Abstract
Chief Complaint and Presenting Problem
History of Present Illness
C. developed motor and vocal tics and obsessive thoughts and compulsive rituals at age 11. His initial tics included eye blinking, sniffing, and throat clearing. His primary obsessions centered around preoccupations and intrusive images of harm befalling his newborn youngest brother, and religious obsessions concerning sacrilege. He also had obsessions that he would become ill due to exposure to contaminants. His compulsive behaviors included frequent checking of locks, windows, and kitchen appliances. He also engaged in repeating rituals, specifically walking in and out of rooms, as well as hoarding small toys, receipts, and small bits of paper. Notably during this period, C. was evaluated by his pediatrician and tested positive for streptococcal bacterial pharyngitis, and was treated with unspecified antibiotics for the infection. Though both the initial bout of streptococcal pharyngitis and the onset of OCD symptoms occurred during the same year, there was no evidence of a temporal relationship between the two. He did not receive any treatment for his obsessive-compulsive symptoms or his tics at that time. His vocal tics resolved by age 12, though his motor tics continued intermittently, without identified precipitants. While he had been popular with a large social network in elementary school, C. reports that he “retreated” during middle school as a result of his anxiety and had few friends during this period.
C. reports that during middle school he began to have difficulty paying attention, frequently lost his homework assignments, daydreamed during class, forgot to complete his work, and became less organized in his work. Despite difficulty sustaining his prior high grades, C. continued to perform well on standardized academic tests. He did report fidgeting and difficulty staying in his seat during class, but denied feeling that he had excessive energy, was always “on the go,” or exhibited any impulsive behavior.
At age 14, C. developed depressed mood and irritability, increased need for sleep, decreased appetite, and experienced some degree of social withdrawal. He denied any loss of interest or thoughts of self harm. These symptoms occurred in the context of the death of his grandfather, with whom he shared a close relationship, and the start of high school. C. reports that his mood symptoms continued for several months and contributed to his relative social isolation during high school. He describes a limited social network in high school, with only two or three friends. He did not reveal the symptoms to his parents, and the depressive symptoms resolved without any mental health treatment. Notably even after the depressive symptoms resolved, C.'s grades continued to decline throughout high school as a result of progressive forgetfulness, disorganization, inability to sustain attention and “dazing out” during class, and inability to complete and turn in homework.
C. reported a waxing and waning course of obsessional thoughts, compulsive behavior, and motor tics throughout high school. His symptoms appeared to follow a pattern of exacerbation during the fall and subsequent improvement as the academic year progressed, with exacerbations during examination periods and attenuation during summer breaks.
C. did not receive mental health treatment until he referred himself to an academic medical center hospital at the age of 19 for treatment of obsessional thoughts and feelings of anxiety. He was subsequently diagnosed with OCD characterized by preoccupation with harm coming to his family members, compulsive prayers and religious preoccupations to ward off harm, and counting rituals centered on the number four. In addition to the OCD, C. also experienced excessive general worry, insomnia, fatigue, and restlessness. At that point, he was referred to a community mental health treatment facility, where he initiated individual weekly supportive psychotherapy and monthly psychopharmacological management. He was initially prescribed fluvoxamine 50 mg daily for the anxiety and OCD symptoms, and quetiapine 100 mg at bedtime for his insomnia. C. reported a partial reduction of his anxiety and insomnia, but his obsessive compulsive symptoms remained problematic. Four months after C. initiated treatment, the mental health treatment center closed.
After a two-month period without psychotherapy, C. presented for treatment at his current mental health care facility with increased OCD symptoms, anxiety, and motor tics. He had continued fluvoxamine and quetiapine at the same dosage. He reported violent images of family members being harmed, contamination obsessions regarding germs, obsessions with symmetry and needing to remember, fear of losing things, fear of not saying “just the right thing,” feeling a need to confess, and inability to eat in the presence of others because of the crinkling of plastic bags or the sounds of chewing. He was spending two hours per day repeating prayers to prevent harm to his family, washing his hands 10 times daily, avoiding touching door handles or subway doors, checking locks and kitchen appliances, checking on travelling family members, rereading his class texts, spending up to an hour a day counting in fours, and staring at a specific number of people on the subway for a specific period of time. In addition, C. reported insomnia due to worry, fatigue, mild irritability, and limited ability to concentrate.
