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IN THIS ISSUE:
April 2007

Paliperidone (Invega)
Paliperidone (Invega), recently approved to treat schizophrenia, is similar to risperidone (Risperidone) in efficacy and adverse effects.

Methylphenidate for ADHD in Preschool Children
Low doses of methylphenidate (Ritalin and others) are effective and safe for preschool children with ADHD but may cause more side effects than in older children.

A Case of Wernicke's Encephalopathy
Wernicke's encephalopathy is caused by thiamine deficiency, usually due to alcoholism or malnutrition.

In Brief
Taste Altered in Mood Disorders; Reduced Gray Matter May Predict Schizophrenia; FDA Issues Methadone Alert

Two Ineffective Adjuncts for Mania
Olanzapine (Zyprexa) and topiramate (Topamax) add no therapeutic benefit as adjunctive treatments for bipolar disorder.

Schizophrenia, Substance Abuse, and Violence
Substance abuse increases the risk of violent behavior in people with schizophrenia.

Methylphenidate for ADHD in Preschool Children

April 2007

We previously reviewed the treatment of attention deficit hyperactivity disorder (ADHD) in school-aged children, adolescents, and adults (BTP 2006;29:31-32, 2005;28:29, 2003;26:36). ADHD can occur in preschool-aged children as well. The incidence of preschool ADHD is unclear, but estimates range from 2% to 5%. Treatments for preschool children with ADHD include psychosocial intervention and stimulants, the most common of which is methylphenidate (Ritalin and others). Methylphenidate, however, does not carry labeling from the US Food and Drug Administration for use in children under 6 years. To expand knowledge in this area, the National Institute of Mental Health undertook a six-site, 70-week clinical trial beginning in 2001.1

Subjects were 303 children, aged 3 to 5.5 years, who were diagnosed with ADHD.

Compared with placebo, significant decreases in ADHD symptoms (P < .01) occurred with methylphenidate, 2.5 mg, 5 mg, and 7.5 mg tid but not for the lowest dose, 1.25 mg tid.2 The mean optimal total daily dose for the entire group was 14.2 ± 8.1 mg/day (0.7 ± 0.4 mg/kg/day). The effect size was modest and lower than that usually reported for methylphenidate in school-aged children, which could reflect the difficulty of rating attention in preschoolers.

The authors recommend that when preschoolers with ADHD are treated with methylphenidate, the prescriber should start with low doses, such as 2.5 mg bid of the immediate-release form. Over the course of a week, it can be increased to 7.5 mg tid.

Adverse events were of concern. Thirty percent of parents spontaneously reported moderate to severe adverse events in their children.3 Behavioral symptoms attributed to the stimulant included emotional outbursts, difficulty falling asleep, repetitive behaviors and thoughts, decreased appetite, and irritability. During titration, there were statistically greater reports of decreased appetite, trouble sleeping, and weight loss in children who were taking methylphenidate compared with placebo. Later, many adverse effects diminished, but trouble sleeping and appetite loss persisted. Five children experienced one-time pulse and blood pressure elevations. Overall, 11% of children discontinued the study medication due to adverse effects. Children who stayed on medication grew at a rate 20.3% less than expected for height (0.5 in) and 55.2% less for weight (3 lb).4 Secondary analyses suggest that both treatment response and side effects might be related to specific genetic polymorphisms.5

The conclusions from this study are that, overall, low doses of methylphenidate are effective and safe for preschool children with ADHD. This age group, however, appears more sensitive than older children to side effects, and there is a price to be paid in slower growth rates. The bottom line appears to be that if ADHD is a problem in a preschool child, and if psychosocial treatments are ineffective, methylphenidate might provide some benefit. Parents should be advised about side effects and effects on growth, and consider the decision carefully. Doses of methylphenidate should be started low, with slow titration to find an effective and tolerated dose.

1Kollins S, Greenhill L, Swanson J, Wigal S, Abikoff H, McCracken J,Riddle M, McGough J, Vitiello B, Wigal T, Skrobala A, Posner K,Ghuman J, Davies M, Cunningham C, Bauzo A: Rationale, design, and methods of the Preschool ADHD Treatment Study (PATS). J Am Acad Child Adolesc Psychiatry 2006;45:1275-1283.

2Greenhill L, Kollins S, Abikoff H, McCracken J, Riddle M, Swanson J, McGough J, Wigal S, Wigal T, Vitiello B, Skrobala A, Posner K,Ghuman J, Cunningham C, Davies M, Chuang S, Cooper T: Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry 2006;45:1284-1293.

3Wigal T, Greenhill L, Chuang S, McGough J, Vitiello B, Skrobala A, Swanson J, Wigal S, Abikoff H, Kollins S, McCracken J, Riddle M,Posner K, Ghuman J, Davies M, Thorp B, Stehli A: Safety and tolerability of methylphenidate in preschool children with ADHD. J Am Acad Child Adolesc Psychiatry 2006;45:1294-1303.

4Swanson J, Greenhill L, Wigal T, Kollins S, Stehli A, Davies M, Chuang S, Vitiello B, Skrobala A, Posner K, Abikoff H, Oatis M, McCracken J, McGough J, Riddle M, Ghuman J, Cunningham C, Wigal S: Stimulant-related reductions of growth rates in the PATS. J Am Acad Child Adolesc Psychiatry 2006;45:1304-1313.

5McGough J, McCracken J, Swanson J, Riddle M, Kollins S, Greenhill L, Abikoff H, Davies M, Chuang S, Wigal T, Wigal S, Posner K, Skrobala A, Kastelic E, Ghuman J, Cunningham C, Shigawa S, Moyzis R, Vitiello B: Pharmacogenetics of methylphenidate response in preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry 2006;45:1314-1322.