Emerging & Investigational Indications

Evidence status. Tourette DBS remains experimental despite trials, registries, and guidelines. Addiction, anorexia nervosa, and other emerging indications should be confined to rigorous research or exceptional institutionally governed pathways.

1.Indication and selection

Tourette syndrome is the most mature emerging indication. Most patients improve through adolescence, and first-line treatment is behavioral therapy (comprehensive behavioral intervention for tics) and pharmacotherapy; DBS is reserved for the rare patient with severe, chronic, genuinely refractory tics causing substantial impairment or medical danger (e.g., self-injurious or "malignant" tics), persisting despite adequate trials. The American Academy of Neurology guideline allows DBS consideration in adults with severe, treatment-resistant tics and disabling impairment after careful counseling, while the European clinical guidelines (version 2.0) emphasize candidacy confirmed by a multidisciplinary team, refractoriness documented over a sustained period, and management of the frequent comorbidities (OCD, ADHD). Notably, the European guideline no longer applies the earlier expert-proposed minimum age of 25: patients should generally be older than 18, younger patients may be considered in severe cases, and ethics committee involvement is recommended when operating on a minor.

2.Targets and evidence

Several targets are in use, reflecting the sensorimotor-limbic basal ganglia loops rather than the orbitofrontal OCD loop: the centromedian-parafascicular (CM-Pf) and CM-Voi thalamus, and the globus pallidus internus (GPi) in both its posteroventrolateral (sensorimotor) and anteromedial (limbic) portions; the ALIC/nucleus accumbens has also been used, particularly with prominent OCD comorbidity. The evidence base now includes the International Tourette Syndrome DBS Registry and Database, eight randomized controlled trials, and two meta-analyses, synthesized in the European guideline; the multisite registry analysis by Johnson and colleagues collected retrospective clinical and imaging data from 123 patients at 13 sites, reported a mean YGTSS total improvement of about 47% at last follow-up (median 13 months to reach 40% tic improvement, with no significant difference across targets), and linked stimulation location to outcome. The public database and registry report by Martinez-Ramirez and colleagues (31 institutions in 10 countries) found the mean YGTSS total score falling from about 75 to 41 at one year, with adverse events in roughly one-third of patients, including intracranial hemorrhage in 1.3%, infection in 3.2%, and stimulation-related dysarthria and paresthesia. Tic improvement is generally meaningful but variable across targets, adverse events include both stimulation-related effects and surgery/hardware complications, and interpretation is limited by small samples and conflicting randomized data; the guideline therefore continues to describe Tourette DBS as experimental and recommends highly selected use.

3.Targeting the reward circuit

Substance use disorders are conceptualized as disorders of reward, motivation, and impulse control, which makes the nucleus accumbens, the ventral striatal reward hub also used in OCD and depression, the natural target. Small case series and pilot trials of NAc DBS (in alcohol and opioid use disorder, among others) have reported reductions in craving and use in some patients, and limited controlled data now exist: a double-blind, sham-controlled multicenter trial in treatment-resistant alcohol use disorder (Bach) randomized 12 patients and did not meet its primary endpoint of continuous abstinence at 6 months, although secondary measures of abstinent days and craving favored early stimulation. In opioid use disorder, a US open-label safety and feasibility study (Rezai) implanted only a handful of participants. A 2024 systematic review of 26 studies and 71 patients (only one RCT) found that 26.8% remained abstinent through follow-up and 73.2% had full or partial relapse. The evidence remains preliminary: cohorts are small and heterogeneous, relapse is intrinsic to the disorder, and the field has not established efficacy. Addiction DBS is appropriately confined to investigational protocols with intensive addiction-medicine co-management.

4.A high-stakes, early indication

Anorexia nervosa carries one of the highest mortality rates in psychiatry, and a subset is severe and enduring despite full treatment, motivating exploration of DBS. Two target rationales are pursued: the subcallosal cingulate, addressing the mood and anxiety dysregulation that often drives the illness, and the nucleus accumbens, addressing reward and compulsivity. The most cited evidence is Lipsman and colleagues' open-label SCC trial in 16 women, whose 1-year follow-up found the procedure feasible in this medically fragile population, with mean BMI rising from 13.83 to 17.34 at 12 months alongside improvements in mood and anxiety. Adverse events were not trivial: prolonged postoperative pain, a hardware infection requiring removal and reimplantation, and a late seizure were reported, and two patients requested device removal; without a control group, these changes cannot establish a DBS-specific treatment effect. The work is early and small, conducted in a population with severe medical instability and complex capacity considerations, and is among the most ethically scrutinized applications of psychiatric DBS.

5.Earlier-stage exploration and shared caveats

Still earlier-stage applications (aggression/self-injury in severe intellectual disability, bipolar depression, schizophrenia, and post-traumatic stress disorder) have been reported in case material but lack the cohort size to support conclusions. Across the entire frontier, the same constraints apply: the vulnerability of the population, the difficulty of blinded sham-controlled trials, the imperative of prospective registries to pool rare-procedure data, and adherence to the multi-society ethical framework discussed on the selection and program page. The history on the foundations and circuits page is the reason this caution is not optional: enthusiasm outrunning evidence is precisely how the field harmed patients before.

6.Ablative and incisionless variants

Each of these indications also has a lesion-based history. In substance addiction, the dominant experience was stereotactic nucleus accumbens ablation in China, reported in roughly 1,000 patients by 2004, largely outside regulated trial frameworks and with memory, motivational, and personality changes reported; in November 2004 the Chinese Ministry of Health halted the procedure as a routine medical service, permitting further work only as supervised clinical research. Anterior capsulotomy has also been applied to addiction in small series and remains ethically contested; reviews suggest short-term improvement but high long-term relapse and neuropsychological trade-offs. In Tourette syndrome and anorexia nervosa, contemporary work is overwhelmingly neuromodulatory; lesion reports (for example, capsulotomy or accumbens ablation for anorexia, mostly from China) are small and uncontrolled. Incisionless capsulotomy by Gamma Knife or MR-guided focused ultrasound is, in principle, applicable wherever a capsulotomy is, but evidence in these emerging indications is minimal and its use should be confined to formal protocols with the same governance these conditions otherwise demand.