C. also reported feeling that he was underachieving at school due to frequent daydreaming, inattention to detail, disorganization, forgetfulness, and distractibility. When asked about tics, he reported premonitory urges of needing to blink until “it felt right” and frequent sniffing, but no other vocal tics since age 12. He did not feel that the tics were causing distress or impairment at that time. C. was referred for psychopharmacological treatment and cognitive behavioral therapy (CBT) for OCD, generalized anxiety, and attention-deficit /hyperactivity disorder (ADHD).
Past Psychiatric History
There was no past psychiatric history other than described above.
Developmental History
C. was the product of an uncomplicated pregnancy and delivery. His motor and language milestones were met in a timely manner. He walked at about 12 months and spoke his first word at about 11 months.
Educational History
C. performed well on both standardized tests and graded academic performance throughout his elementary school years. He initially received high grades in junior high, but found it difficult to maintain his grades because he frequently forgot his homework. However, he continued to receive high scores on standardized tests. In high school his grades were average, but he continued to do well on standardized tests. He reported that his grades were not reflective of his abilities but were low due to frequently forgetting to turn in his homework or complete his assignments. Since starting college, his grades had been somewhat better initially, though they had started to decline. C. has never received academic testing or received any special education services.
Social History
C. was born into an intact family, the second of four siblings, including a 25-year-old sister, and two brothers, ages 17 and 10. His parents are self-employed. He describes his family as “close knit.” He currently resides with his parents and one younger brother in his childhood home. He denies any exposure to physical, sexual, or emotional abuse or domestic violence.
C. describes himself as a “loner with very few close friends.” In elementary school, he reported that he was much more social and had a large group of friends. In junior high, he “retreated” as a result of anxiety and maintained friendships with two or three male friends only during high school. In college, he again became more outgoing and started making friends, though he has had no serious romantic relationships.
Family History
C. has a maternal first cousin who has received treatment for OCD. C. reports that his mother has anxiety symptoms, though she has not been formally diagnosed.
There is no known family history of ADHD, tic disorders, or autistic spectrum disorders.
Medical History
C. had no serious medical problems, hospitalizations, or surgery. He had no history of any major childhood illnesses, no known drug allergies, and had received all his appropriate vaccinations. C. reports a history of annual upper respiratory streptococcal pharyngitis from age eleven through age seventeen.
His electrocardiogram was notable for sinus rhythm with occasional premature ventricular contractions.
Medication History (Table 1)
C. was initially switched to fluoxetine 20 mg daily since he had experienced side effects and limited efficacy on fluvoxamine 50 mg daily. Quetiapine was also tapered, as C. had been prescribed it solely as a hypnotic. Fluoxetine was titrated to 40 mg daily. C. noted a significant improvement in his anxiety, obsessions, and compulsive behavior; for example, he was able to spend just 5–10 minutes per day counting in fours and repeating a “prayer mantra” rather than one to two hours. Additionally, he noted some improvement in his eye blinking and sniffing. He continued to report significant impairment as a result of his inattention, distractibility, forgetfulness, inability to complete or turn in assignments on time, and daydreaming during class.
After C. obtained cardiology clearance, a trial of methylphenidate (OROS) extended release 18 mg was initiated for his ADHD symptoms. Shortly thereafter, C. reported mild elevation in heart rate, grogginess, sedation, and decreased appetite. Methylphenidate was discontinued, and lisdexamfetamine dimesylate 20 mg was started. He tolerated the medication well, reporting some improvement in ability to concentrate, improvement in organizational abilities, continued improvement in OCD symptoms, and reduction of anxiety. C. reported some minor side effects, namely decrease in appetite and loss of effect in the late afternoon. When the lisdexamfetamine dimesylate was titrated to 30 mg daily he was unable to sleep, and still felt that his inattention was not significantly improved.
