Cohen, et al., 1975). Results of various studies are as follows.

CNS Adverse Effects in Double-Blind Placebo-Controlled Studies

Mayes and colleagues (1994) (partially controlled): 18.8 percent lethargy “variously described by raters as tired, withdrawn, listless, depressed, dopey, dazed, subdued and inactive”; 26.1 percent “irritability”; 7 percent severe adverse reactions including one manic-like reaction with “incessant talking,” one “wild” and “out of control,” and one “aggressive behavior.”

Schachar and colleagues (1997): 10 percent of children dropped out because of adverse drug reactions, including serious behavioral aberrations, such as “sadness and behavioral deterioration, irritability, withdrawal, lethargy, violent behavior,” “withdrawal and mild mania,” and “withdrawal and dysphoria.”

Barkley and colleagues (1990): the “percentage of children experiencing proneness to crying also increased by at least 10 percent during the low-dose condition” (p<.05) (p. 187); 3.6 percent were unable to complete the protocol because of serious adverse reactions including one with manic-like symptoms (p. 186).

Gillberg and colleagues (1997): three children developed hallucinations (4.8 percent).

These four controlled clinical trials found psychotic symptoms in at least 2 percent (6 of 260) and higher rates for other CNS effects.

Borcherding and colleagues (1990): “perseverative/compulsive behaviors” in 51 percent administered amphetamine and methylphenidate and one drop out “due to both the severity of the tic he developed during his initial treatment phase (dextroamphetamine) and exacerbated symptoms of separation anxiety.” Solanto and Wender (1989): 42 percent of completers “overaroused”with “cognitive perseveration”(overfocused, obsessive/compulsive reaction). Castellanos and colleagues (1997): 25 percent of children (comorbid for ADHD and Tourette’s) developed “largely transient” obsessive/compulsive behavior during a 3-week exposure to methylphenidate.

Table 1. Adverse effects caused by methylphenidate and amphetamines

(table omitted from text-only version)

Sources: Combination of Dulcan (1994, Table 35- 6, p. 1217), Arnold and Jensen (1995, Table 38- 5, p. 2306), and Drug Enforcement Administration (1995, p. 23). Any additional material indicated by brackets.
* “Zombie” references from Arnold and Jensen (1995, Table 38- 5, p. 2306; Table 38- 7, p. 2307; and column 2, p. 2307); Swanson, Cantwell, Lerner, et al. (1992, p. 15); Fialkov and Hasley (1984, p. 328).
†Arnold and Jensen (1995).
‡For methylphenidate only.

Table 2. Percentages of children experiencing ADRs from stimulants

(table omitted from text-only version)

* These figures are based primarily on reports of children and adolescents treated tbr ADHD.
-- Indicates nonexistence of information, not nonexistence of adverse effects. All data taken from Maxmen and Ward (1995, pp. 365-6).

Psychostimulant-Induced Motor and Vocal Tics

Borcherding and colleagues (1990): approximately 59 percent abnormal movements. Barkley and colleagues (1990): 10 percent increase in tics. Handen and colleagues (1991): (mentally retarded with ADHD) 11 percent stopped methylphenidate because of motor tics.

Lipkin and colleagues (1994) (retrospective): 9 percent tics or dyskinesias, one severe, irreversible case.

Psychostimulant Addiction, Withdrawal, and Rebound

Rapoport and colleagues (1978) (controlled, single amphetamine dose of 0.5 mg/kg): 71 percent of normal children suffered “marked behavioral rebound,” including “excitability, talkativeness, and, for three children, apparent euphoria.” Case reports of “crashing” with depression (Dulcan, 1994; also see Porrino, Rapoport, Behar, et al., 1983). The Drug Enforcement Administration (1995) and International Narcotics Control Board (1996, 1997) express concern about clinical use encouraging addiction and about abuse through illegal diversion.

