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

This is an open-label pilot study of adjunctive asenapine for the treatment of Posttraumatic Stress Disorder (PTSD) in veterans who have not fully remitted to an adequate trial of standard antidepressant treatment.

Study Overview

• Status: Completed
• Conditions: Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: Adjunctive asenapine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35404
      • Tuscaloosa VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 (<age 19), the elderly (>age 65), prisoners and the terminally ill are excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: antidepressant plus asenapine; adjunctive asenapine	Drug: Adjunctive asenapine; participants who are not responding fully to antidepressant therapy for PTSD will receive adjunctive asenapine (flexible dosing beginning with 5 mg sublingual once per day, titrated up to 10 mg twice per day, as tolerated) for a total of 12 weeks.; Other Names: Saphris; asenapine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Administered PTSD Scale (CAPS) Total	CAPS is the clinician rating of posttraumatic stress disorder (PTSD) symptoms; higher scores indicate higher severity of PTSD; 17-item score range 0 to 136. Blake DD, Weathers FW, Nagy LM, et al. The development of a Clinician-Administered PTSD Scale. J Trauma Stress 1995; 8:75-90.	baseline, week 4, 8, and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Brief Psychiatric Rating Scale (BPRS)	BPRS is the clinician rating of psychiatric symptoms; higher score indicates higher severity; 18-items scored 1-7; highest score 126. Overall JE and Gorham DR. The Brief Psychiatric Rating Scale (BPRS): recent developments in ascertainment and scaling. Psychopharmacol Bulletin 1993; 24:97-99.	Baseline, week 4, 8, 12

Collaborators and Investigators

• Sponsor: Lori Davis, MD
• Collaborators: Merck Sharp & Dohme LLC; Forest Laboratories
• Investigators: Principal Investigator: Lori L Davis, MD, Tuscaloosa Research & Education Advancement Corporation

Publications and helpful links

General Publications

• Pilkinton P, Berry C, Norrholm S, Bartolucci A, Birur B, Davis LL. An Open Label Pilot Study of Adjunctive Asenapine for the Treatment of Posttraumatic Stress Disorder. Psychopharmacol Bull. 2016 Aug 15;46(2):8-17.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: April 25, 2012
• First Submitted That Met QC Criteria: April 26, 2012
• First Posted (Estimate): April 27, 2012

Study Record Updates

• Last Update Posted (Actual): June 11, 2019
• Last Update Submitted That Met QC Criteria: June 3, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: PTSD; Posttraumatic Stress Disorder; Adjunctive; antidepressant; Asenapine; neuroleptic
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Trauma and Stressor Related Disorders; Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Asenapine
• Other Study ID Numbers: 00156

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No sharing of individual participant data