Brain stimulation treatment for bipolar disorder

Abstract

Aims: Bipolar disorders are clinically complex, chronic and recurrent disorders. Few treatment options are effective across hypomanic, manic, depressive and mixed states and as continuation or maintenance treatment after initial symptom remission. The aim of this review was to provide an up-to-date overview of research on the efficacy, tolerability and cognitive effects of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST), deep brain stimulation (DBS) and vagus nerve stimulation (VNS).

Methods: References included in this review were identified through multiple searches of the Embase, PubMed/MEDLINE and APA PsycINFO electronic databases for articles published from inception until February 2022. Published reviews, meta-analyses, randomised controlled trials and recent studies were prioritised to provide a comprehensive and up-to-date overview of research on brain stimulation in patients with bipolar disorders.

Results: The evidence base for brain stimulation as an add-on or alternative to pharmacological and psychological treatments in patients with bipolar disorders is limited but rapidly expanding. Brain stimulation treatments represent an opportunity to treat all bipolar disorder states, including cognitive dysfunction during euthymic periods.

Conclusion: Whilst findings to date have been encouraging, larger randomised controlled trials with long-term follow-up are needed to clarify important questions regarding treatment efficacy and tolerability, the frequency of treatment-emergent affective switches and effects on cognitive function.

Keywords: bipolar and related disorders; bipolar depression; bipolar disorder; deep brain stimulation; electroconvulsive therapy; magnetic seizure therapy; mania; transcranial direct current stimulation; transcranial magnetic stimulation; vagus nerve stimulation.

FIGURE 1

Overview of the main ECT electrode placements. Right unilateral electrode placement (left), bitemporal electrode placement (middle) and bifrontal electrode placement (right).

FIGURE 2

Standard repetitive transcranial magnetic stimulation (rTMS) protocols involve identical stimuli spaced by an identical inter‐stimulus interval. Effects depend on stimulation frequency: low‐frequency rTMS (LF rTMS ≤1 Hz) depresses cortical excitability, whereas high‐frequency rTMS (HF rTMS >5 Hz) increases cortical excitability. Theta burst stimulation (TBS) involves bursts of high‐frequency stimulation (3 pulses at 50 Hz) repeated with an inter‐stimulus interval of 200 ms (5 Hz). In an intermittent TBS (iTBS) protocol, bursts are delivered for 2 s, then repeated every 10 s (2 s of TBS followed by a pause of 8 s). In a continuous TBS protocol (cTBS), bursts are repeated for 40 s without any pause. Adapted from Klomjai et al. (2015). [Correction added on January 13, 2023, after first online publication: Figure 2 has been updated to correct the order of the labels "High‐frequency" and "Low‐frequency"].

FIGURE 3

Transcranial direct current stimulation (tDCS) electrode placements used in patients with bipolar disorders: (1) depressive symptoms during depressive episodes, (2) manic symptoms during manic episodes, (3) symptoms during euthymia, (4) neurocognitive functions during depressive episodes or euthymia, (5) sleep and neurological soft signs during euthymia. Blue: anode; red: cathode. Cb, cerebellum; EC, extra‐cephalic (right upper arm); F3, left dorsolateral prefrontal cortex; F4, right dorsolateral prefrontal cortex; F8, right lateral orbit cortex; Fp1, left superior orbital cortex; Fp2, right superior orbital cortex; Electrode placements from Dondé et al. (2018).