Risks of dependence on benzodiazepine drugs: a major problem of long term treatment Heather Ashton BMJ: first published as 10.1136/bmj.298.6666.103 on 14 January 1989. Downloaded from Phlegmatic people dislike taking benzodiazepine drugs. In those with low'anxiety traits benzodiazepines Profiles of dependence on drugs are dysphoric and may paradoxically increase anxiety.' In normal subjects benzodiazepines improve perform- People who become dependent on drugs are suggested ance under experimental stress but worsen it under to be two different populations at the extremes of a conditions of low stress.2 Benzodiazepines relieve pre- normal distribution. Those who take drugs for pro- operative anxiety in patients with high anticipatory tection are anxious, have high scores for neuroticism but not in those with low anxiety.3 (N),46 17 are highly susceptible to punishment,'4 tender anxiety anticipatory minded, and socially compliant.4 Their preferred Thus like 0i receptor blocking agents benzodiazepines drugs are benzodiazepine tranquillosedatives, which require some underlying tone upon which to exert their they tend to take long term in low, prescribed doses. anxiolytic effects. In general, the greater the anxiety They are sensitive to withdrawal largely because of the greater the anxiolytic efficacy. their anxiety and poor abilities in coping with stress. It follows that most people who take benzodiazepines In contrast, those who take drugs for kicks have are anxious. In students a history of prescribed high scores for psychoticism (P),'7 are highly sensitive benzodiazepines correlates with a high anxiety trait.4 to reward,'4 impulsive, tough minded, antisocial, and Long term users likewise have high scores for neuroti- seek sensation.4 '7 They tend to abuse hard and soft cism. 6 These findings apply when benzodiazepines drugs, often illicitly,4 '7 which they take intermittently or long term in high doses. They experience an are used both as anxiolytic and as hypnotic agents. Thus abstinence syndrome largely because of the high doses people who take and keep on taking benzodiazepines used. are a selfselected population with high anxiety traits or The general population, which is less dependent on states. drugs, occupies the middle of the curve. Nicotine and alcohol (which have both tranquillising and directly rewarding properties over a moderate range of doses30) Reasons for dependence on benzodiazepines cover the whole spectrum-a fact which probably Dependence on benzodiazepines in the sense that explains their widespread use. users require the drugs for psychological comfort and suffer withdrawal symptoms when they stop taking Drugs for protection Drugs for kicks them develops rapidly.7 The same patients who find benzodiazepines efficacious are also prone to dependence and to withdrawal effects, which are themselves largely manifestations of anxiety. This vulnerability occurs for several reasons. Firstly, Benzodiazepines Soft drugs,for example anxious people are more likely to complain of symp- Cannabis toms.8 Secondly, long term users of benzodiazepines Hart] drugs tend to have poor abilities in coping with stress. The Personality http://www.bmj.com/ pharmacological basis for both anxiety and a poor High N score, ar4XiOLiS, High P score, irnmulsive, highly susceptible to highly susceptibale to ability to cope with stress may be low activity in punishment, tender reward, tough wilindec], limbic system pathways utilising y-aminobutyric acid9 minded, socially compliant antisocial or high activity in those utilising serotonin,'0 or both. Such activity is counteracted by benzodiazepines." Use of druqs Prescribed, low Recreational anid illicit, Benzodiazepines, however, impair learning of doses, long term lon(g term or intermitten strategies to cope with stress, such as behavioural treatment for agoraphobia.) 2 Other characteristics on 2 October 2021 by guest. Protected copyright. (passive-dependent personality, resourcelessness7 13) also increase the vulnerability to withdrawal symptoms other psychological and somatic symptoms, and and the motivation for continued use. Benzodiazepine perceptual disturbances),'6 1 'although slow with- deprivation in such users leaves them unprotected drawal minimises symptoms.20 Tyrer et al estimated from stress and re-exposes their limitations of coping. that only 30-45% experienced true withdrawal symp- Finally, anxious people may be innately sensitive to toms, defined as a temporary increase in anxiety to half punishing stimuli.'4 Benzodiazepines are "depunish- or more above prewithdrawal values or the develop- ing" drugs. Even in animals they protect against ment of two or more new symptoms ("pseudowith- punishing stimuli'5 and are taken therapeutically by drawal" occurred in some patients who thought that many people as protective drugs.6 In contrast, those they were withdrawing. )13 21 Others report similar who take benzodiazepines at high doses for kicks'6 results. 