Stellate ganglion block for mental disorders – too good to be true?

1 The stellate ganglion anatomy

Figure 1 illustrates the topical and cross-sectional anatomy at the C6 level. The stellate ganglion forms as a result of the fusion of the inferior cervical and first thoracic sympathetic ganglia [4], a configuration observed in approximately 80% of the population. In the remaining 20%, these two ganglia remain unfused, with the inferior cervical ganglion designated as the stellate ganglion [5]. The stellate ganglion communicates with the spinal nerves (C7–T1) by the white (preganglionic fibers) and the gray communicating branches (postganglionic fibers). The stellate ganglion conveys sympathetic fibers either directly by the spinal nerves (C7–T1 [upper limb, neck, upper thoracic wall]) and the thoracic, cardiac visceral nerves (heart, lungs) or indirectly by postganglionic fibers in the outer walls of the arteries (e.g., perivascular plexuses). The visceral branches include the inferior cardiac nerve, contributing to the thoracic cardiac plexus [4]. Additionally, the ganglion sends sympathetic nerve branches to the brachial plexus, innervating the subclavian, carotid, and vertebral arteries.

Figure 1

Panel (a) illustrates surface anatomy for stellate ganglion nerve block by the classic approach. The cricoid cartilage is palpated, and the vascular bundle is displaced laterally. The needle tip is inserted in a plane perpendicular to the insertion point on the skin. Panel (b) illustrates the cross-section at the level of C6, showing the classic approach on the right side of the neck and the ultrasound-guided approach on the left. Note that the needle track is lateral to the vascular bundle and under the major vessels using an in-plane approach under ultrasound guidance. Proximity to various nerves, vessels, thyroid tissue, and esophagus can be appreciated in a cross-sectional view (with permission from the BMJ Publishing Group Ltd., Licensed Content Publication Regional Anesthesia & Pain Medicine, figure from article: Goel V, Patwardhan AM, Ibrahim M, Howe CL, Schultz DM, Shankar H. Complications associated with stellate ganglion nerve block: a systematic review. Reg Anesth Pain Med. 2019. Epub 2019/04/18. doi:0.1136/rapm-2018-100127. PubMed PMID: 30992414; PubMed Central PMCID: PMCPMC9034660) [15].

2 The SGB

The SGB has traditionally been used by anesthesiologists for a variety of pain conditions affecting the head, neck, and upper limbs [6,7]. The technical performance of SGB is described in detail elsewhere [5,8]. While originally guided by anatomical landmarks, modern techniques rely on ultrasound or fluoroscopy for enhanced safety and precision [5]. Over the past two decades, interest in SGB for non-pain indications has grown. These include posttraumatic stress disorder (PTSD), bipolar disorders, depression, menopausal hot flashes, lymphedema, sudden sensorineural hearing loss, anosmia, long-COVID, chronic fatigue syndrome, and ventricular tachyarrhythmias [5,9,10,11,12,13,14].

3 The SGB: Complications

The use of image-guided approaches has significantly reduced procedural risks, underscoring the importance of practitioner expertise. Severe complications from SGBs are rare but not entirely absent [5,8,15]. A comprehensive systematic review detailing complications following SGB, and including 67 studies, has recently been published [15]. Since the tissues investing the stellate ganglion are heavily vascularized, intraprocedural bleeding with hematoma formation is a well-described complication. Accidental pleural puncture may potentially lead to a pneumothorax, and inadvertent epidural, intrathecal, or intra-arterial administration of a local anesthetic may precipitate respiratory arrest or local anesthetic system toxicity with generalized convulsions. Notably, Kirkpatrick and coauthors [5] reported in their literature review five cases of delayed retropharyngeal and cervicomediastinal hematoma leading to airway compression requiring tracheostomy, resulting in either prolonged hospitalization or death (n = 1). However, the incidence of serious adverse events presently is unknown, although a 30-year-old questionnaire-based study indicates an incidence of 0.17% [16]. These data may be prone to reporting bias and were also collected before the mitigating imaging techniques were implemented. The systematic review [15] concludes that SGB is a relatively safe procedure provided that standard monitors for conscious sedation are used and access to resuscitation equipment is available.

