Effects of Paliperidone in Posttraumatic Stress Disorder (PTSD) - Full Text View

Sponsored by:	Yale University
Information provided by:	Yale University
ClinicalTrials.gov Identifier:	NCT00766064

Purpose

Chronic posttraumatic stress disorder (PTSD) is a debilitating disorder and treatment response to pharmacological interventions has been modest for these patients. Chronic elevated anxiety and associated psychophysiological parameters including increased heart rate and alterations in skin conductance are key symptoms of chronic PTSD. Antidepressants, including selective serotonin reuptake inhibitors (SRIs) or norepinephrine-serotonin re-uptake inhibitors are considered treatment of first choice for these patients, however a substantial portion of patients do not respond sufficiently (Zhang and Davidson 2007). Therefore, there is a need to establish novel and effective add-on treatment strategies for these patients. Recently, atypical neuroleptics have received considerable attention since it was shown in multiple controlled and naturalistic trials that these medications are an effective treatment option for patients with PTSD (Davis et al 2006). In chronic PTSD, the psychophysiological responses at baseline and in response to treatment have yet been inadequately studied and may provide novel insight into antidepressant and anxiolytic mechanisms of medications used in the treatment of PTSD. Therefore, in addition to evaluating the antidepressant and anxiolytic effects of paliperidone, a novel atypical neuroleptic, in the treatment of PTSD, we also aim to compare neurophysiological responses at baseline with post-treatment effects in antidepressant-refractory PTSD patients.

Primary Aim 1: Evaluate the anxiolytic and antidepressant effects of paliperidone in patients with PTSD.

Secondary Aim 2: Evaluate the effects of paliperidone on fear conditioned psychophysiological responses (including startle eyeblink, skin conductance, and cardiovascular inter-beat interval) at baseline and after 6 weeks of naturalistic treatment in chronic PTSD patients.

Condition	Intervention	Phase
Posttraumatic Stress Disorder	Drug: Paliperidone	Phase IV

MedlinePlus related topics: Antidepressants Anxiety Post-Traumatic Stress Disorder

Drug Information available for: Paliperidone BaseLine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Effects of Paliperidone in Posttraumatic Stress Disorder (PTSD)

Further study details as provided by Yale University:

Primary Outcome Measures:

Behavioral ratings (e.g. MADRS, HAMA, CGI) and psychophysiological measures. Neurophysiological measurements of startle eyeblink, skin conductance, and cardiovascular inter-beat interval will be done. [ Time Frame: behavioral ratings: weekly; Neurophysiological measurements will be done at baseline, before initiation of treatment with paliperidone (baseline) and after 6 weeks of paliperidone treatment. ] [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	September 2008
Estimated Study Completion Date:	October 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Paliperidone will be gradually increased to a final dose between 3 - 6 mg/day according to the following schedule:

Weeks 1 - 3: 3 mg daily, Weeks 4 - 5: flexible dosing according clinical situation, dose range between 3 mg - 6 mg daily*, Week 6: fixed dose,

*Criteria to increase the dose from 3 mg to 6 mg daily are 1] absence of any side effects, 2] patients not showing a sufficient response to 3 mg paliperidone can be increased to 6 mg daily. Response is defined as change in depression and anxiety ratings of at least 30% compared to baseline.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

willingness to participate in a naturalistic treatment study using paliperidone and in two fear conditioning tests, one at baseline and one at the end of the 6 weeks treatment study.
We will include PTSD subjects on medications (possible medications include antidepressants, benzodiazepines) who have no or only partial treatment response. Paliperidone will be added to the existing treatment regime which will remain unchanged during the study period. PTSD subjects will have a minimum score of 50 on the Clinician-Administered PTSD Scale (CAPS; Blake et al, 1995).

Exclusion Criteria:

a comorbid diagnosis of bipolar illness, schizophrenia or other psychotic disorders, acute or chronic suicidality, acute or chronic unstable medical conditions (including severely impaired hepatic function as indicated with abnormal PT and PTT, abnormal CBC, and liver enzymes more than 50% above the upper normal range, not well controlled blood pressure)
current diagnosis of substance abuse or dependence
unsuccessful treatment history with paliperidone
known hypersensitivity to paliperidone or any of its inactive ingredients
administration of any investigational drug up to 90 days before entry into the study
intake of Class 1A (e.g., quinidine, procainamid) or Class III (e.g., amiodaronme, sotalol) antiarrhythmic medications, antipsychotics, antibiotics (e.g., gatifloxacin, moxifloxacin) (up to 90 days before entry into the study or during the study)
subjects with a positive screen for drugs of abuse
no startle or skin conductance response, or excessively high startle response to the startle probe (100 dB acoustic stimuli) during the pretest.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00766064

Contacts

Contact: Sue Kasserman

203-932-5711 ext 4447

sue.kasserman@va.gov

Locations

United States, Connecticut
VA Connecticut Healthcare System	Recruiting
West Haven, Connecticut, United States, 06516
Contact: Alexander Neumeister, MD 203-932-5711 alexander.neumeister@yale.edu

Sponsors and Collaborators

Yale University

Investigators

Principal Investigator:

Alexander Neumeister, MD

Yale University

More Information

Responsible Party:	Yale University ( Dr. Alexander Neumeister )
Study ID Numbers:	0804003717
Study First Received:	September 30, 2008
Last Updated:	October 2, 2008
ClinicalTrials.gov Identifier:	NCT00766064
Health Authority:	United States: Institutional Review Board

Keywords provided by Yale University:

posttraumatic stress disorder

Study placed in the following topic categories:

Anxiety Disorders
Mental Disorders
Risperidone
Stress Disorders, Post-Traumatic

Stress
9-hydroxy-risperidone
Stress Disorders, Traumatic

Additional relevant MeSH terms:

Tranquilizing Agents
Pathologic Processes
Disease
Therapeutic Uses
Physiological Effects of Drugs

Psychotropic Drugs
Central Nervous System Depressants
Antipsychotic Agents
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009