Psychostimulant Growth Suppression and Retardation

Methylphenidate disrupts growth hormone cycles (Aarskog, Fevang, Klove, et al., 1977; Barter, Kammer, 1978; Brown, Williams, 1976; Joyce, Donald, Nicholls, et al., 1986; Shaywitz, Hunt, Jatlow, et al., 1982; reviewed in Dulcan, 1994, and Jacobvitz, Sroufe, Stewart, et al., 1990). Stimulants inhibit growth (height and weight) (Klein, Mannuzza, 1988; Safer, Allen, Barr, 1975). Spencer and colleagues (1996) conclude that growth deficits are related to ADHD, but the study is flawed, including the use of only one measurement per child and a control group that is 1 year older.

Methylphenidate Cardiovascular Adverse Effects

FDA’s Spontaneous Reporting System (SRS) (1985 through March 3, 1997): 2,821 reports with 8 percent cardiovascular, including arrhythmias and conduction problems (120) and heart arrests and failures (13) (Breggin, 1998b). Psychostimulants have direct cardiotoxic effects (Henderson, Fischer, 1994; Ishiguro, Morgan, 1997).

Further Review of the FDA Spontaneous Reporting System

FDA SRS reports indicate symptom clusters often overlooked in reviews: drug dependency, addiction, and withdrawal (117 reports); hair loss (250); various skin disorders; various blood disorders, including leukopenia; abnormal liver function tests (also see National Toxicology Program, 1995, for cancer threat); and convulsions (69). Adverse mental reactions: depression (48); psychotic depression (11); combined categories of overdose, overdose intentional, and suicide attempt (50); personality disorders (89); agitation (55); hostility (50); abnormal thinking (44); hallucinations (43); psychosis (38); and emotional lability (33).

 

Methylphenidate-Induced Abnormalities of Brain Function

Porrino and Lucignani (1987) (conscious rats): alterations in glucose metabolism in the brain. Bell and colleagues (1982) (rat brain tissue): glucose metabolic rates reduced in the motor cortex and increased in the substantia nigra and other deep structures.

Volkow and colleagues (1997) (PET in normals): reduced relative metabolism of basal ganglia and varied other effects. Wang and colleagues (1994) (PET in normals): decreased overall flow of blood into brain by 23 to 30 percent. Nasrallah and colleagues (1986) (PET): brain atrophy in more than 50 percent of 24 young adults with stimulant-treated hyperactivity in childhood. They conclude “cortical atrophy may be a long-term adverse effect of this treatment.” Brain scan studies that attempt to show pathology of ADHD (Lou, Henriksen, Bruhn, 1984; Giedd, Castellanos, Casey, et al., 1994; Hynd, Semrud-Clikeman, Lorys, et al., 1991) are almost certainly measuring pathology caused by psychostimulants.

Psychostimulant-Induced Abnormalities of Brain Chemistry in Animals

Methamphetamine: chronic exposure can produce irreversible CNS damage to dopamine receptors and norepinephrine function (Wagner, Ricaurte, Johanson, et al., 1980). Large chronic doses cause the death of serotonergic nerves in animals (Battaglia, Yeh, O’Hearn, et al., 1987). Melega and colleagues (1997b) found persistent “neurotoxic” changes in dopamine function (dopamine depletions of 55 to 85 percent) in vervet monkeys at 10 to 12 weeks (2 doses of 2 mg/kg). Sonsalla and colleagues (1996) found dopaminergic cell death in the substantia nigra of mice (approximate cell loss, 40 to 45 percent) (4 i.p. injections at 10 mg/kg).

Amphetamine: in rhesus monkeys, demonstrated long-lasting loss of dopamine and dopamine uptake sites (receptors) (Wagner, Ricaurte, Johanson, et al., 1980); down-regulation (subsensitivity) in the dopamine neurotransmitter system (Barnett, Kuczenski, 1986). Melega and colleagues (1997b) using PET in vervet monkeys found marked decreases in dopamine synthesis (25 percent at 10 to 12 weeks) with a 16 percent reduction in one amphetamine-treated animal at 32 weeks (2 doses of 2 mg/kg). Melega and colleagues (1997a) recorded gradual recovery from neurotoxicity in the striatum over 2 years (4 to 18 mg/kg over 10 days).

Methylphenidate: down-regulation of dopamine receptors (Barnett, Kuczenksi, 1986); reduction of the density of the norepinephrine receptors (Mathieu, Ferron, Dewar, et al., 1989); locus coeruleus loses responsiveness (Lacroix, Ferron, 1988).

