Use of a long-acting substitute in detoxification from benzodiazepines: safety (accumulation) problems and proposed mitigation procedure

OBJECTIVE: In the majority of approaches, detoxification of patients with benzodiazepine (BZD) addiction is preceded by conversion to long-acting BZDs. Resulting BZD accumulation, however, is neither monitored nor prevented. An unrecognized shift of the key low-concentration phase beyond the nominal treatment period may underlie delayed unassisted crises and treatment failures. This open, single-arm, semi-naturalistic study examines the anti-accumulation paradigm to minimize the high-concentration treatment phase and to regain time for medical assistance during the low-concentration phase. METHODS: In 133 of 165 patients with BZD dependency, after conversion to diazepam by titration up to the satiation state, the loading dose and satiating concentration were recorded. The subsequent anti-accumulation procedure consisted of aggressive daily dose reductions under laboratory feedback (serum BZD concentration, radioimmunoassay) until accumulation stopped. The final overaccumulation ratio (OA) and maintenance-dose/loading-dose ratio (MTN) were estimated. The post-conversion peak-concentration/loading-dose ratio was illustratively compared with the concentration/dose ratio in 32 long-term diazepam users demonstrating the natural plateau. RESULTS: Despite gender- and age-related differences in loading and maintenance doses and in satiating and peak concentrations (higher in younger and male patients), their quotients remained similar. The MTN ratio had an average value of 0.29 and a median value of 0.25, with OA ratios of 1.54 and 1.39, respectively. The concentration/dose ratio was approximately 3 times lower than that in regular diazepam users. With effective elimination starting (on average) from the 6th day, the treatment, including post-elimination recovery, lasted on average 52 days. CONCLUSIONS: The MTN values show how harmfully popular tapering schedules intensify and extend the high-concentration stage during alleged detoxification, leading to unrecognized delays in elimination, and delayed withdrawal crises. The common errors are discussed. An individual MTN, estimated from laboratory feedback (the anti-accumulation paradigm), expeditiously moves patients to the onset of actual detoxification. This action regains time to maintain medical assistance until treatment is properly completed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00228-022-03388-x.