Making Sense of Neuromodulation in Psychiatry

In psychiatry, the field is recognizing the limitations of psychiatric medications and targeting of neurotransmitters. There is an expansion from the neurotransmitter focus into a circuit based understanding of both psychiatric and neurologic disorders.   This is (in my humble opinion) a truly an exciting time in psychiatry.

Neuromodulation is one approach that targets network level dysfunction, at both the circuit and neurotransmitter level, but primarily impacts circuits in the brain.   Depression, for example, is associated with dysregulated prefrontal limbic circuits in the brain where as OCD is associated with overactive cortico-striatal-thalamic loops.  What neuromodulation really does is change how the brain regions talk with each other.  And the interesting thing is, once circuits are changed, it causes a downstream effect and then impacts the brain’s chemistry via neurotransmitters. 

When psychiatric medications don’t work for people, neuromodulation often does. That’s because neuromodulation positively impacts network plasticity (the brain’s ability to change and grow).  It also decreases rumination common in psychiatric conditions by lowering the “noise” or overwhelm/chatter in the brain that isn’t relevant.  Neuromodulation can also help the brain be more adaptable and less stuck by helping brain regions become more in sync with each other. Another benefit of neuromodulation is that, like medication, it synergizes with psychotherapy.  

Neuromodulation reframes psychiatric treatment as the targeted modulation of brain networks through the delivery of energy or biologic signals: electrical, magnetic, optical, acoustic, or pharmacologic.  Energy is the currency.  In this sense, what is often dismissed as “energy-based” intervention is not fringe, but already embedded within standard psychiatric care.  Neuromodulation is arguably more rigorously defined and technologically precise compared to other energy-based interventions. 

We can organize neuromodulation approaches across three dimensions:

1. Delivery method Electrical, magnetic, optical, acoustic, or pharmacologic

2. Mode of access Invasive vs non-invasive (Non-invasive defined as requiring no surgery or implanted hardware)

3. Level of clinical evidence Established vs emerging/experimental

Breakdown of Neuromodulation Treatments

Transcranial magnetic stimulation (TMS)

Classification: Magnetic | Non-invasive | Established

TMS is a non-invasive treatment that uses magnetic pulses to stimulate specific regions of the brain, most commonly the dorsolateral prefrontal cortex. Rather than broadly altering brain chemistry, TMS works by repeatedly activating underactive circuits and strengthening top-down regulation of mood and cognition. Over time, this improves the brain’s signal-to-noise ratio.  This makes it easier for adaptive patterns of thinking and emotional regulation to take hold. 

Clinically: TMS is used for treatment-resistant depression and, increasingly, OCD and other conditions. It is well tolerated and scalable, though it requires frequent sessions over several weeks and does not work for everyone. It is covered by insurance for treatment resistant depression and increasingly, for OCD.  Emerging studies are finding possible benefit for migraines, long COVID, and neurodegenerative diseases.  

Electroconvulsive Therapy (ECT)

Classification: Electrical | Non-invasive | Established

ECT is a non-invasive treatment that uses a controlled electrical stimulus to induce a brief therapeutic seizure under anesthesia. Rather than targeting a single brain region, ECT produces a global reset of brain network activity, rapidly reorganizing dysfunctional circuits and restoring synchrony across systems involved in mood, cognition, and behavior. This leads to significant improvements in signal-to-noise ratio and can quickly interrupt severe patterns of depression or psychosis.

Clinically: ECT is used for severe depression, psychotic depression, catatonia, and acute suicidality. It is actually the most effective treatment in psychiatry, particularly when a rapid response is needed. However, it requires anesthesia and coordination with a medical team, and can cause cognitive side effects, particularly around memory. It is covered by insurance and widely available in hospital-based settings.

Ketamine/Esketamine

Classification: Pharmacologic | Non-invasive | Established (esketamine FDA-approved; ketamine off-label)

Ketamine and Esketamine are pharmacologic treatments that act as rapid-acting neuromodulators through effects on glutamate signaling and downstream neuroplasticity. Rather than gradually shifting neurotransmitter levels, they transiently destabilize rigid brain networks, increasing flexibility and allowing new patterns of thought and emotional processing to emerge. This can reduce rumination and “stuckness” as well as improve the brain’s ability to shift out of maladaptive states.

Clinically: These treatments are used for treatment-resistant depression and suicidality, with ketamine offering flexibility in delivery (IV or IM) and esketamine offering an FDA-approved, insurance-covered option through a structured monitoring program. Effects can be rapid, often within hours to days. Limitations include variability in access, cost (especially for ketamine), and the need for monitored administration. Increasingly, ketamine is being paired with psychotherapy (KAP) to enhance and sustain benefits.

