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Lofexidine for withdrawal symptoms works ... (but detoxification usually doesn't).
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PDF version | Dr Andrew Byrne & Associates |
A Harm-Minimisation Research Perspective: Dr Byrne (and his associates) advocate for better policies which are proven to reduce risks for drug users and the general community, under a framework in parallel with Australia’s official policy of harm minimisation. | |
A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Yu E, Miotto K, Akerele E, Montgomery A, Elkashef A, Walsh R, Montoya I, Fischman MW, Collins J, McSherry F, Boardman K, Davies DK, O'Brien CP, Ling W, Kleber H, Herman BH. Drug and Alcohol Dependence 2008 97;1-2:158-168
Dear Colleagues,
This may be a world record for delays in clinical research. Dr Kleber first wrote about the possible effectiveness of lofexidine for withdrawals in 1981 (ref 1). Now, with a stellar cast of senior American colleagues he has produced a small and unsatisfactory report (n = 68, only 17 completers) in the course of attempting to have the drug registered in the United States. With modest but apparently significant benefits noted in a 4 day regimen using the drug, the trial was dramatically called off just over half way thru. This is normally only done where it is considered unethical to continue to using placebo. However those receiving lofexidine also suffered 4 significant side effects, each probably related to hypotension. The benefit of lofexidine was a reduction in withdrawal symptoms/signs from 30 to 20 and an increase in retention from 15 to 38%. While these differences are substantial, the same or better might have been obtained with clonidine, diazepam or even "hospital brandy". Additionally we know that this intervention (detoxification from opioids) has a ~90% failure rate and also a substantial mortality in the period following.
Doctors and health workers can recommend established, effective treatments, yet detoxification should only be initiated by the patient in my view, both due to its inherent dangers and the lack of a proven strategy to achieve this noble goal. It is hard to justify detoxification from opioids in pregnancy, for example, and some would say it is unethical. On the other hand, patients are perfectly entitled to request services which doctors would not normally actively recommend (abortion, contraception, euthanasia, circumcision, etc). As long as the detoxification is patient-initiated, and the patients are aware of the alternatives and the relative risks then there can be no ethical problem.
The authors give a comprehensive literature review, pointing out that there is little current evidence favouring lofexidine over clonidine regarding effectiveness yet the former seems to have less hypotensive side effects in some trials. Some quoted trials compared lofexidine with buprenorphine, a ludicrous comparison in my view. It would be like comparing aspirin with penicillin for bronchitis. So after 25 years I am still not convinced that lofexidine is a sure-thing in detoxification. One might also think that if it were indeed effective that there might be more anecdotal evidence as well as a possible black market in the drug (at least in the UK).
Comments by Andrew Byrne .. http://www.redfernclinic.com/
Washton AM, Resnick RB, Perzel JF, Garwood J, Gold MS, Pottash AC, Annitto WJ, Extein I, Kleber HD. Lofexidine, a clonidine analogue effective in opiate withdrawal. Lancet 1981 317;8227:991-993
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Submitted by ajbugler on Tue, 17/04/2012 - 01:43.
Its 4 weeks 2day i started lofexidine detox off 12 ml methadone, i'd reduced from 55ml over the previous few months...i got 2 say it wasnt as bad as i was expecting, i did get some withdrawals but no sickness or dioreah or stomach cramps, i did get some anxiety but i was prescribed diazepam for a few days, also i had zopiclone sleepers prescribed, buscopan and ibuprophen. Withdrawals were worst on days 3 to 6, i did have a few tramadol for the hardest days (not prescribed) but only took 2 50ml at night and got 7-9 hrs sleep on days 3-6. I wud not take them any longer than that as they are opiate antagonists and i wud have 2 withdraw off those aswell!! The night after i took the last tramadol was bit uncomfortable, i had restless legs n abit anxious n got no sleep for 2 nights, the second week seemed harder than the first for some reason, by the time i got to day 10 the lofexidine had been reduced and stopped, i had no energy for 3 weeks but by day 24 i felt great, bit sweaty but ok. Now on week 4 i've got no symtems at all other than getting really tired early evening, but im sleeping well (9hrs last night)
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