rTMS as an add-on treatment for resistant obsessive-compulsive symptoms in patients with schizophrenia: report of three cases

Dear Editor,

Obsessive-compulsive symptoms (OCSs) occur in approximately 30% of patients with schizophrenia, probably reflecting reduced basal ganglia and prefrontal cortex connectivity, and are associated with poorer prognosis.¹ There is little systematic evidence of treatment effect on OCS schizophrenia, mostly derived from case reports and open label uncontrolled studies. Among new treatments, repetitive transcranial magnetic stimulation (rTMS) is a method of noninvasive electromagnetic neurostimulation that has demonstrated effect on verbal hallucinations and depressive symptoms. ^2,3 Nevertheless, contradictory effects on obsessive-compulsive disorder (OCD) have been reported, ^2,4 depending on the stimulation parameters used (frequency, place, total dose). Furthermore, there has been some evidence of effects on compulsions using the Mantovani's protocol (1 Hz over the supplementary motor area - SMA),⁵ whilst dorsolateral prefrontal cortex failed to reveal consistent effect even at low or high frequency, and right or left hemisphere.

We report on three cases of comorbid schizophrenia or schizoaffective disorder and OCS under stable dose of neuroleptics receiving additional rTMS with the Mantovani protocol (1 Hz, SMA, 100% of motor threshold, 20 minutes, 20 sessions in 4 weeks), showing reduced OCSs after rTMS treatment. The protocol was approved by the Ethics Committee of the HCPA (Hospital de Clínicas de Porto Alegre - GPPG 10-0426), and patients and relatives provided informed consent.

All cases had treatment-resistant schizophrenia (n=2) or schizoaffective disorder (n=1) with at least 3 months under stable dose of clozapine. Diagnosis was based on the DSM-IV-TR criteria administered by the same trained psychiatrist (VMF) and reviewed by a senior psychiatrist (MIRL). Psychopathology was measured by the 18-item Brief Psychiatric Rating Scale (BPRS) and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The characteristics of the three cases are described in Table 1. All subjects displayed improvement on the BPRS and OCD symptoms after the add-on rTMS treatment, but with subsequent relapse after 4 weeks (Table 1).

Table 1
Results obtained in the three cases

Patient	Age, y	Illness duration, y	Gender	DSM-IV diagnosis	Medication used	Y-BOCS			BPRS
						T1	T2	T3	T1	T2	T3
1	42	25	F	SZ	Clozapine 400 mgCitalopram 40 mg	33	24	29	15	10	11
2	27	9	M	SZA	Clozapine 600 mgValproate 2000 mg	17	11	21	4	2	3
3	30	15	M	SZ	Clozapine 600 mgValproate 1500 mgAmitriptyline 125 mg	24	23	24	32	11	26

• BPRS = Brief Psychiatric Rating Scale; SZ = schizophrenia; SZA = schizoaffective disorder; y = years; m = male; f = female; T1 = baseline; T2 = after 20 repetitive transcranial magnetic stimulation sessions; T3 = 4 weeks after treatment cessation; Y-BOCS = Yale-Brown Obsessive Compulsive Scale.

As far as we are aware, this is the first report of the effects of add-on rTMS on the treatment of OCSs in refractory schizophrenia. These three cases provide initial evidence for the use of the Mantovani protocol (SMA) in this group of patients, in addition to previous effects of rTMS on auditory hallucinations. ^2,3

This report must be viewed as initial evidence requiring further studies with larger number of cases and double-blind sham control group. The number of cases (n=3) precluded statistical testing and displayed relatively large age, gender and diagnosis heterogeneity. Nevertheless, despite the limitations that hinder further generalization, patient diagnosis and psychopathology were consistently assessed, and cases had no significant variations in terms of drug dose and psychosocial environment over the observational period. This reinforces the need of additional studies with larger sample size, less variability of age, gender and diagnosis, longer follow-up, and use of additional tools (functional magnetic resonance imaging-positron emission tomography, fMRI-PET) to elucidate efficacy, duration, and underlying mechanisms of action of the rTMS treatment⁵ in comorbid schizophrenia-schizoaffective disorder-OCS.

References

• ¹
  Docherty AR, Coleman MJ, Tu X, Deutsch CK, Mendell NR, Levy DL. Comparison of putative intermediate phenotypes in schizophrenia patients with and without obsessive-compulsive disorder: examining evidence for the schizo-obsessive subtype. Schizophr Res. 2012;140:83-6.
• ²
  Slotema CW, Blom JD, Hoek HW, Sommer IE. Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J Clin Psychiatry. 2010;71:873-84.
• ³
  Stanford AD, Corcoran C, Bulow P, Bellovin-Weiss S, Malaspina D, Lisanby SH. High-frequency prefrontal repetitive transcranial magnetic stimulation for the negative symptoms of schizophrenia: a case series. J ECT. 2011;27:11-7.
• ⁴
  Blom RM, Figee M, Vulink N, Denys D. Update on repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: different targets. Curr Psychiatry Rep. 2011;13:289-94.
• ⁵
  Mantovani A, Simpson HB, Fallon BA, Rossi S, Lisanby SH. Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder. Int J Neuropsychopharmacol. 2010;13:217-27.

Publication Dates

• Publication in this collection
  April-June 2013

History

• Received
  24 Nov 2012
• Accepted
  8 Dec 2012