PHARMACOTHERAPY REVIEW CNS STIMULANTS for treatment of ...

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III.ETIOLOGYThe etiology of ADHD is not known. Genetics, neurotransmitter deficits and perinatalcomplications have been implicated. The genetic and neurobiological etiologies appear to be themost plausible. ADHD has a heritability of 0.75 to 0.91. 10 Dysregulation of the neurotransmitterdopamine in pathways of the brain thought to play significant roles in ADHD (the dopaminehypothesis) has many followers. It postulates that ADHD is due, in large part, to inadequatedopamine in key areas of the brain. The effectiveness of CNS stimulant drugs in the managementof ADHD supports the dopamine hypothesis as they (CNS stimulants) increase the release ofdopamine and norepinephrine from presynaptic neurons in the central nervous system and inhibittheir reuptake, thereby increasing the amount of these chemicals in neuronal synapses.The following have been ruled out as likely causes or contributors to ADHD: head trauma,refined sugar intake, food allergies, artificial flavorings or preservatives, poor schools, poorparenting or too much TV. Abuse of alcohol, illegal drugs or cigarette smoking during pregnancycould interfere with brain development and contribute to the development of ADHD.IV.TREATMENTA. Goal of TherapyThe primary goal in treating ADHD is to produce the best possible therapeutic outcome forthe patient, which translates into improved functional ability at school, at work, in thecommunity and at home. This goal can be achieved in a high percentage of ADHD patientswith drug therapy, psychosocial therapy or a combination of these approaches. Occasionallyone or more additional behavioral disturbances will coexist with ADHD. Thesecomorbidities must be managed specifically while concurrently managing ADHD.Psychiatric or behavioral disorders that underlie ADHD can confound the diagnosis ofADHD significantly.B. Behavior TherapyBehavior therapy is most often an adjunct to drug therapy in managing ADHD It is not asubstitute for drug therapy because it is less effective than drug therapy in managing the coresymptoms of ADHD. Behavior therapy seeks to improve behavior by altering the physicaland social environment, setting specific goals, providing rewards for meeting goals andestablishing consequences for failure to meet goals (i.e., positive and negative reinforcement).C. Drug TherapyPsychostimulant drugs have been the drug treatment of choice for children with ADHD sincea report in 1937 revealed the value of racemic amphetamine in improving the conduct andacademic performance of children with behavioral disturbances. 11 These findings over 65years ago have been confirmed over and over in many controlled, short-term and long-termstudies of children, adolescents and adults diagnosed with ADHD. 12-24The response rate to any single stimulant produces a dramatic and consistent improvement ofcore symptoms of inattention, hyperactivity and impulsivity in approximately 70% ofchildren, adolescents and adults. Up to 90% of children will respond to at least one stimulantindicated for the treatment of ADHD without major adverse effect if drug titration is donecarefully. 222
D. CNS Stimulants Indicated to Treat ADHDCNS STIMULANTS INDICATED TO TREAT ADHDGeneric Name Brand NameGenericAvailableStrength(mg)DosageFormFrequencyOf DoseRAPID ONSET/SHORT DURATION PRODUCTSAmphetamineMixture Adderall Yes5, 7.5, 10,12.5, 15, 20 Tab 1 – 2x/dDexmethylphenidate Focalin No 2.5, 5, 10 Tab 2x/dDextroamphetamineDexedrine;DextroStatYes 5, 10 Tab 1 – 2x/dMethamphetamine Desoxyn No 5 Tab 1 – 2x/dMethylphenidateRitalin,MethylinYes 5, 10, 20 Tab 1 – 2x/dSLOWER ONSET/LONG DURATIONDextroamphetamine DexedrineCapYes 5, 10, 15sulfateSpansule(SR)1x/dMetadateTABNo 10ER(ER)1x/dMetadateTABYes 20ER(ER)1x/dTABMethylphenidate HCl Methylin ER No 10(ER)1x/dMethylin ER Yes 20TAB(ER)1x/dRitalin SR Yes 20TAB(ER)1x/dPemolineCylertRAPID ONSET/LONG DURATIONAmphetamineAdderall XRMixtureMethylphenidate HClMethylphenidate HClYes18.75, 37.5,75Cylert No 37.55, 10, 15,20, 25, 30NoMetadateCD No 20Ritalin LAConcertaNo 20, 30, 4018, 27, 36,No 54TABChewTabCap(ER)Cap(ER)Cap(ER)TAB(ER)Note:1. The mixture of amphetamines in Adderall and Adderall XR are equal amounts ofdextroamphetamine sulfate, dextroamphetamine saccharate, amphetamineaspartate and amphetamine sulfate.2. Pemoline (Cylert) should be avoided, if possible, due to the risk of severe druginducedhepatotoxicity.3. Dexmethylphenidate (Focalin), the d- enantiomer of racemic d-, l-methylphenidate, is a short-acting agent. It has not shown clinical superiority in3 small, short-term clinical trials over racemic methylphenidate. Patients whofail methylphenidate are unlikely to respond to dexmethylphenidate. 281x/d1x/d1x/d1x/d1x/d1x/d3
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