Vortioxetine for Binge Eating Disorder

Binge-eating disorder recently included in the Diagnostic and Statistical Manual, 5th
Edition, is now recognized as a serious public health problem. Binge-eating disorder is
associated with obesity and psychiatric comorbidities, including depression, and may be
predictive of metabolic syndrome. Many patients are undertreated despite functional
impairments and personal and social difficulties leading to a poor quality of life.
Binge-eating disorder is characterized by recurrent episodes of excessive food consumption
accompanied by a sense of loss of control and psychological distress but without the
inappropriate compensatory weight-loss behaviors of bulimia nervosa. Binge eating is seen in
23-46% of obese individuals seeking weight loss treatment and its severity relates to body
mass index and predicts regain of lost weight.

Current treatments for binge eating disorder are often inadequate. Cognitive behavioral
therapy has been shown to reduce binge eating but finding trained psychologists is difficult.
Lisdexamfetamine was recently approved by the Food and Drug Administration for binge eating
disorder but it carries risk of addiction and diversion and so will likely not be prescribed
by most family physicians or psychiatrists. Other currently available medications, used
off-label for binge eating disorder, include anticonvulsants, which may reduce binge eating
but are often poorly tolerated. Therefore, additional clinical trials are needed to identify
effective pharmacotherapies.

Consuming food is necessary for life and involves brain regions that are quite ancient in
evolutionary terms. The intestinal tract itself is almost like a "second brain" in that it
contains vast amounts of neurons used to transmit and process sensory information; indeed the
intestinal tract contains more of the neurotransmitter serotonin than the brain itself.
Peripheral signals from the body (including from the intestinal tract, but also from the
blood stream - e.g. glucose levels) are transmitted to brain regions such as the hypothalamic
nuclei to help regulate appetite/hunger and maintain equilibrium. Another key aspect of
circuitry involved in eating involves the brain reward system, including the nucleus
accumbens, which is regulated by neurotransmitters such as dopamine, opioids, noradrenaline,
and serotonin. In humans, but to a lesser degree in other animals, there is also top-down
control from the prefrontal cortices, which serve to regulate our behaviors and suppress our
tendencies to crave rewards, and allow us to flexibly adapt our behavior rather than get
stuck in repetitive habits. Thus, binge-eating most likely involves dysregulation of all
three above domains regulating behavior: the primitive 'peripheral-hypothalamic' feedback
system, reward circuitry, and top-down control circuitry. On a neurochemical level, binge
eating may be related to dysfunction of the serotonergic, dopamine, glutamatergic, and
norepinephrine systems. Thus, a medication to target binge eating needs to be multi-modal in
terms of its pharmacology.

Inclusion Criteria:

1. Men and women age 18-65;

2. Primary diagnosis of Binge eating disorder;

3. At least 3 binge eating days per week for the 2 weeks before the baseline visit;

4. Ability to understand and sign the consent form.

Exclusion Criteria:

1. Unstable medical illness based on history or clinically significant abnormalities on
baseline physical examination (history of medical illness which is currently stable is
allowed such as diabetes well controlled, treated hypothyroidism, hypertension, etc)

2. Current pregnancy or lactation, or inadequate contraception in women of childbearing
potential

3. Subjects considered an immediate suicide risk based on the Columbia Suicide Severity
rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs)

4. Past 12-month DSM-5 major psychiatric disorder (psychotic disorder, bipolar disorder,
major depressive disorder)

5. Past 6-month alcohol or substance use disorders

6. Illegal substance use based on urine toxicology screening

7. Initiation of psychological or weight-loss interventions within 3 months of screening

8. Use of any other prescription psychotropic medication (except an as needed hypnotic or
as needed benzodiazepine)

9. Previous treatment with Vortioxetine

10. Currently taking over the counter weight loss medications. If willing to stop these
medications, the participant will not be excluded based on this criterion.

10) Cognitive impairment that interferes with the capacity to understand and
self-administer medication or provide written informed consent