Opioid use disorder - Emerging treatments

Ultra-rapid opioid detoxification (UROD)

A recent and controversial treatment that uses sedatives and general anaesthesia in combination with opioid antagonists in an inpatient setting to achieve detoxification in 48 to 72 hours. Serious adverse effects such as pulmonary oedema and aspiration pneumonia have been reported. Two studies have demonstrated that substantial withdrawal symptoms persist well beyond the detoxification period.[147] The expense of the procedure, lack of data from controlled trials, and safety concerns limit its use in clinical practice.[148]

Dihydrocodeine

A full opioid receptor agonist that has been used on a limited basis outside of the US as an alternative to methadone maintenance. Limited data indicate that it is equivalent to methadone in terms of treatment retention. Participants also show an improvement in some secondary outcomes measuring illicit drug use, health-related risks, and quality of life.[149] A Cochrane review found that dihydrocodeine was no more effective than buprenorphine or methadone in reducing illicit opiate use (low-quality evidence).[150] [ ] More supportive data are required before it will be considered as a potential alternative treatment for opioid use disorders.

Heroin maintenance

Some studies have looked at the controlled administration of heroin to heroin-dependent individuals who were unable to maintain abstinence on traditional forms of opioid replacement. While this is controversial, proponents suggest that when viewed in terms of overall harm reduction, there may be a small subgroup of heroin-dependent individuals who could benefit from this treatment.[151][152][153] A Cochrane review of eight studies (n=2007) found some benefit of heroin used in conjunction with flexible doses of methadone for long-term treatment-refractory heroin users.[154] The Canadian Research Initiative in Substance Misuse (CRISM) recommends injectable diacetylmorphine (the active metabolite in heroin) as an option for individuals with severe, treatment-refractory opioid use disorder and ongoing illicit injection opioid use.[155]

Electrical nerve stimulator device

The first device to reduce symptoms of opioid withdrawal has been approved by the US Food and Drug Administration (FDA). The device is a small electrical nerve stimulator placed behind the patient’s ear. It contains a battery-powered chip that emits electrical pulses to stimulate branches of certain cranial nerves that may provide relief from opioid withdrawal symptoms. Patients can use the device for up to 5 days during the acute physical withdrawal phase. The FDA approval was based on data from an open label study of 73 patients, which found that neuromodulation with percutaneous auricular nerve stimulation reduced opioid withdrawal scores by 97% (P <0.001) at end of day 5 and 88% of patients were successfully transitioned to medication-assisted therapy.[156]

Slow-release oral morphine

European clinical studies investigating slow-release oral morphine as an opioid agonist treatment have found that it has comparable efficacy to methadone and may be better tolerated in some patients.[157][158] A systematic review and meta-analysis of slow-release oral morphine clinical trials found it to be equal to methadone in retaining patients in treatment and reducing heroin use, while potentially resulting in less craving.[159] An observational study of German patients who switched from their existing opioid agonist treatment (77.2% were treated with levomethadone or methadone) to slow-release oral morphine found that slow-release oral morphine decreased heroin use and improved measures of mental health, with a retention rate of 61% at 1 year.[160] The most common adverse events included symptoms of withdrawal (e.g., craving, stomach cramps, nausea) and infections such as influenza.[160] Slow-release oral morphine is approved for opioid agonist treatment in Germany and some other European countries, but not in the US.[160]

Extended-release tramadol

Tramadol is a mild to moderate opioid agonist with low affinity for the mu, kappa, and sigma opioid receptors.[161] The extended-release formulation of tramadol is suitable for once-daily dosing.[161] In a phase 1/2 randomised controlled trial, extended-release tramadol was more effective than clonidine and comparable to buprenorphine in reducing opioid withdrawal symptoms.[161] Extended-release tramadol may therefore be useful when treating withdrawal in patients who are discontinuing opioids, or when buprenorphine is not available.[41] Further studies in larger groups of patients are warranted.

Contingency management

Contingency management is a behavioural therapy used in the treatment of drug dependence that aims to weaken drug use and strengthen abstinence.[162] Rewards such as cash, vouchers, or other privileges such as home therapy, are contingent on successfully performing a particular activity such as getting a job or providing a substance-negative urine sample.[162] A systematic review and meta-analysis investigating contingency management for patients receiving medication for opioid use disorder found that it improved abstinence, treatment attendance, and medication adherence.[163] The significant effect of contingency management on abstinence from psychomotor stimulants was particularly notable, as comorbid stimulant disorder is a growing public health concern.[163] Access to contingency management in the US is currently limited by lack of resources and lack of insurance coverage.[163]

Buprenorphine rotation

Rotation to buprenorphine from full mu-opioid receptor agonists could potentially reduce the risk of opioid use disorder in individuals on long-term opioid therapy.[164] A systematic review and meta-analysis found that buprenorphine rotation was associated with reduced pain without precipitating opioid withdrawal or other serious adverse effects (low-quality evidence).[164] Further evidence for buprenorphine rotation in primary prevention is needed, as well as studies to establish an appropriate rotation protocol.[164]