Fenfluramine: (chemically related to amphetamine) causes death of serotonergic neurons (McCann, Seiden, Rubin, et al., 1997).

Psychostimulant Indirect Adverse Effects

Children lose their sense of responsibility for their own behavior (Breggin, 1997, 1998a; Jensen, Bain, Josephson, 1989) and experience many negative emotional reactions that they may not report (Sroufe, Stewart, 1973).

Psychostimulant Mechanism of Action

Spontaneous or self-generated activities¾play, mastery, exploration, novelty seeking, curiosity, and zestful socialization¾are central to the growth and development of animals and humans and necessary for the full elaboration of CNS synaptic connections (Greenough, Black, 1992; Weiler, Hawrylak, Greenough, 1995).

Psychostimulants consistently cause two specific, related adverse drug effects in animals (and also humans). First, stimulants suppress normal spontaneous or self-generated activity and socialization (Arakawa, 1994; Hughes, 1972; Randrup, Munkvad, 1967; Schiørring, 1979, 1981; Wallach, 1974). Second, stimulants promote abnormal stereotyped, obsessive/compulsive, asocial behaviors that are repetitive and meaningless (Bhattacharyya, Ghosh, Aulakh, et al., 1980; Costall, Naylor, 1974; Koek, Colpaert, 1993; Kuczenski, Segal, 1997; Mueller, 1993; Randrup, Munkvad, 1967; Rebec, Bashore, 1984; Rebec, Segal, 1980; Segal, 1975; Segal, Weinberger, Cahill, 1980; early studies reviewed in Wallach, 1974, and Schiørring, 1979). The effects occur in rats at doses as low as 0.63 mg/kg methylphenidate (Koek, Colpaert, 1993) or 0.3 mg/kg amphetamine (Rebec, Bashore, 1984).

The drugs suppress normal spontaneous, self-generated behaviors and socialization; they promote abnormal compulsive, asocial, compliant behaviors deemed suitable to structured and often suppressive situations, such as many classrooms (Breggin, 1997, 1998a; Breggin, Breggin, 1996, 1998; Ellinwood [in Kramer, Lipton, Ellinwood, et al., 1970]; Fialkov, Hasley, 1984; Rie, Rie, Stewart, et al., 1976; Rebec, Bashore, 1984). This drug-induced suppression of behavior and mental function is independent of the child’s mental state; it occurs in healthy animals and children. When children seem to be overactive, impulsive, or distractible, psychostimulants will also suppress these behaviors regardless of the cause, including ADHD-like behaviors that signal boredom, frustration, abuse, conflict, lack of rational discipline or age-appropriate attention, or inadequate educational interventions. This mutes the child’s distress or needs, allowing them to be ignored.

Table 3 lists some of the ADRs that are mistakenly seen as “improvements” when they reflect suppressed, overfocused, asocial behavior.

Risk/Benefit Ratio

There are no positive long-term psychostimulant effects (beyond 7 to 18 weeks) and no improvement in academic performance or learning (Swanson, 1993; also see Breggin, 1998a; Jacobvitz, Sroufe, Stewart, et al., 1990; Popper, Steingard, 1994; Richters, Arnold, Jensen, et al., 1995; Whalen, Henker, 1997). Studies claiming that ADHD leads to bad outcomes have studied children who have been diagnosed and treated with drugs (Mannuzza, Klein, Bessler, et al., 1993, 1998; Weis, Hechtman, Milroy, et al., 1985). Diagnosis, treatment, and other non-ADHD factors may contribute to any bad outcome. Meanwhile, there are many common, severe stimulant hazards. The “therapeutic effects” are in reality toxic effects (Table 3). The use of psychostimulant drugs for the control of behaviors labeled ADHD in children should be stopped.

Future Research Directions

Before the clinical use of psychostimulants for ADHD is continued, large animal psychostimulant studies are needed that focus on (1) the extent and potential irreversibility of abnormalities in gross brain function (blood flow and energy consumption), (2) the extent and potential irreversibility of neurotransmitter down-regulation and receptor loss, (3) neuronal death and atrophy, (4) reduced brain plasticity (fewer synaptic connections), (5) disruption of pituitary and hormonal functions, (6) developmental retardation of growth and behavior, and (7) cardiac toxicity.

