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Dr Reg Peart

Reg Peart

The Benzodiazepines

Toxicity, Cognitive Impairment, Long-Term Damage
& The Post Withdrawal Syndrome

Dr R F Peart BSc, PhD
December 2000

Section B

Click on link below for section A

Section A - Cognitive Impairment/Long Term Damage - Reference List and Extracts

Long-Term Damage and The Post Withdrawal Syndrome (PWS)

The existence of the post withdrawal syndrome is recognised and accepted for other drugs like the barbiturates, opiates and alcohol. (See reference 3, 20, 26). Its occurrence is routine enough for it seldom to be commented upon. Although many alcoholics and hard drug addicts receive primary treatment for four to ten weeks, a minority need and receive residential treatment and rehabilitation for up to 12 months. It would be appropriate if similar opportunities were available to benzodiazepine therapeutic addicts. There is a desperate need for them.

Just as there was (and is) a strong resistance from the medical profession and the drug companies to recognising and accepting therapeutic dose dependence there was (and is) a similar reaction to the benzodiazepine post withdrawal syndrome. There is a strong knee-jerk reaction geared to diverting the blame from the drugs and prescribing practices onto the patients. A range of speculative reasons is offered e.g. the symptoms are a return of the original complaint, latent mental problems exposed by the drugs and the old chestnut, personality disorders.

Contrary to these myths are the following:

  1. Few if any studies have actually checked the original records for prescribing diagnosis, most information is anecdotal. The best evidence there is suggest that at least 85% of prescriptions are given for non psychiatric disorders.
  2. There is no evidence that personality traits or characteristics predispose anyone to dependence (Royal College of Psychiatrists, 1987). The few before, during and after dependency studies show no correlation.
  3. All aspects of drug dependency can be fully explained by biochemical factors (World Health Organisation 1993).
  4. The claim that drugs expose latent problems is unprovable, unsustainable and unscientifc. What is provable is that psychoactive drugs cause psychiatric disorders and marked changes in personality.


From the mid-1980s to the mid-1990s there was an increasing number of papers studying this syndrome up to five years after discontinuation of drug taking. These studies were sometimes in parallel with investigations of the nature of long-term damage and conclude that it is an iatrogenic condition. In addition, there is a significant overlap between the syndrome, acute withdrawals and long-term ingestion of benzodiazepines, clearly establishing a link between the post withdrawal syndrome and adverse reactions caused by these drugs.


  1. There is a very wide range of physical and psychological symptoms for example: paranoia, delusions, shaking and trembling, paraesthesiae, depression, behavioural disorders, unstable mood, headache, irritability, insomnia, anxiety, malaise, poor concentration, gastrointestinal problems, abdominal discomfort, depersonalisation, derealisation, emotional instability, sensory disturbances, perceptual changes, auditory changes, tinnitus, vulnerability to stress, unsteadiness, neck tension, neuro-muscular problems "bursting head", phobias, panic, obsessive features and palpitations.
  2. The post withdrawal syndrome is largely responsible for relapse - from 30 to 70% in different studies, up to five years after discontinuation.



The studies have established that the PWS is:



  1. Patients with a history of benzodiazepine, dependence are unlikely to respond normally to these drugs after discontinuation.
  2. There is a 1:1 correspondence between long-term damage and the post withdrawal syndrome.
  3. Careful management of the PWS is required and should include help from doctors, family, friends, support groups, stress management, cognitive behavioural therapy, knowledge and information - to help the patient come to term with the patients changed life situation.
  4. At least 30% of benzodiazepine dependent patients experience the PWS rising to nearly 100% for long-term chronically dependent patients.


Key papers
4, 5, 6, 7,10,17, 23, 24, 26, 27.

1. Tyrer P. et al. (1983) Gradual Withdrawal of Diazepam after Long-Term Therapy. Lancet i,1482 - 86. At six months follow-up 19 out of 41 patients relapsed, three became seriously ill (?), others had developed paranoia and delusions.

2. Ashton H. (1984) Benzodiazepine Withdrawal, An Unfinished Story. British Medical Journal 288,1135-1140. Patients assessed every one - two weeks in withdrawal. Wide range of persisting symptoms, up to at least six months.

3. Jaffe J.H. (1986) Drug Addiction and Drug Abuse. The Pharmaceutical Basis of Therapeutics, 7th Edit. New York, McMillan 1985 chapter 23, 532-81. Depressive states, unstable mood and insomnia are common during the months following withdrawal of alcohol and opioids.

