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Professor Malcolm H Lader
OBE, LLB, DSc, PhD, MD, FRC Psych, FMedSci
Emeritus Professor of Clinical Psychopharmacology,
Institute of Psychiatry, King's College,
London SE5 8AF, England

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Professor Malcolm Lader of the Institute of Psychiatry has published more than 100 papers on the subject of benzodiazepines. In 1978 he called these drugs "the opium of the masses" because of the very high prescribing rates. In 1981 he warned that in the context of tranquilliser addiction "there is an epidemic in the making" and in 1988 he stated that this was the biggest medically-induced problem of the late 20th Century.

Dalmane [flurazepam] and other similar benzodiazepine tranquillisers can make people much more suggestible and vulnerable to be being taken advantage of while taking the drug. There are cases in which people have shoplifted, crashed cars and behaved violently while under the influence of benzodiazepines which are comparable to the effects of alcohol. Dalmane [like Valium / diazepam] is a long-acting drug which has a cumulative effect and so while there may be fluctuations in the level of confusion, there would be no lucid moments...A person's judgement, insight, memory, ability to plan and perceptions are all impaired. Dalmane should be taken off the market...The prescribing guidelines [published in 1988] have had no effects 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." - Professor Malcolm H Lader, Emeritus Professor of Clinical Psychopharmacology, King's College London, January 2012.

I estimate about 20-30% of people who are on a benzodiazepine like diazepam have trouble coming off and of those about a third have very distressing symptoms. The anxiety or the sleeplessness comes back, they feel as if they're physically ill - we talk about a flu-like illness - then they start to get some very bizarre symptoms which we technically call hypersensitivity but essentially what it is is the brain is starting to wake up and it overwakes - sounds appear loud and lights appear bright, so they're wearing sunglasses indoors and they also have a symptom whereby they feel very unsteady and they will walk round the room holding on to the walls - and they really are then in a bad withdrawal state. It's very difficult to come off these drugs and the facilities are just not available and the great scandal is that the NHS claims to be dealing with these people by referring them to addiction centres, where essentially they'll sit next to a street user who's injecting heroine and of course a housewife who's been put on tranquillisers by her doctor is very upset by this ... There is a change taking place which is that if a general practitioner prescribes for longer than the agreed time - two weeks or four weeks - they can be sued by the patient for substandard clinical care and I suspect in the longer term the prescribing of these drugs will be as much dependent on lawyers' attitudes as it will be on doctors' attitudes. - Professor Malcolm H Lader, Professor of Clinical Psychopharmacology, Institute of Psychiatry, University of London on BBC Radio 4 Face the Facts, July 27, 2011.

On benzodiazepine brain damage reported to the Medical Research Council in January 1982: "The results didn't surprise us because we already knew long-term alcohol use could cause permanent brain changes. There should have been a really good, large-scale study but I was never given the facilities or resources to do it. I asked to set up a unit to research benzos but they turned me down... they could have set-up a special safety committee, but they didn't even do that. I am not going to speculate why; I was grateful for the support they did give me. There were always competing interests for the same resources, so maybe it wasn't regarded as important enough. I was getting on with other research and didn't want to be labelled as the person who just pushed benzos... I should have been more proactive... I assumed the prescribing would peter out, but GPs are still swinging them around like Smarties." – Professor Malcolm Lader, Emeritus Professor of Clinical Psychopharmacology, Institute of Psychiatry, University of London, Independent on Sunday, November 7, 2010.

In a Radio 4 Interview in 1999 Professor Lader said: "It is more difficult to withdraw people from benzodiazepines than it is from heroin. It just seems that the dependency is so ingrained and the withdrawal symptoms you get are so intolerable that people have a great deal of problem coming off. The other aspect is that with heroin, usually the withdrawal is over within a week or so. With benzodiazepines, a proportion of patients go on to long term withdrawal and they have very unpleasant symptoms for month after month, and I get letters from people saying you can go on for two years or more. Some of the tranquilliser groups can document people who still have symptoms ten years after stopping."

