Depot formulations: will pharmacological advances improve treatment options and outcomes for substance abusers?

Abstract

Advances in pharmacological delivery systems are emerging in many aspects of medicine, including the development of drug combination products and longer acting agents. These newer medications can significantly ease the burden of complicated dosing schedules for individuals who take many or frequent drugs. Advances in pharmacotherapies for the treatment of addictive disorders generally parallel, but lag behind, those of more mainstream medicine. The emergence of depot formations of medications for addictions treatments is one such example. The paper by Sigmon et al. (2004) investigates the ability of a depot formulation of buprenorphine to suppress opioid withdrawal symptoms and block the effects of exogenously administered opioids. Results from this study suggest a potential for this new drug formulation to assist in detoxification. Depot buprenorphine may also provide another mechanism for buprenorphine maintenance, requiring less frequent clinic visits without the risk of medication diversion. Although clearly more research with larger sample sizes and in more externally valid situations will be required to determine the safety and efficacy of these techniques, the Sigmon et al. (2004) study provides necessary data to indicate moving forward with such trials. The question remains as to what such trials are likely to show, and how their results may impact on treatment for opioid dependence. In the case of maintenance, other medications such as methadone and LAAM show similar efficacy to buprenorphine in decreasing opioid use so long as the dose is appropriate (Johnson et al. 2000). The depot formulation of buprenorphine is likely to produce effects similar to its parent formulation with respect to decreasing opioid use during maintenance therapy, assuming that blood levels remain relatively consistent with the sublingual version. Effects on patient retention, however, may vary vastly depending upon the patient subgroups to whom the medication is administered. Relatively psychosocially stable individuals may be as or more likely to continue with and respond well to a maintenance medication that is administered as infrequently as monthly compared to one that is administered daily or 3–4 times per week (McLellan et al. 1983, 1993). However, the vast majority of opioid dependent patients do not fit into this category. The lifestyle associated with opioid dependence is characterized by disruption and chaos, yet this depot formulation may be best suited for the highest functioning opioid-dependent patients. With regard to detoxification strategies, the Sigmon et al. (2004) paper provides a nice description of carefully medically monitored opioid detoxification under placebo and buprenorphine depot conditions, allowing for the addition of rescue medication. The relatively minimal problems noted and the reductions in administration of concomitant medications to patients in the buprenorphine condition suggest the possible effectiveness of this depot detoxification strategy. However, as with maintenance treatments, the issue remains that only psychosocially stable opioid dependent patients are likely to comply and successfully refrain from opioid use during detoxification. An extensive literature spanning over 40 years suggests that relapse rates to opioid dependence will be high, regardless of the detoxification procedures used. Unfortunately it is unlikely that buprenorphine in a sublingual or depot formulation alone, or any other medication for that matter, will improve long-term abstinence rates. While medication development and advances in delivery systems may improve short-term outcomes of opioid dependent patients, strategies focusing on enhancing long-term outcomes are necessary. As noted by Sigmon et al. (2004), investigations of behavioral therapies that complement pharmacotherapy developments are needed. In mainstream medicine, compliance with medication regimens is a primary obstacle to successful outcomes, and development of new medication delivery systems may assist in this matter. In addictions treatment, compliance is likewise a critical issue. But, perhaps because of the severity of the patient population, different and radical behavioral approaches may need to be combined with pharmacotherapies to improve outcomes.