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THE BENZODIAZEPINE SCANDAL
FIFTY-TWO YEARS ON AND STILL COUNTING
March 20, 2012
1. An Open letter · Introduction · Proliferation of Benzodiazepines · Safety concerns · The "2-4 weeks only" guidelines · A lack of regulatory power · Inertia
Legal action against prescribers · What's needed · 2. A personal account · Introduction · Background · Withdrawal · Withdrawal symptoms
Long-term problems / permanent damage · Professor Lader's report · Opinion · 3. Causes & Mechanisms · Research · Z-drugs · Concluding thoughts
1. AN OPEN LETTER TO THE DEPARTMENT OF HEALTH,
MEDICAL AUTHORITIES & RESEARCHERS
Introduction. Discovered in the 1950s by Dr Leo Sternbach while working for the pharmaceutical company Hoffman-La Roche in New Jersey it is now 52 years since the first benzodiazepine Librium (chlordiazepoxide) was introduced into the UK (in 1960). From the very outset the alarm bells started ringing. See for example this letter about Librium to The Lancet written by two Glasgow doctors on October 1, 1960.
Since then eminent academics, government advisors, researchers, doctors, health care providers, politicians, charities and campaign groups have issued warnings and expressed grave concerns and fears about the use, side effects of and withdrawal from benzodiazepines. Over the past 12 years I have archived on this web site as much information, medical documents and articles relating to the benzodiazepine issue as possible.
If you care to take a look at the Media Archive on this web site - which is by no means exhaustive - you will appreciate that benzodiazepines are never very far from the news. Journalists have regularly exposed the Benzodiazepine Scandal with stories of celebrity deaths attributed to benzo use as well as the blighted lives of ordinary people. Benzodiazepines were, by all accounts, implicated in the deaths of Elvis Presley, Paula Yates, Michael Jackson, Heath Ledger, Brittany Murphy, Amy Winehouse and Whitney Houston. Other high profile users of benzodiazepines who reputedly also experienced severe problems include Liz Taylor, Judy Garland, tennis champion Boris Becker, singers Marc Almond, Liza Minnelli and Stevie Nicks, and comedian Freddie Starr.
Proliferation of Benzodiazepines. After the introduction of Librium (chlordiazepoxide) in 1960 and Valium (diazepam) in 1963 a number of pharmaceutical companies climbed on a very lucrative bandwagon with a growing number of "me too" drugs from the same benzodiazepine class. The list includes: alprazolam (Xanax), chlordiazepoxide (Librium), clobazam (Frisium), clonazepam* (Rivotril), diazepam (Valium), estazolam (ProSom), flunitrazepam (Rohypnol), flurazepam (Dalmane), halazepam (Paxipam), ketazolam (Anxon), loprazolam (Dormonoct), lorazepam (Ativan), lormetazepam (Noctamid), midazolam (Hypnovel), medazepam (Nobrium), nordazepam (Nordaz, Calmday), nitrazepam (Mogadon), oxazepam (Serenid, Serepax), prazepam (Centrax), quazepam (Doral), temazepam (Normison, Euhypnos) and triazolam (Halcion).
Currently chlordiazepoxide, clonazepam*, diazepam, loprazolam, lorazepam, lormetazepam, nitrazepam, oxazepam and temazepam are prescribed on the NHS while alprazolam, bromazepam, clobazam, clorazepate, flunitrazepam and flurazepam are available on private prescription only.
Why so many? In 1988 Professor Ashton wrote:
"Any benzodiazepine used in lower doses has an anxiety-relieving effect and in higher doses promotes sleep, but differing pharmacological profiles, tradition and marketing have led to the drugs being divided into anxiolytics and hypnotics."
Note: *Clonazepam is only indicated for epilepsy in the UK though it is increasingly being prescribed off-licence for anxiety. "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." - Professor Ashton, June 8, 2010.
Safety concerns. For reasons of cost the number of benzodiazepines on the NHS Prescribed List was reduced in 1985 and since then some of the drugs have been banned or restricted because of safety concerns.
Triazolam was banned in the UK in 1991 because of safety concerns. Most benzodiazepines are Schedule 4 whereas temazepam is Schedule 3. Why ban one benzodiazepine and single out another for special attention? Many of the safety concerns expressed over triazolam and temazepam surely apply to all benzodiazepines.
