An Open Label Pilot Study of Adjunctive Asenapine for the Treatment of Posttraumatic Stress Disorder

Consenting Veterans with the diagnosis of PTSD who have not fully remitted to an adequate
trial of standard antidepressant treatment (sertraline, citalopram, escitalopram,
fluoxetine, venlafaxine, or mirtazapine) are treated with the addition of open-label
asenapine for 12-weeks.

Inclusion Criteria:

- Signed and dated informed consent and acceptable proof of identity.

- Male or female subjects ≥19 to 65 years of age of any race or ethnic origin.

- Not currently pregnant, breastfeeding or planning on becoming pregnant; use of
contraception as follows:

- Males - those that are sexually active must use a double barrier method of
contraception (condom with spermicide) from the first dose of asenapine until 12
weeks after last dose of asenapine

- Women of child-bearing potential - must have a negative urine pregnancy test and
confirmed (by the investigator) use of a highly effective form of birth control for 3
months before enrollment and until 12 weeks after their last dose of asenapine.

- Women of non-child bearing potential - women who are either permanently sterilized
(hysterectomy, bilateral oophorectomy and bilateral salpingectomy but excluding
bilateral tubal occlusion) or who are postmenopausal.

- Diagnosis of PTSD (DSM-IV-TR criteria; confirmed by MINI and CAPS).

- Total CAPS score > 45.

- Currently taking an approved antidepressant at acceptable dose for 8 weeks or more
with non-remission of symptoms.

- No substance use disorders of dependence (except for nicotine, caffeine) in previous
4 wks.

- No substance use disorders of abuse (except for nicotine and caffeine) in the
previous 2 wks.

- Physical and laboratory panel (within past one year) are within normal limits or not
clinically significant

Exclusion Criteria:

- Lifetime history of bipolar I, schizophrenia, schizoaffective or cognitive disorders
(assessed by the MINI)

- Actively considering plans of suicide or homicide (assessed by clinical interview)

- Psychotic symptoms that in the investigator's opinion impair the subject's ability to
give informed consent

- A contraindication to the use of asenapine or antidepessant

- Intolerable side effects or allergic reaction to asenapine or the current
antidepressant

- Women planning to become pregnant or breastfeed during the study

- Clinically significant unstable or severe medical condition that would contraindicate
study participation or expose them to an undue risk of a significant adverse event,
including but not limited to: unstable or severe hepatic, renal, respiratory,
cardiovascular, endocrine, neurologic, or hematologic disease; hypo- or
hyperthyroidism, unless the condition has been stabilized; or a history of seizures
(except for a single childhood febrile seizure, posttraumatic, or alcohol
withdrawal). The following are exclusionary: platelets < 75,000/mm; hemoglobin
<9g/dL; neutrophils, absolute < 1000/mm; LFTs > 3x upper limit; creatinine > 2 mg/dL;
diastolic BP < 60 or > 110mmHg; EKG QTc > 475 msec.

- In regard to vulnerable patient populations, persons with dementia, minors ( the elderly (>age 65), prisoners and the terminally ill are excluded.