Cases that Test Your Skills
Obsessive and inattentive
Mr. C, age 20, has impaired attention, debilitating compulsions, and tic disorder. Can he be safely treated with a psychostimulant without exacerbating his obsessive-compulsive disorder or tics?
CASE: Perfect breath
Mr. C, a 20-year-old college student, is diagnosed with obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and tic disorder (TD). His obsessions consist of a persistent sense that he is not breathing “correctly” or “perfectly.” He compulsively holds his breath to “rush blood to my head” until “the pressure feels just right.” Mr. C says that his OCD has had longstanding, significant negative impact on his academic performance and capacity to engage in other activities. Tics have been present for years and manifest as coughing and throat-clearing. After multiple syncopal epi-sodes from breath-holding with Valsalva maneuver—some of which caused falls and head injury—Mr. C is admitted to a residential psychiatric unit specializing in treating OCD. At the time of his admission, his Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores1,2 are 23 total, 12 on the obsessions subscale, and 11 on the compulsions subscale, indicating moderate to severe illness. Cognitive-behavioral therapy (CBT) is offered, along with a combination of escitalopram, 60 mg/d, and quetiapine, 50 mg/d. Quetiapine is over-sedating at subtherapeutic doses and Mr. C’s compulsions worsen. He reports that “[it] took longer and longer to get the ‘just right’ feeling.’” Quetiapine is discontinued and risperidone, 0.5 mg/d, is started, which decreases the frequency of his tics. When he is discharged after a 36-day stay, Mr. C’s Y-BOCS scores are greatly improved at 13 total, 7 on the obsessions subscale, and 3 on the compulsions subscale.
Mr. C’s psychologist refers him to our outpatient clinic for continued psychiatric evaluation and treatment of his OCD, ADHD, and TD. At this time, he is prescribed escitalopram, 60 mg/d, and risperidone, 0.5 mg/d, along with CBT with his psychologist. We do not readminister the Y-BOCS at this time, but Mr. C reports that his OCD is “60% improved.” However, he describes prominent obsessive thoughts regarding his breathing similar to those he experienced before residential treatment. These obsessive thoughts arise in the context of specific environmental “triggers,” such as other people coughing or his own tics. The obsessions lead to compulsive urges to engage in breath-holding rituals. Mr. C experiences the thoughts and compulsions as deeply troubling and they consume 5 to 6 hours each day. Mr. C reports impaired concentration in class and during studying: “I can focus for 5 minutes, then not for 2 minutes, then for 3 minutes… I can never stay focused for more than a couple minutes,” before becoming distracted “by my OCD” or other environmental stimuli. We note on exam prominent breath-holding occurring several times per minute. Mr. C says his OCD has not impaired his ability to socialize.
Mr. C notes that he has been exposed to an array of CBT techniques, but he has difficulty using these techniques because his “mind wanders” or he lacks “motivation.” He admits he occasionally has taken a classmate’s ADHD medication (mixed amphetamine salts [MAS], dose unspecified) and found it improved his ability to focus on his academic work.