Vagus Nerve Stimulation (VNS)

Classification: Electrical | Invasive | Established

Vagus nerve stimulation is an invasive treatment that involves surgical implantation of a device that delivers intermittent electrical stimulation to the vagus nerve. Rather than directly stimulating cortical regions, VNS works through bottom up modulation of brainstem pathways that influence widespread brain networks involved in mood, arousal, and autonomic regulation. Over time, this can lead to gradual improvements in network stability and emotional regulation.

Clinically: VNS is FDA-approved for treatment-resistant depression but is used pretty infrequently due to its invasive nature and delayed onset of effect, which can take several months. It may be particularly helpful for patients with chronic, refractory illness who have not responded to other treatments. Insurance coverage is variable, and access is typically limited to specialized centers.

Transcutaneous Vagus Nerve Stimulation

Electrical / acoustic | Non-invasive | Emerging

Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive approach that stimulates the vagus nerve through the skin, typically at the ear or neck. While it operates on the same general pathway as implantable VNS, it delivers lower-intensity, intermittent stimulation and is still considered an emerging treatment. Early research suggests potential benefits for anxiety, stress regulation, and autonomic dysfunction, though its clinical effects are more modest and less well established than implantable VNS.

As non-invasive neuromodulation devices become more widely available, clinicians and patients are increasingly faced with how to think about their role in care. There are various devices on the market that have varying amounts of data behind them - and they tend to be heavily marketed. These include vagus nerve stimulators (Truvaga, gammaCore), cranial electrotherapy devices (Alpha Stim), and wearable neuromodulation tools (Apollo Neuro).

Clinically: While the evidence base for many of these technologies remains emerging, they are generally low risk and may offer benefit for symptoms such as anxiety, sleep disturbance, and autonomic dysregulation. In cases where traditional treatments have been ineffective or poorly tolerated, it is reasonable to consider these approaches as adjunctive tools.  It's important that psychiatric clinicians set expectations and engage with patients in a risk/benefit conversation about these devices.  

Deep Brain Stimulation (DBS)

​​Classification: Electrical | Invasive | Established (OCD) / Emerging (depression)

Deep brain stimulation is an invasive treatment that involves surgical implantation of electrodes into specific brain regions, allowing for precise, continuous modulation of targeted circuits. Unlike non-invasive approaches, DBS directly alters activity within key nodes of dysfunctional networks, allowing for more precise control over circuit dynamics. This can improve signal clarity and reduce pathological patterns of activity in conditions characterized by rigid or overactive loops.

Clinically: DBS is FDA-approved for obsessive-compulsive disorder and is being studied for treatment resistant depression. It is typically reserved for severe, refractory cases due to its surgical risks and complexity. Access is limited to specialized centers with neurosurgical expertise, but for carefully selected patients, it offers a highly targeted and potentially transformative intervention.  

Transcranial Direct Current Stimulation (tDCS)

Classification: Electrical | Non-invasive | Emerging

Transcranial direct current stimulation  is a non-invasive treatment that delivers low-intensity electrical current through electrodes placed on the scalp. Rather than directly triggering neuronal firing, tDCS subtly shifts the excitability of underlying brain regions, making it easier or harder for neurons to activate. This can gently modulate circuit activity and support changes in signal-to-noise ratio over time.

Clinically: tDCS is being studied for depression and cognitive enhancement, with some evidence of benefit in mild to moderate cases. It is portable and relatively low cost, with potential for at-home use which we don't really see with other neurmodulation modalities. However, its effects are generally more modest than TMS, and it is not currently considered a standard treatment in psychiatry at this point.  

Photobiomodulation (aka a fancy word for light therapy)

Classification: Optical | Non-invasive | Emerging

Photobiomodulation is a non-invasive, emerging treatment that uses near-infrared or red light to influence brain function at a cellular level. By enhancing mitochondrial activity and increasing energy availability within neurons, it supports more efficient neural signaling and may improve overall network function. Rather than directly stimulating circuits, it works by optimizing the metabolic conditions that allow circuits to function more effectively.  People typically wear a helmet or have targeted panels they are in close proximity to. 

Clinically: Research suggests potential benefits for depression, long COVID, cognitive impairment, and traumatic brain injury. It is well tolerated and really low risk, but remains experimental and is not yet considered part of standard psychiatric care.