OCD – A Treatment Review

Obsessive Compulsive Disorder (OCD) – A Treatment Review

Cherie’ Inglis

The Pennsylvania State University – College of Medicine

2004

 

Obsessive Compulsive Disorder (OCD) is a chronic, waxing and waning, DSM-IV Axis I disorder in which patients have recurrent intrusive thoughts (obsessions) that increase their anxiety level. They usually relieve this anxiety with recurrent standardized behaviors (compulsions). These symptoms are ego-dystonic and cause significant distress in the patients’ lives.

 

1. Epidemiology^1,2,3

 

• Average lifetime prevalence is 2-3%; M = F.

 

• Bimodal peak of onset, first peak is around puberty 11-15 and second peak is early adulthood around age 20; boys have an earlier onset than girls.     80% of patients have an onset before 18 years of age.^3,4

 

• Comprehensive reviews of literature have shown a complete remission rate of childhood-onset OCD of 10-15% by late adolescence.     Of those that persist into adulthood, 1/3 improves, 1/3 has mood improvement and no change in OCD symptoms, and 1/3 stays the same or worsens.

 

• Only 26% of subjects had OCD as their only diagnosis. Frequent comorbidities include tic disorders (30%), major depression (26%), and developmental disorders (24%).²

 

1. Etiology

 

• Genetic – Monozygotic twins have a concordance rate of 80-87% versus dizygotic twins 47-50%. Prevalence is increased among first-degree relatives of patients with OCD.^1,4

 

• Neuroantomical – Neuroimaging studies have implicated abnormalities (hyperactivity, smaller striatal and larger third ventricle volumes, and more gray matter and less white matter than controls) in the orbitofrontal cortex, anterior cingulated cortex, basal ganglia (especially the caudate nucleus), and thalamus as contributors in OCD’s pathogenesis. Successful treatment with various modalities show a decrease in hypermetabolism and hyperprefusion.^4,5,6,7

• Neurochemical – Serotonin hypothesis: It is thought that the serotonergic system may play a role as serotonin re-uptake inhibitors have been successful in treatment.     It is suggested that other neurotransmitters such a dopamine and neurepinephrine also play a role as OCD symptoms improve when pharmacological agents affecting these transmitters are added to SRIs.

 

• Neurological Insult – may be due to encephalitis, streptococcal infection (children only), striatal lesions, or head injury.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) – believed to have antibacterial antibodies that cross-react with brain structures

 

• Diagnostic criteria – presence of obsessive-compulsive disorder and/or a tic disorder, pediatric onset of symptoms (3 to puberty), acute onset/worsening of sx, episodic course of sx severity associated with GABS infection., association with neurological abnormalities.

 

• Genetics – a B lymphocytic antigen D8/17 has been suggested as a peripheral marker of susceptibility to childhood-onset OCD with frequency in children with PANDAS at 85% compared to 17% in healthy controls.^2,4,9

 

• Neuroimaging – MRI scans of 34 children with PANDAS were compared with those of 82 healthy controls. The PANDAS group had a larger caudate nucleus (8%), putamen (5%), and globus pallidus (7%) compared with the control group. These increases were statistically significant (p=0.02 – 0.0004). However, the basal ganglia size in the PANDAS group was not correlated with the duration or severity of sx or with the presence of OCD so the MRI scans are not sufficiently accurate to be useful in diagnosis or clinical monitoring of PANDAS.⁸

 

• Treatment – antibiotic treatment of the acute infection. Cases have been treated successfully with non-conventional treatments such as plasmapheresis and intravenous immunoglobulin. 30 children were randomized to IVIG, plasma exchange (PE), or placebo. OCD sx were reduced by 60% in the PE group and 45% in the IVIG group at one month while the placebo group sx were unchanged. At 1 year, 80% of the PE group had sustained improvement, however 50% remained on their baseline medications so it is not entirely clear that immunomodulatory therapy was beneficial. Thus, given invasiveness, cost, and side effects this therapy is not yet routinely recommended.^9,10

 

III. DSM IV Diagnostic Criteria for OCD¹¹

 

1. Either obsessions or compulsion:

 

Obsessions as defined by 1,2,3, and 4:

 

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 thought, impulses, or images are a

product of his/her own mind.

