Psychoactive medications and disengagement from office based opioid treatment (obot) with buprenorphine

Highlights

• Psychoactive medication use is common among patients on buprenorphine treatment.

• Psychoactive medications overall were not associated with 6-month disengagement.

• Gabapentin, clonidine, and promethazine were not associated with 6-month disengagement.

Abstract

Background

The prevalence of psychoactive medications (PAMs) use in patients enrolled in Office Based Opioid Treatment (OBOT) and its association with engagement in this care is largely unknown.

Objective

To describe the use of PAMs, including those medications with emerging evidence of misuse (“emerging PAMs” – gabapentin, clonidine and promethazine) among patients on buprenorphine, and its association with disengagement from OBOT.

Methods

This is a retrospective cohort study of adults on buprenorphine from January 2002 to February 2014. The association between use of PAMs and 6-month disengagement from OBOT was examined using multivariable logistic regression models. A secondary analysis exploring time-to-disengagement was conducted using Cox regression models.

Results

At OBOT entry, 43% of patients (562/1308) were prescribed any PAM; including 17% (223/1308) on an emerging PAM. In separate adjusted analyses, neither the presence of any PAM (adjusted odds ratio [AOR] 1.07, 95% CI [0.78, 1.46]) nor an emerging PAM (AOR 1.28 [0.95, 1.74]) was significantly associated with 6-month disengagement. The results were similar for the Cox model (any PAM (adjusted hazard ratio [AHR] 1.16, 95% CI [1.00, 1.36]), emerging PAM (AHR 1.18 [0.98, 1.41])). Exploratory analyses suggested gabapentin (AHR 1.30 [1.05–1.62]) and clonidine (AHR 1.33 [1.01–1.73]) specifically, may be associated with an overall shorter time to disengagement.

Conclusions

Psychoactive medication use is common among patients in buprenorphine treatment. No significant association was found between the presence of any psychoactive medications, including medications with emerging evidence of misuse, and 6-month disengagement from buprenorphine treatment.

Introduction

Opioid use disorder (OUD) can be effectively treated with buprenorphine in an integrated primary care setting (Alford et al., 2011, Burns et al., 2015, Kraus et al., 2011, Padwa et al., 2012, Samet et al., 2001, Walley et al., 2012) and efforts to increase integrated addiction and primary care practices are currently underway (LaBelle et al., 2016, Ober et al., 2015, Rutkowski et al., 2012, Tai and Volkow, 2013, Volkow, 2014). This model of care is rapidly expanding, with 2.1 million ambulatory buprenorphine treatment visits in 2013, up from only 160,000 in 2003. This patient population has a high prevalence of psychiatric (Savant et al., 2013) and medical co-morbidities, including chronic pain (Wachholtz et al., 2011). Importantly, the success of OUD treatment can be compromised by poorly controlled psychiatric co-morbidities (Dausey and Desai, 2003, Kessler et al., 1994, Kraus et al., 2011, Savant et al., 2013).

Providers in integrated settings are faced with the difficult mission of optimizing patients’ medical, psychiatric, and addictive disorders while simultaneously avoiding the iatrogenic harm of prescribing medications that may destabilize the patient. Unfortunately, it is not always clear which medications may be harmful versus beneficial. Benzodiazepines are associated with worse outcomes with buprenorphine: decreased retention in OUD treatment (Fareed et al., 2014, Ferri et al., 2014, Lee et al., 2014); increased risk of emergency room visits (Schuman-Olivier et al., 2013); accidental overdose; and death (Häkkinen et al., 2012, Reynaud et al., 1998, Sansone and Sansone, 2015, Seldén et al., 2012).

The majority of literature about the potential risk of psychoactive medications beyond benzodiazepines (e.g., gabapentin, clonidine and promethazine) is based on reviews of patients who either receive methadone for OUD or on opioids for chronic non-cancer pain (Baird et al., 2014, Lynch et al., 2015, Shapiro et al., 2013, Smith et al., 2015, Turner and Liang, 2015). Recently there are increasing numbers of case reports about the misuse potential of some commonly prescribed medications with psychoactive effects, specifically clonidine (Seale et al., 2014), gabapentin (Reeves and Ladner, 2014) and promethazine (Mendhekar et al., 1999, Zhou et al., 2008) in combination with buprenorphine. However, these psychoactive medications, especially gabapentin and clonidine, may be co-prescribed with buprenorphine to manage co-occurring psychiatric or sleep disorders and help maintain patients in recovery. While some psychoactive medications have been shown to increase the short-term (<12 weeks) tolerability of the opioid agonist induction or detoxification taper (Gold, 1993, Kleber et al., 1980, Kowalczyk et al., 2015, Salehi et al., 2011, Sanders et al., 2013, Washton and Resnick, 1982), their association with more long-term treatment outcomes have not been documented. Given the reports of misuse of gabapentin, clonidine and promethazine among patients on methadone and chronic opioids, as well as the emerging case reports for patients on buprenorphine, we hypothesized that these psychoactive medications would be associated with early disengagement from buprenorphine treatment. The goals of this study are to examine the proportion of patients receiving PAMs, and to assess whether these medications, including those with emerging evidence of misuse (“emerging PAMS” −gabapentin, clonidine and promethazine), are associated with early disengagement from an OBOT program.