Presentation Outline 1. History 2. Listing of Psychostimulant Drugs 3. More Details on Some Common Drugs 4. Applications with Children & Adults 5. Characteristics & Mechanisms 6. Potential Negative Effects 7. Controversy 8. References HISTORY Psychostimulants have a long history of medical use for the treatment of childhood psychiatric conditions (Pliszka, 1998).
1937 Bradleys study of the therapeutic effects of Benzedrine on children (Lange et al., 2010; Mayes & Rafalovich, 2007).
1944 compound known as Ritalin was first synthesized in 1944 by Leandro Panizzon (Lange et al., 2010).
HISTORY 1955 Ritalin for children with hyperkenetic behavior syndrome (Mayes & Rafalovich, 2007). 1961 Ritalin approved by U.S. Food & Drug administration in for use with children with behavior problems (Mayes & Rafalovich, 2007).
1967 NIMH awarded first grant to study use of stimulants with children (Mayes & Rafalovich, 2007). By late 1960s, an estimated 150,000-200,000 American children were being treated with stimulants (Mayes & Rafalovich, 2007) 1970 media attention and increased restrictions
History 1975 Pemoline (Cylert) was approved by the FDA for use in the treatment of ADHD
1999 NIMH (National Institute of Mental Health) publishes results from a 14-month study known as the Multimodal Treatment Study of ADHD (MTA Study) (Goodman, 2010)
1999 New delivery systems (Swanson, 2005)
2000 Concerta (Swanson, 2005)
2007 Vyvanse
warnings to ADHD medications (Goodman, 2010)
Listing of Psychostimulant Drugs Methylphenidate Hydrochloride (Concerta & Ritalin) Often the first choice for treating ADHD
Amphetamine (Adderall) Usually the second choice
Dextroamphetamine Sulfate (Dexedrine) Concerta (Methylphenidate Hydrochloride) Taken once/day, time-released formula (taken in morning)
Dosage can be modified With most psychostimulants, start low and work up
Not for children under 6 years
Drug manufacturers warn that it should not be taken by children with significant anxiety, tics or Tourette's syndrome Ritalin (Methylphenidate Hydrochloride) 2 pills (one before breakfast, one before lunch) OR 1 slow release tablet (lasts 8 hours)
Dosage can be modified
Not for children under 6 years
Drug manufacturers warn that it should not be taken by children with significant anxiety, tics or Tourette's syndrome Adderall (Amphetamine) Taken once daily when waking up
Should not be taken by children with high anxiety
Has not been studied in children under 6 years old
Dexedrine (Dextroamphetamine Sulfate) One extended release pill
Ages 6 and older
May exacerbate phonic and motor tics Psychostimulants: Applications with Children and Adults
Stimulant Increases rate of physiologic functioning (CNS) Effect on Neurotransmitters Psychostimulant
Has direct neurological effects: -counteract lethargy -reduce sleepiness -improve concentration and focus
Increased alertness Increased energy Appetite suppression
Euphoria Possible mood enhancer
-Widespread use: may include
clinical or recreational settings Children and adults Adults Children Applications of Methylphenidate (Ritalin, Concerta) in Children and Adults Methylphenidate: improve attention, distractibility, impulsivity and observable classroom behaviour in children with ADHD
Common Alternative
Methylphenidate Methylphenidate ADHD (Ritalin) Depression Narcolepsy Other cognitive impairments- e.g., TBI Apathy (Parkinsons) (Elderly) ODD/CD(reduce aggression) Applications of Amphetamine (Adderall) in Children and Adults Common Alternative
Amphetamine ADHD (Adderall) Narcolepsy Amphetamine Used by US fighter pilots to increase alertness Appetite suppressing effect: obesity Academic enhancement in college students Sometimes used in treatment resistant depression Dextroamphetamine Sulfate (Dexedrine) Applications with Adults and Children Common Alternative Dextroamphetamine Dextroamphetamine ADHD (Dexedrine) Narcolepsy Obesity TBI Characteristics What are the mechanisms acting in the brain? Depend on the drug class
Neurotrasmitters Involved:
Catecholamines (dopamine and norepinephrine) amphetamines/methylphenidates
Serotonin amphetamines
