Treatment of patients with therapy-resistant auditory verbal hallucinations

Abstract

Background People can hear voices without an external cause, i.e. auditory verbal hallucinations (AVH). The content of AVH can vary from harmless to extremely frightening and can even be dangerous. Despite the broad number of studies that has been performed in the field of AVH, many questions remain to be answered. AVH occur in patients with borderline personality disorder (BPD), which is characterized by a pattern of severe instability in identity, mood and relationships. In this population, AVH are thought to be different and less severe than those in patients with schizophrenia, but evidence is lacking. In the treatment of AVH, the effect of antipsychotics has been well established, but side effects, such as an increase in weight or movement disorders, are a burden for the patient. Furthermore, 25 to 30% of the patients still suffer from AVH despite antipsychotics. Repetitive transcranial magnetic stimulation (rTMS) can influence brain function by inducing a magnetic field with a strong and brief electric current. Repetitive TMS is approved for the treatment of depression and side effects are mild. The aims of this thesis were twofold; first, the characteristics and ensuing distress of AVH in BPD were investigated. Second, the effect of rTMS is investigated for therapy-resistant AVH. Methods The characteristics and ensuing distress of AVH were compared among patients with BPD, patients with schizophrenia and individuals without a psychiatric diagnosis. With the aims of a statistical model (meta-analysis), the effect of rTMS for AVH was investigated in the literature. Three clinical trials were performed to explore the additional effects of rTMS applied with a different paradigm. Results Patients with BPD experience AVH for a mean duration of 17 years, in a frequency of at least once per day during several minutes or more. The ensuing distress of AVH is high. These results are comparable to those in patients with schizophrenia. Compared to individuals without a psychiatric diagnosis, the scores for frequency, duration and distress due to AVH were much higher in patients with BPD. Research in a relatively large population did not show a superior effect of real TMS compared to placebo on the severity of AVH. The same held true for priming TMS, in which low-frequency TMS was preceded by a brief period of high-frequency TMS, and TMS directed at the area with maximal hallucinatory activation. With the inclusion of new studies with larger patient samples, the effect of rTMS for AVH is decreasing but still better than placebo. Conclusions The characteristics and ensuing distress of AVH in BPD do not differ from those in patients with schizophrenia. Therefore, more attention should be paid to auditory verbal hallucinations in BPD. The effect of TMS for therapy-resistant AVH is significant but decreasing with the publication of studies with larger patient samples and negative results. But a number of TMS-paradigms have not been investigated until now. Therefore, more studies are needed to explore other TMS-paradigms such as rTMS applied in a frequency of 50 hertz and deep brain rTMS.