The purpose of the study is to evaluate the effectiveness and tolerability of
controlled-release paroxetine (Paxil-CR) compared to placebo (an inactive substance) for
individuals who continue to have symptoms of post traumatic stress disorder (PTSD) despite
receiving prolonged exposure therapy.
Post Traumatic Stress Disorder (PTSD) is common in the general population with the National
Comorbidity Survey reporting a lifetime prevalence of about 8% in the United States
(Kessler, et al 1995). PTSD is associated with marked symptomatic distress as well as
significant impairment, dysfunction and reduction in overall quality of life (Kessler,
2000). Both pharmacotherapeutic interventions, including serotonin selective reuptake
inhibitors (SSRIs), and psychosocial interventions such as cognitive-behavior therapy (CBT)
have demonstrated efficacy for PTSD (Davidson, 2001; Foa, 2000) However, although these
interventions can be helpful, many patients remain symptomatic despite initial treatment.
There is little data available to guide practice regarding the efficacy of "next step"
strategies for patients remaining symptomatic despite treatment.
In this study the researchers will examine the relative efficacy of the addition of the
SSRI, paroxetine-CR, compared to placebo for patients remaining symptomatic despite a brief
and intensive course of CBT.
This is a two phase, 14-16 week research study in which participants who remain symptomatic
at the end of one phase (4-6 weeks) enter into the next phase. In phase I, all participants
receive prolonged exposure (PE) therapy. Participants who continue to have significant
distress because of posttraumatic stress disorder after 8 sessions of therapy will enter
Phase II. In Phase II subjects will receive 5 more sessions of PE therapy and be randomly
assigned (by chance, like a flip of a coin) to receive paroxetine-cr (Paxil-CR) or placebo
(contains no active medication). Participants receive this combined treatment over the next
- Male or female outpatients at least 18 years of age with a primary (the condition
that is most central to the patient's current distress) psychiatric diagnosis of PTSD
as defined by DSM-IV criteria.
- Patients must have remained symptomatic (CGI-S > 3) and a score of at least 6 on the
Short PTSD Rating Interview (SPRINT) after a minimum of 7 sessions of PE (delivered
within 6 weeks) to be eligible for randomized treatment.
- Patients will be excluded from the study for serious medical illness or instability
for which hospitalization may be likely within the next three months.
- Pregnant or lactating women or those of childbearing potential not using medically
accepted forms of contraception will be excluded.
- Concurrent use of other psychotropic medications; all psychotropic medications
(excluding benzodiazepines) must be stopped at least one week prior to entry into the
initial PE phase of the study. Patients may remain on concomitant benzodiazepines
(<2 mg/d clonazepam or its equivalent), as long as the benzodiazepine therapy was
initiated at least 2 months prior to randomization and at a constant dose for >4
weeks prior to randomization; the dose will be held constant through the study.
- Lifetime diagnosis of schizophrenia or any other psychosis, mental retardation,
organic mental disorders, or bipolar disorder; obsessive-compulsive disorder, eating
disorders, cutting or other significant self-injurious behavior or alcohol/substance
abuse disorders within the last 6 months, are study exclusions. Patients with a
current primary diagnosis of major depression, dysthymia, social anxiety disorder and
generalized anxiety disorder are excluded - the presence of these disorders is
permissible as long as the PTSD is the predominant disorder.
- Patients with a history of hypersensitivity or poor response to paroxetine are
excluded. Concurrent dynamic or supportive psychotherapy is permitted as long as it
is has been ongoing for at least 2 months prior to onset of study entry.
- Patients with current compensation or legal actions related to the effects of the
trauma, or those with an ongoing relationship with their assailant.
- Patients with a positive toxicology screen at baseline consistent with evidence of
current substance abuse or dependence as determined by clinical interview.