Maintenance rTMS for Treatment-Resistant Depression

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The fast passage of electric current in the TMS coil induces a transient, high intensity magnetic field that penetrates unimpeded through the scalp and reaches the underlying cortex.
The fast passage of electric current in the TMS coil induces a transient, high intensity magnetic field that penetrates unimpeded through the scalp and reaches the underlying cortex.

Major depressive disorder (MDD) has a lifetime prevalence of nearly 15% in higher-income countries and is associated with substantial mortality and morbidity.1 Despite the demonstrated efficacy of antidepressants, psychotherapy, and electroconvulsive therapy (ECT) in many patients with MDD, more than half of individuals receiving these treatments experience recurrent episodes within 1 year. One-third of patients treated for MDD do not achieve remission even after multiple rounds of antidepressants and other drugs.2 In those who do have remittance, ongoing maintenance therapy is necessary to prevent relapse.

Transcranial magnetic stimulation (TMS) is a noninvasive technique that delivers high-intensity electromagnetic pulses through a coil. “The fast passage of electric current in the coil induces a transient, high-intensity magnetic field that penetrates unimpeded through the scalp and reaches the underlying cortex,” the author explained in a review published online in Psychiatry Research in September 2017.3 “In the targeted cortex, this field can generate an electric current which can induce depolarization of superficial cortical neurons and interconnected areas beneath the coil.”4

There are various types of TMS, including single-pulse TMS, which delivers one pulse at a time, and repetitive TMS (rTMS), in which repeated pulses are administered to the same area. The safety of rTMS is supported by findings of multiple studies, and although various meta-analyses have reported the efficacy of this technique for treatment-resistant depression, the studies were based on acute rTMS rather than rTMS as maintenance treatment.

The new review explored studies that investigated the efficacy and safety of maintenance rTMS following successful acute treatment with rTMS or ECT in treatment-resistant unipolar or bipolar depression. Additionally, these studies were compared with those comparing maintenance rTMS with observation only after acute rTMS.

The author found a limited number of studies (n=19) on the topic, and most of these were case series. Selected findings from the review are summarized briefly below.

  • In a 45-year-old woman who had not had an adequate response to various antidepressants for recurrent MDD, an initial response to 10 sessions of rTMS was followed by relapse 2 weeks after treatment ended. After subsequent weekly or biweekly sessions of maintenance rTMS, she remained episode free for 4 months, and no adverse effects were reported.5
  • Following successful response to acute rTMS, 3 of 7 patients with bipolar depression maintained partial remission after 1 year of weekly maintenance sessions.6
  • A 60-year-old woman with drug-resistant bipolar I depression maintained a therapeutic response to an acute course of rTMS followed by 6 months of maintenance rTMS sessions every other week.7
  • In a naturalistic study, 205 patients with treatment-resistant MDD had a significant decrease in symptoms after successful acute rTMS followed by a 12-month course of maintenance rTMS.8
  • In a 3-armed open label-study, no significant differences were observed between patients assigned to 1 of 3 conditions: venlafaxine (n=22); maintenance rTMS for 12 months (n=25; twice weekly for the first month, followed by once weekly for 2 months, and once every 2 weeks for the remaining 9 months); or a combination of both treatments (n=19).9
  • A randomized, multicenter trial with 49 participants found no significant difference in 12-month outcomes between participants who underwent monthly maintenance rTMS and those assigned to observation only, after both groups previously responded to 6 weeks of treatment with 5 weekly sessions of rTMS.10

There were few adverse effects across studies, including slight headache in one patient and a transient increase in suicidality in another patient. Overall, most studies showed at least moderate benefits, including remission, in the majority of patients after rTMS.

As an alternative to continuing antidepressant medications, maintenance rTMS “can be helpful in preventing depressive relapses, and should be considered a useful therapeutic approach for treatment-resistant depression after successful response to an acute course of rTMS or ECT,” according to the review author, Fady Rachid, MD, a psychiatrist and psychotherapist in private practice in Geneva, Switzerland. However, there are no established protocols for maintenance rTMS. Although the intervention should ultimately be tailored to each patient's clinical picture, it might consist of an rTMS taper of 4 times weekly for the first week, 3 times weekly in the following week, 2 times weekly for the subsequent 1 or 2 weeks, and then 1 session every 2 or 3 weeks over several months to years, depending on the case. 

Future research in the realm of rTMS should include studies with improved design, as well as “more controlled studies with more subjects comparing active maintenance rTMS with a placebo or medications... in order to assess the true efficacy and safety of this technique in the long term,” said Dr Rachid. “That said, there is definitely a place for maintenance rTMS in the management of treatment-resistant depression.”

References

  1. Bromet E, Andrade LH, Hwang I, et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011;9:90.
  2. Gaynes, BN, Warden D, Trivedi MH, Wisniewski SR, Fava M, Rush AJ. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009;60 (11):1439-1445.
  3. Rachid F. Maintenance repetitive transcranial magnetic stimulation (rTMS) for relapse prevention in with depression: a review [published online September 19, 2017]. Psychiatry Res. doi:10.1016/j.psychres.2017.09.009
  4. Hallett M. Transcranial magnetic stimulation: a primer. Neuron. 2007;55(2):187-199.
  5. Abraham G, O'Brien S. Repetitive transcranial magnetic stimulation is useful for maintenance treatment. Can J Psychiatry. 2002;47(4):386.
  6. Li X, Nahas Z, Anderson B, Kozel FA, George MS. Can left prefrontal rTMS be used as a maintenance treatment for bipolar depression? Depress Anxiety. 2004;20(2):98-100.
  7. Deloise B, Altamura AC. Augmentative transcranial magnetic stimulation (TMS) combined with brain navigation in drug-resistant rapid cycling bipolar depression: a case report of acute and maintenance efficacy. World J Biol Psychiatry. 2009;10(4 Pt 2):673-676.
  8. Dunner DL, Aaronson ST, Sackeim HA, et al. A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: durability of benefit over a 1-year follow-up period. J Clin Psychiatry. 2014;75(12):1394-1401.
  9. Haesebaert F, Moirand R, Schott-Pethelaz AM, Brunelin J, Poulet E. Usefulness of repetitive transcranial magnetic stimulation as a maintenance treatment in patients with major depression. World J Biol Psychiatry. 2016 Nov 23;1-5.
  10. Philip NS, Dunner DL, Dowd SM, et al. Can medication free, treatment-resistant, depressed patients who initially respond to TMS be maintained off medications? A prospective, 12-month multisite randomized pilot study. Brain Stimul. 2016;9(2):251-257. 
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