The "2-4 weeks only" guidelines. The damaging effects of long-term benzodiazepine use / prescribing should not be an issue in the UK. In 1988 the then UK Committee on Safety of Medicines wrote to all doctors advising them to prescribe benzodiazepines for no longer than "2-4 weeks only". In 2004 the Chief Medical Officer reiterated this warning in a letter to doctors. So why are an estimated 1.5 million (*see below) people still being prescribed benzodiazepines long-term in the UK? One doctor once said to me: "They are only guidelines. Doctors are not compelled to follow them. Personally, I rely on my clinical judgment when I prescribe benzos. Patients seem to like them." Other doctors - perhaps deliberately - misinterpret the guidelines. They think that it's OK to continue prescribing benzos provided they see the patient at least once a month!
In spite of the guidelines tranquilliser prescriptions have continued to rise. In 2010/11 there were 17.5 million prescriptions - a 29% increase in diazepam alone since 1999.
A lack of regulatory power. The late Pam Armstrong, of the Liverpool based tranquilliser help charity CITA, said in 1997 she knew of hundreds of patients who had been put on the drugs for months and years despite the 1988 warning. She said: "It seems to have made little difference to many doctors. The problem is the Committee has no teeth. Maybe if a few cases get to court doctors will take it seriously. Lives are being devastated." In reply a spokesman for The Royal Oldham Hospital said "The CSM guidelines were for advice only. Doctors are free to make clinical decisions."
I should like to think that the 1988 guidelines were introduced because it was recognised that benzodiazepines have potential not only for rapid addiction but also for exposure to irreparable harm. It is, however, likely that their emergence was also a somewhat apprehensive reaction to the Benzodiazepine Litigation (class action) that was going on at the time. The pharmaceutical company Roche must also have been concerned because they too wrote to prescribers around the same time. See "Benzodiazepines and Your Patients: A Management Programme". Incidentally, the class action failed not because it wasn't a good case - no evidence was actually heard in court - but because of a legal wrangle over funding issues.
Inertia. Tragically, because of ignorance about the effects of benzodiazepines within the medical community and a reluctance on the part of government and medical bodies to enforce the guidelines and address the issue an estimated 1.5 million (*see below) people in the UK are on long-term benzodiazepine prescriptions. Not only are they suffering a deterioration in their quality of life but they are also exposed to permanent physical injury. Successive UK Governments have made the occasional sympathetic noise but have consistently failed to address the benzodiazepine issue, preferring instead to sweep it (and its victims) under the carpet. On July 27, 2011 Anne Milton MP, Public Health Minister said on BBC Radio 4's Face the Facts:
"I've met people who've been addicted to benzodiazepines for 20 or 30 years - wrecked their lives, wrecked their jobs, wrecked their families. It's a silent addiction. We all know about illegal drugs, we all know about alcohol, we don't know about this group... I think there has been some denial of the problem and I think that when you're talking about drugs that are legally, albeit unwisely, prescribed causing a problem - you know it's never really fitted anywhere, nobody wanted to grab hold of it - certainly not in denial now. We are going to get a grip of this and it needs to be dealt with on a number of different fronts, there's no doubt about that... I'm taking this very seriously. It's an issue that's fallen through the cracks. We want to make sure that training and awareness is raised so that GPs know how to prescribe well and then we need to make sure that we've got the right services in place to give them the help and support they need to get off these drugs and get back and enjoy lives as they should be able to."
We're watching and waiting but how much longer shall we wait for action? A year? Five years? Ten years? Another 52 years? Will the Department of Health do what it has always done in the past? Kick the benzo issue into the long grass? Apart from the 1988 guidelines and a couple of restatements of the "2-4 weeks only" rule very little progress has been made. Interestingly, quite a number of official web sites including both national and regional NHS sites refer their visitors to www.benzo.org.uk for help and information about benzodiazepine withdrawal. I find it strangely ironic that the NHS refers people to a website owned by me - someone who was mistreated, incapacitated and deprived of a livelihood by a couple of NHS employees!