Table 3. Adverse drug reactions (ADRs) from stimulants mistakenly labelled beneficial (omitted from text-only version)

*Considered positive or therapeutic by the source. cct = controlled clinical trial

  1. Swanson, Cantwell, Lerner, et al. (1992) [confirms many ADRs in list]
  2. Borcherding, Keysor, Rapoport, et al. (1990) [cct]
  3. Schiørring (1981)
  4. Arnold, Jensen (1995)
  5. Tannock, Schachar, Carr, et al. (1989) [cct]
  6. Mayes, Crites, Bixler, et al. (1994) [cct]
  7. Schleifer, Weiss, Cohen, et al. (1975) [cct]
  8. Dulcan (1994) and Dulcan, Popper (1991) [open trial]
  9. Rie, Rie, Stewart, et al. (1976) [cct]
  10. Bradley (1937) [open trial]
  11. Granger, Whalen, Henker (1993) [cct]
  12. Solanto, Wender (1989) [cct]
  13. Cunningham, Barkley (1978) [cct]
  14. Dyme, Sahakian, Golinko, et al. (1982) [cct]
  15. Barkley, Karlsson, Pollard, et al. (1985) [cct]
  16. Cotton, Rothberg (1988) [cct]
  17. Jacobvitz, Sroufe, Stewart, et al. (1990)
  18. Davy, Rodgers (1989)
  19. Schachar, Tannock, Cunningham, et al. (1997) [cct]
  20. Barkley, McMurray, Edelbrock, et al. (1990) [cct]
  21. Pelham (1989)
  22. Sleator, Ullmann, von Neuwman (1982)
  23. Ellinwood, Tong (1996)
  24. Handen, Feldman, Gosling, et al. (1991) [cct]
  25. Fialkov, Hasley (1984)
  26. Barkley, Cunningham (1979) [cct]
  27. Whalen, Henker, Granger (1989) [cct]
  28. Castellanos, Giedd, Elia, et al. (1997) [cct]

 

References

Aarskog D, Fevang F, Klove H, Stoa K, Thorsen T. The effect of the stimulant drugs, dextroamphetamine and methylphenidate, on secretion of growth hormone in hyperactive children. J Pediatr 1977;90:136-9.

Arakawa O. Effects of methamphetamine and methylphenidate on single and paired rat open-field behaviors. Physiol Behav 1994;55:441-6.

Arnold LE, Jensen PS. Attention-deficit disorders. In: Kaplan HI, Sadock B, editors. Comprehensive textbook of psychiatry. Vol 6. Baltimore: Williams & Wilkins; 1995. p. 2295- 2310.

Barkley RA, Cunningham CE. The effects of methylphenidate on the mother-child interactions of hyperactive children. Arch Gen Psychiatry 1979;36:201-8.

Barkley RA, Karlsson J, Pollard S, Murphy JV. Developmental changes in the mother-child interactions of hyperactive boys: effects of two dose levels of Ritalin. J Child Psychol Psychiatry 1985;26:705-15.

Barkley RA, McMurray MB, Edelbrock CS, Robbins K. Side effects of methylphenidate in children with attention deficit disorder: a systemic, placebo-controlled evaluation. Pediatrics 1990;86:184-92.

Barnett JV, Kuczenski R. Desensitization of rat striatal dopamine-stimulated adenylate cyclase after acute amphetamine administration. J Pharmacol Exp Ther 1986;237:820-5.

Barter M, Kammer H. Methylphenidate and growth retardation. JAMA 1978;239:1742-3.

Battaglia G, Yeh SY, O’Hearn E, Molliver ME, Kuhar MJ, De Souza EB. 3,4- methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain. J Pharmacol Exp Ther 1987;242:911-6.

Bell RD, Alexander GM, Schwartzman RJ, Yu J. The methylphenidate-induced stereotypy in the awake rat: local cerebral metabolism. Neurology 1982;32:377-81.

Bhattacharyya AK, Ghosh B, Aulakh CS, Pradhan SN. Correlation of behavioral and neurochemical effects of acute administration of methylphenidate in rats. Prog Neuropsychopharmacol 1980;4:129-36.

