Substitution with Buprenorphine in Methadone- and Morphine Sulfate-Dependent Patients

Abstract

In France, during the 1990s, there have been some rapid developments in the treatment of opioid addiction with the introduction of legal substitution agents. Originally, some patients were treated with morphine sulfate, but this was superseded by high dose buprenorphine (Subutex^®) and methadone. This resulted in those patients originally treated with morphine being transferred to either of these two licensed products. A study investigating the effects of the transition from morphine to either buprenorphine or methadone was undertaken. Supplementary to this, a trial investigating transition between these new compounds was also conducted. The primary outcome measures for these trials were retention rate, which was assessed at 5, 9 and 12 months, and the precipitation of withdrawal symptoms. The studies showed that transferring patients between substitution agents can be accomplished without severe withdrawal symptoms, although specific management may be required for transfer from high doses of methadone to buprenorphine. High long-term retention rates were observed in the studies, with most drop-outs occurring directly after transfer. Results suggest that patients on long-term buprenorphine maintenance therapy may have good compliance in comparison with other agents.

Practical Consideration for the Clinical Use of Buprenorphine

“…For some patients, the period for transition to buprenorphine may be as little as 4 to 6 hours if they have been using short-acting opioids or as much as 24 to 96 hours for long-acting opioids (Amass, Kamien, and Mikulich, 2000Amass, Kamien, and Mikulich, 2001; Bouchez, Beauverie, and Touzeau, 1998; Johnson, Strain, and Amass, 2003; Law et al, 1997; Levin et al, 1997; Lintzeris, 2000; Lintzeris et al, 2001; Strain et al, 1995; Walsh et al, 1995). …”

“…For some patients, a dose reduction to 30 mg methadone may not be possible or may entail significant risk of relapse. Thus, for patients on higher methadone doses, increasing the time between the last long-acting opioid dose and the initial buprenorphine dose, so that objective signs of withdrawal are present and maximal tolerable withdrawal is achieved, should help avoid a buprenorphine-precipitated withdrawal (Bouchez, Beauveries, and Touzeau, 1998; Lintzeris et al, 2003). For patients on more than 60 mg methadone who are unable to decrease the dose, transfer to buprenorphine in a closely monitored inpatient setting is suggested (Lintzeris et al, 2001).…”

Major Depressive Disorder and Kappa Opioid Receptor

“…It was initially developed as a long acting analgesic for chronic pains [84] and substitution treatment for opioid addiction. [85][86][87] Due to its unique KOR antagonistic and MOR partial agonistic activities, the anti-depression potential of buprenorphine has been investigated extensively in animal models [88] and clinical trials. [86,87,89] An early open label study in patients with treatment-refractory, unipolar, nonpsychotic, major depression, suggested a possible role of buprenorphine in the treatment of refractory depression.…”

Combined Buprenorphine and Clonidine for Short-Term Opiate Detoxification

“…7 Nevertheless, clinical research over the past 10 years has established that buprenorphine is a safe and effectivealternativeto methadone. 8 Its slow dissociation from mu opioid receptors results in a long duration of action and also diminishes withdrawal signs and symptoms on discontinuation. 9 Buprenorphine may produce a level of euphoria due to its opiate effect at the mu receptor and therefore has a potential for abuse itself.…”