Call to revise the Royal Australian and New Zealand College of Psychiatrists’ clinical memorandum on deep brain stimulation for obsessive-compulsive disorder

We commend the Royal Australian and New Zealand College of Psychiatrists (RANZCP) for the July 2022 clinical memorandum on deep brain stimulation (DBS) therapy for psychiatric indications (RANZCP, 2022). However, for refractory obsessive-compulsive disorder (OCD), the memorandum (1) does not adequately report the level of scientific evidence and (2) clinical efficacy; (3) erroneously reports on the quality of previous findings and thus (4) neglects that DBS has met the criteria for an established therapy for OCD. We present a rationale for the RANZCP to review and update the clinical memorandum for OCD indications to reflect the current status of scientific evidence and clinical efficacy more accurately.

The memorandum does not identify the level of clinical efficacy

The memorandum provides ambiguous descriptions of efficacy, for example, ‘A meta-analysis . . . found a positive effect of therapy’. Where as, recent systematic reviews have reported that DBS achieved response in 51% of OCD patients compared to 18% in sham across five randomised controlled trials (RCTs), with an average symptom reduction of 47% and response rate of 66% at the last follow-up visit (up to 9 years), reflecting statistically and clinically significant improvements (Acevedo et al., 2021; Gadot et al., 2022; Mar-Barrutia et al., 2021; Martinho et al., 2020). It is necessary to highlight these statistics as it allows reference to other treatments and evaluation of efficacy in line with relevant criteria. Meaningful clinical changes are also achieved in other domains: 47% of OCD DBS patients reach full response for comorbid depression (Gadot et al., 2022), and global functioning improves by 69–92% on a group level (Chabardès et al., 2013, 2020; Farrand et al., 2018; Graat et al., 2021; Greenberg et al., 2006, 2010; Huff et al., 2010; Huys et al., 2019; Mallet et al., 2008). Furthermore, tractography-guided surgical targeting holds large potential in progressing the clinical efficacy for OCD even further, by delivering personalised targeting and reduced side-effects (Graat et al., 2022).

The memorandum inaccurately reports on the quality of previous investigations

The memorandum critiques the quality of scientific evidence by referring to a risk-of-bias assessment from our recently published systematic review (Acevedo et al., 2021). We would like to note that these data were incorrectly reported in the memorandum. The quality assessment was of OCD and Tourette’s cases and all previous investigations (including case studies), thus not OCD and depression cases as stated in the memorandum. Our quality assessment (Acevedo et al., 2021) specifically of OCD DBS trials, graded out of 11, identified the majority (79%) of such trials (excluding case studies) to be of good/high quality (8–11); a rating of 10 was given to six studies, a rating of 9 for seven studies and two studies each received a rating of 8, 7, and 6. Our quality assessment employed a strict criteria; a full score was given to an RCT only if all clinical characteristics, stimulation parameters, programming parameters, proportion of responders and follow-up outcomes were reported. Thus, the quality of published studies is predominantly high, based on strict criteria, rather than moderate as concluded in the memorandum.

The complex nature of OCD DBS patients must be considered in the evaluation of evidence

RCTs are certainly necessary to establish the efficacy of the therapy, but there are many inherent difficulties with DBS sham conditions that pose risks to efficacy, beneficence and blinding. To reach optimal benefit, it is necessary to conduct programming adjustments in a personalised manner. Optimisation of settings generally takes 6–12 months, yet some patients may require a longer duration to reach optimal settings, thereafter ongoing adjustments are often necessary (Acevedo et al., 2021). Yet, sham conditions usually involve 4 weeks of therapy at predefined stimulation parameters, thus reliable treatment effects are unlikely to be reached. Alternatively, an optimisation period prior to blinded conditions can be implemented, so stimulation parameters are refined. However, this will likely lead to unblinding. Also, withholding or ending treatment in people with severe OCD is arguably unethical, as sham phases can precipitate dramatic symptom recurrence. Thus, blinded studies are likely to lead to an underestimation of treatment effects and challenge non-beneficence. Rather than downgrading the quality of available evidence (as in the memorandum) based on inherent factors relating to sham conditions and considering sufficient RCT evidence has been reached, evidence from open-label trials should be considered. In reality, this provides evidence of robust and long-term efficacy for such real-world treatment applications.

