Download Benzodiazepine Detoxification during Opiate Replacement Treatment

Benzodiazepine Detoxification during Opiate Replacement Treatment
Prepared by Catriona Matheson for CERGA, September 2011.
Key Findings:
1. There is no evidence to determine the best detoxification regimen to use
in opiate dependence as existing evidence excluded opiate users from
trials.
2. A specific trial in opiate users is recommended to inform future practice.
3. 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.
4. 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.
5. 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.
1
Introduction
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
benzodiazepines withdrawal during opiate replacement treatment?
of
2
Methodology
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.
3
Findings
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.
3.3
Miscellaneous 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 selftherapeutic group were significantly more likely to report isolated use of
benzodiazepines. Those in the hedonic group were more likely to report multisubstance 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.
4
Quality of the Evidence
There is no evidence to determine the best clinical practice
benzodiazepine detoxification during opiate replacement treatment.
5
regarding
Existing practice in Grampian
Guidelines exist in Grampian for benzodiazepine withdrawal (not specifically with
opiate treatment) (Eagles et al 2006). These recommend reducing doses by 1020% every fortnight. This is based on the recommendation in the British National
Formulary.
6
Conclusion
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 D Strategies 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.