Benzodiazepines: Risks and Benefits. a Reconsideration

JOP271110.1177/0269881113503509Journal of PsychopharmacologyBaldwin et al. 5035092013

Commentary

Benzodiazepines: Risks and benefits. A reconsideration

Journal of Psychopharmacology 27(11) 967–971 © The Author(s) 2013 David S Baldwin1, Katherine Aitchison2, Alan Bateson3, Reprints and permissions: 4 5 6 7 sagepub.co.uk/journalsPermissions.nav H Valerie Curran , Simon Davies , Brian Leonard , David J Nutt , DOI: 10.1177/0269881113503509 David N Stephens8 and Sue Wilson7 jop.sagepub.com

Abstract Over the last decade there have been further developments in our knowledge of the risks and benefits of benzodiazepines, and of the risks and benefits of alternatives to benzodiazepines. Representatives drawn from the Psychopharmacology Special Interest Group of the Royal College of Psychiatrists and the British Association for Psychopharmacology together examined these developments, and have provided this joint statement with recommendations for clinical practice. The working group was mindful of widespread concerns about benzodiazepines and related anxiolytic and hypnotic drugs. The group believes that whenever benzodiazepines are prescribed, the potential for dependence or other harmful effects must be considered. However, the group also believes that the risks of dependence associated with long-term use should be balanced against the benefits that in many cases follow from the short or intermittent use of benzodiazepines and the risk of the underlying conditions for which treatment is being provided.

Keywords Benzodiazepines, pharmacology, risks, withdrawal, benefits

The Royal College of Psychiatrists has previously provided guid- Pharmacological properties of ance on the risks and benefits of benzodiazepines, in March 1988 and January 1997. Over the last decade there have been further benzodiazepines

developments in our knowledge of the risks and benefits of Benzodiazepines are ‘allosteric modulators’ of GABAA receptors benzodiazepines, and of the risks and benefits of alternatives to (GABA is the widely distributed inhibitory neurotransmitter

benzodiazepines. In addition, the licensing of some selective sero- gamma-aminobutyric acid). A GABAA receptor comprises five tonin reuptake inhibitors and serotonin-noradrenaline reuptake transmembrane glycoprotein subunits arranged around a central inhibitors for treatment of a broad range of anxiety disorders chloride channel. Benzodiazepines bind to a specific site on the

(and the licensing of pregabalin for generalized anxiety disor- GABAA receptor membrane complex, which is distinct from the der) has increased choice among potential pharmacological and GABA binding site. The GABAA receptor has multiple additional psychological interventions. Representatives drawn from both binding sites, including those for benzodiazepines, barbiturates the Psychopharmacology Special Interest Group of the Royal and neurosteroids. It is controversial whether alcohol interacts

College of Psychiatrists and the British Association for directly or only indirectly with the receptor. Different GABAA Psychopharmacology together examined these developments, and subunits are combined together to produce a variety of receptor have provided this joint statement with its recommendations for clinical practice. 1Faculty of Medicine, University of Southampton, Southampton, UK The working group was mindful of widespread concerns about 2Department of Psychiatry, University of Alberta, Edmonton, Canada benzodiazepines and related anxiolytic and hypnotic drugs. The 3Department of Pharmacology, Ross University School of Medicine, group believes that whenever benzodiazepines are prescribed, the Roseau, Commonwealth of Dominica potential for dependence or other harmful effects must be consid- 4Faculty of Brain Sciences, University College London, London, UK ered. However, the group also believes that the risks of depend- 5Centre for Addiction and Mental Health, University of Toronto, ence associated with long-term use should be balanced against the Toronto, Canada benefits that in many cases follow from the short or intermittent 6National University of Ireland, Galway, Ireland use of benzodiazepines and the risk of the underlying conditions 7Faculty of Medicine, Imperial College London, London, UK 8 for which treatment is being provided. The balance of risks and School of Psychology, University of Sussex, Brighton, UK benefits with benzodiazepines or alternative interventions in an Corresponding author: individual patient can be hard to assess, and is ultimately a matter David Baldwin, Department of Psychiatry, University of Southampton, of clinical judgment. The group contends that benzodiazepine pre- Academic Centre, College Keep, 4-12 Terminus Terrace, Southampton, scribing, like other aspects of clinical practice, should be based on SO14 3DT, UK. thoughtful consideration of the likely risks and benefits of benzo- Email: [email protected] diazepines, and of the risks and benefits of alternative interven- Joint Report from a Working Group drawn from the Royal College of tions. This consideration should be made in conjunction with the Psychiatrists Psychopharmacology Special Interest Group and the British patient, and their carers, where appropriate. Association for Psychopharmacology