C. was then switched to mixed amphetamine salts (MAS) extended release 10 mg daily to reduce the insomnia. While he tolerated this well he felt it was limited in efficacy, so the MAS extended release was titrated to 20 mg daily. At this point there was a notable increase in OCD symptoms, including recurrence of violent intrusive images of harm towards his family members, compulsion to repeat prayers, and increased anxiety, though these symptoms dissipated four days after initial titration of the stimulant. C. later reported that he had been taking the fluoxetine inconsistently and had discontinued the stimulant on his own due to appetite suppression, insomnia, and feeling restless. At that point, he was switched to MAS immediate release 20 mg twice a day in an attempt to reduce theses side effects.
C. reported progressive exacerbation of his checking, touching, tapping, and praying rituals, though felt that he was much better able to concentrate during class and complete his assignments in a timely manner. Fluoxetine was titrated to 50 mg daily for his OCD, though he later reported that he had been taking the medication only intermittently. Notably, at that time, C.'s therapist had announced her plan to leave the mental health facility, but C. repeatedly stated that this loss had no impact on his level of anxiety; that said, he expressed a wish to discontinue psychotherapy after his therapist's departure.
When C. returned following the departure of his therapist, he reported that he had discontinued both his stimulant and his fluoxetine for six weeks on his own, and then restarted fluoxetine 40 mg daily and lisdexamphetamine 30 mg daily on his own. He presented with full recurrence of intrusive violent images, checking and praying compulsions, and inability to eat due to noises. He also demonstrated recurrent eye blinking movements, though no sniffing or other motor tics.
Reintroduction of lisdexamphetamine resulted in “intense moods,” recurrence of insomnia, and appetite suppression. C. was advised to taper the stimulant to 20 mg daily, titrate the fluoxetine back to 50 mg daily, and resume cognitive behavioral therapy (CBT). At his next visit, C. reported elevated aggressive, contamination, and religious obsessions, and cleaning, counting and ordering compulsions. He then reported that he had erroneously continued to take the lisdexamphetamine 30 mg daily regimen, and was advised to taper it to 20 mg. His fluoxetine was titrated to 60 mg for OCD symptoms.
C. then reported inadequate relief of distractibility, inattention, forgetfulness, and disorganization with the lower dosage of lisdexamphetamine, though had some relief of his feeling of “uneasiness” and appetite suppression on this regimen. C. requested an increase of the stimulant to 40 mg to focus better on his final examinations, despite side effects and exacerbation of his OCD.
On this regimen C. reported some improvement in his anxiety, “uneasiness,” and OCD, despite increase of his stimulant and no change in his fluoxetine. However, he continued to experience appetite suppression and gastrointestinal distress, culminating in notable weight loss.
C. had initiated OCD focused CBT incorporating exposure and response prevention in his treatment. Over the next several weeks, C. reported increasing gastrointestinal discomfort, including nausea, as well as increase in both anxiety and OCD symptoms. The decision was made to discontinue the lisdexamfetamine dimesylate 40 mg daily for a wash out period, coinciding with a holiday break from classes. His fluoxetine was titrated to 70 mg daily to address the increase in OCD symptoms.
Upon the start of the new semester, C. was prescribed methylphenidate transdermal system 10 mg daily to potentially minimize gastrointestinal side effects while continuing fluoxetine 70 mg daily for his OCD and anxiety symptoms. Due to insurance formulary limitations, C. was unable to initiate the transdermal methylphenidate. At that point, he was prescribed a combination of methylphenidate 10 mg and guanfacine 0.5 mg for his ADHD symptoms and to ameliorate potential adverse tic, anxiety, and OCD exacerbation. After taking this regimen in combination with fluoxetine 70 mg daily, he reported some relief of his tics, insomnia, and anxiety, though C. reported continued difficulty with inattention, focus, and procrastination.