Legal action against prescribers. Clearly a public inquiry into the Benzodiazepine Scandal would be welcome progress but because of the inertia on the part of government and medical bodies individual victims of these drugs have no other recourse but to sue their prescribers for negligence. In January 2012 Professor Malcolm H Lader, Emeritus Professor of Clinical Psychopharmacology, King's College, London said:
"The prescribing guidelines [published in 1988] have had no effect whatsoever on prescribing and GPs are now being sued... they are being picked off one by one and the size of damages being paid will force the medical defence unions to issue further warnings. This is an ongoing problem which has not been addressed by the medical profession, but is at last being addressed by the legal profession."
I have it on good authority that individual prescriber cases are steadily increasing in number so suspect before too long the medical defence unions are going to make some significant noises about the situation. They may feel compelled to intervene, perhaps in favour of more rigorous enforcement of the existing guidelines, or even a withdrawal of legal support in cases of flagrant misprescribing.
What's needed. Campaign groups of the past such as VOT, Beat The Benzos and BAN set out some laudable aims and objectives. At present the All Party Parliamentary Group for Involuntary Tranquilliser Addiction (APPGITA) has detailed proposals in its Manifesto.
Benzodiazepine withdrawal support in the UK is almost entirely in the hands of just a small handful of charities, local and independent support groups such as the Bristol and District Tranquilliser Project, CITA, Oldham Tranx, Mind in Camden, the Bridge Project in Bradford and Recovery Road.
As of first importance I should therefore like to see:
The establishment of dedicated regional / local withdrawal clinics or centres financed by the Department of Health and staffed by trained medical practitioners (counsellors, doctors, nurses, pharmacists) who could also make regular visits to GP surgeries. The special needs of involuntary tranquilliser addicts are not met by drug misuse / illicit use facilities;
A national 24 hour helpline;
Re-education or at least detailed advice to prescribers about benzodiazepine withdrawal and information about where to refer patients for help, advice and support. The Ashton Manual has a wealth of information, provides detailed withdrawal protocols and is recommended reading for both doctors and patients alike;
A public inquiry;
More research into benzodiazepine withdrawal and long-term / permanent damage (see below).
2. A PERSONAL ACCOUNT
Introduction. It is now some 14 years since I withdrew from benzodiazepine tranquillisers and I am still suffering from a variety of debilitating symptoms which have crippled and incapacitated me to such an extent that I am still unable to lead what might be called a normal life. The GP who originally helped me off the drugs fourteen years ago retired a few years after I first saw him and since then I have presented my unrelenting pain to a number of medical practitioners - both GPs and specialists. For the most part I have been greeted with disbelief, denial and, on a couple of occasions, derision. I have been unable to achieve any kind of acknowledgement or recognition let alone any sort of therapeutic treatment. I have been told I am just unfortunate and that I should learn to live with it!
I recall one medical practitioner suggesting that my withdrawal symptomatology was a re-emergence of the "anxiety condition" for which I was prescribed benzodiazepines until I pointed out that I was originally prescribed them as muscle-relaxants and was not at the time suffering from anxiety or insomnia when I first complained of abdominal pain at a doctor's surgery. Over the years I have become well aware that many doctors claim that the benzodiazepine withdrawal syndrome is nothing more than the re-emergence of an underlying anxiety disorder. This somewhat naïve argument crumbles under the weight of evidence to the contrary. Countless people were given these drugs initially for conditions other than anxiety or insomnia, for example as muscle relaxants or for sports injuries. The withdrawal syndrome can affect those prescribed benzodiazepines for an anxiety disorder and those prescribed them as muscle relaxants with equal ferocity. Other doctors, unfamiliar with the withdrawal syndrome, may diagnose, and inappropriately treat, what they perceive as new illnesses or conditions when faced with a patient presenting with symptoms of tolerance and/or withdrawal.
It really does not matter if a person was prescribed benzodiazepines for anxiety, insomnia, epilepsy or muscle spasm - all are at risk of suffering adverse effects, tolerance and withdrawal problems.
I no longer refer to my persisting symptoms as the benzodiazepine withdrawal syndrome. Specifically, the sensory and motor symptoms I still suffer from are the result of long-term benzodiazepine use and are evidence of permanent injury to my central nervous system.
