Stimulants

© Psychostimulants (e.g., methylphenidate anddextro-amphetamine with or without amphetamine) are the most effective agents in treating ADHD. Once the diagnosis of ADHD has been made, a stimulant medication should be consideredfirst-line in treating ADHD (Fig. 42-1). Stimulants are safe and effective and have a response rate of 70% to 90% in patients with ADHD.3,10,14 Generally, a trial of at least 3 months on a stimulant is appropriate, and this includes dose titration to response while balancing

side effects. ■ If treatment with the first stimulant formulation fails, it is recom mended to switch to a different stimulant formulation. 0 For example, if the patient was started on methylphenidate but could not tolerate the side effects, switching to dextroamphetamine with or without amphetamine is rational. The majority of patients who fail one stimulant will respond to an alternative stimulant.10 If the patient fails two appropriate trials of different stimulant medications, a third stimulant formulation or second-line nonstimulant such as bupropion, atomoxetine, or imipramine can be considered. The diagnosis of ADHD should be revalidated as well.

Stimulants theoretically exert their primary effect by blocking the reuptake of dopamine and norepinephrine. Stimulants have been shown to decrease fidgeting and finger tapping, increase on-task classroom behavior and positive interactions at home and in social environments, and ameliorate conduct and anxiety disorders.14

FIGURE 42-1. ADHD diagnosis and treatment algorithm.

8,10,16

FIGURE 42-1. ADHD diagnosis and treatment algorithm.

8,10,16

Stimulants should be initiated at recommended starting doses and titrated up with a consistent dosing schedule to the appropriate response while minimizing side effects (Table 42-2). Generally, stimulants should not be used in patients who have glaucoma, severe hypertension or cardiovascular disease, hyperthyroidism, severe anxiety, or previous illicit or stimulant drug abuse. Further, stimulants can be used, albeit cautiously, in patients with seizure disorders, Tourette's syndrome, and motor tics.14

Stimulant drug formulations can be divided into short-, intermediate-, and extended-acting preparations (Table 42-2). Initial response to short-acting stimulant formulations (e.g., methylphenidate and dextroamphetamine) is seen within 30 minutes and can last for 4 to 6 hours.10,14 This short duration of effect frequently requires that short-acting stimulant formulations be dosed at least twice daily, thus in-

creasing the chance of missed doses and noncompliance. Further, patients using any stimulant formulation, but especially short-acting formulations, can experience a rebound effect of ADHD symptoms as the stimulant wears off.14

Most intermediate-acting stimulants release the medication in a slow, continuous fashion without any early release (except Dexedrine Spansules). The onset of action for this category of stimulants (typically 60-90 minutes) may be inadequate for some patients. Some practitioners prescribe a short-acting stimulant concurrently with an intermediate-acting stimulant in order to curtail the delay in onset of action of the intermediate-acting stimulant.

To minimize rebound problems associated with short-acting formulations and still maintain early stimulant release, extended-acting formulations with rapid onsets have been developed. These formulations have an early release of medication and deliver a delayed release of stimulant in either a pulsed (Adderall XR, Focalin XR, Metadate CD, and Ritalin LA) or continuous manner (Concerta). Formulations available as capsules contain coated beads that can be opened and sprinkled on semisolid food. Concerta tablets have an immediate-release overcoat and then an oral osmotic controlled-release which delivers methylphenidate in an extended manner. Further, patients should be counseled that the empty tablet shell of Concerta can be detected in the stool.

Two extended-acting stimulants with slower-onsets have recently been developed, Daytrana and Vyvanse. Daytrana transdermal patches are to be applied for only 9 hours per day, have a delayed onset of 2 hours, and their effects persist for 3 hours once removed. Skin sensitization and irritation have been reported in some patients. Vyvanse is a prodrug requiring oral ingestion to be hydrolyzed to its active form, dex-troamphetamine. Inhalation or injection abuse potential is minimized due to impeded hydrolysis by these routes. Onset of action for Vyvanse has been reported as soon as 2 hours.15

Table 42-2 Selected Medications in Treating ADHDa

Drug, Generic (Brand Name)_Initial Pose

Titration Schedule

Typical Dosinq Range (Maximum Dose)

Stimulants

Short Acting

Methylphenidate" (Methyfcn. Ritalin)

Dexmethylphenidale* (focalm)

Dextroamphetamine (Dexedrine)

Intermediate Acting Methylphenidate"

(Ritalin SR. Metadate ER. Meth>Vi ER) Dextroamphetamine/ amphetamine" (Adderall)

Dextroamphetamine" (Dexedrine

Spansule) txtovkd Acting Methylphenidate» (Concerta)

(Metadate CO)

(Riialin LA)

Dextroamphetamine/ amphetamine* (Adderall XR)

Dexmethylphenidate* (focalln XR)

Lisdexamfctamine*

(Vyvanse) Nonstlmulants

Atomoxetine* (Str atiera)

Impramine (Tofranil)

Ck>ridr>e<Catapres) Guanfacme (Tenex)

Bupropion (WettxJtria Wetoutrin SR. Welfoutrin XL)

