South Florida Psychiatrist, Dr. Gregory Marsella at Chrysalis TMS Institute using Advanced TMS and rTMS Technology as an Alternative Treatment for many Psychiatric and Neurological Disorders

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South Florida Psychiatrist, Dr. Gregory Marsella discovers Transcranial Magnetic Stimulation is an Alternative Treatment that Reduces Auditory Hallucinations

TMS treatment as an alternative treatment for Auditory Hallucinations and Depression in Schizophrenia at South Florida Psychiatrist, Dr. Gregory Marsella's Chrysalis TMS Institute
Transcranial magnetic stimulation (TMS), an experimental procedure with the potential to replace electroconvulsive treatment (ECT) for resistant depression, now appears to reduce the severity of auditory hallucinations in patients with schizophrenia.

In a letter to The Lancet, Ralph Hoffman, M.D., and colleagues at the Yale Psychiatric Institute reported having successfully reduced auditory hallucinations by focusing TMS pulses into a specific site in the cortex. In positron emission tomography (PET), this site of the cortex has been shown to have blood flow activation during hallucinations (Hoffman et al., 2000). The temporoparietal cortex had been determined by PET to be integral to perceiving spoken speech (Fiez et al., 1996) and implicated with generation of hallucinated speech (Silbersweig et al., 1995). Hoffman and colleagues therefore postulated that the regionalized TMS treatment, depolarizing neurons in this "auditory-linguistic association" cortical site, could interrupt the occurrence of auditory hallucinations.

Hoffman et al. observed that, although auditory hallucinations are reported in 50% to 70% of patients with schizophrenia, "response to drug treatment is often incomplete or nonexistent, and these hallucinations can cause great distress, functional disability, and lack of behavioral control."

The possibility that TMS might benefit symptoms of schizophrenia had little support in the scant research of the procedure in this population, although a growing body of evidence indicates its utility for depression. According to a recent review of studies of TMS in neuropsychiatry (George et al., 1999), one open clinical study in patients with schizophrenia resulted in reduced anxiety (Feinsod et al., 1998); some research showed slowed motor conduction (Puri et al., 1996); and three case reports of reduced auditory hallucinations were reported (Hoffman et al., 1998, as cited in George et al., 1999). In addition, "slightly improved" negative symptoms were found in a study of eight patients with prominent negative symptoms (Nahas et al., in press, as cited in George et al., 1999).

Twelve patients with schizophrenia identified for Hoffman et al.'s study had experienced daily auditory hallucinations for at least six months without remission despite taking antipsychotic medication, which was continued throughout this study. Five of the 12 patients were also maintained on an antiepileptic/mood stabilizing medication (four on divalproex [Depakote] and one on carbamazepine [Tegretol]).

The rTMS active treatment was effective in reducing severity of auditory hallucinations relative to the pretreatment baseline symptomatology, as well as to the level of symptoms during the placebo procedure. The improvement was notable following 12 and 16 minutes of active rTMS treatment, but not at any point during placebo stimulation. The investigators reported that all but one patient had lower hallucination severity after active treatment than after the placebo procedure (Hoffman et al., 2000). Eight patients met responder criteria during active treatment, with an improved hallucination severity score of greater than one point.
Interestingly, the one patient who did not experience relief of symptoms with rTMS, as well as those who demonstrated the least treatment effect, had been receiving antiepileptic medication during the study. Hoffman and colleagues raise the possibility that either the presence of these medications necessitate higher levels of rTMS for optimal effect, "or that symptoms prompting administration of anticonvulsant drugs (e.g., mood lability) are negative predictors of rTMS response."

The rTMS series in this study was well tolerated, with only two complaints of mild headache after active treatment. There was no apparent effect of the series on other positive or negative symptoms, according to the investigators; they did not indicate their method for this assessment. In the follow-up of the eight patients who responded most strongly to treatment, the severity of two patients' auditory hallucinations returned to approximate baseline levels in one day, and two patients' levels returned to baseline in four days. The researchers reported one patient responded at each of the following time points: five days, two weeks, three weeks and two months.

In correspondence with Psychiatric Times, George characterized this study of the effects of rTMS on auditory hallucinations as "interesting and provocative." Hoffman et al. (2000) acknowledged that the variability of response to rTMS may reflect such factors as individual differences in the anatomical location of speech processing and variable locations of cortical activation of auditory hallucinations. Despite the questions that remain about the mechanisms of action of rTMS-and of ECT for that matter-the results of this study delineate a site of action for interrupting this common symptom of schizophrenia.

Temporo-parietal junction stimulation in the treatment of depersonalization disorder

Antonio Mantovani, Sarah Lisanby, Daphne Simeon, Peter Bulow, Nina Urban, Anouk Allart


This is the first clinical trial of repetitive Transcranial Magnetic Stimulation (rTMS) in depersonalization disorder (DPD). After 3weeks of right temporo-parietal junction (TPJ) rTMS, 6/12 patients responded. Five responders received 3 more weeks of right TPJ rTMS showing 68% Depersonalization Disorder (DPD) symptoms improvement. Right TPJ rTMS was safe and effective.

Transcranial Magnetic Stimulation: A Neuroscientific Probe of Cortical Function in Schizophrenia

Antonio Mantovani, Sarah Lisanby, Daphne Simeon, Peter Bulow, Nina Urban, Anouk Allart


Transcranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this article is to examine the utility of TMS as a means to measure neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience treatment Research to Improve Cognition in Schizophrenia initiative. When incorporating TMS paradigms in research studies, methodologic considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety.

Available evidence suggests benefits of TMS alone or in combination with neurophysiologic and neuroimaging methods, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging, functional magnetic resonance imaging, functional near infrared spectroscopy, magnetoencephalography, and electroencephalography, to explore neocortical function.

With the multiple TMS techniques including single-pulse, paired-pulse, paired associative stimulation, and repetitive TMS and theta burst stimulation, combined with neurophysiologic and neuroimaging methods, there exists a plethora of TMS experimental paradigms to modulate neocortical physiologic processes. Specifically, TMS can measure cortical excitability, intracortical inhibitory and excitatory mechanisms, and local and network cortical plasticity. Coupled with functional and electrophysiologic modalities, TMS can provide insight into the mechanisms underlying healthy neurodevelopment and aging, as well as neuropsychiatric pathology.

Thus, TMS could be a useful tool in the Cognitive Neuroscience treatment Research to Improve Cognition in Schizophrenia armamentarium of biomarker methods. Future investigations are warranted to optimize TMS methodologies for this purpose.

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