Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Panic Disorder With Comorbid Major Depression
Condition: Panic Disorder; Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major; Panic Disorder
Study type: Interventional
Phase: Phase 2

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. 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.
    

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.
    

Intervention name(s): Active Repetitive Transcranial Magnetic Stimulation (rTMS); Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
Intervention type(s): Device; Device
Intervention description(s): Strong electromagnetic field (~2Tesla) generated briefly (~1ms) but repetitively (1Hz) for 30min, five sessions a week for up to eight weeks.; 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 intervention name(s): Magstim, Magstim Rapid, Magstim Rapid2; Magstim, Magstim Rapid, Magstim Rapid2
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: TMS; Dorsolateral Prefrontal Cortex