Pharmacotherapeutic Challenges in the Management of Attention-Deficit/Hyperactivity Disorder and Chronic Tics in a School Aged Child

Chief Complaint and Presenting Problem

A. is an 8-year–old boy referred by his pediatrician for evaluation and management of tics in the context of attention-deficit/hyperactivity disorder (ADHD).

History of Present Illness

Parents report that as early as age 3 years, A. was hyperactive, restless and fidgety, had difficulty sitting still, and had problems with focus and concentration. He was reported to be impulsive and had difficulty sleeping. At age 5 years, following an upper respiratory infection, A. developed rather abrupt onset of eye rolling. Parents reported that he seemed sick but did not have a sore throat or fever. Antibody titers were done, but definitive cultures done to confirm whether there had been an acute infection were not done. A.'s tics were treated with antibiotics and seemed to improve. A. subsequently went on to develop eye blinking, initially thought to be related to an infection, and an ophthalmologist prescribed eye drops. A.'s eye blinking persisted despite administration of the drops, and parents subsequently sought neurological consultation.

The pediatric neurologist recommended EEG and MRI, but there were no EEG and MRI abnormalities and no focal neurological exam findings. A.'s eye blinking persisted for six months after the infection, and then stopped and was replaced by repetitive head and neck movements, which where followed by lateral jaw movements over a period of months.

Parents report that A.'s tics are more pronounced during periods of stress, illness, and sleep deprivation. A. is well aware of the movements, but he is not embarrassed by them. Parents report that kids have made fun of him, but he has not gotten into fights, and teachers are sensitive to the potential stress the tics could cause him. When he is highly focused, parents report that A.'s eye blinking, and head/neck/jaw movements diminish. Parents report that most recently, approximately a week prior to referral, A. had begun to make a throat clearing or grunting sound.

Parents report that the pediatric neurologist diagnosed ADHD, which he treated initially with Concerta 18 mg and clonidine 0.1 mg at bedtime. Response was notable for an increase in eye blinking and head and neck movements, but no improvement in ADHD symptoms.

Parents report that despite treatment, A. has continued to have difficulty with restlessness, fidgetiness, and concentration. They report that he needs to be reminded to complete tasks at hand, both at home and at school. He is impulsive, and blurts out answers out of turn. They report increasing oppositional behavior over the past 6 months, as he has had difficulty following rules and refuses to do work. Mother reports that A. has continued to show poor impulse control, evidenced by losing his temper when his younger sister takes his toys. However, A. has reportedly not become physically aggressive when he is upset.

In addition, parents describe A. as a “worrier;” he worries excessively about each family member's well-being and about catastrophic events on the news. Although he worries, parents report that he is able to separate from parents and never had difficulty attending school. He reports anxiety about cats and spiders, which he tries to avoid.

A. has no history of rituals, obsessions, or compulsions. Although he does tend to order and arrange his belongings, it is not excessive. There is no history of anxiety performing activities in front of others. There is no history of hair pulling, skin picking, or other behavioral problems. He has had no problems with excessively elevated or depressed mood.

Past Psychiatric Treatment

There has been no previous contact with mental health practitioners.

Developmental and Personal History

A. is the product of an uncomplicated 40 week pregnancy. Birth weight was 3 kg and Apgars were 10 and 10. The newborn period was uncomplicated. Mother and baby went home together. Parents describe A. as a temperamentally difficult baby who was “colicky.” Developmental milestones for motor and speech and language development were reported to be on target.

Educational History

A. has attended public schools. He has had an individualized education program (IEP) starting in Grade 1. He is currently in Grade 3. Despite the IEP and tutoring once a week, A.'s academic performance declined last year. Parents report that much of the difficulty seemed to be a result of his inattention and refusal to complete assignments. Comments from his teacher indicate he was distractible in class, frequently calling out answers, and had not been completing assignments.

Social History

A. makes friends easily, is invited to birthday parties, and goes on play dates with friends. He enjoys soccer and baseball and plays on community teams, but sometimes argues with the coaches.

Pertinent Family History

Mother, age 36, is a health care professional. She reports a history of anxiety and depression. A maternal first cousin reportedly has tics treated with guanfacine and has responded well.

Father, age 38, is a businessman with no history of psychiatric illness or related symptoms. A paternal uncle has a history of trichotillomania symptoms.

A sister, age 4 years, is healthy.

Medical History/Medications/Recent Physical Examination

A. was hospitalized at age 4 years for a severe cough. A. has a history of cough-variant asthma for which he takes montelukast and albuterol as needed.

He fell on the playground at age 6 years and hit his head, but there was no loss of consciousness. There is no history of seizures.

Neurological evaluations have been reportedly within normal limits.

A. had a history of difficulty falling asleep and waking up at night; parents report he underwent a sleep study and was reportedly diagnosed with mild apnea. Parents report that the sleep issues have resolved.

