Trial of OnabotulinumtoxinA for Depression in Parkinson Disease

Depression is a common, but treatable, comorbid condition often seen in persons with
Idiopathic Parkinson Disease (iPD). Depression in Parkinson Disease may be hard to treat as
patients with iPD may be sensitive to side effect of medication. As a result, other
treatments which have better side effects profiles than antidepressants may be equivalent (or
better) options.

OnabotulinumtoxinA is a purified formulation of botulinum toxin serotype A which is widely
utilized for neurological (and cosmetic) purposes in medicine. OnabotulinumtoxinA has
preliminary studies showing it may be beneficial for the treatment of Major Depressive
Disorder when given in isolated injections to facial muscles (corrugator and procerus). When
given in low doses, onabotulinumtoxinA is thought to have minimal side effects.

The investigators propose that a single treatment onabotulinumtoxinA may improve symptoms of
depression in persons with Parkinson Disease over three months compared to placebo. The
investigators plan to use both subjective and objective evaluations of depression symptoms
and regular physical exams to ensure physical (motor) symptoms of Parkinson Disease do not
worsen.

Inclusion Criteria:

- Written informed consent is obtained in the English language;

- They are a 18 to 95 years old;

- They meet United Kingdom Brain Bank Criteria for probable idiopathic Parkinson
disease;

- They meet Diagnostic and Statistical Manual (DSM)-IV criteria for major depressive
disorder (MDD) as diagnosed by the M.I.N.I. at screening;

- They are judged by the investigator to have the capacity to understand the nature of
the study;

- They are willing to comply with all the requirements of the study;

- They are considered by the investigator to be likely to adhere to the protocol.

Exclusion Criteria:

- They have been treated with onabotulinumtoxinA injected into the facial muscles for
any reason in the 3 months prior to screening;

- They have Bipolar Disorder, Post-Traumatic Stress Disorder, a Psychotic Disorder or
any other non-unipolar depressive disorder as a principal diagnosis in the 6 months
prior to screening;

- They endorse active suicidal ideation at enrollment or during any study visit, or have
attempted suicide in the six months prior to screening;

- They have a history of substance abuse or dependence in the 2 months prior to
screening;

- They test positive for illicit drugs on urine screen, and this has not been adequately
explained to the satisfaction of the investigator

- They are considered to be at significant risk of committing homicide;

- They have an unstable medical condition;

- Women of childbearing potential who are pregnant or are considering becoming pregnant
during the length of the study;

- There has been a change in their PD medication or psychotherapy treatment regimen in
the 30 days preceding screening;

- They are regarded, for any reason, by the principal investigator as being an
unsuitable candidate for the protocol.