Duloxetine for the Treatment of Obsessive Compulsive Disorder (OCD)

Obsessive compulsive disorder affects approximately 3% of the population. Treatment options
include the selective serotonin reuptake inhibitors (SSRIs), dual serotonin and
norepinephrine reuptake inhibitors (SNRIs), and behavioral therapy. Duloxetine is a new SNRI.
This study aims to assess the efficacy of duloxetine for the treatment of OCD.

Before subjects give written informed consent, they are made aware of alternatives to
participation in this study, which can include independently seeking pharmacotherapy or
cognitive behavioral treatment for OCD. Patients will then begin open-label treatment with
duloxetine at 30 mg/day and will be seen again in one week (Visit 2). At Visit 2, patients
will be assessed and, if they are not experiencing any significant side effects, the dose
will be increased to 60 mg/day. Patients who are experiencing significant side effects at 30
mg/day will be discontinued from the study and offered standard treatment in our clinic.
Patients taking 60 mg/day will then return for assessment in four weeks (Visit 3). At this
time, if they are not experiencing any significant side effects, the dose will then be
increased to 120 mg/day. Patients who are unable to tolerate 120 mg/day will have their dose
decreased back down to 60 mg/day and will continue the trial. End of study final statistical
analyses will be conducted both including and excluding these patients. Remaining assessments
will be every 4 weeks (Visits 4, 5, 6). Thus, in total this is a 17-week study with 12 weeks
at the high dose believed to be necessary for response.

At each visit following the initial visit, patients will be assessed using the Y-BOCS, BDI,
BAI, and CGI. The Q-LES-Q will only be administered at the initial and last visit.

The study procedure is similar to standard medical treatment for OCD at MGH. Like standard
care, participants start on the lowest dose of the medication and then increase that dose to
the maximally tolerated level. Barring any significant side effects, the patient remains on
that dose for 4-8 weeks to provide the medication with an adequate trial period. At the end
of that period, efficacy would be assessed and other alternatives would be discussed.

One difference between the study and standard care is that the study will provide more
assessment through verbal and written scales. This additional assessment could greatly
benefit the patient as they decide between other treatment options. Another difference is
that participants cannot be involved in current behavior therapy throughout the study. Many
patients choose to pursue medical treatment without behavior therapy in standard care;
however, in standard care, they have the option of pursuing both concurrently or pursuing
just behavior therapy. If a patient wishes to pursue just behavior therapy or receive
medication and therapy concurrently, then other forms of treatment at MGH might be more
appropriate. If they only want medical treatment, the study is similar to standard care at a
lower cost.

Inclusion Criteria:

- Diagnosis of OCD by DSM-IV

- Age 18-65

- Y-BOCS greater than 20

- Written informed consent

- Females of childbearing potential must have a negative serum or urinary beta-HCG test.

Exclusion Criteria:

- Pregnant women or women of childbearing potential who are not using a medically
accepted means of contraception.

- Patients who, in the investigator's judgment, pose a serious suicidal or homicidal
risk.

- Serious or unstable medical illness including cardiovascular (including hypertension),
hepatic, renal, respiratory, endocrine, neurologic, or hematologic disease. Patients
on anticoagulant therapy.

- History of seizure disorder

- Comorbid bipolar disorder, psychosis, organic mental disorder, or developmental
disorder

- If there is a history of substance abuse, patients in remission at least 6 months.

- Currently being treated with behavioral therapy, specifically exposure and response
prevention, for OCD.

- Other medications for medical disorders that may interfere with duloxetine

- Current major depression or prescribed an antidepressant for major depression within
the past 12 months. We will assess depressive symptoms with the BDI throughout the
course of the study in order to assess subsyndromal depressive symptoms and to assess
for the emergence of depressive symptoms.

- Taken other psychotropic medication within 2 weeks of beginning the study (4 weeks for
fluoxetine).

- More than 1 adequate trial (at least 10 weeks at maximally tolerated dose) with
another SSRI in the past.

- Known hypersensitivity to duloxetine or any of the inactive ingredients.

- Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of randomization or
potential need to use an MAOI drug during the study or within 5 days of
discontinuation of study drug.

- Patients with uncontrolled narrow-angle glaucoma.