"We knew from the start that patients taking markedly increased doses could get dependent, but thought only addictive personalities could become dependent and that true addiction was unusual. We got that wrong. What we didn't know, but know now, is that even people taking therapeutic doses can become dependent."

"I estimate about 20-30% of people who are on a benzodiazepine like diazepam have trouble coming off and of those about a third have very distressing symptoms. The anxiety or the sleeplessness comes back, they feel as if they're physically ill - we talk about a flu-like illness - then they start to get some very bizarre symptoms which we technically call hypersensitivity but essentially what it is is the brain is starting to wake up and it overwakes - sounds appear loud and lights appear bright, so they're wearing sunglasses indoors and they also have a symptom whereby they feel very unsteady and they will walk round the room holding on to the walls - and they really are then in a bad withdrawal state. It's very difficult to come off these drugs and the facilities are just not available and the great scandal is that the NHS claims to be dealing with these people by referring them to addiction centres, where essentially they'll sit next to a street user who's injecting heroine and of course a housewife who's been put on tranquillisers by her doctor is very upset by this ... There is a change taking place which is that if a general practitioner prescribes for longer than the agreed time - two weeks or four weeks - they can be sued by the patient for substandard clinical care and I suspect in the longer term the prescribing of these drugs will be as much dependent on lawyers' attitudes as it will be on doctors' attitudes." Professor Malcolm H Lader, BBC Radio 4 Face the Facts, July 27, 2011.

"We actually knew from some experiments back in the 1960s that you could have dependence - addiction to benzodiazepines but only on high dose. Later it became apparent that some people were having problems trying to stop and that they weren't on high doses; and then the whole question arose: can you actually get dependent - can you actually become addicted - to normal therapeutic doses? And then the alarm bells started to ring, quietly at first and then louder and louder. […] Doctors were not well equipped to deal with this. This was something new in their experience. They don't like dealing with chronic drug use or addiction anyway and here they were being confronted by hundreds in their practices - whom they had put on the tranquillisers - and were now coming for help to come off. And I think they were bewildered by the numbers and severity of some of the reactions. […] The main characteristic of these dependent people was that when they tried to stop they didn't just get their old symptoms back, they didn’t just get their old symptoms back in an exaggerated form, they developed new symptoms which they had not experienced before. […] Some people are put on to these tranquillisers not because they are anxious or have insomnia, they can't sleep, it's because they have muscle spasms - they've been injured in some way - they’ve had a skiing accident, or they've got a bad back. And they're put on and they've had no psychiatric history, they've had no anxiety, no insomnia, and yet they're just as likely to show dependence and withdrawal when they stop as those with a previous psychiatric history." Professor Malcolm H Lader, In Pills We Trust, Discovery Channel, December 4-18, 2002.

"Some older doctors just don't want to change, and they're still giving out repeat prescriptions. Some GPs also deny the drugs' effects, arguing that their patients have addictive personalities. Yet one of the most common benzodiazepines, diazepam (brand name Valium), is also used in patients with sports injuries as a muscle relaxant. We found that people without any psychiatric condition at all have the same withdrawal problem... We found that patients who had been put on Valium were getting withdrawal symptoms when it was stopped. Some of these were similar to alcohol withdrawal. They included mild delirium tremens, sleeplessness, jumpiness, everything seeming loud and bright - some people said they felt as though they were going mad." Professor Malcolm Lader, Sunday Express Magazine, 1999.

The benzodiazepines are still extensively used in psychiatry, neurology and medicine in general. Anxiety disorder and severe insomnia are important syndromal indications, but these drugs are widely prescribed at the symptomatic level, resulting in potential overuse. The official data sheets recommend short durations of usage and conservative dosage. Although short-term efficacy is established, long-term efficacy remains controversial, as relevant data are scanty and relapse, rebound and dependence on withdrawal not clearly distinguished. The risks of the benzodiazepines are well-documented and comprise psychological and physical effects. Among the former are subjective sedation, paradoxical release of anxiety and/or hostility, psychomotor impairment, memory disruption, and risks of accidents. Physical effects include vertigo, dysarthria, ataxia with falls, especially in the elderly. Dependence can supervene on long-term use, occasionally with dose escalation. The benzodiazepines are now recognised as major drugs of abuse and addiction. Other drug and non-drug therapies are available and have a superior risk benefit ratio in long-term use. It is concluded that benzodiazepines should be reserved for short-term use - up to 4 weeks - and in conservative dosage. Professor Malcolm H Lader. Limitations on the use of benzodiazepines in anxiety and insomnia: are they justified? Eur Neuropsychopharmacol 1999 Dec;9 Suppl 6:S399-405.