Doctors seldom encounter people like me because the majority of people exposed to long-term benzodiazepine use are either still on the drugs or have died - for whatever reason - while still taking them. Doctors, in general, do not know what to do with long term-benzodiazepine patients so it is far easier to maintain them indefinitely on the drugs than to encourage them to withdraw. There are actually relatively few who have managed to come off the drugs after long-term use. Those who do come off - and stay off - are very often persuaded by their doctors that they are suffering from something else and, more often than not, are subject to misdiagnoses and may, as a consequence, receive inappropriate treatment.
It's not all doom and gloom though. My current GP is supportive and sympathetic but at a loss to know what to do to help me. He has offered to explore any treatment regime that I may come across. There is of course no current substantive research into long-term benzodiazepine damage so the offer remains unopened on the table. In 2001 I received my one and only apology from an Australian doctor after he visited my web site. It meant a lot to me at the time - and still does.
"Ray, You are right in EVERYTHING you say and as a third generation doctor I apologise unreservedly to you and those like you who may have been prescribed Valium and similar drugs where simple alternatives may have existed. Yes, by 1988 it was abundantly clear that these drugs had many, many dangers and very limited benefits for insomnia or anxiety patients. You are welcome to quote anything I have written to you on your web page, especially my small apology which is VERY real and heartfelt (and, I hope, meaningful)." - Dr Andrew Byrne, General Practitioner, Drug and Alcohol, 75 Redfern Street, Redfern, New South Wales, 2016, Australia, March 25, 2001. See: Benzodiazepine Dependence, 1997 · Benzodiazepines: the end of a dream, 1994.
In the hope that someone might benefit from my experience I shall give a synopsis of my case, describe my current plight and give the most likely cause for my ongoing suffering. After evaluating all the information and evidence at my disposal it seems to me that the reason for my continued suffering is GABA/Benzodiazepine Receptor Deficiency caused by long-term benzodiazepine prescription. The natural mechanism which keeps my nervous system calm has been severely damaged. A PET scan might confirm this but I've been told I can't get one on the NHS!
Background. Following dental treatment in 1984 I had an allergic reaction to Flagyl (metronidazole) - an antibiotic. Among other things I had severe pain in the right side of my abdomen. My GP said it was a muscle spasm and prescribed Xanax (alprazolam) - a benzodiazepine tranquilliser which he called a muscle-relaxant. The pain would not go away so I returned to my GP a number of times and was prescribed a succession of benzodiazepines: Tranxene (clorazepate), Librium (chlordiazepoxide), Frisium (clobazam) as well as Libraxin (chlordiazepoxide + clidinium) and Dormonoct (loprazolam) before I got some pain relief from Valium (diazepam). I was however becoming anxious and depressed but did not realise at the time that the drugs I was being prescribed for muscle pain were themselves responsible for this. I was never warned about the possibility of habituation, or the existence of a withdrawal syndrome. The drugs were described and prescribed to me as muscle relaxants, not anxiolytics. In 1984, with obviously no access to the Internet - or to other medical resources - I saw no reason not to trust my doctor's judgement.
By early 1985 I was prescribed 90mg diazepam daily and I was quite heavily sedated. The anxiety and depression got worse and I was prescribed a variety of anti-depressants both by my doctor and by a psychiatrist I was referred to. The new drugs did not help. For the next fourteen years I was repeatedly told I suffered from anxiety with depression and my GP said I would need to take diazepam for the rest of my life. I became housebound and reclusive - severely depressed and frightened of my own shadow. The abdominal pain I had first presented with continued through all these years too. The GP reduced my dose of diazepam twice - from 90 to 60mg and some time later from 60 to 30mg. On both occasions I experienced major problems but did not at the time realise they were associated with dramatic reductions in dose.
Withdrawal. In 1998 my wife spoke to a new GP in our area and he agreed to help me if I would see him as a patient. He diagnosed benzodiazepine addiction and strongly suspected that my depression was induced by long-term benzodiazepine use. Over a period of 3 months he helped me to reduce the 30mg diazepam to zero although with hindsight, the 5mg reductions I made every two weeks were perhaps a little too aggressive. As I reduced the dosage I began to feel better - the depression started to lift and I became less anxious, agitated and fearful. The abdominal pain I had first presented with in 1984 also disappeared. For about ten days off the drugs I felt really well and then suffered an explosion of symptoms. The reason for this delay is of course because of the half life of diazepam and its long-acting active metabolites.
