Schizophrenia Research 116 (2010) 291–292

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Schizophrenia Research

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Letter to the Editors

Worsening of “passivity” symptoms with low-frequencybilateral temporo-parietal repetitive transcranialmagnetic stimulation used to treat refractory auditoryhallucinations: A case report

Recent meta-analysis evidence supports the use of lowfrequency Repetitive Trans-cranial Magnetic Stimulation(rTMS) applied to left temporo-parietal cortex (TPC) for thetreatment of anti-psychotic refractory auditory hallucinations(AH) (Freitas et al., 2009).

We report here the unusual adverse effect of worsening“passivity” symptoms or delusions of control in a youngwoman with a primary diagnosis of treatment-refractoryschizophrenia that was treated with rTMS for AH at ourcenter.

This 24 year old woman had her first psychotic episodefour years previously. Since then, she had been treated withtypical and atypical antipsychotic medication with limitedsuccess.

She reported experiencing continuous imperative, derog-atory and occasionally, inspirational auditory hallucinationsmainly in the form of three male voices. She reported feelingsof helplessness in regards to the hallucinations and stated itwas nearly impossible to resist many of the commandsrelated to self-hygiene. She also attached emotional signifi-cance to the experiences. For example, she stated one of thevoices “did not like (her) having a shower”.

She reported experiencing passivity of impulse 3–4 timesper week and volition 2–3 times per week but not somatic oraffect passivity. She had a history of one grand-mal seizurethought to have been related to illicit substance use at thetime but no history of epilepsy, and had co-morbid PTSD.

At the time she was on Flupenthixol injection, the dose ofwhich was unchanged throughout rTMS treatment. Clozapinewas offered but declined.

She was offered a course of rTMS for AH as the riskof seizures is small with low-frequency rTMS, which hasbeen used in epilepsy patients safely (Bae et al., 2007). Lowfrequency rTMS (1 Hz.) at 100% resting motor thresholdwas applied to the left TPC initially (3 treatments) andlater, due to limited response to this, bilaterally to TPCidentified as determined by the 10-20-20 EEG leadplacement system and as per practice in published reports(Hoffman et al., 2003; Vercammen et al., 2009). Treatmentwas administered 5 days/week for 4 weeks after whichit was stopped for 1 week to review clinical response.She reported an average of 4.4 cm improvement in audi-tory hallucinations on self-rated visual analogue scale

0920-9964/$ – see front matter © 2009 Elsevier B.V. All rights reserved.doi:10.1016/j.schres.2009.10.027

(VAS) of 10 cm. A second course of bilateral rTMS wascommenced. After 2 treatments, she expressed an in-creased frequency of the passivity experiences of volitionand impulse, which impacted her day-to-day functioningand caused increased distress. rTMS treatment was there-fore discontinued.

The patient attributed this worsening of passivity experi-ences to punishment by the “voices” for silencing them withrTMS. She continued to experience reduced AH for 4 daysafter the last rTMS treatment after which it returned to itsusual level. Interestingly, her passivity experiences lessenedin frequency in inverse relation to the AH.

“Passivity” symptoms, which are experienced by 40%–48%of individuals with schizophrenia (WHO, 1973; Landmarket al., 1990), have been postulated to be related to lesions inthe superior temporal gyrus (Leube et al., 2008). New orworsened passivity symptoms in relation to rTMS treatment,left TPC or bilateral, have not, to date, been reported in theliterature.

It is possible that the worsening in passivity symptomsin this patient could have been part of the fluctuatingcourse of her primary or co-morbid illness, a psychologicalreaction to the reduction of AH, or a result of reversibleinhibition of superior temporal lobe with rTMS. Neverthe-less, awareness of the occurrence of such symptoms andtheir possible relation to auditory hallucinations, at least insome individuals, will assist in the monitoring for suchadverse effects when rTMS is being used as an intervention.

Role of funding sourceNone.

ContributorsDr. Subramanian prepared the initial draft of the manuscript. Dr Burhan

and Dr. Subramanian prapared all subsequent drafts of the manuscript. Bothauthors approved the final draft.

Conflict of InterestNone.

AcknowledgementWritten informed consent was obtained from the patient for publication

of this case report.

References

Bae, E.H., Schrader, L.M., Machii, K., Alonso-Alonso, M., Riviello Jr., J.J.,Pascual-Leone, A., Rotenberg, A., 2007. Safety and tolerability ofrepetitive transcranial magnetic stimulation in patients with epilepsy:a review of the literature. Epilepsy Behav. 10 (4), 521–528.

292 Letter to the Editors

Freitas, C., Fregni, F., Pascual-Leone, A., 2009. Meta-analysis of the effectsof repetitive transcranial magnetic stimulation (rTMS) on negativeand positive symptoms in schizophrenia. Schizophr. Res. 108 (1–3),11–24.

Hoffman, R.E., Hawkins, K.A., Gueorguieva, R., Boutros, N.N., Rachid, F.,Carroll, K., Krystal, J.H., 2003. Transcranial magnetic stimulation of lefttemporoparietal cortex and medication-resistant auditory hallucina-tions. Arch. Gen. Psychiatry 60 (1), 49–56.

Landmark, J., Merskey, H., Cernovsky, Z., Helmes, E., 1990. The positivetriad of schizophrenic symptoms, its statistical properties and itsrelationship to 13 traditional diagnostic systems. Br. J. Psychiatry 156,388–394.

Leube, D., Whitney, C., Kircher, T., 2008. The neural correlates of ego-disturbances (passivity phenomena) and formal thought disorderin schizophrenia. Eur. Arch. Psychiatry Clin. Neurosci. 258 (S 5), 22–27.

Vercammen, A., Knegtering, H., Bruggeman, R., Westenbroek, H.M., Jenner, J.A.,Slooff, C.J., Wunderink, L., Aleman, A., 2009. Effects of bilateral repetitivetranscranial magnetic stimulation on treatment resistant auditory-verbalhallucinations in schizophrenia: A randomized controlled trial. Schizophr.Res. 114 (1–3), 172–179.

World Health Organization, 1973. The International Pilot Study of Schizo-phrenia, vol. 1. WHO, Geneva.

Priya SubramanianDepartment of Psychiatry,

University of Western Ontario and Regional Mental Health Care,E229A, 850, Highbury Avenue, London, Ontario,

Canada N6A 4H1Corresponding author. Tel.: +1 519 455 5110x47520.E-mail address: Priya.Subramanian@sjhc.london.on.ca.

Amer BurhanDepartment of Medicine and Psychiatry,

University of Western Ontario and Regional Mental Health Care,Geriatrics,

850, Highbury Avenue, London, ON, CanadaE-mail address: Amer.Burhan@sjhc.london.on.ca.

18 September 2009