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Pharmacologic Treatment of Obsessive-Compulsive Disorder

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Pharmacologic Treatment of Obsessive-Compulsive Disorder

in Children and Adolescents

Amy Bridgeman

The Pennsylvania State University - College of Medicine

October 2003

I. Diagnosis

DSM IV criteria for Obsessive-Compulsive Disorder (OCD) (8):

A. Either obsessions or compulsions:

Obsessions as defined by:

1. Recurrent and persistent thoughts, impulses, or images that are experienced, at some time during the disturbance, as intrusive and inappropriate and that cause anxiety or distress.

2. The thoughts, impulses, or images are not simply excessive worries about real-life problems.

3. The person attempts to ignore or suppress such thoughts, impulses, or images, or to neutralize them with some other thought or action.

4. The person recognizes that the obsessional thoughts, impulses, or images are a product of his or her own mind.

Compulsions as defined by

1. Repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly.

2. The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts either are not connected in a realistic way with what they are designed to neutralize or prevent or are clearly excessive.

B. At some point the person has recognized the compulsions are excessive or unreasonable. (Does not apply to children)

C. The obsessions or compulsions cause marked distress, are time consuming, or significantly interfere with the person’s normal routine, occupational (or academic) functioning, or usual social activities or relationships.

D. If another Axis I disorder is present, the content of the obsessions or compulsions is not restricted to it.

E. The disturbance is not due to the direct physiological effects of a substance or a general medical condition.

The Multidimensional Anxiety Scale for Children and the Yale-Brown Obsessive Compulsive Scale have been used to aid in the diagnosis and severity assessment of OCD in children and adolescents (1).

II. Epidemiology (1)

· OCD occurs in 2 to 3 percent of the U.S. population, with an average age of onset of 14.5 years.

· Boys have been noted to have an earlier onset than girls with one peak around puberty and another in early adulthood.

· OCD tends to be persistent in adults but childhood onset OCD has shown a complete remission rate of 10-50% by late adolescence.

· Several comorbidities tend to be associated with OCD with one study demonstrating only 26% of children had OCD as their only diagnosis (1).

III. Pathophysiology (2), (9)

· The incidence of OCD is increased in first degree relatives of OCD patients.

· Brain imaging studies have suggested the prefrontal cortex, cingulate gyrus, and basal ganglia (particularly the caudate nucleus) may be areas of the brain that are dysfunctional in OCD.

· Serotonin is a neurotransmitter believed to play a key role in OCD etiology and symptoms.

· A subgroup of OCD patients are children with acute OCD onset after an infection with group A beta-hemolytic streptococcal pharyngitis. Basal ganglia dysfunction has been implicated in this disorder. This syndrome has been named pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS).(1)

IV. Treatment

· Drug trials done in the 1980’s for the treatment of OCD in children showed that clomipramine hydrochloride was an effective treatment (1).

· Research has since demonstrated that the SSRI’s are equally effective with fewer adverse effects.

· SSRI’s are currently the drug of choice for childhood onset OCD and a trial of 10-12 weeks is recommended as response to the SSRI’s tends to be slow.

Some studies looking at the efficacy of various SSRI’s in the treatment of OCD in children and adolescents with the disorder:

“Sertraline in children and adolescents with obsessive-compulsive disorder”(3)

Design was a multicenter, randomized, double-blind, placebo controlled trial completed on 187 children and adolescent patients aged 6-17 years.

The treatment group received sertraline hydrochloride titrated to a maximum of 200 mg/day during the 1st four weeks, and patients continued to receive this dose for 8 more weeks. The control patients received placebo for the entire trial.

Outcome measures used to gauge improvement included:

1. The Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS)

2. The National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH GOCS)

3. The NIMH Clinical Global Impressions of Severity of illness (CGI-S)

4. The NIMH Clinical Global Impressions of Improvement (CGI-I)

· Results demonstrated that participants treated with sertraline demonstrated significantly greater improvement on 3 of the 4 measures (CY-BOCS, the NIMH GOCS, and the CGI-I) than the group treated with placebo. Significant differences first surfaced at week 3 and persisted for the duration of the study.

· Conclusion was that sertraline appears to be a safe and effective treatment for OCD in children and adolescents, at least in the short term.

“Fluvoxamine for Children and Adolescents with Obsessive-Compulsive Disorder: A Randomized, Controlled, Multicenter Trial” (4)

Design was a double-blind, placebo-controlled, multicenter study completed on 120 randomized subjects aged 8-17 years who met DSM-III-R criteria for OCD.

For 10 weeks patients received either fluvoxamine 50-200mg/day or placebo.(Participants who did not respond after 6 weeks could discontinue and enter a long-term, open-label trial of fluvoxamine).