The concepts of dependence, addiction and abuse comprise overlapping clinical phenomena. The earlier anxiolytic drugs, in particular the barbiturates, were prone to abuse, i.e., non-medical use, and to high-dose misuse. Their modern counterparts, the benzodiazepines, are abused in a patchy way and are sometimes taken in regularly high doses. However, the main problem is physical dependence as manifested by a withdrawal syndrome on discontinuation of the drug. The withdrawal syndrome has been carefully described and comprises physical and psychological features. In particular, perceptual symptoms such as photophobia, hyperacusis and feelings of unsteadiness may predominate. The syndrome may come on during dosage reduction but generally starts 2-10 days after cessation of the benzodiazepine, depending on its elimination half-life. About a third of long-term users suffer a recognisable syndrome even after a tapered withdrawal, its duration usually being only a few weeks. A few patients go on to a prolonged withdrawal syndrome, often characterised by muscular spasm. The treatment of the withdrawal syndrome is supportive and non-specific. A few patients started on benzodiazepine therapy escalate the dose. They tend to show the characteristic 'passive-dependent' personality features and may previously have misused other CNS depressants such as the barbiturates and alcohol. Abuse of benzodiazepines occurs in a rather varied way from country to country. Worldwide, flunitrazepam has caused concern but, in the UK, the main problem has been the intravenous use of temazepam. The molecular pharmacology of the benzodiazepine receptor has been extensively studied and is undoubtedly complex. Professor Malcolm H Lader. Anxiolytic drugs: dependence, addiction and abuse, Eur Neuropsychopharmacol 1994 Jun;4(2):85-91.

The widespread usage of the benzodiazepines has inevitably led to thousands of people becoming dependent, perhaps 500,000 in the UK and twice that number in the USA where long-term use is less common. Patients who have become dependent and have either been unable to withdraw or have only done so with great symptomatic distress justifiably feel aggrieved against their doctors and the benzodiazepine manufacturers for not warning them about the risk. In the UK about 2000 people have started legal proceedings, coordinated by about 300 firms of lawyers. It is the largest civil action ever. (p58) Lader M. History of Benzodiazepine Dependence. Journal of Substance Abuse Treatment 1991; 8:53-59.

In a few unfortunate patients symptoms may persist and include feelings of unsteadiness, neck tension, a "bursting" head, perceptual distortions and muscle spasm. The strange nature of these symptoms distresses the patient, perplexes the doctor and may lead to the patient being regarded as a hopeless neurotic or even a malingerer. We believe this to be a genuine part of a protracted withdrawal syndrome as the symptoms are identical with those seen earlier in withdrawal. (p828) Lader M. Benzodiazepine Problems. British Journal of Addiction 1991; 86:823-828.

"The Medical profession, I think, is fairly ashamed of what has happened. It's allowed this very untrammelled prescribing to go on. My estimate is that there’s something between a quarter and half a million people in this country, at this moment, who would have problems trying to stop their tranquillisers. They would need help to do so and there's been a sense that they're difficult to treat, difficult to deal with and a lot of these patients are just kept on their medication indefinitely. No real attempt is made to help them come off ... The Government should tackle this problem face on. There are thousands of people out there who are not receiving treatment, hundreds of GPs who don’t know really how to treat these patients. There are self-help groups who are crying out for funding just to keep going at a very low level. I think the Government should now acknowledge the problem and set funds aside, because if the Government doesn't do that, these people will go to their graves with their tranquilliser bottles beside them." BBC Radio 4, Face The Facts, 1991.