4 The SGB for mental disorders

In the article by Niraj and coauthors [1], a cohort is presented with treatment-refractory disparate mental health disorders treated with SGB. The patients were evaluated by a multidisciplinary team, including a psychiatrist, a clinical psychologist, and a pain medicine physician. Validated outcome measures were assessed at baseline and at 4, 12, and 16 weeks post-intervention. The 16-week follow-up was longer than most published case series and exceeded the duration of the two published RCTs [5,17] evaluating SGB for psychiatric disorders. Only one of the trials showed a positive outcome. Although promising, the present case series’ limitations are acknowledged by the authors.

The use of SGB for mental health problems is not novel. The first reported use of SGB for psychiatric disorders dates back to 1947 for depression [9], with PTSD applications first described in a 1990 case report [10]. Evidence remains mixed; while some patients show symptom improvements, others do not.

In their “evidence-based approach” to the treatment of PTSD, Bajor and coauthors [18] did not include SGB in their core PTSD treatment algorithm, though they addressed it as a potential adjunctive therapy. Conversely, Springer and coauthors [19] argue that SGB is supported by level 1B evidence for PTSD and advocate for its responsible integration into clinical practice.

5 U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) status and off-label use

It is essential to state that SGB is not approved by the FDA or EMA for PTSD, though off-label use may be considered in refractory cases. Clinicians must weigh the limited but promising evidence against the need for more robust data.

6 The SGB: neurobiological mechanisms in PTSD

PTSD is characterized by intrusive memories, heightened arousal, and memory deficits. Peripheral nerve blocks such as SGB are gaining traction as adjunctive treatments. Many of the targeted conditions, including PTSD, chronic fatigue syndrome, and long COVID, share a pathophysiological thread of sympathetic overactivity. Elevated levels of nerve growth factor (NGF) trigger sympathetic sprouting and increase systemic norepinephrine (NE) levels. SGB is thought to reverse this cascade by reducing NGF and NE levels through sympathetic blockade [5]. NGF may also act as a link between genetic and environmental influences on the sympathetic system, with trauma-induced DNA methylation contributing to increased brain-derived neurotrophic factor expression [20]. Additional mechanisms include modulation of the hypothalamic-pituitary-adrenal axis and dampening of hyperactive sympathetic circuits implicated in fear and stress responses [8,21]. Lipov and coauthors [22] further postulate an immune-modulatory role of SGB via central reflex pathways. Thus, while the exact mechanisms remain under investigation, multiple lines of evidence support the neurobiological plausibility of SGB for PTSD.

7 Broader psychiatric and medical context

Psychiatric disorders affect over 1 billion people globally – roughly 16% of the population [23]. Despite advances in medicine, psychiatry continues to face challenges in delivering effective and tolerable treatments, with up to 60% of patients experiencing treatment refractoriness [24]. This reflects the complex nature of psychiatric diagnoses, which rely largely on clinical evaluation using DSM-5-TR criteria without the use of biomarkers for efficient diagnostic subgrouping [25].

Given this background, novel approaches like SGB merit exploration, particularly when supported by plausible neurobiological mechanisms. However, their use in esoteric or poorly understood conditions should be guided by rigorous research. History warns against prematurely embracing treatments as panaceas without sufficient evidence. The essential question remains whether a unifying mechanism, such as dysregulated autonomic function, can be identified across these diverse disorders, thereby justifying SGB as a valid adjunctive treatment.

Lynch [26] emphasize that SGBs are likely most effective when used as adjuncts to existing therapies. Other emerging psychiatric treatments – such as transcranial magnetic stimulation, deep brain stimulation, ketamine, psychedelic-facilitated therapy, and eye movement desensitization and reprocessing – should similarly be studied in large, well-controlled trials. The place of SGB in these evolving treatment algorithms is not yet established.

