Posttraumatic Stress Disorder
Conditions
Keywords
PTSD, Posttraumatic Stress Disorder, Asenapine, Adjunctive, antidepressant, neuroleptic
Brief summary
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.
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.
Interventions
DRUGAdjunctive 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.
Sponsors
Merck Sharp & Dohme LLC
Forest Laboratories
Lori Davis, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Administered PTSD Scale (CAPS) Total | baseline, week 4, 8, and 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Brief Psychiatric Rating Scale (BPRS) | Baseline, week 4, 8, 12 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Antidepressant Plus Asenapine adjunctive asenapine
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. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | nonresponse | 1 |
| Overall Study | Relocation | 1 |
Baseline characteristics
| Characteristic | Antidepressant Plus Asenapine |
|---|---|
| Age, Continuous | 48.3 years STANDARD_DEVIATION 11.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 18 |
| serious Total, serious adverse events | 1 / 18 |
Outcome results
Primary
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.
Time frame: baseline, week 4, 8, and 12
Population: Open label treatment, all participants included.Overall change in values from baseline to week 12, including weeks 4 and 8, using a simple one-way analysis of variance; because the sample size was small, p-values for the paired t-test and one-way results were recalculated using the signed rank test and Kruskal Wallis procedure, respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant Plus Asenapine | Change From Baseline in Clinical Administered PTSD Scale (CAPS) Total | -39 units on a scale | Standard Deviation 18.4 |
p-value: <0.0001ANOVA
Secondary
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.
Time frame: Baseline, week 4, 8, 12
Population: Open label treatment, all participants included.Overall change in values from baseline to week 12, including weeks 4 and 8, using a simple one-way analysis of variance; because the sample size was small, p-values for the paired t-test and one-way results were recalculated using the signed rank test and Kruskal Wallis procedure, respectively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antidepressant Plus Asenapine | Change From Baseline in Brief Psychiatric Rating Scale (BPRS) | -15.5 units on a scale | Standard Deviation 9.3 |
p-value: 0.0006ANOVA