Withdrawal Symptoms. I suffered from a wide range of perplexing and often bizarre symptoms: tinnitus, headaches, sensory disruption (hyperacusis, photosensitivity, vivid 3D vision, blurred vision and seeing thorough a veil, sore, itchy eyes, metallic taste, weird sense of smell [hyperosmia, kakosmia], impaired balance and co-ordination, pins and needles, blepharospasm, fasciculations), electric shock sensations all over my body, muscular and joint problems (aches and pains in face, scalp, jaw, teeth, limbs and back, stinging, burning and twitching muscles, hyperreflexia), dizziness, insomnia, poor short-term memory and concentration, rapid weight loss, gastrointestinal problems, dysphagia, hyperthermia, tremors, hyperventilation, allergic reactions, derealisation and depersonalisation.
LONG-TERM PROBLEMS / PERMANENT DAMAGE. After the first two years off the drugs, most of the above-mentioned symptoms had resolved. However, a number of problems, including constant bilateral tinnitus, paraesthesiae, muscular spasms, fasciculations, headaches and intermittent jaw and facial pain have persisted. After fourteen years, I suspect that these are permanent.
PROFESSOR LADER'S REPORT. In 2000 I contacted a solicitor about suing my prescribers for clinical negligence. My case was ultimately successful and achieved an out-of-court settlement in 2002. As part of the process I was interviewed by Professor Lader on July 20, 2001 in London. Here are some extracts from an 18 page Causation Report prepared by Professor Malcolm H Lader, Professor of Clinical Psychopharmacology, Institute of Psychiatry, London SE5 8AF. The Report speaks for itself. It concludes that the harm inflicted on me was the result of clinical negligence ie. the original misprescription, misdiagnosis of depression and anxiety and failure to recognise drug-induced symptomatology.
(Note: Dr B is the Consultant GP who prepared a report on breach of duty issues; Drs X and Y are the defendants; Dr W a psychiatrist; Appendix 5 is the Ashton Manual)
"The report of Dr B concentrates on the liability issues. After detailing the medical records in section 6, Dr B then gives a commentary on benzodiazepines (section 7). In this, he sets the use of benzodiazepines into its historical context, in particular with respect to warnings such as those of the Committee on Review of Medicines and the Drug and Therapeutics Bulletin. He says that by 1984 the risks and problems for benzodiazepine were widely recognised and were a subject of an editorial in the British Medical Journal of 14th April 1984. In section 8 Dr B discusses the standard of care given by Dr X and Dr Y and concludes that it did "fall below a minimum standard of reasonable medical competence, which would not have been mirrored by a responsible body of General Practitioners certainly from the late 1980s onwards". Dr B also draws attention to the failure of the GPs to follow Dr W's advice concerning phasing out the Valium. He could find no evidence that the GPs warned or tried to help Mr Nimmo to reduce his intake of diazepam. He notes that there were large quantities of 5mg and 10mg tablets prescribed but no specific indication of how to take it. Apart from the referral for psychiatric nurse assessment in 1995 there is no attempt to assess Mr Nimmo's problems. In section 9, Dr B summarises his criticisms and describes the pattern of prescribing as "inexcusable".
At interview, Mr Nimmo came very promptly, having driven down from Scunthorpe and across London. He was very pleased with himself for having done so as this was the first time since 1983 that he had visited London.
He is a bearded articulate man with a slight Yorkshire accent. He was very open in manner and good rapport was quickly established. There was no evidence that he was attempting to exaggerate or distort his account of events. He did not appear to be either anxious or depressed at the time of interview and I detected no features of either obsessionality or a psychotic state. He described his symptoms to me in some detail but not in an obsessive way. He had symptoms whilst on benzodiazepines which essentially were those of inability to concentrate, poor short-term memory and a variety of physical symptoms such as sweating, constipation, flu-like symptoms, dry itchy skin. He also put on a great deal of weight. His most persistent symptom was the persistent abdominal pain over the region of the liver. His main mental symptom was the development of a severe depressive disorder so that he was actually suicidal at times. Later he became increasingly anxious with panic attacks and agoraphobia. He had violent mood swings and also became verbally aggressive, with outbursts and paranoia. He became very tired with fainting attacks and had feelings of hopelessness, worthlessness and guilt.
