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PROFESSOR ASHTON'S COMMENTS
Comments on reports from the National Addiction Centre (NAC)
and the National Treatment Agency for Substance Misuse (NTA)
(These comments apply to prescribed benzodiazepine users
who do not misuse/abuse illegal drugs)
June 8, 2010
(Note: The NAC/NAT reports were forwarded by Jim Dobbin MP to the
Prime Minister and The Health Secretary for their response)
The Ministerial Statement from the Department of Health, issued by the Public Health Minister Anne Milton, states: "For the first time we have a national picture of what is happening in the community and how we can address addiction to pain killers and tranquillisers. Most areas of the country have services in place to support people who develop problems."
Unfortunately, neither of these reports produces a national picture of what is happening in the community, nor do they fully address addiction to pain killers and tranquillisers. In addition, both reports are extraordinarily complacent about the services available to support people who develop problems.
NATIONAL ADDICTION CENTRE
Prescriptions. The Executive Summary of the report states "Literature on the prevalence of benzodiazepine use and misuse in the UK is currently limited." The same is true of Z-drugs. It is therefore impossible to conclude from this review of prescription data how many people are taking benzodiazepines or Z-drugs (prescribed or otherwise) and how many are dependent on them. As the report notes (p.17) they used the Prescription Cost Analysis (PCA) system. On this system ten prescription items may represent a series of repeat prescriptions for one patient or a number of single prescriptions for ten different patients. Nor does it record the indication for the prescriptions, or how many patients become dependent. Therefore this review does not inform, as claimed in its title, "to inform consideration of the extent of dependence and harm."
Population of benzodiazepine and Z-drug users. The report rightly points out (pp.12,13) "Those who become dependent on benzodiazepines or Z-drugs may be subdivided into those who seek medical help for temporary anxiety or insomnia, but continue beyond the recommended timeframe or dosage, or are maintained by the prescriber". "This group is differentiated from a second population who actively seek the drug for its intentional abuse as a psychoactive drug. Members of this second group may be more likely to have another substance abuse disorder and to derive their drug from varied (including illicit) sources." This second group may also be prescribed benzodiazepines as part of their detoxification treatment for illicit drugs.
Having made this useful distinction, the report mixes prescribing data for the two populations, especially in the section (pp. 8, 30, 31) on the sample of a cohort of patients also prescribed opiate substitution therapy. They found in this group that half of all benzodiazepine prescriptions coincided with an episode of opiate substitution treatment with methadone or benzodiazepines.
Earlier estimates indicate that there may be over a million people in the first population but these get "lost" in the plethora of prescribing data. The two populations are composed of quite different groups of individuals who require separate considerations and treatments. Services devoted to illegal drug users are inappropriate for the first population.
Clonazepam (p.17). The decision to omit clonazepam prescriptions from consideration, on the grounds that it is only indicated for epilepsy in the UK, reflects the NTAs ignorance of the true situation. In the words of Anne Milton: "We have a national picture of what is happening in the community." It is true that clonazepam is only licensed for epilepsy but anyone in touch with benzodiazepine users will be aware that clonazepam is increasingly being prescribed off-licence for anxiety in the UK. This use follows a trend in the US where clonazepam is frequently prescribed for anxiety. This is a dangerous situation since clonazepam is 20 times more potent than diazepam, readily causes dependence, and is particularly difficult to withdraw from.
The NTA might have at least inquired why prescriptions for clonazepam at 574,600 were so much greater than those for clobazam (the other benzodiazepine licensed for epilepsy) at 173,500, rather than making the assumption (p.17) "It is assumed …. that including them in the figures here would be misleading". However, it could also be misleading to ignore them without further comment. For example, there might be a greater increase in anxiolytic prescriptions than appears from the figures and tables.
Review of effects of benzodiazepines (p.10), The risk of fatal overdose with benzodiazepines is increased not only with heroin but also with other drugs that depress respiration including barbiturates, alcohol, other opioids and other drugs that depress respiration.
"Complete recovery to levels of non-user does occur a few years after stopping". It would be more accurate to use can instead of does since the possibility of irreversible damage is still not resolved. Only one paper on recovery from cognitive decline 3.5 years after stopping alprazolam is quoted (p.72) (Killic et al. 1999) but there are patients who complain of apparently irreversible tinnitus, muscle spasms, chronic pain and other symptoms lasting many years, apparently related to long-term benzodiazepine use. The possibility of long-term damage is discussed in the 2011 Supplement to the 'Ashton Manual' 2002 available on www.benzo.org.uk, and also the related question of "recurrences" years after successful benzodiazepine withdrawal.
