Assessing the impact of sex on high-frequency repetitive transcranial magnetic stimulation´s clinical response in schizophrenia – results from a secondary analysis

Abstract

Background

The evidence for repetitive transcranial magnetic stimulation (rTMS) to treat negative symptoms in schizophrenia (SCZ) is increasing, although variable response rates remain a challenge. Subject´s sex critically influences rTMS´ treatment outcomes. Females with major depressive disorder are more likely to respond to rTMS, while SCZ data is scarce.

Methods

Using data from the ‘rTMS for the Treatment of Negative Symptoms in Schizophrenia’ (RESIS) trial we assessed the impact of sex on rTMS´ clinical response rate from screening up to 105 days after intervention among SCZ patients. The impact of resting motor threshold (RMT) on response rates was also assessed.

Results

157 patients received either active or sham rTMS treatment. No significant group differences were observed. Linear mixed model showed no effects on response rates (all p > 0.519). Apart from a significant sex*time interaction for the positive subscale of the positive and negative syndrome scale (PANSS) scores (p = 0.032), no other significant effects of sex on continuous PANSS scores were observed. RMT had no effect on response rate.

Conclusion

In the largest rTMS trial on the treatment of SCZ negative symptoms we did not observe any significant effect of sex on treatment outcomes. Better assessments of sex-related differences could improve treatment individualisation.

Keywords:

• rTMS
• sex
• schizophrenia
• negative symptoms
• RESIS

Acknowledgments

None

Statement of interest

MC, TSA, MM, ML, PE, EF, CO, PV, MR, WW and RA report no conflicts of interest.

AH was member of advisory boards of Boehringer-Ingelheim, Lundbeck, Janssen, Otsuka, Rovi and Recordati and received paid speakership by these companies as well as by AbbVie and Advanz. He is editor of the German schizophrenia guideline.

TW is or was a member of advisory boards of Boehringer, Otsuka/Lundbeck, Janssen-Cilag and Rovi, received paid speakership from Boehringer, Otsuka/Lundbeck, Janssen-Cilag, Recordati and Rovi as well as travel and congress support from Rovi. He is a member of the DGPPN schizophrenia guideline expert panel.

EW was invited to advisory boards from Recordati and Boehringer Ingelheim.

JC was a member of an advisory board of Roche, accepted travel or hospitality not related to a speaking engagement from Servier, support for symposia from Inomed, Localite, Magventure, Roche, Mag & More, NeuroConn, Syneika, FBI Medizintechnik, Spitzer Arzneimittel and Diamedic, research and study participation funded by the German Research Foundation and the German Bundesministerium für Bildung und Forschung, Foundation European Group for Research In Schizophrenia, ACADIA Pharmaceuticals Inc., Boehringer Ingelheim Pharma GmbH & Co. KG, Otsuka Pharmaceutical Europe Ltd. and EnVivo Pharmaceuticals.

WG has received symposia support from Janssen-Cilag GmbH, Neuss, Lilly Deutschland GmbH, Bad Homburg and Servier, Munich. He is a member of the Faculty of the Lundbeck Foundation, named ‘Neurotorium’ (former International Neuroscience Foundation (LINF), Denmark.

BL is an advisory board member of Neuromod and Desyncra, received honoraria and speakers’ fees fromANM, Astra Zeneca, Autifony, Lundbeck, Merz, Magventure, Neurolite, Novartis, Pfizer and Servier, research funding from the Tinnitus Research Initiative, the German Research Foundation, the German Bundesministerium für Bildung und Forschung, the American Tinnitus Association, Astra Zeneca, Cerbomed, Neuromod, Otonomy and Sivantos, funding for equipment from Magventure and Deymed and travel and accommodation payments from Lilly, Lundbeck, Servier and Pfizer.

GH has received payments as speaker, consultant, author or for research funding during the last 5 years from Actelion, Affectis, Astra-Zeneca, Bayerische Motorenwerke, Bundesmin­isterium für Bildung und Forschung, Bundesministerium für Strahlenschutz, Bristol-Meyers Squibb, Cephalon, Daimler Benz, Deutsche Forschungsgesellschaft, Elsevier, EuMeCom, Essex, Georg Thieme, Gerson Lerman Group Council of Healthcare Advisors, GlaxoSmithKline, Janssen-Cilag, Lilly, Lundbeck, Meda, Merck, Merz, Novartis, Pfizer, Proctor & Gamble, Sanofi-Aventis, ScheringPlough, Sepracor, Servier, Springer, Urban & Fischer, and Volkswagen.

BM has received paid speakerships from Recordati Pharma.

WS has received paid speakership by Mag & More (neurocare) and Recordati. He was member of an advisory board of Recordati.

PF was honorary speaker for Janssen-Cilag, Astra-Zeneca, Eli Lilly, Bristol Myers-Squibb, Lundbeck, Pfizer, Bayer Vital, SmithKline Beecham, Wyeth, and Essex. During the last 5 years, but not presently, he was a member of the advisory boards of Janssen, AstraZeneca, Eli Lilly, and Lundbeck.

Additional information

Funding

The RESIS study was supported by the Deutsche Forschungsgemeinschaft Grant No. FA–210/1. The trial protocol has been published (Cordes et al. 2009) and is available at [email protected]. This study was endorsed by DZPG (German Center for Mental Health) [to Alkomiet Hasan, FKZ: 01EE2303C].