The effectiveness of Paroxetine vs Trauma Focused Cognitive Behavioural Therapy (TF-CBT) in the treatment of Posttraumatic Stress Disorder (PTSD).

It is widely recognized that PTSD has an excessive health and economic burden
on patients, their relatives and society as a whole. Individuals suffering from
PTSD should therefore be provided the most effective treatments in terms of
patient recovery and cost-effectiveness. Of the psychological interventions for
PTSD, *trauma-focused* treatments such as Cognitive Behavioural Therapy (CBT)
have been found most effective. CBT is the most widely researched treatment and
consists of a broad array of techniques, with exposure to the traumatic memory
and cognitive restructuring as prominent elements. Of the pharmacological
interventions, selective serotonin reuptake inhibitors (SSRIs) have been found
effective in PTSD. Especially paroxetine is a well-tolerated and effective drug
in reducing symptoms of PTSD in both male and female patients. The majority of
PTSD patients (i.e., 80%) is treated with pharmacotherapy in clinical practice.
National and international guidelines, however, recommend trauma focused
psychological therapies as first-choice treatment for PTSD. This recommendation
is not supported by evidence from randomized controlled trials (RCTs) comparing
the efficacy of psychotherapy to pharmacotherapy. Up till now, two RCTs have
been conducted to directly compare trauma-focused therapy with pharmacotherapy.
Findings of one trial (N = 21) show a slightly stronger decrease of PTSD
symptoms at 6 months follow-up in the CBT group than in the paroxetine group
and another trial (N = 88) indicates that PTSD symptom reduction is stronger in
the trauma focused psychological therapy group than in the SSRI group. These
studies are, however, rather small and lack follow-up to examine whether
improvements sustain after cessation of the treatment. A meta-analysis
comparing effect sizes of both psychotherapeutic and pharmacological treatments
for PTSD, showed a slight advantage of CBT compared to other treatments on
observer-related total PTSD symptoms. Caution is, however, required when
comparing effect sizes of pharmacological to psychotherapy trials as in
pharmacological trials control for non-specific attentional effects when a
placebo is used is greater than in psychological therapy trials with waiting
list controls. Although medication treatment has been shown to be effective in
the treatment of PTSD findings of long-term consolidation of this effectiveness
have not been reported. Moreover, increased relapse rates in trials of SSRIs
support the notion that a short-term course of treatment with SSRIs may be
inadequate and that at least twelve months of medication treatment might be
needed to prevent relapse in the treatment of chronic PTSD.

Primary Objective: The main objective is to compare the effectiveness and
cost-effectiveness of Cognitive Behavioural Therapy (CBT) to
psychopharmacological treatment with paroxetine in patients with Posttraumatic
stress disorder (PTSD) in a randomized controlled trial in terms of PTSD
symptom reduction.
Secondary Objective(s): The secondary objective is to compare the effectiveness
of both treatments in terms of costs associated with PTSD symptom reduction,
comorbid anxiety and depression and health-related quality-of-life. Hypotheses
generating subgroup analyses will be performed to evaluate treatment responses
by gender, age, and socioeconomic status (incl. ethnic and cultural
background).
Tertiary objectives:
In sub-study I, effects of treatment of PTSD with trauma-focussed cognitive
behavioural therapy (TF-CBT) and with pharmacotherapy (SSRI) on interrelated
neuroimmune and neuroendocriene measures, i.e, cortisol and cytokine changes
are explored based on potential effects of both treatments on such parameters.
In sub-study II, effects of both treatments, trauma-focussed cognitive
behavioural therapy (TF-CBT) and pharmacotherapy (SSRI, paroxetine), on
neurocognitive functioning, primarily verbal and executive functioning, will be
examined.
In sub-study III, the relation between GR and 5-HTT polymorphisms in PTSD and
their possible relation with in particular HPA-axis activity will be examined.

The patients will randomized be allocated to either the trauma-focused
cognitive behavioural therapy (TF-CBT) or the pharmacotherapy (paroxetine).
Several measurements will be done after the intervention, after 1 week, 3
months, 6 months, 12 months and 18 months, which will include assessments
standardized diagnostic interviews, questionnaires, neurocognitive tests and
neuro-endocriene and neuro-immune measures. Also laboratory analysis will be
done (patients which will receive a Paroxetine treatment (of 24 weeks) will
have several more measurements, at weeks 2, 12 and 20 and patients receiving
TF-CBT (of 12 weeks) at weeks 2, 6 and 10).

Patients participating in this study, will be randomly allocated to one of two
interventions: either paroxetine or TF-CBT.

Paroxetine treatment will have a duration of 24 weeks. The dosage will start at
20 mg and can be increased with increments of 10mg/daily each four weeks up to
a maximum of 60 mg/daily if according to the judgement of the study
psychiatrist, the patient does not respond to lower dosages and if clinically
tolerated (see for details page 18 of the protocol).

The TF-CBT treatment consists of 12 weekly sessions of 45 * 60 minutes. Every
session, subjects will be seen by the same therapist (see for details page 18
of the protocol).

The burden and risks associated with participation in this study is very
limited, due to the naturalistic design of the study. The visits in the context
of the interventions, pre-intervention blood samples and physical examinations
and diagnostic questionnaires are all part of the usual care at the Zorglijn
Angststoornissen, AMC Psychiatrie. Additional and only in the context of the
study are: laboratory assessments (blood samples) during the course of the
treatments (at 2, 12 and 20 weeks), and at 1 week, 3, 6, 12, and 18 months
post-intervention. Additional are also saliva sampling, a dexamethasone
suppression-test and assessment of neurocognitive functioning and some extra
questionnaire on costs and secondary study parameters (e.g., quality of life)
at pre- and post-intervention assessments.