4. Ashton H. (1986) Adverse Effects of Prolonged Benzodiazepine Use. Adverse Drug Reaction Bull.,118, 440-443. Acute withdrawal is followed by a prolonged period (many months) of gradually diminished mixed psychological and somatic symptoms. The illness produced by the protracted syndrome may be more severe than that for which the benzodiazepines were originally prescribed.

5. Ashton H. (1987) Benzodiazepine Withdrawal Outcome in 50 Patients. Br. J. Addiction, 82, 665-71. Patients assessed from 10 - 42 months after withdrawal. 48% had slight symptoms, 22% had moderate symptoms,16% had severe symptoms interfering with life, 6% were polysymptomatic and on other medication, 8% had relapsed on benzodiazepines.

6. Higgit A. et al. (1988) The Natural History of Tolerance to the Benzodiazepines. Psychological Med. Monograph Supple.,13 Cambridge University Press. 'It is no longer debated that tolerance develops over periods of 6 months! Tolerance is still present in patients off benzodiazepines for 5 - 42 months. Low single dose challenge to patients precipitated withdrawal symptoms. It is unlikely that patients with a history of benzodiazepine dependence will respond normally to these drugs'. The presence of permanent changes to the CNS is indicated.

7. Marks J. (1988) Techniques of Benzodiazepine Withdrawal in Clinical Practice. Med. Toxicology, 3, 324-333. Post withdrawal syndrome of many months consists of a fluctuating malaise, poor concentration, abdominal discomfort, depersonalisation, derealisation and emotional liability. Management of the PWS requires various forms of help to come to terms with the patients' life situation, e.g. help from doctors, family friends, support groups and stress management.

8. Busto U. et al. (1988) Protracted Tinnitus after Discontinuation of Long Term Therapeutic Use of Benzodiazepines. J. Clin. Psychopharmacol., 8, 359-61. Sensory disturbances of long term duration are among the most distinctive clinical features of benzodiazepine withdrawal syndrome. Tinnitus present 1 year after discontinuation.

9. Montgomery S.A. et al. (1988) Benzodiazepines; Time To Withdrawal. J. Roy. Coll. Gen. Pract.,1988, 39,146-147. After withdrawal patients remain vulnerable to stress for at least 6 months.

10. Higgit A. et al. (1990) The Prolonged Benzodiazepine Withdrawal Syndrome; Anxiety or Hysteria. Acta. Psychiatr. Scan., 82,165-168. PWS is a genuine iatrogenic condition. 30% of dependent patients get it. Tests point to biological abnormalities. Patients discontinued and tested after 5 to 42 months.

10a. Roche Products Ltd. (C.1990) Benzodiazepines and your Patients: A Management Programme (Sent to prescribers on request). The post withdrawal syndrome can manifest itself as fluctuating levels of malaise, lack of concentration, abdominal discomfort, depersonalisation and emotional liability. If post withdrawal symptoms occur good support from the general practitioner over at least the first year reduces the risk of relapse.

11. Holm M. (1990) One Year Follow up of Users in General Practice. Danish Med. Bull..188-191. First time users more likely to discontinue in one year (55%) than long term users (12%).

12. Holton A. (1990) Five Year Outcome In Patients Withdrawn from Long Term Treatment with Diazepam. BMJ,1241-1242. High level of relapse (75%), taking benzodiazepines for insomnia, anxiety and stress.

13. Ashton H. (1991) Protracted Withdrawal Symptoms. J. Substance Abuse Treatment, 8,19-28. Persistent symptoms may last for many months and are related to long-term benzodiazepine use. Delayed or slow reversal of tolerance may account for some protracted withdrawal symptoms. The possibility is that benzodiazepines produce slowly reversible functional changes in the CNS and cause structural neuronal damage.

14. Lader M. (1991) Benzodiazepine Problems. Br. J. Addiction, 86, 823-828. Persisting symptoms - unsteadiness, neck tension, 'bursting' head, perceptual distortion, muscle spasm, anxiety, phobias, panic, obsessive and depressive features.

15. Rickels et al. (1991) Long Term Benzodiazepine Users - 3 Years after Participation in a Discontinuation Program. Am. J. Psychiatry,148, 6., 757-761. Anxiety and/or depression in patients who had discontinued benzodiazepines for 3-5 years was less than that (but still significant) in patients who continued to take benzodiazepines {benzodiazepines cause depression and anxiety - RFP}.

