Panic Disorder
Conditions
Keywords
Selective serotonin reuptake inhibitor, Anxiety, Pharmacotherapy, Cognitive behavioral therapy, CBT
Brief summary
This study will determine the effectiveness of different treatments for panic disorder symptoms in individuals who still have symptoms after initial treatment with medication.
Detailed description
Panic disorder is a serious condition that may cause significant psychological and physical distress. Many patients with panic disorder remain symptomatic despite initial intervention. Unfortunately, little data is available to guide health care providers in next-step treatment approaches. This study will evaluate the effectiveness of treatments for individuals with panic disorder that is resistant to initial treatment with selective serotonin reuptake inhibitors (SSRIs). This study will last 24 weeks and will comprise three phases. In Phase 1, participants will receive the SSRI sertraline for 6 weeks. Phase 1 will be used to determine participants' resistance to treatment. During Phase 1, participants will begin a medication schedule and symptom diary and will have weekly study visits to assess regimen adherence and any side effects they may be experiencing. In Phase 2, participants will be randomly assigned to 6 weeks of one of two treatments: sertraline at an elevated dose from that given in Phase 1 or a sertraline and placebo regimen. During Phase 2, participants will have 3 study visits. Self-report scales and diary entries will be used to assess panic disorder symptoms and medication side effects. In Phase 3, participants will be randomly assigned to receive either cognitive behavioral therapy (CBT) or sertraline and clonazepam for 12 weeks. All participants will have weekly study visits during Phase 3. Questionnaires and self-report scales will be used to assess participants at the end of Phase 3. Study hypothesis: Combined selective serotonin reuptake inhibitors (SSRIs) and benzodiazepine treatment, increasing the dose of SSRI, and the addition of cognitive behavioral therapy (CBT) each may have benefits for patients with panic disorder who remain symptomatic after initial treatment with SSRIs.
Interventions
DRUGClonazepam
Participants will receive clonazepam.
DRUGSertraline
Participants will receive sertraline.
BEHAVIORALCognitive behavioral therapy
Participants will receive cognitive behavioral therapy
Sponsors
National Institute of Mental Health (NIMH)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of panic disorder
Exclusion criteria
* History of bipolar disorder, schizophrenia, psychosis, or delusional disorders * Post-traumatic stress disorder diagnosis within 6 months prior to study entry * Current use of psychotropic medications * Current use of cognitive behavioral therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6) | Measured at baseline and after Phase 1 (6 weeks) | This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87. |
| Change in Panic Disorder Symptoms, Phase 2 (Week 6 - Week 12) | Measured after Phase 1 (Week 6) and Phase 2 (Week 12) | This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87. |
| Change in Panic Disorder Symptoms, Phase 3 (Week 12 - Week 24) | Measured after Phase 2 (Week 12) and Phase 3 (Week 24) | This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited by advertisement and referral to research at the Center for Anxiety and Traumatic Stress Related Disorders at Massachusetts General Hospital.
Pre-assignment details
46 participants enrolled, but four participants were lost prior to Phase 1, two due to alcohol abuse and two due to follow-up. Participants were not randomized until the start of Phase 2.
Participants by arm
| Arm | Count |
|---|---|
| All Participants | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase II (Weeks 6 to 12) | Remission | 1 | 2 |
| Phase II (Weeks 6 to 12) | Withdrawal by Subject | 1 | 1 |
| Phase I (Weeks 0 to 6) | Loss of Eligibility for Phase 2 | 4 | 0 |
| Phase I (Weeks 0 to 6) | Lost to Follow-up | 6 | 0 |
| Phase I (Weeks 0 to 6) | Remission | 8 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants |
| Age, Continuous | 37.7 years STANDARD_DEVIATION 11.2 |
| Region of Enrollment United States | 42 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 39 | 21 / 24 | 15 / 19 |
| serious Total, serious adverse events | 2 / 39 | 0 / 24 | 3 / 19 |
Outcome results
Primary
Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6)
This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87.
Time frame: Measured at baseline and after Phase 1 (6 weeks)
Population: Analyses in each study phase were for a modified intent to treat (ITT) sample, defined as all participants who had at least one on-treatment assessment during that phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Sertraline Treatment | Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6) | 4.3 Points on a scale | Standard Deviation 4.3 |
p-value: 0t-test, 2 sided
Primary
Change in Panic Disorder Symptoms, Phase 2 (Week 6 - Week 12)
This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87.
Time frame: Measured after Phase 1 (Week 6) and Phase 2 (Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Sertraline Treatment | Change in Panic Disorder Symptoms, Phase 2 (Week 6 - Week 12) | 2.36 Points on a scale | Standard Deviation 3.44 |
| Sertraline Plus Placebo | Change in Panic Disorder Symptoms, Phase 2 (Week 6 - Week 12) | 2.31 Points on a scale | Standard Deviation 4.29 |
p-value: 0.97t-test, 2 sided
Primary
Change in Panic Disorder Symptoms, Phase 3 (Week 12 - Week 24)
This measure is the change in points between baseline and endpoint scores on the Panic Disorder Severity Scale (PDSS). The PDSS is a 7-item scale with each item rated from 0 (none) to 4 (extreme), for a total score range of 0 to 28 points, and an established interrater reliability of 0.87.
Time frame: Measured after Phase 2 (Week 12) and Phase 3 (Week 24)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Moderate Sertraline Treatment | Change in Panic Disorder Symptoms, Phase 3 (Week 12 - Week 24) | 3.78 Points on a scale | Standard Deviation 3.8 |
| Sertraline Plus Placebo | Change in Panic Disorder Symptoms, Phase 3 (Week 12 - Week 24) | 2.9 Points on a scale | Standard Deviation 3.63 |
p-value: 0.061t-test, 2 sided