Mechanisms Psychostimulants act to increase the levels of dopamine within the synapse of nerve cells in the PFC by: Push additional dopamine from a nerve cell to the synapse Disrupt DAT molecules and prevent dopamine re- uptake Reverse functions of DAT molecules causing increased dopamine production At high clinical doses amphetamines can: Stimulate efflux of norepinephrine Block reuptake of serotonin
Characteristics Onset of action for amphetamine and methylphenidate compounds is 20 mins - 1 hour after ingestions
Effects lasting 3 - 6 hours on average depends on dosage, mechanism of drug chosen, type of action (long, intermediate, short) Characteristics Substrate Action Medication Duration Methylphenidate Short Ritalin, Focalin, Methylin 3 4 hr
Intermediate Ritalin SR, Metadate ER, Methylin ER 6 8 hr
Long Concerta, Metadate CD, Ritalin LA 12 hr 8 10 hr
Amphetamine Short Dexedrine Dextrostat 3 5 hr
Intermediate Adderall 4 8 hr
Long Dexedrine Adderall XR 8 12 hr
(Carlate Psychiatry Report, 2003) Negative Effects of Psychostimulants in Children Common Short Term Side Effects Potential Long Term Side Effects Decreased appetite Slower growth (especially in first year of taking meds) Difficulty falling asleep Stomachache Headache Short term side effects normally wear off after the first little while on meds, and with dosage adjustments
Children who experience slower growth normally catch up in height and weight
Many psychostimulant medications have not been studied in children under the age of 6
Dependency can occur with abuse of psychostimulant drugs
Generally safe to use CONTROVERSY Ethical considerations Side effects Addiction/Misuse Role of the media
Controversy: Social/Ethical Considerations Is stimulant use means of socially controlling children? By treating the restlessness of youth as a medical, rather than a moral, challenge, those resorting to behavior-modifying drugs might deprive that child of an essential part of this education. They might also encourage him to change his self-understanding, by coming to look upon himself as governed largely by chemical impulses and not by moral decisions grounded in some sense of what is right and appropriate. (Singh, 2013) Informed consent Parents/Guardians must consent on behalf of the child. What occurs when what is in the childs best interest is not agreed upon? (Taylor, 2013)
Controversy: Social/Ethical Considerations Standards of practice Should medical interventions be used before attempting other behavioral/social interventions?
Neuroenhancement
Controversy: Side Effects Can the use of stimulants cause stunted growth in children? No consensus in the research: some studies indicate no effect while others report growth attentuation; others report it is dosage dependent (Negrao & Vilijoen, 2011).
Can the use of stimulants cause sudden death? Stimulants have cardiovascular effects increased heart rate and blood pressure (Mazza et al., 2013)
Stimulants do not increase the risk of cardiovascular events (Mazza et al., 2013; Winterstein, 2013; Wilens et al., 2006)
Controversy: Addiction/Misuse Do children prescribed stimulants for ADHD become addicted? Children prescribed stimulant medication for ADHD are at no greater risk for substance abuse (Greydanus) Adolescents with ADHD who went untreated were 3-4 times more likely to use illicit substances than adolescents who were treated with stimulant medication (Greydanus) Illicit drug use in adulthood is not associated with childhood stimulant treatment of ADHD (Greydanus) Greydanus,www.acha.org/Continuing_Education/docs/ACHA_Use_Misuse_of_ Stimulants_Article2.pdf)
Controversy: The Role of the Media References Bradley, C. (1950). Benzedrine and Dexedrine in the Treatment of Childrens Behavior Disorders. Pediatrics, 5(1), 24-37.
Berridge, C. W., & Devilbiss, D. M. (2011). Psychostimulants as cognitive enhancers: The prefrontal cortex, catecholamines and attention-defici/hyperactivity disorder. Biological Psychiatry, 69(12), 101-111. doi: 10.1016/j.biopsych.2010.06.023
Busch, S.H. (2009). Medication treatment for ADHD: controversy abounds. Health Affairs, 28(5), 1549- 1550. doi: 10.1377/hlthaff.28.5.1549
Chatterjee, A., & Fahn, S. (2002). Methylphenidate treats apathy in Parkinson's disease. The Journal of neuropsychiatry and clinical neurosciences, 14(4), 461-462.
