Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Panic Disorder With Comorbid Major Depression (rTMS)

September 16, 2014 updated by: New York State Psychiatric Institute

Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Panic Disorder (PD) With Comorbid Major Depression

This study will evaluate the efficacy of 1-Hz rTMS applied to the right Dorsolateral Prefrontal Cortex (DLPFC) in patients with Panic Disorder (PD) and comorbid Major Depressive Disorder (MDD) who have not fully responded to conventional therapies.

The investigators hypothesize that:

  1. compared to sham (placebo), active rTMS will improve symptoms of PD and MDD as assessed with the Panic Disorder Severity Scale (PDSS), Hamilton Depression Rating Scale (HDRS), and Clinical Global Impression (CGI);
  2. active (but not sham) rTMS will normalize levels of motor cortex excitability relative to pre-treatment baseline.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study tests the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of Panic Disorder (PD) with comorbid Major Depression (MDD).

Despite major advances in the treatment of PD, standard therapeutic interventions are not effective for all patients, and the most common reasons for treatment failure in PD are side effects and major depression comorbidity. rTMS is a non-invasive procedure that allows stimulation of the brain using magnetic fields. Some studies have reported that rTMS may be helpful in reducing panic and depressive symptoms. While promising, prior research has several limitations (e.g., relatively small sample sizes, relatively short durations of treatment, and lack of sham (placebo) comparison).

This study addresses the drawbacks of prior work, and will provide data that will be important in determining whether rTMS can be useful for PD patients with comorbid MDD and resistant to conventional therapies. In this trial, 20 adult outpatients with PD and comorbid MDD, that have been only partially responsive to conventional therapies, will be randomly assigned to one of two treatment groups (active low frequency (1 Hz) rTMS or sham-placebo) applied to the right Dorsolateral Prefrontal Cortex (DLPFC) daily for up to four weeks. If rTMS will be added onto ongoing pharmacotherapy, the doses must have been stable for 1 month prior to study entry. The right DLPFC was selected because it is one among several brain regions implicated in PD, and functional abnormalities in DLPFC have also been consistently replicated in MDD. Pilot work indicates that stimulation of right DLPFC with low frequency rTMS was beneficial in patients with PD and MDD. Low frequency rTMS has the added benefit of a better safety profile (i.e. low risk of seizure) compared to high frequency rTMS.

Rating scales for symptom change will be obtained at baseline, during the rTMS course, and at the end of 4 weeks of treatment. Patients who do not meet response criteria after four weeks of sham will be offered an open-label cross-over phase for an additional four weeks of daily active rTMS treatment while partial responders to either active or sham will be offered an open-label cross-over phase for an additional four weeks of daily active rTMS treatment. Patients who meet response criteria in either the randomized phase or the cross-over phase will continue routine clinical care under the supervision of their treating psychiatrist, and will be invited back for a repeat assessment at 1, 3 and 6 months to determine the persistence of benefit.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with a primary diagnosis of Panic Disorder and Major Depressive Disorder, as confirmed by the Structured Clinical Interview for the DSM-IV-TR (SCID)
  • Residual panic attacks and MDD symptoms, defined as a total PDSS score of ≥ 20 and HDRS-17 score ≥18, despite treatment with an adequate trial of a serotonin reuptake inhibitor (SRI)
  • A duration of the index episode of at least a month will be included.
  • An adequate SRI trial is defined as treatment for at least 6-8 weeks on the SRI, that meets the maximum recommended dosage level for PD and MDD (fluoxetine 40-60 mg/d, sertraline 100-200 mg/d, paroxetine 40-60 mg/d, fluvoxamine 200-300 mg/d, citalopram 40-60 mg/d, escitalopram 20-30 mg/d).
  • Individuals who cannot tolerate medications of class and dose at the specified duration as described above will also be included.
  • Patients currently on medication must be at the same stable dose(s) for one month prior to enrollment and be willing to continue at the same dose(s) through the duration of the study.

