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

Sponsored by:	New York State Psychiatric Institute
Information provided by:	New York State Psychiatric Institute
ClinicalTrials.gov Identifier:	NCT00521352

Purpose

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.

Condition	Intervention	Phase
Panic Disorder Major Depressive Disorder	Device: Repetitive Transcranial Magnetic Stimulation (rTMS) (active) Device: Repetitive Transcranial Magnetic Stimulation (rTMS) (sham)	Phase II

MedlinePlus related topics: Depression Panic Disorder

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Panic Disorder (PD) With Comorbid Major Depression

Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:

Panic Disorder Severity Scale (PDSS) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Hamilton Depression Rating Scale (HDRS) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Clinical Global Impression (CGI) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Motor Cortex Excitability Normalization [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical Improvement [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	October 2007
Estimated Study Completion Date:	October 2011
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active: Active Comparator	Device: Repetitive Transcranial Magnetic Stimulation (rTMS) (active) Strong electromagnetic field (~2Tesla) generated briefly (~1ms) but repetitively (1Hz) for 30min, five sessions a week for up to eight weeks.
Sham: Sham Comparator	Device: Repetitive Transcranial Magnetic Stimulation (rTMS) (sham) 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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00521352

Contacts

Contact: Clinic Coordinator	212-543-5767	bbclinic@columbia.edu
Contact: Antonio Mantovani, MD	212-543-6081	am2518@columbia.edu

Locations

United States, New York
New York State Psychiatric Institute	Recruiting
New York, New York, United States, 10032
Contact: Clinic Coordinator 212-543-5767 bbclinic@columbia.edu
Contact: Antonio Mantovani, MD 212-543-6081 amantovani@hotmail.com
Principal Investigator: Antonio Mantovani, MD
Sub-Investigator: Sarah H Lisanby, MD
Sub-Investigator: Helen B Simpson, MD, PhD
Sub-Investigator: Alexandra Sporn, MD
Sub-Investigator: Peter Bulow, MD

Sponsors and Collaborators

New York State Psychiatric Institute

Investigators

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

More Information

Study summary on Brain Stimulation Division web site This link exits the ClinicalTrials.gov site

Publications of Results:

Nordahl TE, Stein MB, Benkelfat C, Semple WE, Andreason P, Zametkin A, Uhde TW, Cohen RM. Regional cerebral metabolic asymmetries replicated in an independent group of patients with panic disorders. Biol Psychiatry. 1998 Nov 15;44(10):998-1006.

Prasko J, Horacek J, Zalesky R, Kopecek M, Novak T, Paskova B, Skrdlantova L, Belohlavek O, Hoschl C. The change of regional brain metabolism (18FDG PET) in panic disorder during the treatment with cognitive behavioral therapy or antidepressants. Neuro Endocrinol Lett. 2004 Oct;25(5):340-8.

Pizzagalli DA, Nitschke JB, Oakes TR, Hendrick AM, Horras KA, Larson CL, Abercrombie HC, Schaefer SM, Koger JV, Benca RM, Pascual-Marqui RD, Davidson RJ. Brain electrical tomography in depression: the importance of symptom severity, anxiety, and melancholic features. Biol Psychiatry. 2002 Jul 15;52(2):73-85.

Garcia-Toro M, Salva Coll J, Crespi Font M, Andres Tauler J, Aguirre Orue I, Bosch Calero C. [Panic disorder and transcranial magnetic stimulation] Actas Esp Psiquiatr. 2002 Jul-Aug;30(4):221-4. Spanish.

Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, De Castella A, Kulkarni J. Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2003 Oct;60(10):1002-8.

Klein E, Kreinin I, Chistyakov A, Koren D, Mecz L, Marmur S, Ben-Shachar D, Feinsod M. Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study. Arch Gen Psychiatry. 1999 Apr;56(4):315-20.

Mantovani A, Lisanby SH, Pieraccini F, Ulivelli M, Castrogiovanni P, Rossi S. Repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of Panic Disorder (PD) with comorbid major depression. J Affect Disord. 2007 Sep;102(1-3):277-280. Epub 2007 Jan 9.

Mantovani A, Lisanby SH, Pieraccini F, Ulivelli M, Castrogiovanni P, Rossi S. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). Int J Neuropsychopharmacol. 2006 Feb;9(1):95-100. Epub 2005 Jun 28.

Cowley DS, Ha EH, Roy-Byrne PP. Determinants of pharmacologic treatment failure in panic disorder. J Clin Psychiatry. 1997 Dec;58(12):555-61; quiz 562-3.

Other Publications:

Zwanzger P, Minov C, Ella R, Schule C, Baghai T, Moller HJ, Rupprecht R, Padberg F. Transcranial magnetic stimulation for panic. Am J Psychiatry. 2002 Feb;159(2):315-6. No abstract available.

Responsible Party:	New York State Psychiatric Institute ( Dr. Antonio Mantovani )
Study ID Numbers:	5517
Study First Received:	August 23, 2007
Last Updated:	September 8, 2008
ClinicalTrials.gov Identifier:	NCT00521352
Health Authority:	United States: Institutional Review Board

Keywords provided by New York State Psychiatric Institute:

TMS
Dorsolateral Prefrontal Cortex

Study placed in the following topic categories:

Panic Disorder
Depression
Anxiety Disorders
Mental Disorders

Mood Disorders
Depressive Disorder, Major
Depressive Disorder
Behavioral Symptoms

Additional relevant MeSH terms:

Pathologic Processes
Disease

ClinicalTrials.gov processed this record on January 16, 2009