Proposals to trial deep brain stimulation to treat addiction are premature

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Proposals to trial deep brain stimulation to treat addiction are premature because it is an expensive and invasive procedure that carries substantial risks, there is a poor scientific rationale for its use and the evidence for its safety and efficacy is confined to uncontrolled case studies in highly selected patients.

Deep brain stimulation (DBS) is a neurosurgical intervention that has been used to treat intractable cases of Parkinson's disease (PD). DBS involves inserting microelectrodes into specific brain regions to modulate neural activity via a battery-controlled external stimulator in the patient's chest. DBS is being trialled in intractable psychiatric conditions, including Tourette's syndrome, obsessive–compulsive disorder (OCD) and depression [1]. Drug addiction has been proposed recently as another disorder in which to trial DBS [2]. We believe that this proposal is premature.

MINIMAL ETHICAL REQUIREMENTS FOR A TRIAL OF DBS IN ADDICTION

DBS is often advocated as a ‘reversible’ alternative to neurosurgery. It is none the less an invasive intervention that has significant risks: 11% of patients have adverse events from surgery and 4% of PD patients suffer intracerebral haemorrhages [3]. Insertion of stimulating electrodes can cause serious infections and produce cognitive, behavioural and emotional disturbances [3]. Given these risks, the following minimum requirements should be met before DBS is trialled to treat addiction.

First, there needs to be strong evidence that any participants in such trials have a severely debilitating form of addiction that carries a high risk of morbidity or premature mortality that has not responded to adequate trials of effective treatment.

Secondly, there needs to be a reasonable expectation that the intervention will improve the patients' quality of life. This should include: pre-clinical evidence of likely benefit; evidence on the long-term effects of DBS on patients with other psychiatric conditions (e.g. OCD and depression); and a good theoretical basis for stimulating the targeted brain region to reduce addictive behaviour.

These conditions cannot yet be satisfied.

EVIDENCE ON THE EFFECTS OF DBS ON ADDICTION

In rats, stimulation of various regions in the dopaminergic reward pathway reduce self-administration of addictive drugs (e.g. [4]). Evidence on the effects of DBS in humans consists of case studies of its effects on addictive behaviour in patients treated for other disorders. For example, two PD patients were treated successfully with DBS for dopamine dysregulation syndrome (DDS) [5], an addictive use of their dopamine medication. However, a later study reported that 12 of 17 such patients were unimproved or worse after DBS [6].

DBS has also been reported as treating successfully seven Parkinson's disease patients who developed problem gambling or hypersexuality while on dopamine replacement therapy (DRT) [7]. However, DBS has also been reported to induce addictive behaviour when applied in brain regions suggested as targets for DBS in addiction (e.g. [8]).

Some advocates of trialling DBS to treat addiction appeal to the ‘positive’ reports of neurosurgical treatment of addiction that involve ablating the anterior cingulate (e.g. [9]) and nucleus accumbens (NAc) (e.g. [10]). While these procedures were reported to reduce drug use in some patients in the short term, the follow-up was too short to evaluate their long-term safety and effectiveness [11].

There have been five reports of the use of DBS to treat addiction to nicotine, alcohol and heroin [12–16]. In the first, a woman was treated unsuccessfully for agoraphobia by bilateral DBS of the NAc but her comorbid alcohol dependence was ameliorated [14]. The same group reported smoking cessation in three of 10 patients who underwent DBS of the NAc for Tourette's syndrome, OCD or anxiety [13]. A 47-year-old woman treated with DBS of the NAc for treatment-refractory OCD quit smoking and lost weight post-surgery [16]. However, these changes emerged 10 months after her OCD symptoms disappeared, suggesting that this may have been an indirect effect of successful treatment of her OCD.

There has only been one report of the effects of DBS used to treat addiction. Craving for alcohol and alcohol consumption were greatly reduced in three long-term, treatment-refractory alcohol-dependent individuals who underwent DBS of the NAc [12]; two were abstinent after 1 year and a third had markedly reduced their drinking [15].

This is a weak evidence base to assess the long-term safety and efficacy of DBS in addiction [17]. The history of neurosurgical treatment in psychiatry warns against acceptance of early ‘positive results’ in uncontrolled, possibly selectively reported clinical cases [17]. We support proposals for a registry of all trials of DBS in individual patients to minimize the selective publication of positive outcomes [18].

SHOULD WE TRIAL DBS TREATMENT OF ADDICTION?

A reasonable case has been made for using DBS in treatment-resistant PD patients who face an irreversible deterioration of structure and function, but the course of addiction differs in important ways from that of PD.

Addiction is not a disorder that involves an inexorable path to severe disability and death and is more amenable to pharmacological and psychotherapeutic treatment [19]. A major impediment to effective addiction treatment is often lack of access to effective treatment. Stigmatization also discourages addicted individuals from seeking treatment, and punitively operated programmes often undermine its effectiveness. The addition of an expensive neurosurgical treatment that costs of the order of US$50 000 (with maintenance costs of approximately US$10 000 every few years) will worsen this situation by utilizing scarce health resources to treat a very small number of patients with the income to pay for it. The case for trialling DBS to treat addiction is therefore nowhere near as compelling as in PD.

CONCLUSIONS

DBS has been advocated prematurely for trial as a treatment of addiction on the basis of limited animal models, isolated and selected case studies and the evidence from uncontrolled studies of neurosurgical treatment of opioid addiction. These proposals raise major ethical issues. We believe that this is a poor evidence base to support trials of DBS in addiction. We have discussed elsewhere the type of research in animals and individuals that may make a case for limited trials in the future [17], but we believe that the opportunity costs of providing DBS, even if it proved to be safe and effective, make such trials a low priority for public funding.

Declaration of interests

None.

Acknowledgements

This manuscript was prepared with financial assistance from a National Health and Medical Research Council Australia (NHMRC) Fellowship (grant no. 3020774) awarded to Professor Hall and a NHMRC Postdoctoral Fellowship (grant no. 628935) awarded to Dr Carter.

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