Following withdrawal from diazepam in late summer/autumn of 1998, he developed sensations of electric shocks, all over the body. He found his balance was impaired and he developed tinnitus which has continued. He also had out of body experiences, and derealisation which lasted for about 18 months. He had bowel upsets, difficulty swallowing and alternating diarrhoea and constipation. He had perceptual hypersensitivity with sounds seeming very loud. He also experienced strange and unpleasant smells and burning sensations on the left side of the scalp. His symptoms came in waves. During the first year after withdrawal he suffered from insomnia but is now sleeping much better. He still has problems with concentration and poor short-term memory. His appetite is good but he has lost weight and is down now to 12 stone. He still remains irritable but this is now much less. He has muscle twitching and tightness and cramp in the legs. He describes vividly that 10 days after stopping the Valium the symptoms suddenly surged to a maximum, "like hell breaking loose". I asked him to describe how severe the symptoms were now compared with the maximum and he said they were down to about 20%. He varies from day to day. He is not taking any drugs or herbal remedies.
Opinion. I have been instructed to prepare a report dealing with causation issues in connection with the treatment received. With respect to the symptoms developed by Mr Nimmo, I am of the opinion that the depression and anxiety symptoms, were a consequence of the prescription of the benzodiazepines, including diazepam. The history suggests that it was only at the excessive dose of 90mg that Mr Nimmo felt comfortable from a symptomatic point of view. Therefore the use of 30mg was insufficient to suppress any breakthrough withdrawal symptoms. In other words, all the time that Mr Nimmo was on 30mg a day he was actually suffering from partial benzodiazepine withdrawal. The symptoms that he described such as flu-like symptoms, very profuse sweating, and itchy skin are characteristic of the benzodiazepine withdrawal. Furthermore, he was also suffering from the effects of the benzodiazepines themselves, thus alternating between the side effects such as oversleeping and the withdrawal effects such as insomnia.
The causation for the depression, the main symptom, therefore, is that of a withdrawal symptom from the benzodiazepine (see table 3, appendix 3). This is a known complication since it was described by myself and a colleague (appendix 4). I believe that the symptoms were so severe that this resulted in his inability to work throughout the entire time.
The injuries caused to Mr Nimmo by the prescription of benzodiazepines include many years of symptomatic complaints including depression. I also believe that his abdominal pain, although not caused by the benzodiazepines, was perpetuated by them. These drugs are known to be associated with pain and it is significant that this pain disappeared on full withdrawal. There was also the injury reflected in the inability to work for so many years.
Mr Nimmo still has some withdrawal symptoms which are suggestive of a protracted withdrawal (appendix 5). This is quite common following withdrawal after many years of usage of benzodiazepines. However, he is neither anxious nor depressed and is optimistic about the future.
I believe that Mr Nimmo's depression has resolved following withdrawal. The symptoms that he is left with will gradually wane but he may be left with some symptoms indefinitely."
Professor Malcom H Lader, OBE, LLB, DSc, PhD, MD, FRC Psych, FMedSci, July 20, 2001.
When this report was prepared in 2001 I was still very optimistic about recovery. Sadly, I am still dogged by a constellation of sensory and motor symptoms and am somewhat resigned to the fact that I shall never fully recover.
3. CAUSES & MECHANISMS
In her Protracted Withdrawal from Benzodiazepines: The Post-Withdrawal Syndrome (1995) Professor Ashton describes likely causes and mechanisms of benzodiazepine withdrawal syndrome:
"Such protracted perceptual and muscular disturbances raise the possibility that benzodiazepines are capable of inducing long-term hyperexcitability of central sensory and motor neural pathways." (See also Table 2 for some protracted symptoms.)
In her Manual - Benzodiazepines: How They Work & How to Withdraw, (2002) Professor Ashton suggests protracted and possibly permanent symptoms may be caused by:
"Biochemical alterations caused by benzodiazepines; nervous system hyperexcitability due to persisting changes in GABA/benzodiazepine receptors; structural or functional damage to brain tissue."