Withdrawal strategies for benzodiazepines and Z-drugs (p.11). The report rightly states that there is a lack of good research evidence on the management of benzodiazepine withdrawal. The results from meta-analyses of clinical trials are difficult to interpret because different trials use different rates of withdrawal, different adjuvant drugs and allow only for short-term follow-up. This difficulty is not surprising since the report admits that "discontinuation strategies should be flexible". However, the report also recommends that "regimens beyond 6 months should be avoided, unless clearly clinically indicated." But the length of the withdrawal schedule must depend on type of benzodiazepine, starting dose, and many individual factors in the patient. The British National Formulary (BNF) clearly recommends "time needed for withdrawal can vary from 4 weeks to a year or more". The report does not mention substitution with diazepam in patients on short-acting benzodiazepines or psychological help, both of which are recommended in the BNF and in numerous literature sources.
Withdrawal symptoms are described in the report but the incidence of these is said to be "only in about 20-30% of patients (Lader 1998)". This is a wild estimate which does not specify whether it refers to anxiolytics, hypnotics or benzodiazepines prescribed for other reasons, type of patient, dose or other factors and does not take into account that there is a large population of long-term prescribed benzodiazepine users in which the incidence of withdrawal symptoms has never been studied. The report (p.68) cites King (1992) who concludes "that some long-term users may persist in taking benzodiazepines because of chronic or recurrent anxiety rather than dependence". There is no mention of the observed fact that long-term benzodiazepine use may itself cause anxiety (e.g. Ashton, B.J. Addiction (1987) 82, 665 and Ashton Psychiatric Annals (1995) 25, 158).
The report also states that "discontinuation strategies for Z-drug use should include tapering". It does not say how this can be achieved since zaleplon, zolpidem, and zopiclone are all marketed in capsules or tablets of only two strengths.
In describing withdrawal symptoms (p.68) the report states "Withdrawal symptoms come on within 2-3 half lives of the particular benzodiazepine (e.g. 2-3 days after short and medium-acting … compounds)." This statement shows how out of touch the NCA is with the general population of benzodiazepine users. Interdose withdrawal symptoms have been well documented in the literature and occur within hours of the last dose of lorazepam (half-life 10-20 hrs). This is the reason why it is recommended to be taken in divided doses, in practice three times daily for anxiety. The same is true for alprazolam (half-life 6-12 hrs). It is also notable in a number of patients addicted to short-acting Z-drugs. Although prescribed as hypnotics, some of these patients end up taking Z-drugs several times during the day as well as at night.
The severity of withdrawal symptoms is not mentioned. These can be severe and lead to many socioeconomic consequences (Ashton 1995, Psychiatric Annals 25, 158-165). There have been a number of suicides, particularly if the withdrawal has not been competently managed, or carried out 'cold turkey' in hospital or detoxification in clinics.
Knowledge gaps and future research recommendations (pp. 89,90). The final table with research recommendations is disappointing. The report shows that the NAC is aware of present gaps in knowledge, including prevalence, populations at risk, long-term harms, treatment plans and management guidelines, why misuse occurs and prevention strategies, but for these gaps it simply states: "more research is needed".
This document has been long awaited by long-term prescribed benzodiazepine and Z-drugs in the expectation that it would provide specific proposals for the type of research needed, and particularly that it would advocate the setting up of dedicated NHS withdrawal services designed for their particular needs. "More research is needed" are empty words for this population and they will be disillusioned, with their hopes dashed. They have expressed their needs in numerous applications to the Department of Health, some of which are listed below.
To find out the number of people in this population (prevalence of prescribed long-term use) it should be possible to access GP computer records. (a) These would be need to record the number of people receiving long-term benzodiazepine and Z-drug prescriptions in each GP practice (including clonazepam but excluding those on opiate or other illegal drug detoxification regimes). (b) Patients involved would need to be specified into those receiving the drugs for e.g. over 1-2 months. (c) The indications for their prescription and the type of benzodiazepine and dosage prescribed should be noted. (d) These patients should be characterised by recording symptoms, previous attempts at withdrawal etc to provide evidence of dependence. (e) These patients should be contacted and the possibility of reducing benzodiazepine withdrawal should be explored (see Heather et al. 2004 Addiction Research and Theory 12, 141-154).