Growth and development are described as on target.

He does not have medication, food or environmental allergies.

Medication History

A. was treated initially with methylphenidate (Concerta) 18 mg and clonidine 0.1 mg at bedtime by his pediatrician. Eye blinking and head and neck movements increased, but there was no improvement in ADHD symptoms. Methylphenidate was increased to 18 mg in the morning and 18 mg at noon. Clonidine was increased to 0.2 mg for difficulty with sleep initiation and increase in tics. Methylphenidate was continued at 18 mg twice a day for several months; risperidone 0.25 mg twice a day was added to target impulsivity and tics, and clonidine was discontinued. A. continued to experience difficulty with impulsivity, restlessness, and tics. A. was then switched to guanfacine (Intuniv) 1 mg at bedtime for several weeks, but it was discontinued, since he was unable to fall asleep.

Mental Status Exam

A. is a handsome, well developed, well-nourished, 8-year-old boy who looks his stated age. He is casually and age appropriately dressed and makes good eye contact. Frequent eye blinking and mild facial grimacing was noted. No vocal tics were noted. A. was able to maintain his position and remained fairly calm throughout the interview. A. was pleasant and cooperative and showed a range of affect.

A. acknowledged worries about the wellbeing of others, particularly his parents and younger sister. When discussing this topic, he became quiet and his eye blinking and grimacing increased. He seemed to be aware of this, and changed the subject and the movements attenuated.

There was no evidence of thought disorder, suicidal, or homicidal ideation, and judgment and insight appeared very good for age.

Brief Formulation

In summary, A. is an 8-year-old boy referred for evaluation and management of multiple motor tics over the past 3 years, consistent with a diagnosis of chronic motor tic disorder. Given the very recent onset of vocal tics one week ago, Tourette's disorder cannot be ruled out. The onset of motor tics, reportedly rather abrupt, occurred in the context of an upper respiratory infection, which had been presumed, but not shown by laboratory documentation, to be streptococcal in nature. Notably, A.'s tic history must be viewed in the context of his diagnosis of ADHD, combined type. Whether his decline in academic performance is secondary to his ADHD and/or tic disorder must be disentangled from any other problems such as specific learning disorders.

From a biopsychosocial perspective, biological factors are important. A. has a diathesis for tics/Tourette's disorder and obsessive-compulsive disorder (OCD), given anxiety, tics, and mood symptoms on the maternal pedigree. From a medical perspective, asthma has been mild and well controlled. Certainly cough-variant asthma symptoms can overlap and co-occur with tics, and can be difficult to disentangle. Given a reported past history of sleep apnea, ongoing monitoring of sleep symptoms is necessary, as ADHD symptoms may be exacerbated or even associated with a primary sleep disorder.

From a psychosocial perspective, A. is on a healthy trajectory. He appears to be bright and engaging. There is concern that his impulsivity and inattention could lead to further academic decline, given that he has already been treated pharmacologically and has received educational intervention. His loving parents, ability to make friends, and care for those close to him are among his strengths.

Multi-Axial Diagnoses (DSM-V)

Discussion

This case is a typical example of a clinical problem that most pediatricians, neurologists, and child and adolescent psychiatrists encounter on a regular basis: The co-occurrence of ADHD symptoms and tics in young children. As tic disorders usually onset at age 5–6 years at the time that ADHD symptoms may be becoming more problematic in the early years of school, tics may be missed in this context.

Bidirectional overlap between ADHD and tic disorders has long been reported. Twenty percent of children with ADHD may meet diagnostic criteria for a tic disorder. The prevalence of provisional tic disorder in school-age children is estimated to be up to 20% (Khalifa and Von Knorring 2003). A prevalence of approximately 6.5% for all tic disorders was reported in a Spanish study of more than 800 children ages 4 to 16 years. The vast majority of tics were mild in severity and of short duration (Linazasoro et al. 2006). Prevalence estimates of chronic tic disorders suggest occurrence in between 2% and 4% (Mason et al. 1998).

Comorbidity of tics with psychiatric disorders such as ADHD and OCD is very common in clinical settings. The most common comorbid diagnosis in children with Tourette's disorder was ADHD/ADD, reported in more than 60% of children ages 6–17 (CDC 2007). As many as half of clinically referred Tourette's disorder patients reveal symptoms of ADHD prior to tic onset, usually by age 2 to 3 years. Other research on comorbidity has reported that 50–75% of Tourette's disorder patients also meet criteria for ADHD, whereas 20%–30% of ADHD patients meet criteria for a tic disorder (Freeman 2007, Spencer et al. 1999). One population-based study of school children reported comorbid psychiatric disorders in 92% of the children with Tourette's disorder. ADHD was the most frequent co-occurring condition (Khalifa and Von Knorring 2006).