Borcherding BG, Keysor CS, Rapoport JL, Elia J, Amass J. Motor/vocal tics and compulsive behaviors on stimulant drugs: is there a common vulnerability? Psychiatry Res 1990;33:83-94.

Bradley C. The behavior of children receiving Benzedrine. Am J Psychiatry 1937;94:577-85.

Breggin PR. SRS data obtained from the FDA through the Freedom of Information Act and compiled and analyzed by the author. 1998a.

Breggin PR. Talking back to Ritalin. Monroe (ME): Common Courage Press; 1998b.

Breggin PR. Brain-disabling treatments in psychiatry. New York: Springer Publishing Company; 1997.

Breggin PR, Breggin G. The war against children of color. Monroe (ME): Common Courage Press; 1998.

Breggin PR, Breggin G. The hazards of treating “attention-deficit/hyperactivity disorder” with methylphenidate (Ritalin). Journal of College Student Psychotherapy 1995;10:55-72.

Brown WA, Williams BW. Methylphenidate increases serum growth hormone concentrations. J Clin Endocrinol Metab 1976;43:937-9.

Castellanos FX, Giedd JN, Elia J, Marsh WL, Rathke GF, Hamburger SD, et al. Controlled stimulant treatment of ADHD and comorbid Tourette’s syndrome: effects of stimulant and dose. J Am Acad Child Adolesc Psychiatry 1997;36:589-96.

Costall B, Naylor RJ. The involvement of dopaminergic systems with the stereotyped behavior patterns induced by methylphenidate. J Pharm Pharmacol 1974;26:30-3.

Cotton MF, Rothberg AD. Methylphenidate v. placebo: a randomized double-blind crossover study in children with attention deficit disorder. S Afr Med J 1988;74:268-71.

Cunningham CE, Barkley RA. The effects of methylphenidate on the mother-child interactions of hyperactive identical twins. Dev Med Child Neurol 1978;20:634-42.

Davy T, Rodgers CL. Stimulant medication and short attention span: a clinical approach. J Dev Behav Pediatr 1989;10:313-8.

Drug Enforcement Administration (DEA). Methylphenidate (background paper). Washington (DC): Drug and Chemical Evaluation Section, Office of Diversion Control, DEA, U.S. Department of Justice; October 1995.

Dulcan M. Treatment of children and adolescents. In: Hales R, Yudofsky S, Talbott J, editors. The American Psychiatric Press, Inc. Textbook of Psychiatry. 2nd ed. Washington (DC): American Psychiatric Press; 1994. p. 1209-50.

Dulcan M, Popper C. Concise guide to child and adolescent psychiatry. Washington (DC): American Psychiatric Press; 1991.

Dyme IZ, Sahakian BJ, Golinko BE, Rabe EF. Perseveration induced by methylphenidate in children: preliminary findings. Prog Neuropsychopharmacol Biol Psychiatry 1982;6:269-73.

Ellinwood EH, Tong HL. Central nervous system stimulants and anorectic agents. In: Dukes MNG, editor. Meyler’s side effects of drugs: an encyclopedia of adverse reactions and interactions. 13th ed. New York: Elsevier; 1996. p. 1-30.

Fialkov JM, Hasley S. Psychotropic drug effects contributing to psychiatric hospitalization of children: a preliminary study. J Dev Behav Pediatr 1984;5:325-30.

Giedd JN, Castellanos FX, Casey BJ, Kozuch P, King AC, Hamburger SD, et al. Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder. Am J Psychiatry 1994;151:665-9.

Gillberg C, Melander H, von Knorring AL, Janols LO, Thernlund G, Hagglof B, et al. Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry 1997;54:857-64.

Granger DA, Whalen CK, Henker B. Perceptions of methylphenidate effects of hyperactive children’s peer interactions. J Abnorm Child Psychol 1993;21:535-49.

Greenough WT, Black JE. Induction of brain structure by experience: substrates for cognitive development. In: Gunnar M, Nelson C, editors. Developmental behavioral neuroscience. Vol. 24. Minnesota Symposia on Child Development. Hillsdale (NJ): Lawrence Erlbaum; 1992. p. 155- 200.

