Therapies for Treatment-Resistant Panic Disorder Symptoms

This study has been completed.

Study NCT00118417 Information provided by National Institute of Mental Health (NIMH)

First Received: July 6, 2005 Last Updated: June 5, 2009 History of Changes

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Parallel Assignment
Condition:	Panic Disorder
Interventions:	Drug: Clonazepam Drug: Sertraline Behavioral: Cognitive behavioral therapy

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
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
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)

Participant Flow for 3 periods

Period: Phase I (Weeks 0 to 6)

	Sertraline / Increased Dose / Medication Optimization	Sertraline / + Placebo / Cognitive Behavior Therapy Augment.
STARTED	39	0^[1]
COMPLETED	21	0
NOT COMPLETED	18	0
Remission	8	0
Lost to Follow-up	6	0
Loss of Eligibility for Phase 2	4	0

[1]	In Phase 1, all participants received open label SSRI - no second treatment arm.

Period: Phase II (Weeks 6 to 12)

	Sertraline / Increased Dose / Medication Optimization	Sertraline / + Placebo / Cognitive Behavior Therapy Augment.
STARTED	11^[1]	13
COMPLETED	9	10
NOT COMPLETED	2	3
Withdrawal by Subject	1	1
Remission	1	2

[1]	Three new participants on Phase 1 endpoint doses of SSRIs entered at Phase 2.

Period: Phase III (Weeks 12 to 24)

	Sertraline / Increased Dose / Medication Optimization	Sertraline / + Placebo / Cognitive Behavior Therapy Augment.
STARTED	9	10
COMPLETED	8	9
NOT COMPLETED	1	1

Baseline Characteristics

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Reporting Groups

	Description
All Participants	No text entered.

Baseline Measures

	All Participants
Number of Participants [units: participants]	42
Age [units: participants]
<=18 years	0
Between 18 and 65 years	42
>=65 years	0
Age [units: years] Mean ± Standard Deviation	37.7 ± 11.2
Gender [units: participants]
Female	24
Male	18
Region of Enrollment [units: participants]
United States	42

Outcome Measures

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1. Primary:

Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6) [ Measured at baseline and after Phase 1 (6 weeks) ]

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Measure Type	Primary
Measure Title	Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6)
Measure Description	This measure is the reduction 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)
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Moderate Sertraline Treatment	This group will receive moderate sertraline or escitalopram treatment

Measured Values

	Moderate Sertraline Treatment
Number of Participants Analyzed [units: participants]	39
Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6) [units: Points on a scale] Mean ± Standard Deviation
Phase 1	4.3 ± 4.3

Statistical Analysis 1 for Change in Panic Disorder Symptoms, Phase 1 (Week 0 - Week 6)

Groups ^[1]	Moderate Sertraline Treatment
Method ^[2]	t-test, 2 sided
P Value ^[3]	0.0000

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Degrees of Freedom = 38
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Paired ttest between endpoint and baseline PDSS

2. Primary:

Change in Panic Disorder Symptoms, Phase 2 (Week 6 - Week 12) [ Measured after Phase 1 (Week 6) and Phase 2 (Week 12) ]

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3. Primary:

Change in Panic Disorder Symptoms, Phase 3 (Week 12 - Week 24) [ Measured after Phase 2 (Week 12) and Phase 3 (Week 24) ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.

Results Point of Contact:

Name/Title: Naomi M. Simon, MD
Organization: Massachusetts General Hospital
phone: 617-726-7913
e-mail: nsimon@partners.org

No publications provided

Responsible Party:	Massachusetts General Hospital ( Naomi M. Simon, MD, MSc )
Study ID Numbers:	K23 MH001831, DSIR AT-CD
Study First Received:	July 6, 2005
Results First Received:	June 5, 2009
Last Updated:	June 5, 2009
ClinicalTrials.gov Identifier:	NCT00118417 History of Changes
Health Authority:	United States: Federal Government