Psychopharmacology Update: Pediatric Psychopharmacology Update: Psychostimulants and Tics – Past, Present and Future

For over three decades, there has been an intriguing association between transient tics, tic disorders and ADHD. One of the most compelling findings is that about half of the children with Tourette’s syndrome also have ADHD (Allen et al., 2005). In addition, a history of tic disorders or transient tics has been observed in approximately 27% of children with ADHD (Gualtieri and Patterson, 1986). For comparison, Zahner and colleagues (1988) noted that approximately 5 -18% of boys and 1 11% of girls present with tics, twitches, or habit spasms at some point in their lives. In fact, the highest incidence of tic disorders is observed in those between the ages of 7 and 13 years. However, several children are also initiated on psychostimulant medications around this age range. This article reviews the literature and examines the association between psychostimulant use and the emergence and/or exacerbation of tics. Denckla (1976) was one of the first to document an association between stimulant use and tics in a study of 1,520 subjects diagnosed with ‘Minimal Brain Dysfunction’ (now called Attention Deficit Hyperactivity Disorder (ADHD)). In this study, Denckla found that approximately 1% of children, none of whom had a history of a tic disorder, experienced tics when prescribed MPH. Of those with a pre-existing tic disorder, approximately 13% (6 of 45 children) had an exacerbation of their tics. Furthermore, the tics either improved or disappeared in 13 of the 20 children (65%) when the stimulant was discontinued. Denckla’s observations were later confirmed by Lowe in 1982 when she published a similar report of precipitating motor and vocal tics in children having a positive family history and receiving MPH. Resultant to studies such as these, many clinicians suggested that the use of MPH be avoided in those with a current or family history of tic disorders (Castellanos, 1999; Mick, 1996; Varley 2001). By 1986, three more case reports regarding the association of tics with psychostimulants were published (Erenberg, 1985; Casat, 1986; Gualtieri, 1986). These reports added to the literature by demonstrating that the motor and vocal tics, which emerged after MPH administration, were effectively treated with other medications commonly used for tic disorders (such as thioridazine, haloperidol, or clonidine). These authors, however, commented that the data available at that time was insufficient to confirm whether stimulants directly caused tics and suggested that larger scale clinical trials would be required. By 1999, our understanding of tics and their correlation with psychostimulant use at various dosages had somewhat improved. Castellanos and colleagues (1999) conducted a nine week, placebo controlled, double-blind crossover study to determine the effects of stimulant use on tic severity in 20 patients with Tourette’s syndrome and comorbid ADHD. They compared the rates of tics observed at various dosages of MPH (means were 0.43, 0.67, and 1.20 mg/kg BID), DEX (means were 0.2, 0.41, and 0.64 mg/kg BID) and placebo. At lower doses (e.g., 15 mg BID for MPH) tics in the study group were, on average, not worsened by either stimulant. At higher doses however, there was a significant increase in mean tic severity for both medications (21% increase for MPH and 25% increase for DEX) compared to placebo. For those receiving MPH, tic severity for the majority returned to placebo levels within 1 to 3 weeks while only one child receiving DEX had a decline in tic severity. It is important to note that individually, some children did have worsening tics while others noted an improvement. Law and Schachar (1999) conducted a double blind (DB) randomized control trial (RCT)