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
Intervention: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: TMS; Dorsolateral Prefrontal Cortex

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.
    

Eligibility 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.