Oxytocin Add-on for Stable Depressed Patients

Depression patients treated with even the best currently available antidepressant drugs
continue to experience significant symptoms. There is a strong need for better treatments
including treatments that can safely be given adjunctively with concurrent antidepressants
in order to improve overall efficacy of treatment.

Oxytocin is a neurohypophyseal peptide best known for its role as a neurohormone involved in
parturition and lactation. In addition to these well established peripheral effects, there
is a compelling body of converging evidence indicating that oxytocin plays a critical role
in the regulation of a number of diverse centrally-mediated behavioral and cognitive
processes that are highly relevant to mood regulation and mood disorders, including social
attachment (Argiolas and Gessa 1990; McCarthy and Aaltemus 1997).

Each subject will be enrolled for a 8 week treatment period after a screening phase. Study
procedure involves weekly clinic visits as an outpatient. Twenty patients will be randomly
assigned to either 40 IU oxytocin twice daily or vehicle placebo. After 4 weeks, treatments
will be crossed over such that subjects that received oxytocin will receive placebo and vice
versa. The study ratio is 1:1. Dose of oxytocin is based upon previous studies in humans
showing improvement in psychiatric populations related changes in behavior and brain
function (Kosfeld et al, 2005; Kirsch 2005; Heinrich M 2003).

The total study duration for each individual subject will be approximately 9 weeks, which
includes up to 31-day screening period, a baseline (randomization) visit, four week
treatment period, 1 week washout, baseline 2 visit, and four weeks cross over treatment.

Inclusion Criteria:

1. Adult men or women, 18 years of age or older.

2. Meet DSM-IV criteria for Major Depressive Disorder or Dysthymia Disorder

3. Women of childbearing potential must test negative for pregnancy at the time of
enrollment based on urine pregnancy test and agree to use a reliable method of birth
control during the study.

4. Must be on a therapeutic dose of 1 or 2 antidepressants with no major dose changes
for at least 4 weeks at randomization.

5. MADRS score of >17 at randomization

6. Have a Clinical Global Impressions-Severity (CGI-S) scale score of at least 4
(moderately ill) at baseline.

7. Must be able to communicate effectively with the investigator and study coordinator
and have the ability to provide informed consent.

8. Must be able to use nasal spray

9. Must demonstrate an acceptable degree of compliance with medication and procedures in
the opinion of the investigator. (If patient cannot then he/she will be considered
for the acute only portion of this study.)

Permitted:

Subjects on up to 2 sleep medication (diphenhydramine, zolpidem, zaleplon, or diazepam),
at a reasonable dose, as judged by the investigator, is permitted in this study.

Minor adjustments in sleep medication is acceptable. Patients will be asked to notify the
study doctor of any changes to sleep aids.

Exclusion Criteria:

Subjects will be excluded from the study of they meet any of the following criteria:

1. Are pregnant or are breastfeeding (negative pregnancy test at screening)

2. A urine drug screen performed at screening must not show evidence of recent use of
drugs of abuse

3. Any active medical condition that in the opinion of the investigator will interfere
with the objectives of the study

4. Are unsuitable in any way to participate in this study, in the opinion of the
investigator.

5. Another current DSM-IV diagnosis other than Major Depressive Disorder or Dysthymia
Disorder