Overview of Neuromodulation For Depression: Review in the Green Journal With Section on ECT

Out on PubMed, from investigators in the Midwest and New England, is this paper:

Neuromodulation Strategies for the Treatment of Depression.

Conroy SK, Holtzheimer PE.Am J Psychiatry. 2021 Dec;178(12):1082-1088. doi: 10.1176/appi.ajp.2021.21101034.PMID: 34855452

The abstract is copied below:

For many decades, psychiatric treatment has been primarily guided by two major paradigms of psychopathology: a neurochemical paradigm leading to the development of medications and a psychological paradigm resulting in the development of psychotherapies. A third paradigm positing that psychiatric dysfunction results from abnormal communication within a network of brain regions that regulate mood, thought, and behavior has gained increased attention over the past several years and underlies the development of multiple neuromodulation and neurostimulation therapies. This neural circuit paradigm is not new. In the late 19th and early 20th centuries, it was a common way of understanding psychiatric illness and led to several of our earliest somatic therapies. However, with the rise of effective medications and evidence-based psychotherapies, this paradigm went mostly dormant. Its recent reemergence resulted from a growing recognition that medications and psychotherapy leave many patients inadequately treated, along with technological advances that have revolutionized our ability to understand and modulate the neural circuitry involved in psychiatric disorders. In this overview, the authors review the history and current state of neuromodulation for psychiatric illness and specifically focus on these approaches as a treatment for depression, as this has been the primary indication for these interventions over time.

Keywords: Depressive Disorders; ECT; Neurostimulation; Vagus Nerve Stimulation.

And from the text, the section on ECT:

In this overview, we begin with a discussion of ECT.

Although not a targeted neural circuit approach per se, ECT

was one of the first attempts to directly affect neural

function via stimulation, and subsequent efforts to optimize

ECT have frequently been conceptualized within a neural

circuit framework. We then discuss surgical approaches to

neuromodulation, which developed contemporaneously

with ECT and have been greatly refined and optimized over

time. Next, we review “noninvasive” neuromodulation

approaches, which have only become possible as a result of

technological advances over the past 20–30 years; these

interventions offer a neuromodulation strategy with fewer

side effects and risks compared with ECT and surgical procedures

and are therefore more scalable and disseminable.

We end with a discussion of potential future directions for

neuromodulation for depression and other neuropsychiatric

disorders.

ECT

In 1938, Cerletti and Bini first used therapeutic electrical

stimulation to elicit a seizure in a patient with mania; after

10 treatments, the former engineer who had been found

wandering the streets of Rome in a delusional state was able

to reunite with his wife and return to work. When he was

assessed a year later, he was still employed and married (2,

3). Since then, refinements to multiple aspects of ECT have

improved its safety and tolerability while preserving its efficacy

(4), and ECT remains the single most effective treatment

for depression (5, 6). Adding the combination of a

short-acting anesthetic and paralytic agent prior to the procedure

in the 1950s greatly reduced anxiety and virtually

eliminated the bodily injury associated with early forms of

ECT. Anesthesia regimens continue to be optimized to allow

the production of seizures of high quality and adequate

duration with minimal side effects. The electrical stimulation

itself is now delivered in a brief-pulse square wave

form, using much less energy overall while still producing

therapeutic seizures. This has greatly improved the cognitive 

side effect profile of today’s ECT compared with early forms of treatment. 

Continued refinement has led to the adoption of ultrabrief pulse stimulation, 

further reducing side effects.

Routine EEG monitoring allows precision in measuring

seizure length while also providing seizure quality

measures—in addition to increasing safety by providing

assurance that the seizure is in fact terminated after treatment.

Right unilateral, rather than bilateral, stimulation was

introduced in the 1970s. It is associated with good efficacy

and improved cognitive side effects, although further study

has shown that comparatively more suprathreshold energy

is required to achieve a therapeutic effect comparable to

bilateral stimulation (7).

Like any treatment, ECT has limitations. The relapse

rate for major depression is high—well over 50% if treatment

is stopped completely when remission is reached;

continuation and maintenance ECT, as well as various

pharmacologic regimens, are often required to maintain

improvements (8). Social stigma continues to be a barrier

to treatment for many patients. Despite great improvements

since the early forms of treatment, today’s ECT

still has cognitive side effects, particularly during the initial

treatment, although overall, meta-analyses show

return to or improvement over pretreatment baseline in

all cognitive domains (9). Autobiographical memory loss

is problematic in a subset of patients, although this is

very difficult to study or quantify. Because of the amount

of energy required to cause a generalized seizure, the

brain regions initially stimulated by ECT are relatively

nonspecific, and a generalized seizure is by definition

nonfocal. This lack of focality may represent a limitation,

particularly related to the cognitive side effect burden of

ECT. New forms of and variations on ECT attempt to

improve on this with the hope of minimizing side

effects.

Multiple forms of investigational convulsive therapies

have been developed. Focal electrically administered seizure

therapy, or FEAST, is a form of ECT developed in the early

2000s that focuses unidirectional electrical stimulation to

initiate seizure activity in the right prefrontal cortex (10). A

recent open-label trial comparing FEAST to right unilateral

ECT showed similar efficacy with decreased cognitive side

effects (11). Magnetic seizure therapy (MST) uses targeted

magnetic stimulation to induce a seizure. As in ECT, general

anesthesia is required. However, unlike electrical stimulation,

magnetic stimulation doesn’t encounter impedance

from the tissues between the stimulator and the brain, so a

more focal stimulus can be delivered. MST has been studied

in open-label (12–14) and double-blind (15) trials and

appears to have fewer cognitive side effects and faster postictal

recovery and similar efficacy to ECT. FEAST, MST,

and other variants of convulsive therapies show great promise

in their improved focality of stimulation and thus

improved side effect burden, and work is ongoing to further

optimize targeting; however, these methods are not yet

widely adopted. Many thousands of patients have benefited

from the lifesaving potential of ECT over the past 80 years,

and this treatment will remain a critical part of our repertoire

for years to come (16).

The ECT section of this review is pretty good: ECT is discussed first and quite reasonably. It is however, conspicuously absent from the final "Future Directions" section. And while ECT is considered under its own separate heading, having a separate heading for "Noninvasive Neuromodulation" makes it seems as if it is considered "invasive."

There is only passing mention that ECT treats severely ill patients; in fact, one of the shortcomings of this review is the lack of discussion of integrity of diagnosis.

Most ECT practitioners will want to read this update/review, ~15 minutes.