Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS☆
Introduction
Recently, transcranial magnetic stimulation (TMS), widely used in human cortical neurophysiology (Barker et al., 1985, Hallett, 1996), has been reported to have therapeutic effects in several neuropsychiatric disorders, including major depression (George et al., 1999). In case reports and open pilot studies, antidepressant effects were observed after repetitive TMS (rTMS) (Höflich et al., 1993, Grisaru et al., 1994, George et al., 1995, George et al., 1998, Kolbinger et al., 1995, Geller et al., 1997, Feinsod et al., 1998, Avery et al., 1999, Nahas et al., 1999). Three placebo-controlled trials and two larger open-label studies showed an antidepressant action of rTMS in depressed outpatients and patients with pharmacotherapy-resistant depression (Pascual-Leone et al., 1996, George et al., 1997, Figiel et al., 1998, Klein et al., 1999, Pridmore et al., 1999). However, largely varying stimulation parameters have been used in studies of therapeutic rTMS, and optimal parameters have not been established.
The majority of studies investigating rTMS as an antidepressant treatment suggested that a high-frequency or fast rTMS (defined as a frequency >1 Hz) is particularly effective (George et al., 1995, George et al., 1997, Pascual-Leone et al., 1996, Figiel et al., 1998, Avery et al., 1999, Pridmore et al., 1999). In contrast, several open trials and case reports indicated antidepressant effects of low-frequency or slow rTMS (defined as a frequency ≤1 Hz) (Höflich et al., 1993, Grisaru et al., 1994, Kolbinger et al., 1995, Conca et al., 1996, Geller et al., 1997, Feinsod et al., 1998). Recently, these results were confirmed by a randomized placebo-controlled study where a 1-Hz slow rTMS of the right prefrontal cortex was successfully applied (Klein et al., 1999).
The aim of the present study was to compare the antidepressant efficacy and tolerability of fast, slow and sham stimulation in patients with medication–refractory major depression. In order to monitor cognitive side effects, we tested verbal learning and reaction time before and after rTMS. Length of rTMS treatment and number of daily stimuli were similar to a prior pilot study which indicated antidepressant effects of slow rTMS (Kolbinger et al., 1995).
Section snippets
Patients
Eighteen right-handed patients from the Department of Psychiatry, Ludwig–Maximilian University Munich were included [age=51.2±16.1 years, 11 women (age: 51.1±15.1 years), seven men (age: 51.3±18.3 years)]. All patients met DSM-IV criteria for Major Depressive Disorder (single episode in three, recurrent depression in 15). All patients gave their written informed consent for this study, after the procedure had been fully explained. The study was approved by the local ethics committee. Patients
Clinicians’ ratings
HDRS scores tended to decrease from pre-treatment to post-treatment across groups (F1,15=3.58; P<0.10). No overall difference was found between treatment groups (F2,15=0.93; n.s.). The interaction of treatment groups and time was significant (F2,15=3.76; P<0.05). In the sham rTMS group, the mean HDRS score was unchanged between baseline (22.2±8.8) and day 5 (23.5±10.4) [t(5)=−0.62; n.s.]. In the slow rTMS group, the HDRS score significantly decreased by 19% from 26.7±9.4 to 21.5±21.5 [t
Discussion
In this double-blind parallel study, two active rTMS conditions with different stimulation frequencies were compared to sham rTMS. HDRS scores showed a statistically significant time×group interaction and were decreased by 19% from baseline after slow rTMS. MADRS scores showed a statistical trend towards a time×group interaction. Tolerability of rTMS treatment was excellent and no serious side effects occurred.
The finding of a mild antidepressant effect of slow rTMS is consistent with previous
Acknowledgements
The authors thank Dr. Patrick Mikhaiel for helpful discussions, as well as Simon Neulinger and Felician Iancu for their assistance. They also thank Magstim Company Ltd. and Micromed Medizin-Elektronik GmbH for kind support.
References (36)
- et al.
Noninvasive magnetic stimulation of human motor cortex
Lancet
(1985) - et al.
A combined TMS/fMRI study of intensity-dependent TMS over motor cortex
Biological Psychiatry
(1999) - et al.