The criteria of an established therapy has been met

The World Society for Stereotactic and Functional Neurosurgery criteria for an established therapy and the American Association of Neurological Surgeons/Congress of Neurological Surgeons criteria for level 1 evidence were met for DBS for OCD, following two independent RCTs in which DBS led to ⩾25% improvement in OCD symptoms compared to sham (Denys et al., 2010; Luyten et al., 2016). Furthermore, several systematic reviews and meta-analyses have identified response rates around 60% from open-label DBS for OCD (Acevedo et al., 2021; Alonso et al., 2015; Cruz et al., 2022; Gadot et al., 2022; Hamani et al., 2014; Mar-Barrutia et al., 2021; Vicheva et al., 2020). A further systematic review (Mar-Barrutia et al., 2021) showed that response was higher (70%) at long-term follow-up (155 patients) than at short-term follow-up (60%, 230 patients), which highlights the longevity of the treatment, and that symptom improvement cannot be due to placebo effects. First-line pharmacological interventions for OCD lead to sub-optimal outcomes; 40–60% does not reach response and thus experience significant disability, and up to 80% relapse upon discontinuation (Pallanti and Quercioli, 2006). Thus, the efficacy of DBS is comparable, or rather beyond that of pharmacological interventions for OCD. These reported outcomes have led several experts to argue that DBS is now an established therapy for refractory OCD (Acevedo and Rossell, 2022; Gadot et al., 2022; Mosley et al., 2021; Müller et al., 2022; van Wingen et al., 2022). Although the memorandum identifies DBS as a potential treatment option for refractory OCD patients, it encourages applications solely within investigational contexts (clinical trials) and classifies DBS as an emerging therapy.

Further considerations in the evaluation of evidence and efficacy and patient management

The memorandum states that more research is necessary to validate DBS as an established therapy, yet while DBS continues to be seen as investigational and is thus restricted, treatment barriers remain. As such, the therapy fulfils scientific and clinical criteria as an effective and safe therapy, yet there is a crisis in access to care due to (1) bias associated with the technique, (2) scepticism from limited cases, (3) lack of awareness in the psychiatric community, and (4) lack of insurance coverage (Visser-Vandewalle et al., 2022). Indeed, the primary reason for eligible OCD patients not undergoing DBS (in the United States) is lack of insurance (Pinckard-Dover et al., 2021). This is expected to also be the case in Australia, where there are no Medicare-funded item codes related to DBS therapy for OCD indications.

Indeed, the memorandum encourages greater access to DBS through clinical trials. Currently people with OCD in Australia can access DBS through a clinical trial or as a clinical service at one providing hospital in Melbourne. Yet, due to funding and resource restraints in both scenarios, the demand outweighs the availability of care. Therefore, without changing legislative reform, barriers to treatment access remain. An application has been submitted within the Medicare Benefit Scheme (http://www.msac.gov.au/Internet/msac/publishing.nsf/Content/1727-public). Progressions such as this are necessary to ensure equitable and necessary treatment access. The limited number of cases arguably reflects a treatment access gap, rather than a lack of efficacy.

Finally, the memorandum states that DBS ‘can occur in conjunction with psychological therapies or medications’, yet we assert that DBS should only occur in conjunction with these additional treatments. DBS is able to break the association between anxiety and obsessions, allowing the individual to engage in CBT; in turn, CBT is able to break the association between obsessions and compulsions, which augments and consolidates the effects of DBS (Denys et al., 2020; Mantione et al., 2014). Due to the chronicity, severity and disability associated with severe OCD, those undergoing DBS should be afforded a personalised multidisciplinary approach addressing symptomatic and psychosocial recovery. Adjunct psychotherapeutic models are not adequately discussed in the literature yet are critical to optimising patient outcomes. We have developed a clinical guideline for managing these patients including considerations at each stage of the care process (Acevedo et al., 2022).

In conclusion, the clinical memorandum on DBS for OCD does not capture critical evidence and misreports the quality of previous investigations. Barriers to treatment access are prominent and must be broken down to achieve greater access to care and translational progression. If treatment practices are optimised and open-label investigations and global outcomes are considered in the evaluation of efficacy, the benefits of DBS may be better elucidated.