Mental Status Exam
Mental status examination revealed a tall, thin, lanky older adolescent male, neatly groomed, attired casually but carefully in jeans, a designer T-shirt, baseball cap, and sneakers. C. had an engaged, cooperative, and well-related demeanor, maintaining good eye contact throughout the interview. He demonstrated +1 eye blinking and sniffing intermittently throughout the interview, more notably when discussing the nature of his OCD symptoms. He was somewhat fidgety, drumming his fingers along his knees and tapping his feet during the interview, though not in any specific or rhythmic pattern. His speech was articulate and appropriately inflected, but somewhat soft in volume, slow in rate, and slightly halting in spontaneous production. He reported his mood as “fine, a little tired.” C.'s affect was anxious but generally stable, of full range, reactive, and appropriate to both content and situation. His thought process was linear, logical, and goal related. His thought content centered on his history and was conversationally appropriate. There was no evidence of perceptual disturbance, suicidal or homicidal ideation, intent, or attempt. He was able to pay attention throughout the interview, was alert and oriented to three spheres, and demonstrated intact recent memory and capacity for abstract reasoning. C. demonstrated fair insight and judgment, as he had referred himself for treatment.
Brief Formulation
In summary, C. is a 19-year-old adolescent male who meets diagnostic criteria for OCD, generalized anxiety disorder, chronic motor tic disorder, and ADHD. C's history is notable for childhood onset of obsessive-compulsive symptoms, and motor and vocal tics. During adolescence, C's OCD progressed, and he developed symptoms of generalized anxiety followed by a brief and circumscribed period of depressive symptoms. He likely experienced exacerbation of his OCD and anxiety symptoms in the context of mounting academic pressure, complicated by symptoms consistent with an undiagnosed ADHD.
Biologically, C. has a predisposition to OCD and comorbid anxiety symptoms, given his maternal pedigree. Additionally, he demonstrated a sudden onset of tics and OCD symptoms in close proximity to reported streptococcal pharyngitis, which may be a contributing etiological factor. Notable also are the contributions of iatrogenic exacerbation of anxiety as an adverse consequence of treatment with stimulants, as well as the role of lack of full adherence to his pharmacological regimen. His clinical picture is typical of childhood onset OCD given the complex comorbidity with ADHD, generalized anxiety, and tic disorders.
C.'s symptoms occurred in the context of notable psychosocial stressors, including the birth of a new sibling, the death of his grandfather, a dissipating social network, the premature termination of psychotherapeutic relationships, and academic stresses associated with a new school year and examination cycles.
Despite numerous psychosocial stressors, C. demonstrates significant strengths, including insight regarding his diagnoses, motivation for treatment, academic achievement, and intelligence.
Multi-Axial Diagnoses
Discussion
This interesting case illuminates the complex interplay between the roles of biological predisposition, psychopharmacology, psychosocial and developmental factors, and the multidisciplinary team in the comprehensive evaluation and treatment of childhood onset anxiety, tics, and ADHD.
OCD in children and adolescents is well known to be highly comorbid with other anxiety disorders, tic disorders, depression and ADHD (Stewart et al. 2012). Some reports indicate that patients with OCD and comorbid tic disorders or Tourette's disorder frequently present with other comorbid anxiety disorder and mood disorders. Other reports indicate that comorbid OCD and ADHD may lead to an elevated risk of substance abuse and dependence, or more severe OCD. The prognosis for children and adolescents with OCD is impacted by the actual comorbid condition itself, but also diverges based on the timing, order, and severity of the comorbid diagnosis (Gomes de Alvarenga et al. 2012 and de Mathis et al. 2013). C. was clearly able to delineate the onset of his vocal and motor tics, as well as his obsessive and compulsive symptoms, in the setting of numerous psychosocial stressors. Notably, he also reported an exacerbation of these symptoms in the context of the academic year, in which his previously undiagnosed symptoms of inattention and distractibility were likely compounding his underlying anxiety symptoms.
The pharmacological management of children and adolescents with comorbid OCD, tic disorder, and ADHD requires a balance of often competing treatment strategies and vigilance for potential symptom exacerbation of one disorder when another is being treated. Stimulants, particularly amphetamine, have been reported to exacerbate tics in some patients. In cases of comorbid ADHD and tic disorders, treatment of ADHD is often prioritized over tics due to the generally greater impairment caused by the ADHD symptoms (Pringsheim et al. 2011). While alpha-2 agonists, atomoxetine, and desipramine are recommended for treatment of both tic and ADHD symptoms (Bloch et al. 2009), these medications are considered second-line agents for treatment of ADHD. Less widely described in the literature, but very common in clinical practice, is the exacerbation of anxiety symptoms during treatment with stimulants. In these situations, the priority is not as clear, as OCD and anxiety symptoms may be equally, if not more, impairing than the ADHD symptoms.
