Is theta burst stimulation ready as a clinical treatment for depression?

ABSTRACT

Introduction: Major depression is a common and debilitating mental disorder that can be difficult to treat. Substantive evidence over the past two decades has established repetitive transcranial magnetic stimulation (rTMS) as an effective antidepressant therapy, although scope exists to improve its efficacy and efficiency. Theta burst stimulation (TBS) is a novel rTMS pattern attracting much research interest as a tool to study neurophysiology and treat neuropsychiatric disorders.

Areas covered: This article outlines rTMS’ state of development and explores the physiology studies underpinning TBS development and its observable neuronal conditioning and metabolic effects. We present a systematic review of studies that applied TBS to treat depression, followed by commentary on safety and practical considerations.

Expert opinion: Much experimental and clinical research have advanced our understanding of the antidepressant effects of TBS, although unanswered questions remain relating to its physiological effects, response variability and optimal parameters for therapeutic purposes. A small number of sham-controlled trials, and one large comparative trial, support the therapeutic efficacy of TBS and demonstrates its non-inferiority relative to traditional rTMS. In this light, TBS can reasonably be offered as an alternative to rTMS in treatment-resistant depression, while ongoing research is likely to inform its therapeutic potential.

KEYWORDS:

• Brain stimulation
• depression
• repetitive transcranial magnetic stimulation
• theta burst stimulation
• treatment resistant depression

Article highlights

• Repetitive transcranial magnetic stimulation (rTMS) has been established over the past two decades as an effective and evidence-based treatment for treatment-refractory major depressive disorder, but scope exists for improvement in its efficiency and efficacy.

• Theta burst stimulation (TBS) is a novel pattern of applying rTMS shown to induce significant and long-lasting neuronal conditioning responses in motor cortical studies, while electrophysiological and metabolic effects in the prefrontal cortex have also been observed.

• A limited number of open-label and sham-controlled randomized trials of modest sample sizes point to TBS therapeutic potential in major depression. A recent, large, non-inferiority study found TBS equally effective as rTMS in treating depression, leading to approval for use in treatment-resistant depression by US and European regulatory bodies.

• From a weight of evidence perspective, as an antidepressant therapy rTMS has been systematically investigated to greater lengths compared to TBS. Clinical practice guidelines and comprehensive safety data to guide TBS practices are lacking. Development of these can help standardize practice and improve safety.

• Given the current evidence base, TBS can reasonably be offered as a clinical alternative to traditional rTMS in treatment-resistant depression. In the consenting process, it is advisable patients are informed TBS is a novel patterned rTMS protocol which is not supported by the same weight of evidence as standard rTMS treatment.

• Inter- and intra-individual response variability with TBS and uncertainties related to mechanisms of action remain, warranting ongoing research. Electrophysiological and functional connectivity measures indicate the potential to predict and/or individualize treatment outcomes.

• Large-scale sham-controlled trials investigating TBS's efficacy can further consolidate TBS's empirical evidence base as an antidepressant therapy.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

K Hoy is supported by a National Health and Medical Research Council (NHMRC) Fellowship (APP1135558). P Fitzgerald is supported by a NHMRC Practitioner Fellowship (1078567)