7 July 2003

Benzodiazepine dependence - randomised reduction study.

In-patient benzodiazepine withdrawal: comparison of fixed and symptom triggered taper methods. McGregor C, Machin A, White JM. Drug and Alcohol Review (2003) 22:175-180

Dear Colleagues,

This group from Adelaide University has come up with yet another instructive study of great clinical relevance. Benzodiazepine dependence has been neglected for too long. Considering the substantial profits made by drug companies it is disappointing (cynics may say predictable) that so little funding has been given to the potential for harm from benzodiazepines in vulnerable populations such as the elderly and recreational drug users.

The authors remind us that although many treatment agencies give supervised tapering doses of diazepam, this procedure has not been systematically evaluated. As with nicotine, opiates and even stimulants, such therapeutic substitutions and subsequent reductions can be a feasible way of addressing dependency management. Longer term drug maintenance is a 'fall back' position, generally using long acting, oral forms with low toxicity, in cases where reductions repeatedly result in relapse.

This study showed no significant differences between those given fixed reductions versus symptom initiated dosing with diazepam. The intervention demonstrated numerous positive outcomes at one month follow-up in such poly-drug users up to a month after treatment. Patients had used a spectacular daily mean 'Valium-equivalent' of 115mg or 23 tablets! Two thirds were using more than one type of sedative on the week of admission. At least half of the 44 subjects were also opioid habitu├ęs. The mean hospital stay was 5 days, with subsequent tapering doses offered as outpatient treatment. At the end of one month, sedative use had declined dramatically from previous levels.

We know from the British 'NTORS' research and other opioid studies that even poor quality, non-evidence-based treatments can yield positive outcomes. Hence there still needs to be much more comparative work with benzodiazepine addiction. In the meantime, either of the treatments offered in this study would seem to be appropriate, safe and effective, at least in the short term. The fixed dose regimen started with an estimated equivalent up to 80mg diazepam daily in four divided doses, reducing at 10mg daily down to 40mg and by 5mg daily thereafter. Although supervised consumption is preferable, excessive supervision may cause patients to drop out. Also, hospital admission is neither acceptable nor necessary for the majority in community practice.

In our own practice, we have found that daily attendance with supervised dosing is suitable for patients whose drug use is chaotic. Later, second or third daily attendance can suffice as patients demonstrate features of stability. A small proportion seem to need to continue daily doses of diazepam indefinitely. Some may have pre-existing anxiety or panic disorders and a proportion may have unacceptable withdrawal symptoms. This distinction may become blurred with time, but the required treatment may be the same for either diagnosis.

comments by Andrew Byrne ..

Buprenorphine comparison office-based vs. clinic no differences!

A comparison of buprenorphine treatment in clinic and primary care settings: a randomised trial. Gibson AE, Doran CM, Bell JR, Ryan A, Lintzeris N. MJA 2003 179;1:38-42

Dear Colleagues,

This trial of buprenorphine for heroin addiction has shown for the first time, to my knowledge, that agonist treatment can be given in primary care settings with results equivalent to those obtained in specialist clinics when patients are randomised at enrolment.

These researchers randomised 115 consenting heroin addicts who were seeking detoxification and offered them a 5 day course of buprenorphine in community practice or clinic practice. After two days without medication (days 6 and 7), they were given an option to transfer to maintenance therapy on day 8.

About 75% of patients returned at day 8, and one third of them chose to have no further drug treatment. Of the other two thirds, all but 4 chose buprenorphine maintenance (2 went onto methadone while another 2 chose naltrexone). It is to the credit of these researchers that of the 64/115 (56% of original group) who started maintenance, 40 (35%) remained in treatment at 3 months. This is a derived retention rate of 62% for continuing patients by my calculations.
There were no significant differences in any of the measures between the primary care group and the clinic group. Costs were also similar. The medication was administered in the doctors' offices for the primary care cases and at the clinic dispensary for the clinic patients during the detoxification phase (doctors are permitted to administer S8 drugs 'in the normal course of medical practice' as long as they comply with appropriate local legislative requirements for documentation, etc). For the maintenance phase, prescriptions were filled at community pharmacies where patients paid $25 per week, contrasting with the clinics which were free of charge, making the outcomes for primary care even more impressive. There must be some doubt about some of the authors' derived conclusions regarding comparative costings owing to the necessarily approximate nature of the figures between private and public sectors.

The nature of this trial was rather unusual as it offered subjects the prospect of one thing (opioid detoxification) but ended up by giving most subjects quite the opposite (opioid maintenance). The rationale behind this 'ruse' was not discussed although the consent included the possibility of maintenance if detox was not succeeding. It meant that although, by definition, all maintenance patients had 'failed' at their initial goal, their maintenance treatment was evidence based and very likely life-saving, unlike detoxification. Further, maintenance is, or should be, a flexible treatment which can be given by GPs and community pharmacists.

comments by Andrew Byrne ..