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

NCT00521352 | Completed Phase 2 Results DMC

• 1 other identifier: 5517
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 2.active (but not sham) rTMS will normalize levels of motor cortex excitability relative to pre-treatment baseline.

Conditions

Panic Disorder; Major Depressive Disorder

Keywords

TMS; Dorsolateral Prefrontal Cortex

Outcome Measures

Primary Outcomes (2)

• Panic Disorder Severity Scale (PDSS)

  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

  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 Outcomes (1)

• Clinical Improvement (CGI-S)

  4 weeks

Study Arms (2)

Active rTMS

ACTIVE COMPARATOR

Active Repetitive Transcranial Magnetic Stimulation (rTMS)

Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS)

Sham rTMS

SHAM COMPARATOR

Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

Interventions

Active Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

Strong electromagnetic field (\~2Tesla) generated briefly (\~1ms) but repetitively (1Hz) for 30min, five sessions a week for up to eight weeks.

Also known as: Magstim, Magstim Rapid, Magstim Rapid2

Active rTMS

Sham Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

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.

Also known as: Magstim, Magstim Rapid, Magstim Rapid2

Sham rTMS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (11)

• 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. doi: 10.1176/appi.ajp.159.2.315-a. No abstract available.

  PMID: 11823280 BACKGROUND

• 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. doi: 10.1016/s0006-3223(98)00026-2.

  PMID: 9821564 RESULT

• 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.

  PMID: 15580167 RESULT

• 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. doi: 10.1016/s0006-3223(02)01313-6.

  PMID: 12113998 RESULT

• 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.

  PMID: 12217271 RESULT

• 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. doi: 10.1001/archpsyc.60.9.1002.

  PMID: 14557145 RESULT

• 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. doi: 10.1001/archpsyc.56.4.315.

  PMID: 10197825 RESULT

• 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):277-80. doi: 10.1016/j.jad.2006.11.027. Epub 2007 Jan 9.

  PMID: 17215046 RESULT

• 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. doi: 10.1017/S1461145705005729. Epub 2005 Jun 28.

  PMID: 15982444 RESULT

• 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. doi: 10.4088/jcp.v58n1208.

  PMID: 9448663 RESULT

• Mantovani A, Aly M, Dagan Y, Allart A, Lisanby SH. Randomized sham controlled trial of repetitive transcranial magnetic stimulation to the dorsolateral prefrontal cortex for the treatment of panic disorder with comorbid major depression. J Affect Disord. 2013 Jan 10;144(1-2):153-9. doi: 10.1016/j.jad.2012.05.038. Epub 2012 Aug 1.

  PMID: 22858212 DERIVED

Related Links

• Study summary on Brain Stimulation Division web site

MeSH Terms

Conditions

Panic Disorder; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders; Depressive Disorder; Mood Disorders

Results Point of Contact

• Title: Dr. Antonio Mantovani
• Organization: Columbia University Department of Psychiatry, City University of New York

AMantovani@med.cuny.edu

212-650-5417

Study Officials

• Antonio Mantovani, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

• Sarah H Lisanby, MD

  Columbia University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2007
• First Posted: August 27, 2007
• Study Start: October 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: September 22, 2014
• Results First Posted: September 22, 2014

Record last verified: 2013-11

Locations

US (1)