A study entitled "Benzodiazepine receptor deficiency and tinnitus" by Shulman et al. 2000; International Tinnitus Journal 6 (2) 98-111) demonstrated benzodiazepine receptor deficiency in subjects with tinnitus. Professor Ashton commented thus:
"This paper seems to suggest that there is a deficiency of benzodiazepine receptors in tinnitus. This makes sense since GABA/benzodiazepine receptors shut down during chronic benzodiazepine use as a result of tolerance. When the person comes off the benzodiazepines they are often left with a receptor deficiency - that could be why tinnitus is so common in acute withdrawal. In most cases the receptors return to normal and the tinnitus disappears. The unlucky ones who have protracted tinnitus may be the ones whose receptors in that particular part of the brain (temporal cortex) do not return to normal. One of the many functions of GABA/BZ must be to keep the brain quiet!"
See also: "High frequency localised "hot spots" in temporal lobes of patients with intractable tinnitus: A quantitative electroencephalographic (QEEG) study", Heather Ashton et al., August 2007 which also demonstrates the low density of benzodiazepine receptors and an epileptic-like temporal lobe focus in tinnitus patients. See complete study.
In a letter of June 30, 2009 Professor Ashton wrote (on my behalf):
"Tinnitus is extremely common in benzodiazepine withdrawal, as are paraesthesiae and muscle twitches in many parts of the body. These too may become protracted and in some cases appear to be permanent.
I have also seen many cases of facial pain, usually unilateral, affecting neck, teeth and jaw, sometimes accompanied by facial tingling, numbness and altered sensation, during the course of benzodiazepine withdrawal. These symptoms have puzzled dentists, pain specialists and neurologists and have usually been diagnosed finally as "atypical facial pain". Sometimes the symptoms persist chronically or intermittently for many years.
Such symptoms are thought to be manifestations of CNS hyperexcitability which is physiologically controlled by the balance between glutamate (excitatory neurotransmitter) and GABA (gamma aminobutyric acid, inhibitory neurotransmitter which is enhanced by benzodiazepines). It is possible that a deficiency in GABA/benzodiazepine receptors can result from long-term benzodiazepine use. Decreased density of benzodiazepine receptors has been demonstrated in subjects with tinnitus (Shulman et al. 2000; International Tinnitus Journal 6 (2) 98-111)."
In 2003 Professor Ashton commented:
"Withdrawal symptoms can last months or years in 15% of long-term users. In some people, chronic use has resulted in long-term, possibly permanent disability." (Good Housekeeping, August 2003).
Estimates vary but it is clear that a significant number of people suffer from long-term / permanent disability post-withdrawal.
Over the last 12 years or so I have been in regular contact with Professor Heather Ashton, DM, FRCP who is familiar with my case. During that time she has offered me some very helpful advice and explanations so am indebted to her not only for her kindness and compassion towards me but also for all her hard work, selflessness and persistence for the benzo cause over the years.
From a personal point of view and as a sufferer of some intense physical problems caused by long-term benzodiazepine use I should like to see some research into "GABA/ Benzodiazepine Receptor Deficiency" as a cause of Benzodiazepine Withdrawal Syndrome and long-term / permanent damage.
For more information about benzodiazepine-induced structural damage to the brain and nervous system see: Drugs linked to brain damage 30 years ago, Independent on Sunday, November 7, 2010. In particular, also read the Letter from Professor M Lader to Professor R Cawley, January 6, 1982. Clearly more research is needed.
Research. Unfortunately there is no ongoing research at the moment. In 1995 Professor Ashton proposed research into Long-Term Effects of Benzodiazepine Usage: Research Proposals but was denied funding. These detailed proposals still stand but it is unlikely that her patient base can be replicated very quickly even if someone could be found to embrace the research. In a speech to the Bridge Street Project, Bradford in December 2011 she said:
"No-one took over my clinic when I retired [in 1994], and Professor Lader's clinic in London also closed. So it is now up to organisations such as this one to provide services for these patients."