8 Nonspecific effects of interventional procedures

The efficacy of interventional procedures in the management of chronic neuropathic pain is limited, being associated with no more than 40–60% of patients obtaining lasting, although often partial, pain relief [27]. Not unexpectedly, there is a lack of conclusive studies, whether it is injection therapies, neurostimulation, or intrathecal drug therapies in chronic pain [28]. Interestingly, a substantial proportion of the beneficial therapeutic outcomes can be attributed to various nonspecific effects often included in the placebo response,^[1] i.e., the natural disease course, regression to the mean, the Hawthorne effect, cognitive dissonance reduction, conditioning effect, response bias, and, not the least, the placebo effect, i.e., expectation effect. These aspects should also be considered when evaluating SGB procedures for non-pain disorders.

9 Specific effects of interventional procedures

Control groups are inherent to pharmacological RCTs, either as a placebo group or a group including a head-to-head comparison with a gold standard reference drug. The use of a placebo in interventional procedures, e.g., a sham GSB with saline, poses an ethical problem since exposing a vulnerable patient to risks without, or at least with, less benefit may cause additional distress [28]. Difficulties with blinding the patient, the anesthesiologist performing the block, and the observer are evident drawbacks for many blocks (see below) [28]. Presenting information about an invasive placebo sham procedure may, however, challenge the recruitment of an adequate number of patients, although the ratio of the number of individuals receiving sham block vs. active block could be changed to 1:2 or 1:4 (however, affecting the sample size estimate).

Regarding other interventional procedures, a recent systematic review and meta-analysis of the use of placebo and non-operative control groups in 100 large surgical RCTs (n = 10,800) indicated that the change in health outcomes after surgery was composed largely of nonspecific effects, with no evidence supporting a large placebo effect [29]. The authors concluded: “ … the lack of a large placebo effect in surgery means that the use of ineffective surgical interventions for a placebo effect cannot be justified.” Extrapolating these findings from surgical studies to GSB studies, sham procedures would seem unnecessary, although saline injections were administered at an inert site in the sham groups in the two RCTs [2,3].

10 Future trial designs

High-quality, double-blinded RCTs with larger sample sizes are essential. However, such studies face challenges, particularly the transient development of ipsilateral Horner’s syndrome, which can unblind participants and observers. Patients with a successful GSB will experience Horner’s syndrome (miosis, ptosis, and conjunctival injection) with varying degrees of subjective symptoms. Nearly one-third of patients experience procedure-related or local side effects, and more than two-thirds will experience systemic or medication-related side effects. The SGB procedure often requires conscious sedation due to the discomfort regarding the site of the block (neck) and its invasiveness (needle puncture). While Horner’s syndrome usually resolves within 2–6 h, it can persist for up to 48 h [30,31], and outcome assessment should be performed beyond this window. Alternatively, pulsed radiofrequency ablation of the stellate ganglion may avoid Horner’s syndrome and preserve blinding.

Whether to perform unilateral or bilateral blocks also remains unclear. Mulvaney and coauthors [32] reported that 4.4% of patients who are unresponsive to right-sided SGB showed significant benefit from left-sided SGB. Additionally, as SGB is often used adjunctively, future studies should distinguish between its standalone effects and those arising from combined treatment approaches [33]. Long-term follow-up is necessary to determine the duration of therapeutic benefit.

Parallel basic science research should aim to elucidate the mechanisms underlying SGB’s effects in psychiatric disorders to optimize patient selection and therapeutic protocols.

11 Conclusion

SGB holds promise as an adjunctive treatment for certain mental health disorders. When paired with psychotherapy, it is feasible and generally well-tolerated. SGB is associated with low complication rates and may offer a cost-effective alternative to some conventional therapies. Level 1B evidence supports its use in PTSD, though definitive guidelines have yet to be established. Rather than viewing SGB as a standalone solution, it should be integrated into multidisciplinary care frameworks and rigorously studied through high-quality prospective research.