Transcranial Magnetic Stimulation of Left Temporoparietal Cortex and Medication-Resistant Auditory Hallucinations
Hoffman RE, Hawkins KA, Gueorguieva R, Boutros NN, Rachid F, Carroll K and Krystal JH;
Commented by , 29 Jan 2003
Aim of the study
Treatment resistance is an important issue, because approximately 25% of patients with schizophrenia do not respond to antipsychotic drugs. The only antipsychotic with a proven efficacy in treatment resistant schizophrenia is clozapine.
Various augmentation strategies such as the addition of mood-stabilisers to antipsychotic drugs do not appear to be very effective. Thus, non-pharmacologic interventions are needed.
One potential adjunctive treatment is repetitive transcranial magnetic stimulation (rTMS) where brain areas are stimulated with magnetic pulses produced by a coil. Brain imaging studies showed that auditory hallucinations (AHs) of speech arise, at least in part, from activation of brain areas underlying speech perception. rTMS leads to marked reductions in cortical activation.
A pilot study had shown that 4-day administration of 1-Hz rTMS to left temporoparietal cortex was superior as compared to sham stimulation in reducing auditory hallucinations.
The aim of the current study was to examine if a larger and longer trial of rTMS could significantly reduce auditory hallucinations in patients who were resistant to antipsychotic drugs.
Method
Twenty-four patients with schizophrenia or schizoaffective disorder were randomly allocated to receive rTMS or sham stimulation for 9 days at 90% of motor threshold. All participants were treatment resistant as defined by a persistence of auditory hallucinations despite at least two adequate trials with antipsychotic drugs.
Real- and sham rTMS were administered to the left temporoparietal cortex, but for sham rTMS an ineffective angle of 45° away from the skull was used. Patients receiving sham stimulation were subsequently offered an open-label trial of rTMS.
The following psychopathological assessments were administered at baseline and during and following each arm of the trial:
- a hallucination change scale
- the PANSS
- the CGI
- a number of neuropsychological tests
Results
Repetitive transcranial magnetic stimulation was well tolerated and there was no evidence of neuropsychological impairment. Auditory hallucinations improved over time in both groups, but statistically significantly more in the rTMS group relative to the group which received sham stimulation.
Frequency and attentional salience were the 2 aspects of hallucinatory experience that showed greatest improvement. Duration of putative treatment effects ranged widely, with 52% of patients maintaining improvement for at least 15 weeks.
Discussion
These data suggest that one-hertz rTMS may be an effective treatment for auditory hallucinations associated with schizophrenia. Furthermore, the data suggests that the mechanism of auditory hallucinations involves activation of the left temporoparietal cortex.
The most obvious limitations of the trial are the small sample size and the use of sham stimulation as the control condition rather than active stimulation to another brain area, although the patients were not able to detect whether they received real- or sham rTMS.
Therefore, the data are still of hypothesis generating nature, and larger and longer studies are needed. In addition, the applicability of rTMS in the daily routine needs to be established.