C. experienced an exacerbation of his generalized anxiety and obsessional thoughts when his ADHD symptoms were not managed pharmacologically. Yet he experienced an exacerbation of OCD symptoms in association with an increase in his stimulant medication. His inability to tolerate the adverse anxiogenic and physical effects of his multiple stimulant trials was intermittently outweighed by the benefits of treatment of his ADHD, which resulted in relief of his subjective anxiety.
One of the key factors impacting the efficacy of a psychiatric treatment regimen in an adolescent population, as opposed to a child or adult population, is the intersection of emerging autonomy, developmental trajectory, and medication adherence. Adolescents and young adults demonstrate high rates of treatment nonadherence, despite residual functional impairment from untreated symptoms of ADHD (Brinkman et al. 2012). There are multiple etiological factors contributing to premature discontinuation of stimulant medication, including psychological side effects or perceived inadequate medication effectiveness, negative feelings toward medication due to side effects, selective use of medication, and overall low satisfaction with stimulant medication (Pelham et al. 2013 and Toomey et al. 2012).
Unlike children, who are generally monitored by their parents or caretakers, and adults, who have generally developed insight into the functional impact of ADHD or the risks of selective usage or nonadherence to a prescribed treatment, adolescents may not have reached that level of insight or judgment. The ramifications of nonadherence are notable, as adolescents and young adults with ADHD face an elevated risk of academic, social, and vocational difficulties, as well as behavioral problems, including substance abuse, unsafe driving, and criminal activity (Montano and Young 2012).
A multifactorial approach should be incorporated to improve rates of adherence to psychopharmacological treatment in adolescents with ADHD. Proposals include addressing disparities and inadequacies in ADHD education, increasing support in the college health care system, reforming inadequate health insurance coverage and utilizing transitional planning integrating parents, teachers, doctors, and/or other stakeholders to facilitate a developmentally appropriate transition from family to self-management of ADHD (Brinkman et al. 2012 and Montano et al. 2012). Additionally, multiple studies indicate greater adherence and persistence with long acting stimulant formulations, such as methylphenidate LA and lisdexamfetamine dimesylate, methylphenidate OROS and atomoxetine, over immediate release formulations of stimulant medications (Setyawan et al. 2013 and Lachaine et al 2012).
Multiple studies demonstrate the efficacy of a cognitive-behavioral therapy intervention (CBT) in the treatment of OCD, ADHD, or comorbid anxiety disorders. According to the Pediatric OCD Treatment Study II (POTS II), the addition of CBT to medication management compared with medication management alone resulted in a significantly greater response rate (Franklin et al. 2011). Adolescents diagnosed with ADHD and comorbid anxiety or depression have also demonstrated benefit from CBT intervention (Antshel et al. 2012 and Houghton et al. 2013).
C. demonstrated reduction in subjective anxiety and OCD in concert with his engagement in weekly cognitive behavior psychotherapy, regardless of the status of his stimulant or adherence to his selective serotonin reuptake inhibitor (SSRI) regimen. Conversely, C. experienced a significant relapse of these symptoms as well as inconsistent adherence to his medication regimen following the departure of his psychotherapist. Though the role of the therapist may have been limited to cognitive restructuring and exposure and response prevention, the therapist also likely served as an additional stakeholder to ensure medication compliance and facilitate C.'s young adult development.
Given the high degree of comorbidity between OCD, ADHD, tic disorders, and other anxiety disorders, relatively few studies examine the effects of treatment of ADHD on the phenomenology of the anxiety/obsessive compulsive spectrum disorders. As there is very limited data on the exacerbation of obsessive compulsive symptoms during stimulant trials, this is an important direction for future research given the high comorbidity and notable impairment associated with these diagnoses.
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. Anam has no disclosures to report.
Footnotes
Acknowledgment
We would like to acknowledge and thank Resham Gellatly and Laura Ibanez-Gomez for their assistance in review and preparation of the manuscript.