16. Tyrer P. (1991) The Benzodiazepine Post Withdrawal Syndrome. Stress med., 7,1-2. Feelings of tension, threat, bodily feelings, unsteadiness, shaking, palpitations, gastrointestinal symptoms, agoraphobia. There is a considerable overlap between symptoms of the post withdrawal syndrome and the acute withdrawal syndrome.

17. Lader M. (1992) Pilot Study of the Effects of Flumazenil on Symptoms Persisting after Benzodiazepine WithdrawaI. J. Psychopharmacology, 6. 357- 363. Patients off benzodiazepines for 1 month to 5 years had persisting benzodiazepine withdrawal symptoms significantly lessened. Symptoms include clouded thinking, tiredness, muscular symptoms, neck tension, cramps, shaking, pins and needles, burning skin, pain and sensations of bodily distortion and mood disorder. The benefits lasted several hours to several days.

18. Higgit A. et al. (1992) Withdrawal from Benzodiazepines and the Persistent Benzodiazepine Withdrawal Syndrome. In Granville Crossman (ed) Recent Advances in Clin. Psychiatry: No. 8, London, Churchill Levingstone,1992, 49-59. 30% of patients experiencing acute withdrawals continue with the persistent withdrawal syndrome. Cognitive processes linked to high risk of PWS. {Impaired cognitive processes induced by benzodiazepine ingestion - RFP}.

19. Landry M.J. et al. (1992) Benzodiazepine Dependence and Withdrawal, Identification and Management. J. Amer. Board Fam. Pract., 5(2),167-75. A prolonged sub acute low dose benzodiazepine withdrawal syndrome can last for months or even years.

20. Eduards R. (1993) Benzodiazepines and Dependence. Statens Offentliga Utredninger, 5,135-140. Duration of withdrawal phenomena; recent figures of over 1 year have been proposed. It is well recognised that withdrawal syndromes from barbiturates, narcotics and other psychoactive drugs may also be similarly prolonged.

21. Lader M. (1994) Anxiety or Depression During Withdrawal of Hypnotic Treatments. J. Psychosomatic Res.,18, Suppl. 1,113-123. Hypnotic withdrawal. Persistent withdrawal syndrome dominated by anxiety (generalised, phobic or both) phobic behavioural disorder and panic attacks. Many of the litigants involved in the UK court case suffered form prolonged disabilities of this type.

22. Geller A. (1994) Management of Protracted Withdrawal. Amer. Soc. of Addiction, Ch.2,1-6. Persistent symptoms - impaired concentration, derealisation, depersonalisation, headaches, sleep disturbances, tension, irritability and lack of energy.

23. Ashton H. (1995) Protracted Withdrawal from Benzodiazepines; The Post Withdrawal Syndrome. Psychiatric Annals, 25,174-179. A substantial minority of patients have a PWS including perceptual symptoms and gastrointestinal symptoms gradually receding, lasting at least one year and occasionally permanent.

24. Ashton H. (1995) Toxicity and Adverse Consequences of Benzodiazepine Use. Psychiatric annals, 25,158-165. Some symptoms decline more slowly merging into a period of increased vulnerability to stress lasting many months. Protracted symptoms include prolonged anxiety and depression, gastrointestinal disturbances, tinnitus, neuromuscular abnormalities and paraesthesiae.

25. Okada C. (1995) Treating the Patient with Benzodiazepine Addiction. Hospital Update Sept. 396-401. A small proportion of patients report significant withdrawal symptoms up to 3 years following withdrawal.

26. O'Brien C. P. et al.(1996) Myths About the Treatment of Addiction. Lancet, 1996, 347, 237-240. Addiction drugs produce changes in brain pathways that endure long after drug taking stops. The associated medical, social and occupational difficulties that develop during addiction do not disappear with detoxification. Protracted brain changes, personal and social difficulties put the former addict at great risk. Treatments for addiction should be regarded as long-term. {A paper refuting the myths - RFP}.

27. Roche Products Ltd. (ca.1990) Benzodiazepines and your Patients: A Management Programme (Sent to prescribers on request). The post withdrawal syndrome can manifest itself as fluctuating levels of malaise, lack of concentration, abdominal discomfort, depersonalisation and emotional liability. If post withdrawal symptoms occur good support from the general practitioner over at least the first year reduces the risk of relapse.

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