Compulsions as defined by 1 and 2:

 

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.

 

1. At some point the person has recognized the compulsions are excessive or

unreasonable. (Does not apply to children)

 

1. The obsessions or compulsions cause marked distress, are time consuming (>1 hr/d) ,

or significantly interfere with the person’s normal routine, occupational (or academic) functioning, or usual social activities or relationships.

 

1. If another Axis I disorder is present, the content of the obsessions or compulsions is

not restricted to it.

 

1. The disturbance is not due to the direct physiological effects of a substance or a

general medical condition.

 

1. Treatment

 

• Multiple structured test have been developed to aid in the diagnosis and assessment of severity of OCD and other anxiety disorders^2,5,23:

 

• o Yale-Brown Obsessive Compulsive Scale (Y-BOCS) – used to establish the diagnosis of OCD by ascertaining current and past obsessions and compulsions (10 item, 40 point scale). Also the Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS).

 

• o The National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH-GOCS) – provides a global measure of symptom severity (scale of 1-15).

 

• o Multidimensional Anxiety Scale for Children (MASC) – self report measure useful for the assessment of anxiety in 8-19 year olds.

 

• o Family Assessment Device (FAD) – 53 item self report measure that assesses family functioning across 6 dimensions (higher scores indicate less healthy family functioning).

 

• o Clinical Global Improvement Scale (CGIS) – assesses the general adjustment of the patient (Scale of 0-10 with 0 being the worse score).

 

• o Childrens Depression Inventory (CDI) – 27 items assessing symptoms of depression (score 0-54, higher scores indicate increasing severity).

1. Pharmocotherapy

 

• Currently 5 Serotonin Re-uptake Inhibitors (SRIs) are approved by the FDA for treatment of adult OCD: clomipramine, fluvoxamine, fluoxetine, sertraline, and paroxetine. Only 3 of these are currently FDA approved for treatment of childhood OCD: clomipramine, fluvoxamine, and sertraline.^2,11

 

• Drug trials done in the 1980s and 1990s showed that clomipramine hydrochloride was effective for the treatment of OCD in adults and children.^1,2,5,11,12

.

• Research has demonstrated that the SSRI’s are equally effective to clomipramine with few adverse effects such that SSRIs have become the drug of choice in treatment of childhood and adolescent OCD.^1,2,5,11,12

 

1. Clomipramine (CMI)¹³

 

• Design was an 8 week, multicenter, double-blind, placebo-controlled, randomized study with 60 subjects ages 10-17 meeting DSM III criteria for OCD, and OCD for > 1 year.

 

• Patients received either Clomipramine Hydrochloride to maximum dose of 200 mg or 3mg/kg (whichever was less) or placebo.

 

• The primary outcome measure used to assess improvement was the CY-BOCS. Secondary measures were the NIMH-GOCS, a physician global assessment (scale of 1-7 with 1 being much improved over course of treatment), and a patient self-rating scale.

 

• Results – The trial demonstrated significant improvement of CY-BOCS scores in the CMI treatment group compared to the placebo group at weeks 3 and 5-8. The CMI group showed mean reduction in CY-BOCS scores of 37% compared to 8% in the placebo group. NIMH-GOCS scores showed a statistical difference at weeks 2-8 with CMI showing a 34% reduction versus placebo with a 6% reduction. The physician assessment showed 60% of the CMI patients as very much or much improved versus 10-17% among placebo patients. Self-ratings demonstrated 53% of the CMI patients felt they were much improved compared to 8% in the placebo group.

 

• Conclusions – Clomipramine appears to be a safe and effective drug for treatment of childhood OCD at least in the short run

 

2. Fluvoxamine¹⁴

 

• Design was a 10 week, multicenter, double-blind, placebo-controlled, randomized study with 120 subjects aged 8-17 who met DSM-III-R criteria for OCD.
• Patient received either fluvoxamine 50-200 mg/d or placebo.

 

• The primary outcome measure used to assess improvement was the CY-BOCS. Secondary measures were the NIMH-GOCS as well as the CGIS completed by the clinician, parent, and subject.

