Benzodiazepine Detoxification during Opiate Replacement Treatment
Prepared by Catriona Matheson for CERGA, September 2011.
Key Findings:
- There is no evidence to determine the best detoxification regimen to use in opiate dependence as existing evidence excluded opiate users from trials.
- A specific trial in opiate users is recommended to inform future practice.
- A systematic review (Fatseas et al, 2006) suggests the best evidence for benzodiazepine withdrawal in a non opiate dependent population supports switching to diazepam and to reduce the dose by 25% of the initial dose each week in a controlled environment.
- Current local guidelines are more cautious (reducing by 10-20% per fortnight) which may be appropriate due to the community based setting of local treatment. Local guidelines are currently being reviewed.
- Whilst there is concern that diazepam has higher abuse potential in an opiate dependent population it is still the preferred option (if the treatment setting is appropriate to minimise diversion) given the lack of evidence to the contrary.
1Introduction
Misuse of benzodiazepines alongside heroin is common. However concurrent use is hazardous. In the recent analysis of drug related deaths (ISD, 2010) benzodiazepines had been used in 39.2% of cases. For those entering treatment the level of benzodiazepines use must be carefully assessed. Sudden cessation of benzodiazepines can lead to convulsions and is not recommended. However, how best to manage patients is a key clinical challenge. The Orange Guidelines state there is little evidence to support the long term substitute prescribing of benzodiazepines and suggests there is evidence that long term doses of over 30mg diazepam equivalent can be harmful (no reference is given). The Orange guidelines recommend a gradual benzodiazepine dose reduction to zero after careful assessment and sufficient evidence of dependence. Thus the guidelines are slightly vague and do not appear to be evidence based other than being underpinned by the need to avoid sudden withdrawal.
CERGA identified the need to determine the evidence base for management of benzodiazepine withdrawal during opiate replacement treatment. Thus the Research Question is:
What evidence exists to determine the best clinical management of benzodiazepines withdrawal during opiate replacement treatment?
2Methodology
Medline, Scopus and Embase databases were searched from 1990-present. In medline an initial keyword search using benzodiazepine detoxification and opiate dependence as a keyword search identified >1000 papers. Thus the search strategy was revised and a title search was used on keywords ‘opiate’ and ‘benzodiazepine’. This was applied in Medline, Embase and Scopus.
3Findings
3.1 Studies of benzodiazepine withdrawal in opiate replacement
The search identified no papers that directly studied benzodiazepine withdrawal during opiate treatment. However there was one review article identified which covered this exact topic (Fatseas et al, 2006). This review found fewer controlled studies than expected on benzodiazepine detoxification, and all excluded patient who misused opiates or were in opiate replacement treatment. The best identified evidence supported a procedure where the patient is switched to a long-lasting benzodiazepine and the dose then tapered by 25% of the initial dose each week. However this was described as being conducted in a ‘controlled setting’ which may not be equivalent to our community based treatment setting. Diazepam was the drug most often used. In opiate users, diazepam may raise special problems of misuse, as suggested by clinical and epidemiologic studies which identified it as particularly desirable to opiate users. Nonetheless, diazepam is the only benzodiazepine found to be effective for withdrawal in controlled studies and some studies indicate that unprescribed diazepam use in heroin users is sometimes motivated by the desire to alleviate withdrawal symptoms and discomfort. The authors concluded that the available data does not rule out its therapeutic use for benzodiazepine withdrawal in patients on opiate substitution treatment in an ‘adequate’ treatment setting. (By this it is assumed that it means where the risk of diversion is minimized.) Thus it appears there is no evidence to determine best clinical practice and specific studies of this population are needed.
3.3Miscellaneous Related Studies of Interest
The search identified a number of papers that described the characteristics of benzodiazepine and opiate users. The two most recent examples of these were Sobrino et al (2009) and Lavie et al (2009). These are not covered in detail but some interesting key finds are that simple users do not differ statistically from non users in their mental health and general health profile. However problematic users of benzodiazepines have significantly higher depression and anxiety levels with poorer quality of life (Lavie et al, 2009).