Handen BL, Feldman H, Gosling A, Breaux AM, McAuliffe S. Adverse side effects of methylphenidate among mentally retarded children with ADHD. J Am Acad Child Adolesc Psychiatry 1991;30:241-5.

Henderson TA, Fischer VW. Effects of methylphenidate (Ritalin) on mammalian myocardial ultrastructure. Am J Cardiovasc Pathol 1994;5:68-78.

Hughes RN. Methylphenidate induced inhibition of exploratory behaviour in rats. Life Sci 1972;11:161-7.

Hynd GW, Semrud-Clikeman M, Lorys AR, Novey ES, Eliopulos D, Lyytinen H. Corpus callosum morphology in attention deficit-hyperactivity disorder: morphometric analysis of MRI. J Learn Disabil 1991;24:141-6.

International Narcotics Control Board (INCB). INCB sees continuing risk in stimulant prescribed for children. INCB Annual Report Background Note No. 4. 4 March 1997. Vienna, Austria. International Narcotics Control Board (INCB). Control of use of methylphenidate in the treatment of ADD: expert meeting on amphetamine-type stimulants, Shanghai. 25-29 Nov 1996. Vienna, Austria.

Ishiguro Y, Morgan JP. Biphasic inotropic effects of methamphetamine and methylphenidate on ferret papillary muscles. J Cardiovascular Pharmacol 1997;30:744-9.

Jacobvitz D, Sroufe LA, Stewart M, Leffert N. Treatment of attentional and hyperactivity problems in children with sympathomimetic drugs: a comprehensive review. J Am Acad Child Adolesc Psychiatry 1990;29:677-88.

Jensen PS, Bain MW, Josephson AM. Why Johnny can’t sit still: kids’ ideas why they take stimulants. Unpublished paper from the Division of Neuropsychiatry, Walter Reed Army Institute of Research, Washington (DC); 1989.

Joyce PR, Donald RA, Nicholls MG, Livesey JH, Abbott RM. Endocrine and behavioral responses to methylphenidate in normal subjects. Biol Psychiatry 1986;21:1015-23.

Klein RG, Mannuzza S. Hyperactive boys almost grown up. III. Methylphenidate effects on ultimate height. Arch Gen Psychiatry 1988;45:1131-4.

Koek W, Colpaert FC. Inhibition of methylphenidate-induced behaviors in rats: differences among neuroleptics. J Pharmacol Exper Ther 1993;267:181-91.

Kramer JC, Lipton M, Ellinwood EH Jr, Sulser F (chairmen). In: Ellinwood EH, Cohen S, editors. Current concepts on amphetamine abuse: discussion of Part II. Proceedings of a workshop; 1970 Jun 5-6; Duke University Medical Center. Rockville (MD): National Institutes of Mental Health; 1970.

Kuczenski R, Segal DS. Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. J Neurochem 1997;68:2032-7.

Lacroix D, Ferron A. Electro-physiological effects of methylphenidate on the coeruleo-cortical noradrenergic system of the rat. Eur J Pharmacol 1988;149:277-85.

Lipkin PH, Goldstein U, Adesman AR. Tics and dyskinesias associated with stimulant treatment for attention-deficit hyperactivity disorder. Arch Pediatr Adolesc Med 1994;148:859-61.

Lou HC, Henriksen L, Bruhn P. Focal cerebral hypoperfusion in children with dysphasia and/or attention deficit disorder. Arch Neurol 1984;41:825-9.

Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M. Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry 1998;155:493-8.

Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M. Adult outcome of hyperactive boys: educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry 1993;50:565-76.

Mathieu JF, Ferron A, Dewar KM, Reader TA. Acute and chronic effects of methylphenidate on cortical adrenoreceptors in the rat. Eur J Pharmacol 1989;162:173-8.

Maxmen JS, Ward NG. Psychotropic drugs fast facts. 2nd ed. New York: WW Norton; 1995.

Mayes SD, Crites DL, Bixler EO, Humphrey FJ 2nd, Mattison RE. Methylphenidate and ADHD: influence of age, IQ and neurodevelopmental status. Dev Med Child Neurol 1994;36:1099-1107.

McCann UD, Seiden LS, Rubin LJ, Ricaurte GA. Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine: a systematic review of evidence. JAMA 1997;278:666-72.

