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| ID | Type | Description | Link |
|---|---|---|---|
| K23MH001831 | U.S. NIH Grant/Contract | View source | |
| DSIR AT-CD |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
This study will determine the effectiveness of different treatments for panic disorder symptoms in individuals who still have symptoms after initial treatment with medication.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Participants in phase II will receive sertraline, or an equivalent medication, up to 100 mg plus a placebo pill. Participants in phase III will receive the same medication with cognitive behavioral therapy. |
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| 2 | Experimental | Participants in phase II will receive sertraline, or equivalent medication, up to 200 mg. Participants in phase III they will receive the same medication with flexible clonazepam augmentation. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clonazepam | Drug | Participants will receive clonazepam. |
| |
| Sertraline |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Measured at baseline and after Phase 1 (6 weeks) |
| 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. | Measured after Phase 1 (Week 6) and Phase 2 (Week 12) |
| 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. | Measured after Phase 2 (Week 12) and Phase 3 (Week 24) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Naomi M. Simon, MD, MSc | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19814948 | Derived | Simon NM, Otto MW, Worthington JJ, Hoge EA, Thompson EH, Lebeau RT, Moshier SJ, Zalta AK, Pollack MH. Next-step strategies for panic disorder refractory to initial pharmacotherapy: a 3-phase randomized clinical trial. J Clin Psychiatry. 2009 Nov;70(11):1563-70. doi: 10.4088/JCP.08m04485blu. Epub 2009 Oct 6. |
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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 were recruited by advertisement and referral to research at the Center for Anxiety and Traumatic Stress Related Disorders at Massachusetts General Hospital.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sertraline / Increased Dose / Medication Optimization | In Phase 1, this group will receive a moderate dose of sertraline (or escitalopram, an equivalent SSRI); In Phase 2, this group will receive an increased dosage of their SSRI; In Phase 3, this group will receive medication optimization, which includes an SSRI and clonazepam |
| FG001 | Sertraline / + Placebo / Cognitive Behavior Therapy Augment. | In Phase 1, this group will receive a moderate dose of sertraline (or escitalopram, an equivalent SSRI); In Phase 2, this group will receive their SSRI plus a placebo; In Phase 3, this group will receive their SSRI plus cognitive behavioral therapy (CBT) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase I (Weeks 0 to 6) |
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| Phase II (Weeks 6 to 12) |
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| Phase III (Weeks 12 to 24) |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | Points on a scale | Measured at baseline and after Phase 1 (6 weeks) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase I: Sertraline | In Phase 1, this group will receive a moderate dose of sertraline (or escitalopram, an equivalent SSRI). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Patient admitted to inpatient rehabiliation center for alcohol abuse | General disorders |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal distress | Gastrointestinal disorders |
Power in Phase 2 limited detection to a large effect size. High drop-out for increased SSRI dose may indicate poor tolerability. Effectiveness of adding an SSRI to initial CBT was unexamined, limiting generalization to community treatment decisions.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Naomi M. Simon, MD | Massachusetts General Hospital | 617-726-7913 | nsimon@partners.org |
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| ID | Term |
|---|---|
| D016584 | Panic Disorder |
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D002998 | Clonazepam |
| D020280 | Sertraline |
| D015928 | Cognitive Behavioral Therapy |
| ID | Term |
|---|---|
| D001570 | Benzodiazepinones |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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| Drug |
Participants will receive sertraline. |
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| Cognitive behavioral therapy | Behavioral | Participants will receive cognitive behavioral therapy |
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| Loss of Eligibility for Phase 2 |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| 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. | Posted | Mean | Standard Deviation | Points on a scale | Measured after Phase 1 (Week 6) and Phase 2 (Week 12) |
|
|
|
|
| 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. | Posted | Mean | Standard Deviation | Points on a scale | Measured after Phase 2 (Week 12) and Phase 3 (Week 24) |
|
|
|
|
| 2 |
| 39 |
| 33 |
| 39 |
| EG001 | Phase II: Cont. SSRI Plus Placebo OR Increased Dose SSRI Alone | 0 | 24 | 21 | 24 |
| EG002 | Phase III: Cont. Medication Plus CBT OR SSRI and Clonazepam | 3 | 19 | 15 | 19 |
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| Patient admitted to the hospital after experiencing symptoms similar to panic attacks. | General disorders | This patient in Phase I of the study was admitted to the hospital after experiencing symptoms similar to, but more intense than panic attacks. The subject had not yet initiated study medication when the event occurred. |
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| Patient was in a motorcycle accident of unknown etiology | General disorders | This patient completed Phase III of the study (Sertraline and Clonazepam), and was involved in a motorcycle accident months after study completion. There is no evidence to indicate that the medication was related to the accident. |
|
| Patient was found to have blockage of one cardiac vessel | General disorders | Patient presented to the emergency room with sudden onset leg pain and was found to have blockage of one cardiac vessel. These symptoms were determined to be unrelated to the study medication (escitalopram); thus, her study treatment was not altered. |
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| Headache | General disorders |
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| Nausea or Vomiting | General disorders |
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| Jitteriness or Restlesness | General disorders |
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| Insomnia | General disorders |
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| Sedation | General disorders |
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| Dizziness | General disorders |
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| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D015057 | 1-Naphthylamine |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |