Oxybutynin and Omega-3 for OAB (Overactive Bladder)

Overactive bladder (OAB) is a troubling condition affecting over 17 million people in the
U.S. with an estimated prevalence of 16.9% among women. The cost of this burden nationally
was estimated at $66 billion in 2007. The morbidity of the disease impacts quality of life
scores and increases risks of falls and fractures.

First-line therapeutic modalities for OAB focus on anticholinergic medications and behavioral
modification. However, the indirect impact of these medications on the gut and salivary
glands, have been troubling. Resultant side effect profiles with anticholinergic medications
have caused a high rate of cessation, with some studies showing as low as 14% of patients
still taking their medication at a one-year follow up. Given the burden and morbidity
associated with this highly prevalent condition among women, our aim is to improve our
therapeutic options, while possibly reducing subsequent side effects. As such, there is
potential to revolutionize treatment for this condition.

Omega-3 fatty acids have been evaluated with success in treating many medical conditions.
Specifically, diseases with an inflammatory component, such as Crohn's disease, ulcerative
colitis, and rheumatoid arthritis have seen promising improvements with the addition of
Omega-3 fatty acids. Other studies have shown a beneficial role in the treatment of dry eyes,
depression, burn injuries, and even cancer. Although not previously explored in the setting
of irritative bladder conditions, we believe that Omega-3 fatty acids may be helpful in
interventions for OAB via several purported mechanisms.

Prostaglandin E2 (PGE2) and inflammation have both been implicated in the biochemistry of
overactive bladder. Reduction in PGE2 may be paramount in reducing the symptoms of overactive
bladder. In fact, a proposed mechanism of action of the success of anticholinergic
medications, commonly first line treatment for OAB, is reduction of PGE2. Animal models have
demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) can be used to decrease
micturition frequency, which is thought to be a result of the anti-inflammatory process. In
humans, anti-inflammatory medications have been shown to decrease nocturia and even cause
urinary retention in high doses. Omega-3 fatty acids have been shown to have
anti-inflammatory actions and the ability to reduce PGE2. We therefore, have reason to
believe it may be an effective adjunct to current therapy to improve overactive bladder
symptoms.

Additionally, Omega-3 fatty acids have been implemented in the treatment of dry eyes and
animal studies have shown their role in increasing intestinal motility.Hence, we propose that
Omega-3 fatty acids may help alleviate the common side effects of dry eyes and constipation
associated with common anticholinergic therapies.

Inclusion Criteria:

Women between the ages of 18-85; Desiring treatment for symptoms of urinary frequency,
defined as >8 voids/day and/or nocturia > 1 void/night or urge incontinence episodes of
>1/day

Exclusion Criteria:

Bleeding disorder; Uncontrolled diabetes; Hypotension; Liver disease, such as hepatitis
A/B/C, cirrhosis, acute fatty liver, liver tumors; Post voiding residual (PVR) > 150 on
more than one occasion; Uncontrolled narrow-angle glaucoma; Hematuria of unknown cause;
Obstructive uropathy; Known hypersensitivity to study medications; Recent use of
study/omega 3 or anticholinergic medication in the prior 3 weeks with an inability to
discontinue this medication; Planning any surgery in the 6 weeks of study duration