Melega WP, Raleigh MJ, Stout DB, Huang SC, Phelps ME. Ethological and 6-[18F]fluoro-L-DOPA- PET profiles of long-term vulnerability to chronic amphetamine. Behav Brain Res 1997a;84:259-68.

Melega WP, Raleigh MJ, Stout DB, Lacan G, Huang SC, Phelps ME. Recovery of striatal dopamine function after acute amphetamine- and methamphetamine-induced neurotoxicity in the vervet monkey. Brain Res 1997b;766:113-20.

Mueller K. Locomotor stereotypy is produced by methylphenidate and amfonelic acid and reduced by haloperidol but not clozapine or thioridazine. Pharmacol Biochem Behav 1993;45:71-6.

Nasrallah H, Loney J, Olson S, McCalley-Whitters M, Kramer J, Jacoby C. Cortical atrophy in young adults with a history of hyperactivity in childhood. Psychiatry Res 1986;17:241-6.

National Toxicology Program. NTP technical report on toxicology and carcinogenesis studies of methylphenidate hydrochloride in F344/N rats and B6C3F mice (feed studies). Rockville (MD): National Institutes of Health. NIH Publication No. 95-3355; 1995.

Pelham WE. Behavior therapy, behavioral assessment and psychostimulant medication in the treatment of attention deficit disorders: an interactive approach. In: Bloomingdale LM, Swanson JM, editors. Attention deficit disorder. IV. Emerging trends in attentional and behavioral disorders of childhood. New York: Pergamon; 1989. p. 169-202.

Popper CW, Steingard RJ. Disorders usually first diagnosed in infancy, childhood, or adolescence. In: Hales NR, Yudofsky S, Talbott J, editors. Textbook of psychiatry. 2nd ed. Washington (DC): American Psychiatric Press; 1994. p. 729-832.

Porrino LJ, Lucignani G. Different patterns of local brain energy metabolism associated with high and low doses of methylphenidate. Relevance to its action in hyperactive children. Biol Psychiatry 1987;22:126-38.

Porrino LJ, Rapoport JL, Behar D, Ismond DR, Bunney WE Jr. A naturalistic assessment of the motor activity of hyperactive boys. II. Stimulant drug effects. Arch Gen Psychiatry 1983;40:688- 93.

Randrup A, Munkvad I. Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacologia 1967;11:300-10.

Rapoport JL, Buchsbaum MS, Zahn TP, Weingartner H, Ludlow C, Mikkelsen EJ. Dextroamphetamine: cognitive and behavioral effects in normal prepubertal boys. Science 1978;199:560-63.

Rebec GV, Bashore TR. Critical issues in assessing the behavioral effects of amphetamine. Neurosci Behavioral Rev 1984;153-9.

Rebec GV, Segal DS. Apparent tolerance to some aspects of amphetamine stereotypy with long-term treatment. Pharmacol Biochem Behav 1980;13:793-7.

Richters JE, Arnold LE, Jensen PS, Abikoff H, Conners CK, Greenhill LL, et al. NIMH collaborative multisite multimodal treatment study of children with ADHD. I. Background and rationale. J Am Acad Child Adolesc Psychiatry 1995;34:987-1000.

Rie HE, Rie ED, Stewart S, Ambuel JP. Effects of methylphenidate on underachieving children. J Consult Clin Psychol 1976;44:250-60.

Safer DJ, Allen RP, Barr E. Growth rebound after termination of stimulation drugs. J Pediatr 1975;86:113-6.

Schachar RJ, Tannock R, Cunningham C, Corkum PV. Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate. J Am Acad Child Adolesc Psychiatry 1997;36:754-63.

Schiørring E. Psychopathology induced by “speed drugs.” Pharmacol Biochem Behav 1981;14, Suppl 1:109-22.

Schiørring E. Social isolation and other behavioral changes in groups of adult vervet monkeys (Cercopithecus aethiops) produced by low, nonchronic doses of d-amphetamine. Psychopharmacology (Berl) 1979;64:297-302.

Schleifer M, Weiss G, Cohen N, Elman M, Crejic H, Kruger E. Hyperactivity in preschoolers and the effect of methylphenidate. Am J Orthopsychiatry 1975;45:33-50.