 

• Results – The trial demonstrated significant improvement of CY-BOCS scores in the fluvoxamine treatment group compared to the placebo group at weeks 1,2,3,4,6, and 10. Significant differences were also seen on all secondary outcome measures.

 

• The fluvoxamine group reached maximum improvement at the end of 3 weeks.

 

• Conclusions – Fluvoxamine is effective for short term treatment of childhood OCD. It has a rapid onset of action and is well tolerated.

 

3. Sertraline¹⁵

 

• Design was a 12 week, double-blind, placebo-controlled, randomized study with 187 subjects (107 between the ages of 6-12 and 80 between 13-17 years old).

 

• Patient received either Sertraline (titrated over 4 weeks up to 200 mg/d or maximum tolerated dose) or placebo.

 

• The outcome measures used to assess improvement were the CY-BOCS, the NIMH-GOCS, and the CGI-S/CGI-I.

 

• Results – The trial demonstrated significant improvement of CY-BOCS scores by week 1, CGI-S/CGI-I scales by week 6, and the NIMH-GOCS scale by 10 weeks in the sertraline treatment group compared to the placebo group.

 

• Conclusions – Sertraline appears to be safe and effective for short term treatment of childhood OCD. Although rapid results were seen in CY-BOCS scores, it took several weeks to see significant effects in the other scales so patients should be advised to expect a slow response to this drug.

 

4. Trials assessing several other non-FDA approved drugs for primary or adjunctive treatment of childhood and adolescent OCD have been conducted. The research demonstrates that several of the drugs appear to be both effective and well tolerated. Trials conducted include Fluoxetine, Citalopram, Venlafaxine, and Clonazepam to name a few.^11,17,18,19

 

 

1. Cognitive-Behavioral Therapy (CBT)/Cognitive-Behavioral Family Therapy (CBFT)

 

• The OCD Expert Consensus Guidelines (1997) for treating childhood OCD recommend CBT as the first-line treatment of choice for all prepubertal children and for adolescents with mild or moderate OCD.²⁰

 

1. CBF of Childhood OCD: A Controlled Trial²¹

 

• Design was a 14 week, randomized study of 72 children and adolescents from ages 7-17 who met DSM IV criteria for OCD.

 

• Patients were assigned to 1 of 3 groups: individual CBFT, group CBFT, or a waitlist control group.

 

• Treatment involved 14 weekly sessions and 2 booster sessions at 1 month and 3 months post treatment. Sessions included individual or group CBFT (50 min), parent skills training (30 min), and family progress review (10 min).

 

• The components of the program were 1) psycho education, anxiety management, and cognitive therapy; 2) intensive exposure/response prevention; and 3) maintenance of gains, including resiliency building and relapse prevention.

 

• The primary outcome measures used to assess improvement were the CY-BOCS and the NIMH-GOCS. Secondary measures were assessed using CDI, FAD, and MASC.

 

• Children were assessed pre and post treatment, and at 3 and 6 month follow-ups.

 

• Results – The trial demonstrated significant improvement in the individual and group CBFT scores. The individual CBFT showed a 65% reduction between pre and post treatment CY-BOCS scores compared to 61% in the group CBFT. Individual NIMH-GOCS scores decreased 60% compared to 63% in the group CBFT. There was no significant difference in improvement ratings between these two groups. There were no significant changes across measures in the control group.
• Treatment gains were maintained up to 6 months of follow-up.

 

• Conclusions – Group CBFT appears to be as effective in reducing OCD symptoms as individual treatment and may be an attractive alternative . Findings support the efficacy and durability of CBFT in treating childhood OCD.

 

• Similar finding were demonstrated in a smaller, 14 week CBFT study conducted by Waters, Barrett, and March.²²

 

2. Combination of Behavior Therapy (BT) with fluvoxamine vs. BT plus placebo²³

 

• Design was a 10 week, double-blind, randomized study of 49 adult patients who met DSM III-R criteria for OCD and had a Y-BOCS score >16.