Fatseas et al (2009) reported on self perceptions of benzodiazepine use in opiate dependent patients in a French treatment population. Three motivations had been previously identified through interviews: self therapeutic motivation only, hedonic motivation only and use for both self-therapy and hedonic motivations. There were no demographic differences between groups. Those in the self-therapeutic group were significantly more likely to report isolated use of benzodiazepines. Those in the hedonic group were more likely to report multi-substance use, obtaining benzodiazepines on the black market and using other routes such as nasal or intravenous. Flunitrazepam was the drug of choice in this group.
Finally a survey was conducted of 174 NHS substance misuse services in England and Wales to determine the perceived level of benzodiazepine use (Williams et al, 2005) and strategies used to tackle it (Cooke et al, 2007). A good response rate of 71% was achieved. Responding services estimated that 40% of patients used benzodiazepines and 25% were dependant. Over a third (35%) reported providing benzodiazepine maintenance prescribing. In a separate paper based on the same survey 56% of respondents gave suggestions for future strategies to manage benzodiazepine use. These included stricter prescribing safeguard, more use of non-pharmacological interventions and national guidance. Guidance in the form of the Orange Guide has since been published.
4Quality of the Evidence
There is no evidence to determine the best clinical practice regarding benzodiazepine detoxification during opiate replacement treatment.
5Existing practice in Grampian
Guidelines exist in Grampian for benzodiazepine withdrawal (not specifically with opiate treatment) (Eagles et al 2006). These recommend reducing doses by 10-20% every fortnight. This is based on the recommendation in the British National Formulary.
6Conclusion
There is no evidence to determine the best detoxification regimen to use in opiate dependence. However the French review suggests the best evidence supports switching to diazepam and reducing the dose by 25% of the initial dose each week. However this is recommended in a ‘controlled’ setting that may not be equivalent to the local community based treatment setting. A specific trial in opiate users is recommended to inform future practice.
References
Cooke J., Williams H., Handyside DStrategies needed to tackle benzodiazepine misuse in opiate addicts: A national postal survey.Public Health Medicine. 6 (2) (pp 68-70), 2007
Clinical Guidelines on the Management of Drug Misuse (the Orange Guide). Departments of Health 2007.
Drug Related Deaths in 2009 report. (2010) Information and statistics Division, Scottish Health Department, Edinburgh.
Eagles L., Sutherland F. Guidance for the prescribing and withdrawal of benzodiazepines & hypnotics in General Practice. NHS Grampian 2006.
Fatseas M., Lavie E., Denis C., Franques-Reneric P., Tignol J., Auriacombe M. Benzodiazepine withdrawal in subjects on opiate substitution treatment.Presse Medicale. 35 (4/I):599-606, 2006.
Fatseas M. Lavie E., Denis C., Auriacombe M. (2009) Self-perceived motivation for benzodiazepine use and behavior related to benzodiazepine use among opiate-dependent patients. J Substance Abuse Treatment 37:409-411.
Lavie E.Fatseas M.Denis C.Auriacombe M. Benzodiazepine use among opiate-dependent subjects in buprenorphine maintenance treatment: Correlates of use, abuse and dependence. Drug and Alcohol Dependence. 99 (1-3) (pp 338-344), 2009. Date of Publication: 01 Jan 2009
Sobrino A. Ma.F., Rodriguez V.F., Castro J.L. Benzodiazepine use in a sample of patients on a treatment program with opiate derivatives (PTDO). <Consumo de benzodiacepinas en una muestra de pacientes en Programa de Tratamiento con Derivados Opiaceos (PTDO). Adicciones. 21 (2) (pp 143-146), 2009. Date of Publication: 2009.
Williams H., Handyside D., Bashford K., Ovefeso A (2005) Service response to benzodiazepine use in opiate addicts: a national postal survey. Irish J Psychological Medicine 22(1):15-18.