Most studies suggest that ADHD places a greater burden on patients than do tics. The Tourette Syndrome International Database Consortium study reported that Tourette's disorder plus ADHD was associated, for example, with a higher rate of oppositional defiant disorder, sleep difficulties, learning disability, mood disorders, and social skills deficits. Learning and academic problems are common in children with Tourette's disorder. In a database of 5,450 patients with Tourette's disorder, 1,235 (22.7%) had learning disabilities. Other investigators have demonstrated that co-occurrence of these disorders leads to a more complicated course and outcome (Spencer et al. 1998, Pierre et al. 1999).

Optimal treatment outcome of children with ADHD and chronic tics will depend on management of both ADHD symptoms and tics when they co-occur. Research in the past decade has shown that these conditions can be safely treated simultaneously.

Despite case reports/series starting in the 1980s on the induction or exacerbation of tics in children treated with stimulants, and labeling contraindication for the use of methylphenidate-based stimulants in the Physician Desk Reference (PDR 2013), more recent work has suggested that in some children with ADHD and tic disorders, stimulants can be safely and effectively used (Gadow et al. 1995). Bloch and team reviewed pharmacotherapy for youth with ADHD and tic disorders in a meta-analysis. Effective treatment for ADHD symptoms with comorbid tics included methylphenidate, alpha-2 agonists, desipramine, and atomoxetine. Supra-therapeutic doses of dextroamphetamine reportedly worsened tics, but therapeutic doses did not. In the short term, there was no evidence of tic exacerbation due to methylphenidate (Bloch et al. 2009).

Guanfacine or clonidine are currently considered first-line medications for mild-to-moderate tics in the context of ADHD, and are also effective for ADHD symptoms. Low-dose clonidine produces presynaptic noradrenergic effects that decrease tics and reduce impulsivity, hyperactivity, and inattention. Treatment with clonidine was examined retrospectively over a 4-year period in children with ADHD with and without tic disorders and resulted in improvement of both ADHD and tic symptoms in a significant majority of patients (Steingard et al. 1993). Guanfacine is also efficacious for hyperactivity, impulsivity, and tics as it activates postsynaptic prefrontal α-adrenergic cortical receptors (Scahill et al. 2006, Boon-Yasidhi et al. 2005, Chapell et al. 2005).

Both medications are available in short-acting and long-acting formulations. There is established evidence for the efficacy of the short-acting alpha agonists for tic disorders, and evidence for the efficacy of long-acting agents for ADHD, but there is not yet evidence for the efficacy of long-acting agents for tics. Adverse effects include sedation, hypotension, headache, dry mouth, mid-sleep awakening, and irritability. Sedation often dissipates over a few weeks. Hypotension is unlikely at the low doses used, but blood pressure, heart, and ECG rates should be monitored at baseline and follow up. Rebound hypertension, anxiety, and tics are risks if medication is abruptly discontinued.

The use of stimulants for ADHD symptoms in tic disorder patients has been frequently controversial. FDA recommendations still caution against their use in individuals with tics since the publication of case reports in 1963, and particularly, due to an influential case series in the early 1980s (Lowe et al. 1982). However, over the last 20 years, extensive data has shown that stimulants may be used safely and effectively for ADHD symptoms in patients with tics (Gadow et al. 1995, Tourette's Group 2002).

Our current understanding is that there is no significant risk of tics when using stimulants in individuals with ADHD and tics. However, some patients may experience at least a transient increase in tics. Stimulants may be used judiciously in the treatment of ADHD in the context of tic disorders, monitoring for tic exacerbation. If tics worsen, the stimulant dose may be adjusted, or the patient switched to another agent.

Atomoxetine, a selective norepinephrine reuptake inhibitor, is another alternative. It has also been investigated in youth with ADHD and chronic tics, and reduced both ADHD and tic symptoms. Tachycardia, nausea, and decreased appetite and weight are the associated adverse effects (Allen et al. 2005, Spencer et al. 2008).

A. is a candidate for a switch to guanfacine to target his chronic motor tics and ADHD symptoms. Monotherapy is often recommended as a first-line treatment in children for equally problematic ADHD and tic symptoms, as both tic and ADHD symptoms may respond. If ADHD symptoms do not improve, a methylphenidate-based stimulant, either short or long acting, may be added, although the evidence base for efficacy and safety is limited to one study (Kurlan 2002). Ongoing monitoring over the next year is indicated for follow up of his course of tics, particularly with the recent development of a vocal tic.

Disclosures

Dr. Coffey has received research support from Eli Lilly Pharmaceutical, NIMH, NINDS, Tourette Syndrome Association, Otsuka, Shire, Bristol-Myers Squibb, Pfizer, and Boehringer Ingelheim. Dr. Sood has no disclosures to report.