Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Panic Disorder With Comorbid Major Depression (rTMS)
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:
- 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);
- active (but not sham) rTMS will normalize levels of motor cortex excitability relative to pre-treatment baseline.
|Panic Disorder Major Depressive Disorder||Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS) Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Panic Disorder (PD) With Comorbid Major Depression|
- 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.
- 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.
- 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.
- = Normal, not at all ill
- = Borderline mentally ill
- = Mildly ill
- = Moderately ill
- = Markedly ill
- = Severely ill
- = Among the most extremely ill patients
|Study Start Date:||October 2007|
|Study Completion Date:||June 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
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 Name: 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 Name: Magstim, Magstim Rapid, Magstim Rapid2
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00521352
|United States, New York|
|New York State Psychiatric Institute|
|New York, New York, United States, 10032|
|Principal Investigator:||Antonio Mantovani, MD||Columbia University|
|Study Chair:||Sarah H Lisanby, MD||Columbia University|