X-Concord Seminar on benzodiazepine dependence: 29 Feb 2012 plus tribute to honour Dr Alex Wodak whose retirement coincided with this seminar.
A panel discussion was given at Royal Prince Alfred Hospital chaired by Dr Richard Hallinan, Staff Specialist in Addiction Medicine. Present were numerous experienced clinicians, some by invitation, others out of habit. Pharmacist Denis Leahy, Nick Lintzeris, director of Langton Centre and a doctor from Redfern. There were over 70 people in the packed audience.
Dr Hallinan gave a short presentation on the ion channel GABA receptor and the difference in its interaction with barbiturates and benzodiazepines and why the latter are so much safer in overdose. We were shown the basic molecular structure involving the fusion of a benzene ring (“benzo”) with a heterocyclic, two-nitrogen (“di-azo”) molecule and various attachments to form the individual characteristics of the different forms of benzodiazepines.
We were then told of the variations in absorption rates, half-lives, metabolic pathways, active and inactive metabolites, blood levels, fat and water solubility and volumes of distribution (initial and steady state) of the common benzodiazepines. These included chlordiazepoxide, diazepam, oxazepam, temazepam, nitrazepam, flunitrazepam, alprazolam, medazolam, clobazam and clonazepam. We learned a little of the history of these drugs which largely replaced the barbiturates in the 1960s. Their effects on convulsive thresholds, anxiety, sedation, muscle relaxation, amnesia, panic disorders and PTSD were canvassed, including mention of a recent comprehensive review by Malcolm Lader, the widely published English benzodiazepine ‘guru’ in the Addiction journal.
Dr Jenny James who is a GP at a western Sydney Aboriginal Medical Service was then asked to present a case. This was an enormously complex case which Dr James and her GP colleagues had looked after for several years, amongst their busy and varied general practice. She pointed out that there are no dedicated staff for counselling, family therapy, case management or other ancillary services which are either carried out by the doctors as a drop-in service or not done at all. There were issues of dual chronic viral infection, doctor shopping, mental illness and intercurrent drug use while on methadone treatment. There followed a question and answer session with response from panel members, including a pharmacist and two drug specialists. It was clear from the history that the difference between general practice and specialist practice is that history and progress can be gleaned over months by the former while the latter cannot afford to get it wrong and thus needs to be more comprehensive and multi-disciplinary … where this is possible considering the ‘urgency’ of our patient group and the lack of resources in the face of large numbers seeking treatment.
The main question of the evening was whether the treating doctors should be prescribing benzodiazepines for patients like this one and if so, with what degree of supervision, quantities and restrictions (alcohol was the big contraindication). It was contended that alprazolam (Xanax) was not an appropriate drug for any definable psychiatric condition and some present felt that like Rohypnol and Normison (capsules) before it, it should be banned from the Australian market. Personally I have not prescribed Xanax (alprazolam) for over a decade and I would be delighted if it were off the market or at least limited to 0.5mg tablets.
The concept of ‘staged supply’ in community pharmacy was mentioned by Dennis Leahy from Stanmore Station Pharmacy. The last federal budget included a small subsidy from the PBS for employing this strategy for those with impulsive and compulsive drug consumption … which means most of our patients, at some of the time.
Dr Jill Roberts said that about 90% of prison inmates on OTP have current benzodiazepine histories on admission, requiring careful diagnosis and management. The Justice Health service has a routine detoxification regimen, using a withdrawal scale. A common starting dose is 20mg diazepam twice daily, especially in those with a history of seizures. This high figure of 90% would seem to be consistent with the extraordinary finding from Malcolm Lader that ‘in the UK about half of all BZD prescriptions were given to patients who are currently in an opioid treatment program’.
Experience has shown that some patients fare well taking substantial quantities of benzodiazepines while others seem to lurch between episodes of varying intoxication which often involve aberrant behaviour, legal diversions and occasionally injuries or even worse.
It was interesting to note from the delegates at this meeting just how much the field has changed. In the past there were significant numbers of doctors who claimed that prescribing sedatives to opiate maintenance patients was never appropriate. At this meeting, however, nobody expressed this sentiment. In fact virtually everyone had been involved with certain dependent patients being prescribed a limited supply of (usually) diazepam for certain periods of time, under supervision, despite the logistic difficulties. In also seemed agreed that there was a certain minority group in whom complete withdrawal was not realistic, just as occurs with opiates, alcohol, tobacco, etc.
So can one use methadone maintenance as a paradigm? Is there a diagnosis of dependence? Have there been reasonable efforts to withdraw? Are there episodes of serious sequelae from the benzodiazepine use? Is there dual or poly drug abuse? Psychiatric diagnosis? Has the patient been compliant with their opiate treatment? Is alcohol a factor? Some of our colleagues are currently asking these very questions regarding stimulants, however for sedatives the response is simpler as diazepam, for instance, is not an S8 (restricted) drug in most states.
What would be the minimum criteria for prescribing diazepam to a dependent patient? Having a good history, physical examination, urine test, experienced dispensary would all be essential in my view. An absence of current alcohol use would also be another safeguard. Given all of these factors, we still need a working diagnosis, goals and review process. Does the patient have anxiety or depression? Some may contend that the diagnosis does not matter too much, just like the reason for which a person allegedly uses heroin. ‘If they are dependent, they are dependent’. And the treatment, or at least the principles, should be the same.
So in our own service we use diazepam 5mg - 25mg according to history, initially daily or second daily from the dispensary along with the methadone (or buprenorphine in the few such cases who are taking the ‘weaker’ maintenance drug). Some patients state that they prefer to take some of their dose in the evening and we try to accommodate this where possible. If they state they are sedated on 5 to 10mg Valium we question the diagnosis of dependence and ask to examine the patient 3 hours after such a dose. Others seem to be able to take much higher doses and show no signs of intoxication (on gross testing).
Our goals and follow-up review are the same as for any other behavioural treatment: housing, social, financial, drug-use and general medical parameters are reviewed before further ‘dispensed’ doses are permitted up to a week’s supply at a time (one day supervised) which seems to suit a large proportion of long-term dependent patients. Even without active prompting, doses have generally reduced and a small number have withdrawn, some long-term. A proportion can be expected to relapse to sedative use, just as happens with every other chemical addiction. Better luck next time!
The use of diazepam and other tranquillisers for ‘maintenance’ therapy may be off-label in some cases yet in many there will be a diagnosis of panic disorder, anxiety or insomnia (where benzodiazepines have been shown to be effective) or PTSD, convulsions or depression where such drugs do not have an established evidence base.
Dr Nick Lintzeris gave a heart-felt sentiment of sadness but gratitude regarding the retirement that very day of Dr Alex Wodak to whom so much is due for making the D&A field what it is today in Australia. His influence on policy and practice here and overseas has been unsurpassed, even by Griffith Edwards in the UK … and we all remain in his debt.
Commentary by Andrew Byrne ..
Clinic web page: http://methadone-research.blogspot.com/
Ref: Lader M. Benzodiazepines revisited - will we ever learn? Addiction 2011 106:2086-2109
Liebrenz M, Boesch L, Stohler R, Caflisch C. Agonist substitution-a treatment alternative for high-dose benzodiazepine-dependent patients? Addiction 2010 105;11:1870–1874
Byrne A. Benzodiazepines: the end of a dream. Aust Fam Physician 1994 Aug; 23(8):1584-1585