Downloaded from jop.sagepub.com by guest on November 21, 2013 968 Journal of Psychopharmacology 27(11) subtypes, which have distinct distributions within the central for Health and Care Excellence (NICE), the British Association nervous system as well as specific pharmacological properties. for Psychopharmacology and other bodies suggests that other Binding of a benzodiazepine to its site on the receptor increases approaches should be used in preference to benzodiazepines, the affinity of the receptor for GABA, which in turn leads to a which are generally reserved for patients who do not respond to greater likelihood of the receptor ‘opening’ to allow the passage of other treatments. Benzodiazepines do not have an antidepressant chloride ions through the membrane. This normally results in neu- effect when used alone, which is a disadvantage in patients with ronal hyper-polarization and reduced excitability of the target cell. anxiety disorders who are also depressed, but they may sometimes Unlike barbiturates at high doses, benzodiazepines do not mimic be used to cover the period of illness before antidepressants the effects of GABA and do not activate chloride channels directly. become effective (typically a few weeks) and to reduce possible The benzodiazepines can be divided into different groups exacerbations of anxiety during this period. based on their chemical structure and pharmacokinetic properties, Benzodiazepine anxiolytics should be prescribed primarily although all share a common mechanism of action and produce a either for the short-term relief of severe anxiety symptoms, or range of similar clinical effects. There are other compounds of where anxiety disorders are disabling and severe and causing both unrelated structure that also bind to the benzodiazepine site on the significant personal distress and substantial impairment of daily

GABAA receptor and share some, but not all, of the pharmaco- activities. Where the rationale for treating anxiety symptoms does logical properties of benzodiazepines. Currently these are the not meet either of these criteria, psychological or pharmacological ‘Z-drugs’ (zaleplon, zolpidem and zopiclone), which are used as treatments with an evidence base for long-term use are more hypnotics only. They show subtle differences in pharmacology suitable. from the benzodiazepines as well as having an improved kinetic To reduce the risk of dependence on benzodiazepines they profile for sleep induction with reduced ‘hangover’. The general should generally not be prescribed as a regularly administered principles that apply to benzodiazepine prescribing also apply to medication for longer than four weeks. Ideally they should be the Z-drugs. given on an ‘as required’ basis and intermittently every few days The benzodiazepines differ in their potency, time to effect and during this period. Benzodiazepines may exert beneficial effects duration of action, with some needing repeated daily dosing and within a few days of starting treatment, and may offer the prospect others once-daily dosing to achieve their desired clinical effects. of symptom relief while other treatments such as cognitive– Many benzodiazepines (for example, diazepam) have longer- behavioural therapy have yet to be started or before antidepressant lasting active metabolites, which can accumulate with repeated drugs have had time to act. dosing, especially in elderly patients and those with physical There are clinical circumstances in which longer-term prescrip- health problems, or those with genetic variants leading to low or tion of benzodiazepines might be considered desirable because the absent activity of relevant cytochrome P450 enzymes. alternatives are probably worse than the continued use of benzodiazepines. This may be the case in conditions such as chronic treatment-resistant anxiety disorders or in patients who have established Beneficial effects of benzodiazepines dependence and who have not been able to stop treatment successfully. In rare instances longer-term prescriptions of benzodiaz- The beneficial effects of benzodiazepines include the reduction of epines may be seen as a form of harm reduction in patients who anxiety, the induction and maintenance of sleep, muscle relaxa- would otherwise consume illicit benzodiazepines or abuse alcohol tion, and the treatment and prevention of epileptic seizures. These to ‘cope’ with anxiety: again, efforts should be made to reduce the properties are shared by most currently approved benzodiazepines dosage over time, wherever possible. There are other situations but to varying degrees, depending on their potency and pharma- where anxiety is complicated by other medical conditions, or cokinetic properties. where the risk of dependence with benzodiazepine use may be considered acceptable because of the severity of illness and potential hazards associated with other treatment approaches, such as Treatment of anxiety disorders may occur in some patients with schizophrenia. Randomized controlled trials have provided evidence for the efficacy of some benzodiazepines in certain anxiety disorders, usu- Induction of sleep ally in acute treatment for the reduction of anxiety symptoms, but sometimes in longer-term treatment, designed to prevent a relapse Adequate treatment of insomnia is often difficult, and depends on of symptoms in someone who has made a good response to acute many factors such as age, presence of physical illness, pain, use of treatment. There is good evidence for efficacy in acute treatment concomitant medication, and history of drug or alcohol misuse. of generalized anxiety disorder, social anxiety disorder and panic The adoption of ‘sleep hygiene’ techniques forms the initial part disorder, but limited evidence for efficacy in obsessive-compulsive of management. The benzodiazepines and Z-drugs are the most disorder. Benzodiazepines have not been found to be efficacious effective drugs for the short-term treatment of insomnia that is in randomized controlled trials in post-traumatic stress disorder, severe, disabling and causing distress. They can reduce the time and may indeed be unhelpful in preventing the emergence of post- taken to fall asleep, increase the duration and efficiency of sleep, traumatic symptoms after traumatic events. and reduce periods of wakefulness after the onset of sleep. Drugs There have not been many direct comparisons of the efficacy with a relatively short half-life can facilitate falling asleep with a of benzodiazepines with alternative pharmacological treatments lower risk of residual daytime drowsiness (“hangover”) than is such as selective serotonin reuptake inhibitors. Alternative phar- seen with drugs that have longer half-lives. macological approaches are generally somewhat better tolerated, The use of benzodiazepines as hypnotic agents should be only one and for these reasons recent guidance from the National Institute aspect of general management. As in the treatment of patients with