Exclusion Criteria:

  • Individuals diagnosed with bipolar disorder (lifetime), any psychotic disorder (lifetime), or an Axis II personality disorder
  • A history of substance abuse or dependence within the past year (except nicotine and caffeine)
  • Significant acute suicide risk will be excluded.

Other exclusion criteria include those common to every TMS protocol:

  • Individuals with a clinically defined neurological disorder, with an increased risk of seizure for any reason, with a history of treatment with TMS, deep brain stimulation for any disorder will be excluded.
  • Patients with cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed will be excluded.
  • Current use of any investigational drug, any medications with proconvulsive action, such as bupropion, maprotiline, tricyclic antidepressant, clomipramine, classical antipsychotics, and daily use of any medications with a known inhibitory effect on cortical excitability measures (e.g., anticonvulsants, standing doses of benzodiazepines, sedative/hypnotics, and atypical antipsychotics) will not be permitted.
  • If participating in psychotherapy, patients must have been in stable treatment for at least three months prior to entry into the study, with no anticipation of change in frequency therapeutic sessions, or the therapeutic focus over the duration of the TMS trial.
  • Finally, current significant laboratory abnormality, known or suspected pregnancy, women who are breast-feeding or women of childbearing potential not using a medically accepted form of contraception when engaging in sexual intercourse will also be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active rTMS
Active Repetitive Transcranial Magnetic Stimulation (rTMS)
Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS)
Strong electromagnetic field (~2Tesla) generated briefly (~1ms) but repetitively (1Hz) for 30min, five sessions a week for up to eight weeks.
Other Names:
  • Magstim, Magstim Rapid, Magstim Rapid2
Sham Comparator: Sham rTMS
Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
Generates a field with the same parameters as active rTMS (see active arm for parameters), however, the actual magnetic fields are blocked by an electromagnetic shield built into a sham coil. The field is impeded from stimulating the brain.
Other Names:
  • Magstim, Magstim Rapid, Magstim Rapid2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Panic Disorder Severity Scale (PDSS)
Time Frame: 4 weeks

The Panic Disorder Severity Scale is a questionnaire developed for measuring the severity of panic disorder symptoms.

The PDSS consists of seven items, each rated on a 5-point scale, which ranges from 0 to 4. The items assess panic frequency, resulting distress, panic-focused anticipatory anxiety, phobic avoidance of situations and of physical sensations, impairment in occupational and social functioning. The overall assessment is made by a total score, which is calculated by summing the scores for all seven items. The total scores range from 0 to 28.

Higher scores indicate high levels of panic symptomatology. Reduction in score from baseline indicates clinical improvement of panic symptoms.
4 weeks
Hamilton Depression Rating Scale (HDRS), 28 Item Version
Time Frame: 4 weeks

The Hamilton Rating Scale for Depression (HRSD) is a multiple item questionnaire used to provide an indication of depression severity. The 28-, rather then 17- or 24-, item version was used to assess subjects in this protocol.

28-item minimum score = 0 28-item maximum score = 84

Higher scores indicate high levels of symptomatology. Reduction in score from baseline indicates clinical symptom improvement.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Improvement (CGI-S)
Time Frame: 4 weeks

Minimum CGI-S score: 1 Maximum CGI-S score: 7

Higher scores indicate the presence of high symptom severity. Decrease in scores from baseline reflects clinical symptom improvement.

Patients will be classified as responders with a CGI-S = 1 or 2; and partial responders CGI-S = 3.

  1. = Normal, not at all ill
  2. = Borderline mentally ill
  3. = Mildly ill
  4. = Moderately ill
  5. = Markedly ill
  6. = Severely ill
  7. = Among the most extremely ill patients
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Investigators

  • Principal Investigator: Antonio Mantovani, MD, Columbia University
  • Study Chair: Sarah H Lisanby, MD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

August 23, 2007

First Submitted That Met QC Criteria

August 23, 2007

First Posted (Estimate)

August 27, 2007

Study Record Updates

Last Update Posted (Estimate)

September 22, 2014

Last Update Submitted That Met QC Criteria

September 16, 2014

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5517

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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