5mg2xdaily 25 mg2xdady 25-5 nig every morning

10 mg once daily

25-5 mq once to twice daily

5 mg ewy morning

18 mg every morning

20 mg every mornmg

20 rr»g every morning

5-10 mj e.-ery morning <childenh20mgonce daily CKluhs)

S mg every morning (chiklen); 10 mq every moinng (adults) 30 ing every morntig (chikten and adults)

Less thin or equal to 70 kg:0-5 mg/kg/day drvicfcd once to twee daily

Greater than 70 kg 40 mg once daily 15 mg-kg/day in one or two dvkJcd doses

OjOS mg once daily 0.5 mgai bedtime

3 mg/kj/day foi 7 days (childen); ISO mg once daily of SR or XI (adults)

Increase S-10 mg/day In weekly Intervals Increase 2.5-5 mg/day in weekly intervals Increase 25-5 mgAJay in weekly intervals increase 10 mg/day in weekly intervals Increase 2.5-5 mg/day in weekly intervals increase 5 mg/day in weekly intervals Increase 9-18 mg/day r> weekly Intervals

(60 mg/day) S-10 mg twice darfy

20-40 mg daily in the morning (60 mg/day) 10-30 mg every morning or 5-20 mg twice dady (40 mg/djy) 5-30 mg daily 0» 5-15 mg twice da^y (40 mg/day)

18-S4 mg every morning (S4 mg/day)

Increase 10-20 mg/day In weekly intervals 20-40 mg daily In the morning (60 mg/day)

Increase 10 mg/day in weekly intervals

Increase 5-10 mg/day in weekly intervals

Increase S mg/day in weekly intervals increase 10-20 mg/day in weekly intervals

Increase to target dose of 12 mg/kq /day after 3 days

Increase 40 mg/day after 3 days (may t to total of 100 mg/day after 2-3 weeks) Increase I mg/kg/day every 3-4 days

Increase OOS mg/day every 3-/ days Increase 05 mg every 3-14 days

Increase 3 mg/kg/day in weekly intervals (children* increase 150-300 mg/day in weekly intervals (adults)

20-40 mg daily in the morning (60 mg/day)

10-30 mg every morning or 5-15 mg twice daily (30 mg/day. chddren) (60 mg/day. adult)

10-20 mg daily in the morning (20 mg/day)

30-70 mg daily in the morning (70 mg/day)

40-60 mg/day (1.4 mg/kg or 100 mg/day. whichever eless)

40-80 mg/day divided once to twice daily 000 mg/day) 15-3 mg/kg/day in one or two dr.-ided doses <S mg/kg/day. cWd) 100-300 mg/day in one or two divided doses (300 mg/day. adult) 0.1 mg 1 to 4 times dady (0.4 mg/day)

15-3 mg/day drvided into 2-3 x daily (4 mg/day) 6 mg/kg/day or 400 mg/ day—whichever is smaller (Children): 150-450 mg«day (400 mg/day SR; 450 mg/ day XL—adults)

-Pediatric dos*vg except where adult dosing specified, ■f DA appro-zed for treatment of ADHD.

Adverse effects of stimulants can be generalized to the whole class (Table 42-3). Most of these side effects can be managed by changing dosing routine (i.e., giving with food, dividing daily dose, or giving the dose earlier in the day). Serious side effects such as hallucinations and abnormal movements require discontinuation of med-ication.10,14

Growth suppression or delay is a major concern for parents of children taking stimulants. However, the evidence of this side effect is not clear. At present, growth delay appears to be transient and to resolve by midadolescence, but more data are needed to firmly resolve this issue.10 Another concern is the risk of substance abuse with stimulant use. A diagnosis of ADHD alone increases the risk of substance abuse in adolescents and adults. However, stimulant use has not been shown to further increase this risk but actually may decrease this risk, provided ADHD is treated adequately.16

Table 42-3 ADHD Medication Side-Effect Profiles, Management, and Monitoring

Drug

Side Effect!

Management

MaiKmlnj

MeTiiytohefUctite, deslroamphelamine, de*lruoiíiCihclí¡m¡rn:/

i irifrtieianvrie (nnii«*d-salls amphetamine, dexmei hylplvnidai^, hsdexarnñftamine)

appetite, potential growth deli/

^ikifi [lhn.li lhil>: H* MOOdlntsJ

Uriblfrt»

Increased hlacxt pressure and pufce Tin

Adirtrti^Mr .lirei irni.il'. Encourage high-calorie (reals Divicie doie

Give inacki m the evening

Change to sfcortw-aciing SllrtMant

Ote iinilj holiday ch tiiifefent mtdmnon n severe growth delary MM etfcf InthnJqjiindïliMrtlnue lata day doseif poblcm lieras Giw ckjiiidinf oi guiji'.fjcinc ul bedtime Change to 9 ftate^Kimg slinrManr Ouikjc tu Iothjit jciiikj stimulant iiimulanr deling DfcirtiBé dew or lo lorniLi-jt ting ihntulant Verify diagnosis/coirobdity ÍVÍKJÍW timecíoGCrfWíe Farly onsec Decnease dose of change ro longer act mg stimulant Lute enrol: 'í.vilch to longe? acting stimulant Evaluate iof comorbidity or thange ici longer-acting stimulant

Dlsoounnnue or change to a different stimulant Give ckn-icfcne or guanfaclnp

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