The authors’ observations
Researchers have established a relationship among OCD, ADHD, and TD across all combinations of comorbidity (OCD and ADHD,3 ADHD and TD,4 OCD and TD,5,6 and all 3 entities7). Data suggests a poorer prognosis for OCD when comorbid with either or both of these conditions.8 Researchers have raised concerns that psychostimulants could exacerbate or potentiate tic behaviors in patients with ADHD,9,10 although safe and effective use of these medications has been documented in controlled trials of patients with comorbid ADHD and tics.11-13 Furthermore, tic suppression has been reported with psychostimulants,14 as well as a differential effect of stimulants on motor vs vocal tics.15 Despite these data (Table 1),9-15 the FDA regards using psychostimulants in patients with TD as a contraindication,16 although clinicians often recognize that this practice may be unavoidable in some circumstances because of high comorbidity rates. Psychostimulants could exacerbate obsessions or compulsions in some patients because of their dopaminergic properties or through mitigation of the purported anti-obsessional properties of dopamine antagonists.17
Although there is evidence that the prevalence of prescribed psychostimulant abuse is low among ADHD patients,18 diversion of prescribed medication is a risk inherent in the use of these agents, particularly among college-age patients.19,20
Evidence of effect of psychostimulants on tics
Medication and study design
Lipkin et al, 19949; ADHD without TD
Chart review (N = 122) to determine the incidence of tics or dyskinesias in children treated with stimulants
Approximately 9% of children developed tics or dyskinesias, which predominantly were transient, with <1% developing chronic tics or Tourette’s syndrome. Personal or family tic history and medication selection or dosage were not related to onset of tics or dyskinesias
Gadow et al, 199515; ADHD with TD
Methylphenidate variable dose, placebo-controlled, 2-week trials (N = 24)
All children’s ADHD symptoms improved. At a 0.1 mg/kg dose, motor tics observed in the classroom increased, but there were fewer vocal tics observed in the lunchroom
Castellanos et al, 199710; ADHD with Tourette’s syndrome
Methylphenidate, dextroamphetamine, variable-dose, double-blind, placebo-controlled, 9-week crossover (N = 20)
3 patients had consistent worsening of tics while taking stimulants. Stimulants reduced hyperactivity rates compared with placebo (P = .03). Stimulants improved ADHD symptoms and had acceptable effects on tics. Methylphenidate was better tolerated than dextroamphetamine
Gadow et al, 199911; ADHD with TD
34 methylphenidate-treated children, followed at 6-month intervals for 2 years
No evidence that frequency or severity of motor or vocal tics changed during maintenance therapy
Tourette Syndrome Study Group, 200213; ADHD with TD
Clonidine alone, methylphenidate alone, clonidine plus methylphenidate, or placebo
Worsening of tics was not reported in any group at a rate significantly higher than placebo. Tic severity was more reduced in the 2 clonidine groups than in the methylphenidate group
Lyon et al, 201014; ADHD with Tourette’s syndrome
Dexmethylphenidate, single-dose challenge. Ten patients with or without TSP
Acute dexmethylphenidate administration resulted in tic suppression but did not augment TSP
Gadow et al, 200712; ADHD with TD
Double-blind, placebo-controlled, 2-week trials each of 3 doses of methylphenidate and placebo (N = 71)
MPH-IR did not alter the overall severity of TD or OCD behaviors. Teacher ratings indicated that MPH-IR therapy decreased tic frequency and severity
ADHD: attention-deficit/hyperactivity disorder; MPH-IR: methylphenidate immediate release; OCD: obsessive-compulsive disorder; TD: tic disorder; TSP: tic suppression protocol
TREATMENT: Weighing options
To manage impaired attention and executive function difficulties secondary to ADHD, we offer Mr. C several options, including bupropion, modafinil, and memantine augmentation. Mr. C asks for a psychostimulant because exam week is approaching and he wants a treatment with quick therapeutic effect. We discuss with Mr. C the potential for dopaminergic agents, such as psychostimulants, to exacerbate tics or OCD symptoms. Ultimately, we prescribe immediate-release MAS, 20 mg/d.
Two days later, Mr. C says he has taken 3 MAS doses and describes a marked reduction in obsessions, significant decrease in frequency of “triggers,” and greater capacity to use CBT saying, “when I am [triggered], I am able to move past the urges without doing any compulsions.” Daily time spent “stuck on” obsessions or compulsions decreases from 5 to 6 hours per day to “about 2 and a half minutes.”
Mr. C reports a modest increase in the prevalence of tics, experienced as “little throat clears and quick stuttering of breath.” He notes that, although in the past such tics would be followed by urges for “perfecting the tic and making it feel just right,” he presently “had no desire to do so.”