 

• Patients were assigned to 1 of 2 groups: BT plus fluvoxamine to a maximum dose of 300 mg/day or BT plus placebo.

 

• BT included exposure with response prevention, cognitive restructuring, and development of alternative behaviors.

 

• The several scales were used to assess improvement in symptomatology and functioning, but the primary outcome measures used were the Y-BOCS and the NIMH-GOCS.

 

• Results – Both groups showed highly significant symptom reduction after treatment. The BT plus fluvoxamine group demonstrated a 15.5 point reduction in Y-BCOS scores compared to 12.5 in the BT plus placebo group. There were no significant differences between the groups concerning compulsions. However, obsessions were significantly more reduced in the fluvoxamine/BT group compared to the placebo/BT group.

 

• Conclusions – When compulsions dominate the clinical picture, BT alone appears to be sufficient to effectively treat the patient. If the patient suffers predominantly from obsession, the addition of an SSRI may improve treatment outcome.

 

• Another study reviewed CBT as an adjunctive therapy to SRIs in patients who remained symptomatic despite therapeutic drug levels. Similar results to the above were obtained in that there was a significant reduction in OCD symptoms (49% mean decrease in Y-BOCS scores) with the addition of CBT.²⁴

 

3. CBT and Medication in the Treatment of OCD: A controlled Study²⁵

 

• Design was a 5 month, partially randomized study of 29 adult patients who met DSM III-R criteria for OCD.

 

• Patients were assigned to 1 of 4 groups: medicine and CBT simultaneously, CBT only, medication while on a wait-list for CBT, and no treatment while on a wait-list for CBT.

 

• The primary outcome measure used was the Y-BOCS.
• Results – Multivariate analysis revealed that Y-BOCS scores significantly improved in all groups except the nontreament wait-list control group. The patients in the 2 active treatment groups receiving CBT showed reduced strength in their obsessional beliefs. The subsequent administration of CBT to those groups on the wait-list also decreased the strength of their primary obsessional beliefs and beliefs about the consequences of no performing the rituals.

 

• Conclusions – The results suggest that either CBT or medication alone is more effective than no treatment. The combination of CBT and medication seems to potentiate treatment efficacy. It was also found to be more clinically beneficial to introduce CBT after a period of medication rather than start both therapies simultaneously.

 

1. Neurosurgery and other treatment options for refractory OCD

 

• Despite lack of data from controlled trials, several types of operations for severe, treatment-refractory OCD are performed around the world: anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leucotomy. All, have the common objective of severing connections between dorsolateral and the orbitomedial areas of the frontal lobes and limbic and thalamic structures using radio frequency-heated electrodes or gamma knife techniques.^1,5,26

 

• Preliminary data from uncontrolled trials suggest that deep brain stimulation involving surgically implanted electrodes has efficacy in OCD.^1,5

 

• In one preliminary study, transcranial magnetic stimulation, whereby pulses of magnetic energy are intermittently administered to surface regions of the brain through the skull, appeared to be effective.^1,5,7

 

1. Cingulotomy for Treatment-Refractory OCD²⁶

 

• Prospective long-term follow-up (mean follow-up of 32 months) of 44 patients who received cingulotomy for treatment refractory OCD. Patients must have met DSM III-R criteria for OCD, had severe symptoms and functional impairment, and have failed a specific and rigorous regimen of medication and behavior therapy trials.

 

• The primary outcome measure used to assess improvement was the Y-BOCS. The criteria used to determine substantial benefit (treatment response) from the procedure was a 35% or greater improvement in the Y-BOCS score.

 

• Results – At mean follow-up of 32 months after one or more cingulotomies, 32% met criteria for treatment response and 14% were partial responders. Few adverse effects were reported.

Conclusions – 45% of patients previously unresponsive to medication and behavioral therapy for OCD were at least partly improved after cingulotomy. Thus, cingulotomy remains a viable treatment option for patient with sever treatment-refractory OCD.

 

Although significant advances have been made in the treatment of OCD in both adults and children over the last 2 decades, continued studies are necessary to determine which treatment modalities are the safest and most efficacious in the treatment of this chronic condition. This is especially true for childhood and adolescent OCD.

 

 

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