Downloaded from jop.sagepub.com by guest on November 21, 2013 Baldwin et al. 969 anxiety disorders, the use of benzodiazepines should generally be Risks of benzodiazepines limited to a maximum of four weeks, though there is little evidence that longer-term use is more hazardous than short-term use. In the Benzodiazepines have a range of untoward adverse effects that United Kingdom, though not in the the United States and some other may outweigh the benefits in certain patient populations, which countries, all hypnotics are licensed for short term use only. therefore limits their use in clinical practice. Prescriptions should preferably be at the lowest effective dose and given intermittently. Care should be taken to exclude or manage associated conditions such as mood disorders or substance misuse. Some Cognitive effects conditions such as sleep apnoea may be aggravated by the use of Controlled studies and systematic reviews have shown that benzodi- benzodiazepines. In patients with chronic insomnia, benzodiazepines azepine administration can result in sedation and drowsiness, mental should be used only in the short term while more appropriate longer- slowing and anterograde amnesia (difficulty in forming new memo- term treatments are started. Elderly individuals are more vulnerable ries). These effects are all dose-dependent. Some but not all of these to the adverse effects of prescribed medication, but consume the adverse cognitive effects reduce with continued administration – for majority of sleeping tablets. They often have co-existing physical dis- example, sedation and drowsiness become less prominent with con- ease, and a pragmatic approach to treatment may need to be adopted, tinued use, but memory problems are likely to continue. Withdrawal whilst paying attention to issues such as drug–drug interactions. from benzodiazepines may be associated with some improvement in Alternatives to benzodiazepines such as zopiclone, zolpidem cognitive performance after abstinence. and zaleplon are now available for managing insomnia. They have It has been argued that these untoward effects can reduce the pharmacological similarities to benzodiazepines and produce sim- likelihood of responding to psychological interventions, although ilar side-effects, but have relatively shorter half-lives and in some the evidence of this is limited. Similar concerns have been expressed cases are more selective for specific GABAA receptor subtypes. about impairment in the ability to adjust to psychological traumas Like benzodiazepines, these drugs are licensed for short-term use such as bereavement; despite this, it remains common (although not only. Where the effects are selective on certain GABAA receptor necessarily best) practice to provide a benzodiazepine to the subtypes, the anxiolytic effects are few. However, the Z-drugs recently bereaved. However, this may defer the emergence of a may have some limited advantages over traditional benzodiaz- bereavement reaction until the benzodiazepine is stopped. epines in terms of dependence and withdrawal, and should be considered as an alternative, particularly if there seems to be a potential need for longer-term treatment or in patients presumed Psychomotor effects to be at increased risk of dependence. Benzodiazepine administration can result in an impairment of performance whilst driving similar to that seen with blood alco- Other beneficial effects hol levels below the current UK legal limit, the magnitude of effects being influenced by the drug, dosage and other factors. Benzodiazepines have anticonvulsant and muscle relaxant effects There is also an interaction with alcohol that potentiates the that are considered to be independent of their anxiolytic actions. degree of impairment seen with either drug alone. These effects can be valuable in the emergency treatment of sei- Pharmacoepidemiological studies suggest that benzodiazepine zures or in the management of spasticity or muscle spasms, or use is associated with an increased risk of road traffic accidents, movement disorders associated with the use of antipsychotic over and above that seen with untreated mental disorders. Patients drugs. Tolerance may develop with long-term use, particularly to should be advised to contact the Driver and Vehicle Licensing their anticonvulsant effects, and they are therefore not generally Agency (DVLA) when they are taking medications that may recommended for prophylactic use in epilepsy, other than in some impair driving performance, and to avoid drinking alcohol. Due rare childhood syndromes. They are sometimes used as part of to drug accumulation, use of drugs with longer half-lives may be induction procedures prior to anaesthesia. more hazardous than use of drugs that have a shorter half-life. Although the evidence for potential benefit is rather mixed, Elderly patients are more vulnerable to the cognitive and psycho- some patients with excitement, agitation or severe psychotic motor effects of benzodiazepines and eliminate long-acting drugs symptoms may be prescribed short-term benzodiazepines as part more slowly than younger patients, and an increased risk of falls of acute ‘rapid tranquillization’, or as an adjunct to the use of should be considered when contemplating possible benzodiaze- antipsychotic drugs. In these situations, the dose and duration of pine prescription to such patients. treatment needs to be monitored closely. Certain benzodiazepines such as clonazepam can be used in the treatment of patients with acute mania. When these compounds are no longer required, Tolerance patients should be withdrawn from them, in a tapered manner. Benzodiazepines – notably diazepam and chlordiazepoxide – are Tolerance to the effects of benzodiazepines can occur; this is useful in managing withdrawal from alcohol in patients with alcohol more pronounced for the anticonvulsant and sedative effects. dependence, especially in the prevention of epileptic seizures and Tolerance to the hypnotic and anxiolytic effects can also develop, delirium tremens. There is only limited evidence to suggest that ben- but probably less often and more slowly. It is unusual for patients zodiazepines may be useful in the management of patients with to steadily increase their dosage, but this can occur in some acute confusional or delirious states, and their use in these conditions patients, particularly those with a history of alcohol dependence is not recommended. There is little evidence that previously alcohol- or other substance misuse. Should tolerance occur, possible rea- dependent patients may derive benefit from benzodiazepines in sons for this need to be explored, and the possibility of misuse helping to facilitate continuing abstinence from alcohol. considered.