Currie, J., Stabile, M., & Jones, L. E. (2013). Do Stimulant Medications Improve Educational and Behavioral Outcomes for Children with ADHD? (No. w19105). National Bureau of Economic Research.
Goodman, D. W. (2010). Lisdexamfetamine dimesylate (vyvanse), a prodrug stimulant for attention- deficit/hyperactivity disorder. Pharmacy and Therapeutics, 35(5), 273.
References Gonalves, J., Baptista, S., & Silva, A. P. (2014). Psychostimulants and brain dysfunction: a review of the relevant neurotoxic effects. Neuropharmacology.
Carlat Psychiatry Report. (2003). Psychostimulants: bringing order out of chaos. Retrieved from http://pro.psychcentral.com/2013/psychostimulants-bringing-order- out-of-chaos/001371.html Food & Drug Administration (FDA). Medication Guide - Adderall. http://www.fda.gov/downloads/Drugs/DrugSafety/ucm085819.pdf References Haleem, D. J. (2013). Extending therapeutic use of psychostimulants: Focus on serotonin-1A receptor. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 46, 170-180.
Kollins, S. H. (2008). ADHD, substance use disorders, and psychostimulant treatment current literature and treatment guidelines. Journal of Attention Disorders, 12(2), 115-125.
Lange, K.W., Reichl, S., Lange, K.M., Tucha, L., & Tucha, O. (2010). The history of attention deficit hyperactivity disorder, 2(4): 241-255. Published online Nov 30, 2010. doi: 10.1007/s12402-010-0045-8
Liptzin, B., & Hobgood, C. (2011). Use of Antidepressants in Geriatric Patients.The Evidence-Based Guide to Antidepressant Medications, 227.
Mazza, M., D'Ascenzo, F., Davico, C., Biondi-Zoccai, G., Frati, G., Romagnoli, E., ... & Gaita, F. (2013). Drugs for attention deficithyperactivity disorder do not increase the mid-term risk of sudden death in children: A meta-analysis of observational studies. International journal of cardiology, 168(4), 4320-4321.
Mayes, R., & Rafalovich, A. (2007). Suffer the restless children: the evolution of ADHD and paediatric stimulant use, 190080. History of Psychiatry, 18(4), 435-457.
References Negrao, B. L., & Viljoen, M. (2011). Stimulants and growth in children with attention- deficit/hyperactivity disorder. Medical hypotheses, 77(1), 21-28.
Pajo, B., & Cohen, D. (2013). The problem with ADHD: Researchers constructions and parents accounts. International Journal of Early Childhood,45(1), 11-33.
Partridge, B. (2013). A bubble of enthusiasm: How prevalent is the use of prescription stimulants for cognitive enhancement?. In Cognitive Enhancement(pp. 39-47). Springer Netherlands.
Pliszka, S. R. (1998). The use of psychostimulants in the pediatric patient.Pediatric Clinics of North America, 45(5), 1085-1098.
References Rosenberg, D.R. (2002). Psychostimulants. In Rosenberg, D.R., Davanzo, P.A., & Gershon, S., Pharmacotherapy for child and adolescent psychiatric disorders (pp. 113-167). Retrived from http://site.ebrary.com.ezproxy.lib.ucalgary.ca/lib/ucalgary/docDetail.action?docID =10051456&p00=pharmacotherapy%20child%20adolescent Singh, I. (2013). Not robots: children's perspectives on authenticity, moral agency and stimulant drug treatments. Journal of medical ethics, 39(6), 359-366.
Stotz, G., Woggon, B., & Angst, J. (1999). Psychostimulants in the therapy of treatment-resistant depression Review of the literature and findings from a retrospective study in 65 depressed patients. Dialogues in clinical neuroscience, 1(3), 165. Whyte, J., Vaccaro, M., Grieb-Neff, P., & Hart, T. (2002). Psychostimulant use in the rehabilitation of individuals with traumatic brain injury. The Journal of head trauma rehabilitation, 17(4), 284-299.