"When somebody comes into my office and says that they've been trying to stop their lorazepam, my heart sinks because I know I shall have twice as much of a problem as getting them off, say, Valium: the symptoms are more severe, they're more persistent, more bizarre, and people are much more distressed by them... I feel that this compound should not now be prescribed because of the problems which may arise in some patients." Professor Malcolm Lader, member of the Committee on the Review of Medicines, Brass Tacks, BBC2, October 20, 1987.

"In the UK, 11.2% of all adults take an anti-anxiety drug at some time during any one year. But over a quarter of these people (3.1% of all adults) are chronic users, taking such medication every day. Even at a conservative estimate, 20% of these will develop symptoms when they attempt to withdraw. That means a quarter of a million people in the UK. The sooner the medical profession faces up to its responsibilities towards these iatrogenic addicts, the sooner it will regain the confidence of the anxious members of our community." M.H. Lader, A.C. Higgitt. Management of benzodiazepine dependence – Update 1986, Brit J Addiction, 1986, 81,7-10.

Withdrawal Syndrome: The fully-developed benzodiazepine withdrawal syndrome has been described as a severe sleep disturbance, irritability, increased tension and anxiety, panic attacks, hand tremor, profuse sweating, difficulty in concentration, dry retching and nausea, weight loss, palpitations, and muscular pains and stiffness. Instances are also reported of more serious developments such as epileptic fits, psychotic reactions and even death. During the last year we have withdrawn, under double-blind, placebo-controlled conditions, 24 patients (13 males, 11 females) from low-dose, long-term benzodiazepine treatment. Their psychiatric diagnosis was anxiety neurosis, depression, or personality disorder, and none were alcoholic or took other drugs. They had all received benzodiazepines in therapeutic doses for at least one year (range: 1-16 years). All have experienced some form of withdrawal reaction, but more importantly, the changes on withdrawal of normal doses have in most cases been indistinguishable from those on withdrawal of high doses in other patients either in quality or quantity. The withdrawal reaction has ranged from anxiety and dysphoria to severe affective and perceptual changes. Anxiety ratings rise as the drugs are discontinued but usually subside to pre-withdrawal levels over the next two to four weeks This in itself suggests that the symptoms represent a true withdrawal syndrome and not a revival of the original anxiety symptoms. Furthermore, some of the symptoms are untypical of anxiety. The dysphoria is an amalgam of anxiety, depression, nausea, malaise and depersonalisation. Perceptual changes are common; patients complain of intolerance to loud noises, bright lights and touch, numbness, paraesthesiae, unsteadiness, and a feeling of motion. Some patients have complained strange smells and a metallic taste; some chronic, heavy smokers have even given up their cigarettes temporarily.

Conclusion: As with their predecessors, benzodiazepines are fully capable of inducing both physical and psychological dependence. Human experimental studies confirm those in animals that definite dependence can be induced by giving high doses for a prolonged period but that dependence on therapeutic doses is more apparent as a syndrome complex on withdrawal rather than as marked drug-seeking behaviour. Even so, the withdrawal syndrome is often underplayed as a recrudesce of the original anxiety for which the benzodiazepine was prescribed... Despite this apparent lack of published evidence, the extent of chronic usage of the benzodiazepines - although reflecting the chronic nature of their indications may mean that a proportion of users become dependent, even at normal therapeutic dosage. In view of the psychological impairment associated with chronic sedative ingestion and the socio-economic implications, a careful examination of the problem in an epidemiological framework is a matter of urgency. Petursson H, Lader MH. Benzodiazepine Dependence. Br J Addict 1981; 76:133-45. 3.

Benzodiazepine dependence would be of minor clinical significance if it occurred only in those few individuals taking high doses of drugs; but it would be very important indeed if it supervened even to a minor degree in patients on usual clinical doses. Our clinical impression is that many patients experience symptoms on reduction or withdrawal of their benzodiazepine medication, and that whilst these symptoms somewhat resemble those of anxiety they differ qualitatively and are often more severe than those for which the medication was originally given.