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Dependence abused drug (temazepam) has probably limited its use by this route. Some ‘benzodiazepines’ sourced through the Internet are of Probable dependence on benzodiazepines is usually manifest by uncertain nature and strength, and may contain hazardous con- the emergence of withdrawal symptoms on either stopping or too taminants. Clinicians should be aware of the increased risks in rapidly reducing treatment. Withdrawal symptoms can be physi- overdose when benzodiazepines are mixed with other respiratory cal (such as flu-like complaints and muscle cramps) or psycho- depressants. logical (such as irritability, insomnia, nightmares, perceptual Benzodiazepines are often used as an alternative when sup- changes, and depersonalization or derealization). Symptoms can plies of other drugs of abuse are scarce. Benzodiazepines are also be prolonged and are sometimes hard to distinguish from those of sometimes used by young people to ‘come down’ after taking underlying anxiety disorders, although perceptual disturbances stimulant ‘party drugs’. Prescriptions of benzodiazepines should are relatively infrequent in untreated patients with anxiety disor- be subject to regular review. Doctors should be aware that the ders. Withdrawal reactions are generally short-lived, typically medication they prescribe may be diverted into the wrong hands lasting less than one month, although duration is influenced by and enter the ‘black market’, and so should be wary of prescribing individual pharmacokinetic factors. There is controversy about to certain individuals, such as those with a history of multiple drug whether symptoms persisting for many months (reported by abuse. Prescription of benzodiazepines in conjunction with meth- approximately one-quarter of patients) are withdrawal reactions, adone is no longer regarded as good clinical practice. or simply the features of an underlying disorder, or worsening of that condition triggered by treatment withdrawal. Established benzodiazepine dependence is preferably treated ‘Disinhibition’ by advice, pharmacological optimization or substitution, gradual withdrawal and psychological support. In some patients, pharma- There is some controversy about whether benzodiazepine use cological and psychological interventions will be of only limited alone can result in disinhibited or impulsive behaviour. Studies in benefit, so certain individuals will be unable to stop benzodiaz- patients with personality disorders suggest that benzodiazepines epines. Risk factors for continuation include a history of substance may increase the risk of suicidal behaviour, especially when com- misuse, comorbid depression, dependent personality disorder and bined with alcohol. In theory, use of benzodiazepines by predis- physical ill-health. In patients with persistent symptoms, a joint posed individuals may ‘release’ aggressive behaviour towards decision should be made about whether they are generally better others, but it is hard to distinguish this possible effect from the off with or without treatment. features of an underlying disorder.

