How effective is repetitive transcranial magnetic stimulation for bipolar depression?

Previous studies of rTMS for bipolar depressed (BD) patients have yielded mixed results. In this retrospective, naturalistic, observational study, we reviewed charts of 317 patients undergoing rTMS treatment between 1/2015–2/2018, yielding 283 unipolar depressed (UD) and 34 BD patients. All were treated with a figure-of-8 coil, with either high-frequency (HF) left-sided, sequential bilateral (HF left-sided and low-frequency right-sided), or mixed protocols (switched from unilateral to bilateral mid-course).  Outcomes were the Generalized Anxiety Disorder scale (GAD-7) and Patient Health Questionnaire (PHQ-9). Total number of treatments and initial PHQ-9 scores did not differ between groups. BD patients had greater PHQ-9 change by treatment conclusion than UD patients. GAD-7 changes showed no between-group differences overall. PHQ-9 changes differences between groups were only seen with unilateral treatment, not with bilateral or mixed protocols. Unilateral treatment resulted in 45% remission (9/20) for BD patients vs. 15% (24/160) for UD patients by treatment end. Response was seen in 80% (16/20) of the unilaterally-treated BD patients vs. 39% (62/160) in UD patients. Regression analyses within BD patients found that unilateral treatment, use of non-lithium mood stabilizers, male sex, and number of treatments predicted PHQ-9 improvement.

Repetitive transcranial magnetic stimulation (rTMS) is an increasingly used treatment for patients with depression. The use of rTMS in depression is supported by over 20 years of clinical trials. There has been a significant increase in knowledge around the use of rTMS in recent years.

The aim of this paper was to review the use of rTMS in depression to provide an update for rTMS practitioners and clinicians interested in the clinical use of this treatment.

A targeted review of the literature around the use of rTMS treatment of depression with a specific focus on studies published in the last 3 years.

High-frequency rTMS applied to the left dorsolateral prefrontal cortex is an effective treatment for acute episodes of major depressive disorder. There are several additional methods of rTMS delivery that are supported by clinical trials and meta-analyses but no substantive evidence that any one approach is any more effective than any other. rTMS is effective in unipolar depression and most likely bipolar depression. rTMS courses may be repeated in the management of depressive relapse but there is less evidence for the use of rTMS in the maintenance phase.

The science around the use of rTMS is rapidly evolving and there is a considerable need for practitioners to remain abreast of the current state of this literature and its implications for clinical practice. rTMS is an effective antidepressant treatment but its optimal use should be continually informed by knowledge of the state of the art.

The safety and efficacy of neuronavigated intermittent theta burst stimulation (iTBS) in patients with bipolar depression has not yet been investigated. We hypothesized the superiority of active iTBS over sham. Twenty-six patients were randomly allocated to receive either active (n = 12) or sham (n = 14) iTBS. Response and remission rates according to changes in depression MADRS score were high following active iTBS (72% and 42% for response and remission rates, respectively), but no significant difference was found after sham stimulation (42%and 25%). No adverse events were observed. This study revealed the safety and tolerability of twice daily iTBS in patients with bipolar depression. Larger controlled studies are warranted to prove iTBS superiority in treatment-resistant bipolar depression.

La stimulation magnétique transcrânienne répétée (rTMS) est un outil thérapeutique d’utilisation encore récente en psychiatrie. Cet article a pour objectif d’actualiser l’état des connaissances sur la rTMS dans le traitement des troubles de l’humeur. La rTMS possède une efficacité certaine (niveau de preuve de grade 1) dans le traitement initial curatif de la dépression unipolaire à condition d’utiliser des paramètres efficaces, c’est-à-dire, pour les schémas classiques à haute fréquence (5 à 20 Hz) : 20 à 30 séances, plus de 1200 pulses/séance, 5 Hz à 20 Hz, et au moins 110 % du seuil moteur. Les protocoles à 1 Hz sont également efficaces et bien tolérés. La durée de l’efficacité varie avec des taux de rechutes autour de 50 % à 1 an. Un traitement pharmacologique est, en règle, associé. La rTMS se positionne préférentiellement comme un traitement adjuvant aux psychotropes après échec ou efficacité partielle d’un ou deux antidépresseurs (niveau de résistance peu élévée) pour traiter des épisodes non chroniques (< 2 ans), sans critère de gravité (absence de symptômes psychotiques, risque suicidaire faible). En ce qui concerne les états maniaques et les états mixtes, les résultats ont encore un faible niveau de preuve se limitant à une possible réduction des symptômes. Dans le risque suicidaire associé aux troubles de l’humeur, l’intérêt de la rTMS est encore à démontrer, ainsi que dans la catatonie.

Repeated transcranial magnetic stimulation (rTMS) is still a recent treatment in psychiatry. This article aims at updating the clinicians’knowledge about rTMS in the treatment of mood disorders (uni and bipolar depressive disorders, manic/mixed states, suicidal risk, catatonia). It is intended for clinicians who are required to indicate and/or use rTMS in their current practice. rTMShas the highest level of evidence for the treatment of unipolar depression, provided that effective parameters are used, that is to say, for classical high frequency protocols: 20 to 30 sessions, 1000 pulses/session, 5 to 20 Hz, and 110 % of the motor threshold. Low frequency protocol are also efficient and well tolerated. The duration of the efficacy varies with relapses rates around 50 % at one year. Pharmacological treatment generally remains associated. With regard to manic states, and mixed states the results are preliminary and limited to a possible reduction in symptoms. In the suicidal risk associated with mood disorders, the interest of rTMS is still to demonstrate, as well as in catatonia. The current place of the rTMS is no longer disputed in the curative treatment of major depressive disorder, preferentially used after one or two lines of antidepressants upstream. Further studies are needed to confirm preliminary positive findings in other aspects of mood disorders.

The presence of comorbid anxiety is generally associated with poorer treatment outcomes in people with depression. Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective for treatment resistant depression, but there has been little research examining rTMS in depressed patients with comorbid anxiety disorders. This study aimed to investigate the efficacy of rTMS in patients with treatment resistant Major Depressive Disorder (MDD) and comorbid anxiety disorders.

This study included 248 patients with treatment resistant MDD who were treated with rTMS. Of these, 172 patients had one or more comorbid anxiety disorders, so their outcomes were compared with patients who did not have comorbid anxiety.

Patients both with and without comorbid anxiety disorders showed improvement in depression ratings after rTMS treatment, with no significant difference in remission rates between groups. In those with comorbid anxiety disorders, 23.3% met criteria for remission and 39.5% met response criteria. For each anxiety disorder diagnosis, there was a significant reduction in HAM-A, HAM-D21, MADRS and ZUNG scores (p = <0.001 for all).

This was not a sham-controlled study, so placebo response rates are not known. Patients were referred by private psychiatrists so are not representative of all patients with depression.

Our study indicates that rTMS is an effective treatment for Major Depressive Disorder in people who have comorbid anxiety disorders.