The important feature of the study, however, is that the subjective and objective changes on discontinuing benzodiazepine medication are much the same in quality and quantity in high and low dose subjects. As some of these symptoms were not typical of a recrudescence of anxiety and showed a tendency to remit in time, they must be considered as a possible true withdrawal syndrome. Although our study was open, and conducted on selected subjects, with incomplete data on all subjects, our data do illustrate our findings and clinical experience with many other patients. These results suggest that one reason why chronic users of benzodiazepines experience difficulty in stopping their medication may be the development of a withdrawal syndrome even after modest dosage. The high rate of repeat prescriptions for diazepam and other benzodiazepines might also stem from such a form of dependence. (p243) Cosmo Hallström, Malcolm Lader. Benzodiazepine withdrawal phenomena, Int. Pharmacopsychiat, 1981; 16:235-244.

CURRICULUM VITAE

Professor Malcolm Harold Lader is an external member of the Scientific Staff of the Medical Research Council and Professor of Clinical Psychopharmacology at the Institute of Psychiatry, King's College London, University of London. Professor Lader is also an Honorary Consultant at the Bethlem Royal and Maudsley Hospital (a Post-graduate Teaching Hospital) and conducts and supervises clinics dealing with anxiety, sleep and depressive disorders and drug treatment problems. His experience in psychiatry and clinical pharmacology now extends to over 35 years.

His main research interest is the drugs used in psychiatry, in particular, their side effects. These researches have resulted in the publication of 15 books and about 630 scientific articles (including more than 100 papers on benzodiazepines).

He advises the Ministries of Health, Agriculture, Defence and Transport in various capacities. He is a member of other national and regional advisory committees. He is on the advisory boards of about 30 international scientific journals. Professor Lader is an adviser to the World Health Organisation on drugs used in psychiatry. He is an Honorary Fellow of the American College of Psychiatry. He has been Vice-president of the International College of Psychopharmacology President of the Society for the Study of Addiction and, President of the British Association for Psychopharmacology. Professor Lader was a member of the Committee on the Review of Medicines from 1978 -1989, and was involved in the licensing of medicines. Professor Lader was a member of the Home Office's Advisory Council on Misuse of Drugs from 1981-2000, and Chairman of its Technical Committee from 1984-2000, and advised on drugs of addiction.

Professor Lader trained in physiology with biochemistry, medicine, pharmacology and psychiatry and has formal qualifications in each of these disciplines. He is a Fellow of the Royal College of Psychiatrists, and of the prestigious Academy of Medical Sciences.

He has now had experience of over 500 medico-legal cases and has attended Court on numerous occasions to give expert evidence. He specialises in cases which involve the use of drugs and medicines in psychiatry and on the psychiatric effects of drugs and toxic substances. He is listed in the UK Register of Expert Witnesses.

Entries in current Who's Who, International Who's Who, Who's Who in the World, Debrett's People of Today, etc.

Professor Malcolm Lader OBE, LLB, DSc, PhD, MD, FRC Psych, FMedSci
Emeritus Professor of Clinical Psychopharmacology,
Institute of Psychiatry, University of London, England

Correspondence:
Professor M H Lader,
Institute of Psychiatry,
King's College,
London SE5 8AF, England
Tel: 0207 848 0372
Fax: 0207 252 5437
e-mail: malcolm.lader@kcl.ac.uk

MORE PROF LADER

• Solutions to the tranquilliser trap, Letters to The Times, Professor Lader, October 6, 2012.

• Benzodiazepine Brain Damage, Prof. Malcolm Lader / Medical Research Council File, January 1982.

• Benzodiazepines and Brain Damage, MRC Files, 1980 - 82 (Freedom of Information disclosure, October 2010).

• Letter from Professor M Lader to Professor R Cawley, January 6, 1982.

• Computed axial brain tomography in long-term benzodiazepine users, Lader MH, Ron M, Petursson H, Psy. Med., 14, 203-206 (1984).

• History of Benzodiazepine Dependence. Lader M., Journal of Substance Abuse Treatment 1991; 8:53-59.

• Benzos and Memory Loss: More Than Just "Old Age", Lader M., Prescriber 1992; 3: 13.

• Benefits and risks of benzodiazepines in anxiety and insomnia, Professor MH Lader.

• Dependence on tranquillisers and antidepressants, Professor MH Lader, 1999.


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