Z-Drugs. I should point out that my remarks about the damaging effects of benzodiazepines also apply to the group of drugs known as Z-drugs which are prescribed as hypnotics in the UK: zopiclone (Zimovane), zaleplon (Sonata) and zolpidem (Stilnoct). These drugs are chemically different from benzodiazepines but have the simlilar effects on the body and act by the same mechanisms. They are equally addictive and have the same potential for harm.
Concluding thoughts. It has never been satisfactorily demonstrated why a small but significant number of people never fully recover though it is likely that there is a genetic cause. Not all people start out in life with the same number or density of GABA/benzodiazepine receptors so those with low concentrations are very vulnerable and most likely to be most adversely affected by long-term / high dose benzodiazepine use. They can ill afford to be left deficient by the drug! Of course, if I am correct, it also follows that those with average or above average concentrations of GABA/benzodiazepine receptors are likely to recover more quickly and even fully. The good news for those in the early stages of withdrawal is that the majority of people recover fully (or at least recover enough to resume a normal life) over a period of up to two years.
Although the long-term symptoms I suffer from are mainly of a sensory and motor nature others complain of a variety of problems caused by benzo use including variations of sensory and motor problems eg. numb gums and teeth, neck and head pain, burning feet, back and arms, sweating while cold, painful leg muscles, foot pain, joint pain, cramps, jerks, fatigue and exhaustion, muscle weakness and twitching, and insomnia. Other protracted symptoms may include anxiety, depression, poor memory and cognition, and gastrointestinal symptoms. See Professor Ashton, Manual, Chapter 3, Table 3.
I am aware that my personal account is anecdotal but it is nonetheless very real to me and I have heard similar accounts by many others I've spoken to over the years. Some of my thoughts on the causes of benzodiazepine damage may be speculative but I hope, at the very least, they will give food for thought. Who knows? One day someone, somewhere, may rise to the challenge and conduct a scientific investigation into the whole business of benzodiazepine damage. I shan't hold my breath of course. As Professor Ashton pointed out to me:
"This would require recruiting a large number of patients and doing imaging studies for benzodiazepine receptor density. Expensive and very few medics would be interested. As you know, I have applied many times in the past for grants to study long-term benzodiazepine effects. Also in vain. Money is so tight in academia these days that it is almost impossible to get a grant for basic research. Many of the medical grants are from drug companies!!"
I'll keep my fingers crossed. Just in case.
Benzodiazepine receptor deficiency and tinnitus. Shulman A, Strashun AM, Seibyl JP, Daftary A, Goldstein B.Int Tinnitus J. 2000;6(2):98-111.
Martha Entenmann Tinnitus Research Center, Inc., Health Sciences Center at Brooklyn, State University of New York, Box 1239, 450 Clarkson Avenue, Brooklyn, New York 11203, USA.
Abstract: As regards the symptom of a predominantly central tinnitus of the severe, disabling type, it has been hypothesized that a deficiency in the benzodiazepine receptor exists in the medial temporal lobe system of brain and is directly related to affect impairments including anxiety, stress, depression, and fear. This hypothesis has been investigated with single-photon emission computed tomography using the benzodiazepine radioligand 123I Iomazenil. Visual analysis revealed preliminary results of diminished benzodiazepine-binding sites in the medial temporal cortex of all patients with severe tinnitus (N = 6), a finding that is consistent with the hypothesis implicating GABAergic mechanisms in the pathophysiology of the disorder. An abnormal gamma-aminobutyric acid--A benzodiazepine receptor density may be an objective neurochemical measure of the severity of a central-type tinnitus and a rationale for treatment. Clinical correlation with the history, clinical course of the patient, and stress questionnaire are presented. PMID: 14689626 [PubMed - indexed for MEDLINE]
*In a recent speech Professor Heather Ashton said, "A recent GP study in Newcastle showed that there is still an average of 185 long-term (over 6 months) prescribed benzodiazepine users in every GP practice." According to the BMA there are over 10,000 GP practices in the UK so if these findings are replicated nationwide there are potentially in excess of 1,850,000 patients on long-term benzodiazepine prescriptions.
In the UK and interested in taking legal action against your prescriber? Contact Miss Caroline Moore, Medical Solicitors, Unit 8B, South West Centre, Troutbeck Road, Sheffield S8 0JR. Visit website.