Patients with affective disorders Withdrawing benzodiazepines Benzodiazepines may reduce early adverse drug effects in the In general, benzodiazepines should be prescribed in as low a dose treatment of depression and bipolar affective disorder. However, as possible to afford adequate symptom relief. It is difficult to they may sometimes appear to worsen depressive symptoms, per- produce a ‘risk table’, but compounds with higher potency and haps by reducing prominent anxiety symptoms and thereby shorter half-life are associated with a greater likelihood of devel- ‘revealing’ underlying depression. They have minimal effects in oping dependence. Unless there are clear risks of more severe reducing the severity of mild depressive symptoms and in some problems if the drug is stopped, patients should be encouraged to patients may reduce the likelihood of responding to antidepressant withdraw gradually after long-term use. Many patients who were treatment. Stopping benzodiazepines can also be associated with previously treated with benzodiazepines over long periods have the emergence of depressive symptoms. Benzodiazepines are no already withdrawn successfully, but newly dependent patients are substitute for effective continuation treatment with antidepressant still accruing, as prescriptions for benzodiazepines are not declin- drugs in patients with recurrent unipolar depression. ing. Many of those who remain on benzodiazepine anxiolytics will have trouble stopping unless expertly and sympathetically managed, including being offered psychological and other alter- Patients with psychosis native therapies. Concerns about the use of benzodiazepines as hypnotics are Lorazepam (either orally or intramuscularly) is commonly pre- different from the concerns in patients with anxiety disorders. The scribed in inpatient settings for the management of patients with sudden withdrawal of a long-established treatment can be psychosis and prominent behavioural disturbance. If regular ben- extremely distressing and possibly dangerous, for example zodiazepine prescription is required, clonazepam may be prefera- through inducing epileptic seizures. Dependence is more likely ble, as its long half-life makes it suitable for once-daily dosage. with higher dosages but can also occur with low doses, and formulations of compounds at lower strengths and with longer half-lives Abuse of benzodiazepines may be useful in helping patients reduce from higher doses. Even after short-term use, a tapering-off regime (i.e. at least two weeks Some individuals abuse benzodiazepines (especially temazepam, at reduced dosage) should be considered to minimize the risk of flunitrazepam and diazepam) and/or related drugs, as part of a rebound phenomena, that is, the reappearance of symptoms pre- wider drug (e.g. heroin, crack cocaine) and/or alcohol problem. sent prior to treatment. After longer-term use this reduction Intravenous injection of temazepam can result in emboli and gan- period should probably be extended, sometimes to several months grene. Altering the formulations of certain drugs has made them in patients who have been treated for many years. Where benzodi- less easy to inject, and restricting the previously most widely azepine dependence is diagnosed but a considered decision is made