OUTCOME: Sharper focus
Increasing MAS immediate release from 20 mg/d to 30 mg/d suppresses Mr. C’s obsessions and compulsions for 8 hours. On the 19th day of treatment, MAS immediate release was replaced with an extended release formulation, 30 mg/d, which preserves therapeutic effect and tolerability for 16 weeks. Repeat Y-BOCS yields 9 total, 3 on obsessions subscale, and 6 on compulsions subscale scores.
One month later, Mr. C reports that his symptoms have been “improving ever since” the previous appointment. He continues to be able to access skills for managing his OCD and is doing well in his 2 accelerated summer courses, saying “I focus really well” in 3-hour class sessions. On exam, tic behaviors are nearly absent. Mr. C describes occasional bouts of anxiety associated with urges to engage in tic behaviors, in turn arising from fear of symptomatic recurrence as he worked toward stopping smoking as advised by his primary care physician and psychiatrist.
The authors’ observations
The results of the repeat Y-BOCS are consistent with improvement in obsessions but possible worsening of compulsions since Mr. C was discharged from residential treatment. Alternatively, compulsions may have worsened immediately after discharge and declined again with introduction of MAS.
A substantial body of literature describes the challenges associated with treating ADHD with comorbid tics, including the relative degree of risk of tic exacerbation associated with treating ADHD with psychostimulants. The range of FDA-approved pharmacologic options for treatment of this comorbidity is limited (Table 2),21 particularly given the risk for tardive dyskinesia associated with the typical antipsychotics haloperidol and chlorpromazine. Data support using the α-2 agonist clonidine to treat hyperactivity associated with ADHD22 and TD23 and an extended-release preparation of this medication is FDA-approved for the former but not the latter indication (an α-2A receptor subtype agonist, guanfacine, also is FDA-approved for ADHD in pediatric patients). Mr. C’s experience of robust, sustained reduction in obsessions, if not compulsions, after treatment with MAS is consistent with the few studies of stimulant use in ADHD with comorbid OCD.24,25
Effective treatment of ADHD may help Mr. C better access CBT strategies and thereby potentiate treatment of comorbid OCD.
FDA-approved medications for ADHD, OCD, and TD
Amphetamine (racemic), atomoxetine, chlorpromazine (hyperactivity), clonidine extended release, dexmethylphenidate, dextroamphetamine, guanfacine extended release, haloperidol (hyperactivity, second-line), lisdexamfetamine, methylphenidate (racemic)
Clomipramine, fluoxetine, fluvoxamine, paroxetine, sertraline
Haloperidol (Tourette’s), pimozide (Tourette’s)
ADHD: attention-deficit/hyperactivity disorder; OCD: obsessive-compulsive disorder; TD: tic disorder
- Pliszka SR. Treating ADHD and comorbid disorders: psychosocial and psychopharmacological interventions. New York, NY: The Guilford Press; 2011.
- Pollak Y, Benarroch F, Kanengisser L, et al. Tourette syndrome-associated psychopathology: roles of comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder. J Dev Behav Pediatr. 2009;30(5):413-419.
Drug Brand Names
- Atomoxetine • Strattera
- Bupropion • Wellbutrin, Zyban
- Chlorpromazine • Thorazine
- Clomipramine • Anafranil
- Clonidine extended release • Kapvay
- Dexmethylphenidate • Focalin
- Dextroamphetamine • Dexedrine
- Escitalopram • Lexapro
- Fluoxetine • Prozac
- Fluvoxamine • Luvox
- Guanfacine • Intuniv, Tenex
- Haloperidol • Haldol
- Lisdexamfetamine • Vyvanse
- Memantine • Namenda
- Methylphenidate • Methylin, Ritalin
- Modafinil • Provigil
- Pimozide • Orap
- Quetiapine • Seroquel
- Risperidone • Risperdal
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: I. Development, use and reliability. Arch Gen Psych. 1989;46(11):1006-1011.
2. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale: II. Validity. Arch Gen Psych. 1989;46(11):1012-1016.