Dedicated hospital benzodiazepine and Z-drug withdrawal clinics should be set up within the NHS for this population, separate from those for illegal drug (opiates etc.) substance abuse disorders. At present the iatrogenically dependent population which does not use illegal drugs depend largely on advice from volunteer projects such as the Bristol and District Tranquilliser Project and Council for Information on Tranquillisers and Antidepressants (CITA). A few of these receive financial support from the DOH, such as the Oldham Tranx Support Group and the Bridge Project in Bradford, but they are not medically run with full access to clinical pharmacologists, clinical psychologists, trained nurses and to other hospital services like the benzodiazepine withdrawal clinics historically run by Professor Malcolm Lader in London and by Professor Heather Ashton in Newcastle. Patients complain that their GPs are not experienced in benzodiazepine withdrawal (and have not time to devote to it) and there are no referral centres for this particular population.
There is a need for more clinical psychologists and/or other staff trained in the effects of benzodiazepines and their withdrawal (many clinical psychologists are ignorant on this subject) as well as non-drug methods of anxiety control, sleep problems etc. ranging up to more formal psychological techniques such as cognitive behavioural therapy (CBT). Some years ago the Department of Health undertook to increase the number of clinical psychologists; it would be interesting to know whether this project is progressing and by how much. Quick access to such therapies would be invaluable for the prevention of misuse, by allowing patients to obtain treatment before they are prescribed benzodiazepines.
Research should be devoted and funded to examine the possible long-term effects of benzodiazepines, particularly functional changes in brain activity. Techniques for such studies are available including fMRI, PET, SPECT, QEEG and MEG but none of these have been utilised in controlled studies of long-term benzodiazepine users despite the fact that many complain of long-term functional damage (see 2011 Supplement to Ashton Manual on www.benzo.org.uk).
NATIONAL TREATMENT AGENCY FOR SUBSTANCE MISUSE
The Executive Summary of this report states that the NTA was well placed to investigate the potential extent of misuse of prescription-only medicines and the current availability of services to help people addicted to them. In fact the NTA was not well placed since the numbers of people taking long-term benzodiazepines ("misusing" benzodiazepines because of doctors' prescriptions) is not known, nor is it known how many of these people are dependent, and there are no dedicated NHS or GP services devoted to helping this population. Most of these people have been taking prescribed benzodiazepines for many years – often 20 years or more. Many will have developed iatrogenic drug dependence.
This population does not in general use illegal drugs and services devoted to illegal drug users are entirely inappropriate for them. The report admits that it has not been possible to establish a definite prevalence or dependency in the general population. However, it recognises a level of need in relation to problematic use for local areas but states that people who access treatment services find the support to achieve recovery. This statement is misleading since the number of people who need treatment for benzodiazepine addiction is not known and support for them is generally not available since GPs know little about benzodiazepine withdrawal and non-drug treatments or psychological treatments are very difficult to obtain and involve long waiting lists.
The report further states "Treatment for substance use disorders in England is readily available and quickly accessible." They also state "The National Treatment data evidences that those who develop problems in relation to prescribed medicines (e.g. benzodiazepines) without problematic illegal drug use, do not suffer long waits and can access local treatment services that support them to achieve recovery." These statements are simply not true for iatrogenically dependent long-term benzodiazepine users who are often refused admission to illegal drug treatment centres which are, in any case, inappropriate for them. Furthermore, waiting lists for psychological therapies are exceedingly long – many months to more than a year.
The report states in several places that the needs of people for prescribed medicines are "difficult to quantify" and that the population of drug misusers that they consider "may be under-representative of the wider population of people who experience problems with prescribed medicines and yet they state "the primary focus of this report is on the needs of those whose problems are related to the prescribed use of prescription-only medicines". Thus, the report appears to contain too many illogical or conflicting statements. Furthermore, the report confuses the population of people who take benzodiazepines long-term with illegal drugs and the much larger population (estimated as over a million) of compliant patients who only take benzodiazepines on the advice of their doctors.
The NAC and NAT have gathered an impressive array of statistics but have shown little understanding of the underlying problems. They have conflated different populations of benzodiazepine misusers and abusers and have largely ignored the needs of the iatrogenically dependent population. Thus the reports fail to provide "a national picture of what is happening in the community or how we can address addiction to pain killers and tranquillisers" as claimed by the Public Health Minister. They are complacent in regard to the further claim that "most areas of the country have services in place to support people who develop problems." They recognise that there are many gaps in our knowledge for which "more research is needed" but they make no specific recommendations about what particular research is required.
Emeritus Professor of Clinical Psychopharmacology
University of Newcastle upon Tyne
June 8, 2011
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