The primary outcome measure used to assess improvement was the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Secondary measures were the NIMH-GCOS and Clinical Global Impression Scales completed by the clinician (CGI-C), the parent (CGI-P), and the subject (CGI-S).

Results demonstrated significant improvement of CY-BOCS scores in the fluvoxamine treated group compared to the placebo group at weeks 1, 2, 3, 4,6, and 10. Significant differences between the fluvoxamine and placebo groups were also seen on all secondary outcome measures at all follow-up visits.

Improvement in the fluvoxamine group tended to reach a maximum at the end of 3 weeks (this is in contrast to adults who generally don’t see significant improvement until at least week 4) (4).

Conclusions of this study were that fluvoxamine is effective in the short term for treating pediatric OCD, it tends to have a rapid onset of action, and it is well tolerated.

“Citalopram treatment of children and adolescents with obsessive-compulsive disorder: A preliminary report” (5)

This was an 8-week open label study.

Fifteen patients aged 6-17 years were treated with citalopram at a range of doses of 20-30mg/day.

The CY-BOCS was used as a measure of improvement. Ratings were completed at baseline, at the 4th week, and at the 8th week of treatment.

Results showed that 14/15 patients had a significant decrease in total CY-BOCS score from baseline to the 4th treatment week and baseline to the 8th treatment week.

These results suggest that citalopram may be both an effective and well-tolerated treatment option for children and adolescents with OCD.

Shortcomings of this study include the small sample size and the open label study design. However, this represents the 3rd study of citalopram in pediatric OCD to demonstrate the medication’s beneficial effects (5).

“Fluoxetine Treatment for Obsessive-Compulsive Disorder in Children and Adolescents: A Placebo-Controlled Clinical Trial” (6)

This was a randomized, double-blind, placebo-controlled study.

Study participants were 103 children and adolescents ages 7-17 years old, 71 of whom received fluoxetine. The remainder received placebo.

Dosage was begun at 10 mg daily for 2 weeks and then increased to a maximum of 60 mg daily. Total study time was 13 weeks.

The primary measure of efficacy was CY-BOCS.

Results showed that fluoxetine resulted in significantly improved CY-BOCS scores as compared to placebo without significant side effects.

Differences in CY-BOCS scores began to tend toward significance beginning at week five. This is a somewhat slower time to response than reported for other SSRI’s but may, at least in part, be due to a slower upward titration schedule than reported in some other studies.

Conclusion was that fluoxetine was shown to be an effective and well-tolerated treatment of OCD in children and adolescents, a result duplicated in several other studies (6).

Conclusions: Currently 3 medications are FDA approved for the treatment of OCD in children and adolescents, clomipramine, fluvoxamine, and sertraline. Although all have been shown to be effective, current treatment tends to favor the SSRI’s over clomipramine because of reduced occurrence of side effects (7).

Although only 2 of the SSRI’s are currently approved for OCD treatment in children and adolescents, research has demonstrated several other SSRI’s appear to be both effective and well tolerated. Research continues to further study which agents may have the shortest treatment response times along with the greatest efficacy and fewest side effects so as to improve the pharmacological treatment of this disorder.

References

(1) Snider, L.A., Swedo, S.E. Pediatric obsessive-compulsive disorder. JAMA 2000;284(24):3104-3106.

(2) Baxter, LR Jr., Schwartz, JM, Bergman, KS, et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Archives of General Psychiatry 1992; 49:681.

(3) March, J.S., Biederman, J., Wolkow, R., et al. Sertraline in children and adolescents with obsessive-compulsive disorder. JAMA 1998; 280(20): 1752-1756.

(4) Riddle, M.A., Reeve, E.A., Yaryura, J.A. et al. Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial. Journal of the American Academy of Child and Adolescent Psychiatry 2001; 40(2): 222-229.

(5) Mukaddes, N.M., Abali, O., & Kaynak, M. Citalopram treatment of children and adolescents with obsessive-compulsive disorder: A preliminary report. Psychiatry and Clinical Neurosciences 2003; 57: 405-408.

(6) Geller, D.A., Hoog, S.L., Heiligenstein, J.H. et al. Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: A placebo-controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry 2001; 40(7): 773-779.

(7) Kaplan, A., & Hollander, E. A review of pharmacologic treatments for obsessive-compulsive disorder. Psychiatric Services 2003; 54:1111-1118.

(8) Diagnostic Criteria from DSM-IV-TR, American Psychiatric Association, Washington, DC 2000.

(9) Swedo, S.E., Leonard, H.L., Garvey, M., et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases. American Journal of Psychiatry 1998; 155:264.

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