Segal DS. Behavioral and neurochemical correlates of repeated d-amphetamine administration. In: Mandell AJ, editor. Neurobiological mechanisms of adaptation and behavior. New York: Raven Press; 1975. p. 247-62.

Segal DS, Weinberger SB, Cahill J, McCunney SJ. Multiple daily amphetamine administration: behavioral and neurochemical alterations. Science 1980;207:904-7.

Shaywitz SE, Hunt RD, Jatlow P, Cohen DJ, Young JG, Pierce RN, et al. Psychopharmacology of attention deficit disorder: pharmacokinetic, neuroendocrine, and behavioral measures following acute and chronic treatment with methylphenidate. Pediatrics 1982;69:688-94.

Sleator EK, Ullmann RK, von Neuwman A. How do hyperactive children feel about taking stimulants and will they tell the doctor? Clin Pediatr 1982;21:475-9.

Solanto MV, Wender EH. Does methylphenidate constrict cognitive functioning? J Am Acad Child Adolesc Psychiatry 1989;28:897-902.

Sonsalla PK, Jochnowitz ND, Zeevalk GD, Oostveen JA, Hall ED. Treatment of mice with methamphetamine produces cell loss in the substantia nigra. Brain Res 1996;738:172-5.

Spencer TJ, Biederman J, Harding M, O’Donnell D, Faraone SV, Wilens TE. Growth deficits in ADHD children revisited: evidence for disorder-associated growth delays? J Am Acad Child Adolesc Psychiatry 1996;35:1460-9.

Sroufe LA, Stewart MA. Treating problem children with stimulant drugs. NEJM 1973;289:407- 13.

Swanson JM. Medical intervention for children with attention deficit disorder. Proceedings of the Forum on the Education of Children with Attention Deficit Disorder. 1993 Jan 27-29.

Washington (DC): U.S. Department of Education, Office of Special Education and Rehabilitation Services and Office of Special Education Programs, Division of Innovation and Development; 1993. p. 27-34.

Swanson JM, Cantwell D, Lerner M, McBurnett K, Pfiffner L, Kotkin R. Treatment of ADHD: beyond medication. Beyond Behavior 1992;4(1):13-6 and 18-22.

Tannock R, Schachar RJ, Carr RP, Logan GD. Dose-response effects of methylphenidate on academic performance and overt behavior in hyperactive children. Pediatrics 1989;84:648-57.

Volkow ND, Wang GJ, Fowler JS, Logan J, Angrist B, Hitzemann R, et al. Effects of methylphenidate on regional brain glucose metabolism in humans: relationship to dopamine D2 receptors. Am J Psychiatry 1997;154:50-5.

Wagner GC, Ricaurte GA, Johanson CE, Schuster CR, Seiden LS. Amphetamine induces depletion of dopamine and loss of dopamine uptake sites in caudate. Neurology 1980;30:547-50.

Wallach, MB. Drug-induced stereotypical behavior: similarities and differences. In: Usdin E, editor. Neuropsychopharmacology of monoamines and their regulatory enzymes. New York: Raven Press; 1974. p. 241-60.

Wang GJ, Volkow N, Fowler J, Ferrieri R, Schlyer D, et al. Methylphenidate decreases regional cerebral blood flow in normal human subjects. Life Sci 1994;54:143-6.

Weiler IJ, Hawrylak N, Greenough WT. Morphogenesis in memory formation: synaptic and cellular mechanisms. Behav Brain Res 1995;66:1-6.

Weis G, Hechtman L, Milroy T, Perlman T. Psychiatric status of hyperactive adults. J Am Acad Child Adolesc Psychiatry 1985;24:211-20.

Whalen C, Henker B. Stimulant pharmacotherapy for attention-deficit/hyperactivity disorders: an analysis of progress, problems, and prospects. In: Fisher S, Greenberg R, editors. From placebo to panacea: putting psychotherapeutic drugs to the test. New York: J. Wiley & Sons; 1997. p. 323-56.

Whalen C, Henker B, Granger DA. Ratings of medication effects in hyperactive children: viable or vulnerable? Behavioral Assessment, 1989;11:179-99.

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