1622 23 form a different population, innately less sensitive to Withdrawal criteria based on differences from pre- punishment'4 that also tends to abuse other drugs4 17 withdrawal measures, however, underestimate the (see box). true incidence. I have observed that long term users of benzodiazepines develop further symptoms while taking the drugs." ' These include increasing anxiety Clinical Withdrawal syndrome with benzodiazepines and also paraesthesiae and perceptual disturbances, Psychopharmacology Unit, The overall incidence of a withdrawal syndrome new symptoms generally associated with withdrawal.' Medical School, Newcastle to some upon Tyne NE2 4HH after long term therapeutic doses of benzodiazepines is These symptoms may result from tolerance Heather Ashton, FRCP, unknown. Estimates vary with the population studied, effects of benzodiazepines so that a withdrawal syn- reader in clinical the duration of drug use, the rate of withdrawal, the drome emerges despite continued drug use. Support- psychopharmacology length of follow up, and the definition. Lader and ing this observation is the fact that increasing the dose colleagues reported a 100% incidence: all patients of benzodiazepines temporarily alleviates symptoms. BrMedJf 1989;298:103-4 experienced withdrawal symptoms (increased anxiety, A large escalation in dose is reputedly rare7 no doubt BMJ VOLUME 298 14 JANUARY 1989 103 because benzodiazepines are medically prescribed to probably requires learned changes in endogenous patients who are generally compliant. Nevertheless, y-aminobutyric acid transmission rather than the Controversies 7 5-10-0 mg lorazepam daily" is not uncommon imposition of an exogenous cover up with benzodiaze- in (equivalent to 75-100 mg diazepam24). pines. Withdrawal symptoms occurring during long term Therapeutics use are more noticeable with potent benzodiazepines 1 Parrott AC, Kentridge R. Personal constructs of anxiety under the 1,5 that are rapidly eliminated. Patients taking lorazepam' benzodiazepine clobazam related to trait-anxiety levels of the personality. BMJ: first published as 10.1136/bmj.298.6666.103 on 14 January 1989. Downloaded from Psychopharmacology 1982;75:353-7. or alprazolam25 commonly experience craving or 2 Parrott AC, Davies S. Effects of a 1,5 benzodiazepine upon performance in an dysphoria between doses, and daytime withdrawal experimental stress situation. Psychopharmacology 1983;79:367-9. effects from the use of triazolam as a hypnotic are 3 O'Boyle CA, Harris D, Barry H, Cullen JH. Differential effects of benzodiaze- pine sedation in high and low anxious patients in 'real life' stress setting. well recognised." Thus the motivation to use ben- Psychopharmacology 1986;88:266-9. zodiazepines for anxiolysis or hypnosis gradually 4 Golding JF, Cornish AM. Personality and life-style in medical students: psychopharmacological aspects. Psychology and Health 1987;1:287-301. merges with the need to avoid withdrawal effects. For 5 Ashton H. Benzodiazepine withdrawal: an unfinished story. Br Med J this reason it may be impossible to measure withdrawal 1984;288: 1135-40. 6 Ashton H, Golding JF. Tranquillisers: prevalence and possible consequences: effects precisely. data from a large United Kingdom survey. BrJ3 Addict (in press). Recently Murphy et al broadened their withdrawal 7 Murphy SB, Tyrer P. The essence of benzodiazepine dependence. In: Lader criteria to include a temporary increase in anxiety to M, ed. The psychopharmacology of addiction. Oxford: Oxford University Press, 1988:157-67. less than initial values.'6 In this study ratings before 8 Bond MR. Personality and pain. In: Lipton S, ed. Persistent pain: modern benzodiazepine were available and the incidence of methods oftreatment. Vol 2. London: Academic Press, 1980:1-26. 9 Leonard BE. New antidepressants and the biology of depression. Stress withdrawal symptoms was again 30%. Diazepam was, Medicine 1985;1:9-16. however, given for only six weeks and the results may 10 Gray JA. The neuropsychology ofanxiety. Oxford: Clarendon Press, 1982. 11 Ashton H. Benzodiazepine withdrawal: outcome in 50 patients. Br J Addict not apply to those who use it for longer. Furthermore, 1987;82:665-7 1. many long term users (46 out of 86 in one study27) 12 Gray JA. Interactions between drugs and behaviour therapy. In: Eysenk HJ, decline to undertake withdrawal and many drop out Martin I, eds. Theoretical foundations of behaviour therapy. New York: Plenum Press, 1987:433-47. (18 of the remaining 4027) because of fear or experience 13 Tyrer P, Owen R, Dawling S. Gradual withdrawal of