Slow magnetic stimulation of prefrontal cortex in depression and schizophrenia
Progress in Neuro-Psychopharmacology and Biological Psychiatry
(1997) - et al.
Transcranial magnetic stimulation in depression and schizophrenia
European Neuropsychopharmacology
(1994) - et al.
Beneficial effect of rapid-rate transcranial magnetic stimulation of the left dorsolateral prefrontal cortex in drug-resistant depression
Lancet
(1996) Risk and safety of repetitive transcranial magnetic stimulation: report and suggested safety guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996
Electroencephalography and Clinical Neurophysiology
(1998)- et al.
Repetitive transcranial magnetic stimulation in the treatment of medication-resistant depression: preliminary data
Journal of Nervous and Mental Disease
(1999) - et al.
Effects of repetitive transcranial magnetic stimulation over dorsolateral prefrontal and posterior parietal cortex on memory-guided saccades
Experimental Brain Research
(1998) - et al.
Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation
Neurology
(1997) - et al.
Transcranial magnetic stimulation: a novel antidepressive strategy?
Neuropsychobiology
(1996)
Preliminary evidence for a beneficial effect of low-frequency, repetitive transcranial magnetic stimulation in patients with major depression and schizophrenia
Depression and Anxiety
The use of rapid-rate transcranial magnetic stimulation (rTMS) in refractory depressed patients
Journal of Neuropsychiatry and Clinical Neurosciences
Imaging human intra-cerebral connectivity by PET during TMS
NeuroReport
Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) improves mood in depression
NeuroReport
Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled crossover trial
American Journal of Psychiatry
Low frequency daily left prefrontal rTMS improves mood in bipolar depression: a placebo-controlled case report
Human Psychopharmacology
Transcranial magnetic stimulation
Archives of General Psychiatry
Transcranial magnetic stimulation can measure and modulate learning and memory
Neuropsychologia
Cited by (261)
Safety of transcranial magnetic stimulation in unipolar depression: A systematic review and meta-analysis of randomized-controlled trials
2022, Journal of Affective DisordersCitation Excerpt :All of our studies (characteristics present in Table 1) were published between 1999 and 2020. Most studies were performed in North America (Avery et al., 2006; Blumberger et al., 2016, 2012; Boutros et al., 2002; Carpenter et al., 2017; George et al., 2010; Holtzheimer et al., 2004; Jin and Phillips, 2014; Kaster et al., 2018; Kauffmann et al., 2004; Kim et al., 2019; Leuchter et al., 2015; Levkovitz et al., 2015; Manes et al., 2001; Mantovani et al., 2013; O'Reardon et al., 2007; Pallanti et al., 2010; Stern et al., 2007; Taylor et al., 2018b; Trevizol et al., 2019; Triggs et al., 2010; Yesavage et al., 2018), while 16 were performed in Europe (Aguirre et al., 2011; Anderson et al., 2007; Brunelin et al., 2014; Carretero et al., 2009; Concerto et al., 2015; Garcia-Toro et al., 2001; García-Toro et al., 2001; Herwig et al., 2003; Januel et al., 2006; Padberg et al., 2002, 1999; Plewnia et al., 2014; Poulet et al., 2004; Schutter, 2009; Theleritis et al., 2017; Valkonen-Korhonen et al., 2018), 12 were performed in Asia (Bakim et al., 2012; Chen et al., 2013; Dai et al., 2020; Huang et al., 2012; Kang et al., 2016; Li et al., 2014, 2020; Lingeswaran, 2011; Minmin et al., 2015; Pan et al., 2020; Wang et al., 2017; Zheng et al., 2015, 2010), one was performed in South America (Rumi et al., 2005), and one was performed in Australia (Fitzgerald et al., 2012). All of the studies included subjects aged 18 years or older except for two studies (Lingeswaran, 2011; Pan et al., 2018) .
Evaluation of memory performance in patients with brain disorders following rTMS treatment. A systematic review
2022, Clinical Neurophysiology
- ☆
This work was presented in part at the XXIst Congress of the Collegium Internationale Neuro-Psychopharmacologicum, Glasgow, UK, July 12–16, 1998, and at the International Symposium on Transcranial Magnetic Stimulation, Göttingen, Germany, September 30–October 4, 1998.