Repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of Panic Disorder (PD) with comorbid major depression

doi:10.1016/j.jad.2006.11.027

Journal of Affective Disorders

Volume 102, Issues 1–3, September 2007, Pages 277-280

https://doi.org/10.1016/j.jad.2006.11.027 Get rights and content

Abstract

Background

Studies suggest that the dorsolateral prefrontal cortex (DLPFC) participates in neural circuitry that is dysregulated in Panic Disorder (PD) and Major Depressive Disorder (MDD). We tested whether low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) could normalize the overactivity of right frontal regions and thereby improve symptoms.

Methods

Six patients with PD and comorbid MDD were treated with daily active 1-Hz rTMS to the right DLPFC for 2 weeks in this open-label trial.

Results

Clinical improvements were apparent as early as the first week of treatment. After the second week, 5/6 of patients showed improvements in panic and anxiety, and 4/6 showed a decrease in depression, with sustained improvement at 6 months of follow-up. Right hemisphere resting motor threshold increased significantly after rTMS.

Limitations

Limitations of this study are the open design and the small sample size.

Conclusions

Slow rTMS to the right DLPFC resulted in significant clinical improvement and reduction of ipsilateral motor cortex excitability. Replications in larger sample will help to clarify the relevance of this preliminary data and to define the potential role of right DLPFC rTMS in panic with major depression.

Introduction

The dorsolateral prefrontal cortex (DLPFC) is one among several brain regions implicated in Panic Disorder (PD), and functional abnormalities in DLPFC have also been consistently replicated in Major Depressive Disorder (MDD). Lateral asymmetries in DLPFC activity have been reported in both PD and MDD (van den Heuvel et al., 2005, Mayberg et al., 1999). For example, unmedicated panic patients showed more asymmetry of activation (right > left) in DLPFC and, when treated with Cognitive Behavioral Therapy or antidepressants, showed decreases in prefrontal metabolism with a prominent right > left difference (Nordahl et al., 1998, Prasko et al., 2004). Moreover, anxiety-depression comorbidity has been characterized by more right than left frontal activity in MDD subjects, consistent with a key role of right PFC in anxiety disorders (Pizzagalli et al., 2002).

A few groups have examined whether PD could be treated by targeting right DLPFC overactivity with low-frequency repetitive Transcranial Magnetic Stimulation (rTMS), reported to have inhibitory action on cortical excitability (Chen et al., 1997). To date, only 4 PD patients have been treated with right DLPFC 1-Hz rTMS. Zwanzger et al. (2002) found reduced panic symptoms with marked improvement in anxiety lasting 1 month in 1 patient. Three patients in an open case series experienced modest symptom improvements. Alternating 1-Hz with 20-Hz rTMS on left DLPFC added no benefit (Garcia-Toro et al., 2002). While most of the work with rTMS in depression has focused on the left DLPFC (Lisanby et al., 2002), two studies suggest that right DLPFC 1-Hz rTMS has antidepressant activity (Klein et al., 1999, Fitzgerald et al., 2003). The use of 1-Hz rTMS in patients with comorbid panic and depression has not previously been reported.

We present an open trial of rTMS in PD and comorbid depression, and the first data on its effect on motor cortex excitability.

Section snippets

Methods

This was a pilot study of rTMS in adults resistant to at least 1 medication taken at recommended dosage for at least 12 weeks or intolerant to medications when side effects prevented them from being able to take the recommended dosage for at least 12 weeks. Six right-handed outpatients (3 male; mean age = 50 years, SD = 18.46) who met DSM-IV-TR criteria for PD and unipolar depression in a current major depressive episode were recruited from the psychiatric clinic at Siena University Polyclinic “Le

Results

All patients completed the study without side effects. Baseline, 1-week and 2-week mean scores, and the mean effect of time on clinical and neurophysiological measures are presented in Table 1. Patients demonstrated significant reductions in SCRAS, HARS and HDRS scores at the first and second week of treatment (Table 1). Change in SCRAS and HDRS was not correlated. Moreover, SCRAS change remained significant when covarying for baseline HRSD (F = 4.455, df = 2, 8, p = 0.050). Self-report scales showed

Discussion

This open study suggests that right DLPFC 1-Hz rTMS may be worthy of further study regarding its potential benefit in patients with PD and comorbid major depression. A clinically significant and sustained improvement of panic symptoms was observed in more than 80% of patients, similar to that reported with conventional treatments (Bandelow and Ruther, 2004). Improvements in panic symptoms appear to be independent from antidepressant effects and were not correlated with baseline depression

Acknowledgement

Funding support for the study has been provided by the Department of Neuroscience, at Siena University.

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Brief reportRepetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of Panic Disorder (PD) with comorbid major depression

Abstract

Background

Methods

Results

Limitations

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgement

Biological Psychiatry

Biological Psychiatry

Clinical Neurophysiology

Treatment-resistant panic disorder

CNS Spectrums

Depression of motor cortex excitability by low frequency transcranial magnetic stimulation

Neurology

Determinants of pharmacologic treatment failure in panic disorder

Journal of Clinical Psychiatry

Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial

Archives of General Psychiatry

Panic disorder and transcranial magnetic stimulation

Actas Espanolas de Psiquiatria

Brief report
Repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of Panic Disorder (PD) with comorbid major depression