3. Geller DA, Biederman J, Faraone S, et al. Re-examining comorbidity of obsessive compulsive and attention-deficit hyperactivity disorder using an empirically derived taxonomy. Eur Child Adolesc Psychiatry. 2004;13(2):83-91.
4. Freeman RD. Attention deficit hyperactivity disorder in the presence of Tourette syndrome. Neurol Clin. 1997;15(2):411-420.
5. Geller DA. Obsessive-compulsive and spectrum disorders in children and adolescents. Psychiatr Clin North Am. 2006;29(2):353-370.
6. Eapen V, Fox-Hiley P, Banerjee S, et al. Clinical features and associated psychopathology in a Tourette syndrome cohort. Acta Neurol Scand. 2004;109(4):255-260.
7. Kano Y, Ohta M, Nagai Y, et al. Association between Tourette syndrome and comorbidities in Japan. Brain Dev. 2010;32(3):201-207.
8. Grados M, Riddle M. Do all obsessive-compulsive disorder subtypes respond to medication? Int Rev Psychiatry. 2008;20(2):189-193.
9. Lipkin PH, Goldstein IH, Adesman AR. Tics and dyskinesias associated with stimulant treatment in attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med. 1994;148(8):859-861.
10. Castellanos FX, Giedd JN, Elia J, et al. Controlled stimulant treatment of ADHD and comorbid Tourette’s syndrome: effects of stimulant and dose. J Am Acad Child Adolesc Psychiatry. 1997;36(5):589-596.
11. Gadow K, Sverd J, Sprafkin J, et al. Long-term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder. Arch Gen Psychiatry. 1999;56(4):330-333.
12. Gadow KD, Sverd J, Nolan EE, et al. Immediate-release methylphenidate for ADHD in children with comorbid chronic multiple tic disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):840-848.
13. Tourette’s Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002;58(4):527-536.
14. Lyon GJ, Samar SM, Conelea C, et al. Testing tic suppression: comparing the effects of dexmethylphenidate to no mediation in children and adolescents with attention-deficit/hyperactivity disorder and Tourette’s disorder. J Child Adolesc Psychopharmacol. 2010;20(4):283-289.
15. Gadow KD, Sverd J, Sprafkin J, et al. Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder. Arch Gen Psychiatry. 1995;52(6):444-455.
16. Bloch MH, Panza KE, Landerso-Weisenberger A, et al. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry. 2009;48(9):884-893.
17. McDougle CJ, Goodman WK, Price LH. Dopamine antagonists in tic-related and psychotic spectrum obsessive compulsive disorder. J Clin Psychiatry. 1994;55(suppl):24-31.
18. Wilens TE, Morrison NR. The intersection of attention-deficit/hyperactivity disorder and substance abuse. Curr Opin Psychiatry. 2011;24(4):280-285.
19. Kollins SH. A qualitative review of issues arising in the use of psycho-stimulant medications in patients with ADHD and co-morbid substance use disorders. Curr Med Res Opin. 2008;24(5):1345-1357.
20. Schubiner H. Substance abuse in patients with attention-deficit hyperactivity disorder: therapeutic implications. CNS Drugs. 2005;19(8):643-655.
21. Stahl SM. The prescriber’s guide. Stahl’s essential psychopharmacology. 3rd ed. New York NY: Cambridge University Press; 2009.
22. Jain R, Segal S, Kollins SH, et al. Clonidine extended-release tablets for pediatric patients with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2011;50(2):171-179.
23. Hedderick EF, Morris CM, Singer HS. Double-blind crossover study of clonidine and levetiracetam in Tourette syndrome. Pediatr Neurol. 2009;40(6):420-425.
24. Joffe RT, Swinson RP, Levitt AJ. Acute psychostimulant challenge in primary obsessive-compulsive disorder. J Clin Psychopharmacol. 1991;11(4):237-241.
25. Insel TR, Hamilton JA, Guttmacher LB, et al. D-amphetamine in obsessive-compulsive disorder. Psychopharmacology (Berl). 1983;80(3):231-235.