Downloaded from jop.sagepub.com by guest on November 21, 2013 Baldwin et al. 971 that continued prescription is nonetheless appropriate, they should reasonable than the alternatives, provided the patient peri- be prescribed at gradually reducing doses wherever possible. odically attempts to slowly reduce the dosage at regular intervals and tries to stop altogether when or if possible. 10. If the alternative to benzodiazepine treatment is the use of Recommendations another form of treatment, either psychological or pharmacological, which proves to have little benefit in prac- 1. Benzodiazepines have a range of beneficial effects and a tice, a patient may return to the prescriber and ask to be range of untoward effects, like all forms of pharmacologi- put back on a benzodiazepine. This request should not be cal and psychological treatment. automatically declined but there should be a sympathetic 2. Benzodiazepines may be prescribed safely in the short consideration of whether or not this is appropriate. term and can be effective treatments in many patients whose quality of life is significantly affected by distressing anxiety symptoms or troublesome insomnia. Conflict of interest 3. Some other classes of psychotropic drugs have proven AB, HVC, SD, BL, DS and SW all declare no potential conflict of interest. efficacy in anxiety disorders, so it is important to consider KA declares support from Bristol-Myers Squibb, Lundbeck, Otsuka and alternatives to prescribing benzodiazepines. Consideration GlaxoSmithKline. DSB declares support from Eli Lilly, GlaxoSmithKline, of alternatives should include a balanced appraisal of the Lundbeck, Pfizer and Servier. DN makes this declaration for the period relative benefits and risks of the range of options, in acute 2010-2013: advisor to the British National Formulary, MRC, GMC and Department of Health; Vice President of the European Brain Council, and longer-term treatment. Psychological interventions President of the British Neuroscience Association, Chair of the should always be considered as alternatives or additions Independent Scientific Committee on Drugs (UK) and Member of the to pharmacological treatment. International Centre for Science on Drug Policy; Editor of Journal of 4. Dependence is recognized as a significant risk in some Psychopharmacology, and member of advisory boards to Lundbeck, patients receiving treatment for longer than one month, Servier, Pfizer, Reckitt Renkiser, D & A Pharma and Novartis. and health professionals should be conscious of this when considering the relative benefits and risks of treatment. Funding The potential risks of long-term treatment need to be con- The Royal College of Psychiatrists made a room available and provided sidered prior to starting short-term treatment. refreshments for a half-day meeting, and reimbursed submitted travel 5. As with all interventions, health professionals should expenses (economy class). No other support was provided by the Royal examine the likely benefits and risks in each individual College of Psychiatrists, the British Association for Psychopharmacology, case early in treatment, so that if problems occur, they or any other organization or company, to the members of the working have been anticipated by doctors, patients and their group for the development of this consensus statement. carers. 6. If dependence on benzodiazepines has become established, it is often difficult to treat and can become a long- Further Reading term and distressing problem. Baldwin DS, Anderson IM, Nutt DJ, et al. (2005) Evidence-based guide- 7. Many health professionals have been dissatisfied with lines for the pharmacological treatment of anxiety disorders: recom- previous guidance that benzodiazepines should be used mendations from the British Association for Psychopharmacology. J for short-term treatment only and no longer than four Psychopharmacol 19: 567–596. weeks in regular dosage. All patients should be made Chick J and Nutt DJ (2011) Substitution therapy for alcoholism: Time for a reappraisal? J Psychopharmacol 26: 205–212. aware of the risks of dependence if they continue benzo- Dell’osso B and Lader M (2013) Do benzodiazepines still deserve a major diazepines in regular dosage over a longer period. A clini- role in the treatment of psychiatric disorders? A critical reappraisal. cal judgement has to be made as to whether alternatives Eur Psychiatry 28: 7–20. may be more suitable, for each patient, and for each pro- Lingford-Hughes A, Welch S, Peters L, et al. (2012) BAP updated guide- posed medication. lines: Evidence-based guidelines for the pharmacological manage- 8. Many patients are able to take short courses of benzo- ment of substance abuse, harmful use, addiction and comorbidity: diazepines (or to use them on an ‘as required’ basis) Recommendations from BAP. J Psychopharmacol 26: 899–952. quite safely and to stop them when no longer needed. If Nutt DJ and Sharpe M (2008) Uncritical positive regard? Issues in the treatment courses lasting longer than four weeks are efficacy and safety of psychotherapy. J Psychopharmacol 22: 3–6. required, this should not necessarily be regarded as a Stephens DN and King SL (2013) Neuropharmacology of Benzodiaze- pines. In: Blume AW, Kavanagh DJ, Kampman KM, et al. (eds) Bio- deviation from good clinical practice, although con- logical Research on Addiction: Comprehensive Addictive Behaviors tinuing vigilance of potential hazards is needed and Disorders. San Diego, USA: Academic Press, pp.605–614. throughout treatment. Wilson SJ, Nutt DJ, Alford C, et al. (2010) British Association for Psy- 9. If there is no history of drug dependence, and positive chopharmacology consensus statement on evidence-based treatment indicative ‘lifestyle’ factors are present, a conscious deci- of insomnia, parasomnias and circadian rhythm disorders. J Psycho- sion to continue benzodiazepine treatment may be more pharmacol 24: 1577–1600.

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