Prescribing drugs of dependence in general practice

Part B - Benzodiazepines - Chapter 2

Evidence-based guidance for benzodiazepines

Last revised: 03 Mar 2020

Overview

The evidence base for benzodiazepine use continues to evolve, but despite the length of time they have been used in clinical practice, the evidence remains incomplete in many areas.93 The clinical recommendations and practice points presented in this guide are based on the best available evidence.

Benzodiazepines are used for a broad range of conditions including:

  • insomnia
  • anxiety disorders
  • alcohol withdrawal
  • mania/hypomania
  • epilepsy
  • acute seizures
  • arousal/agitation in the in-patient setting
  • palliative care
  • musculoskeletal disorders.

Insomnia and anxiety disorders are commonly managed in general practice and are the main focus of this chapter. Alcohol withdrawal may be managed in general practice and is covered briefly. However, GPs wishing to manage patients withdrawing from alcohol will need to consult other resources.

The following sections demonstrate how benzodiazepines fit into the context of treatment for a range of conditions, but do not represent comprehensive guidance. Additional resources are provided for each condition.

Key points

  • Insomnia is a common problem seen in general practice. The understanding of chronic insomnia is still evolving.
  • In acute insomnia, sleep often returns to normal once the precipitating factor has resolved.
  • In chronic insomnia, treatment is focused on addressing underlying comorbid precipitants (where present), and psychological and behavioural management.
  • Pharmacotherapy for acute and chronic insomnia may be necessary for severe or resistant cases of insomnia. The decision to prescribe should be on an individual basis and involve serious consideration of all risks and possible benefits.
  • Benzodiazepines and Z drugs have been shown to be effective treatments and may be prescribed for short-term or intermittent use. Harm, such as dependence and adverse events, may occur with both drug groups.
  • Dose reduction and cessation should be discussed with the patient on first prescription and commenced once sleep patterns return to normal.
  • Pharmacological treatment should be accompanied by specific patient education and regular review.

Sleep disturbance is the third most common psychological reason for patient encounters in general practice. Population surveys found 13–33% of adult Australians have regular difficulties getting to sleep or staying asleep.104

Insomnia is defined in DSM-5 as a difficulty in getting to sleep, staying asleep or having non-restorative sleep despite having adequate opportunity for sleep, together with associated impairment of daytime functioning, with symptoms being present for at least 4 weeks.40

Acute insomnia meets the DSM-5 definition of insomnia, but with symptoms occurring for less than 4 weeks.40 It is experienced by up to 80% of the population at some stage, generally due to one or more precipitating factors.105

Factors that can precipitate acute insomnia include:104

  • physiological – hyperarousal due to stress, being ‘on-call’, caring for a sick child/relative, being in a strange situation (eg in hospital)
  • pharmacological – prescribed drugs (eg newly prescribed diuretic causing nocturia) and non-prescribed drugs
  • physical – coughing, environment (eg noise, temperature)
  • disruption of circadian rhythm (eg jet lag).

Provided patients adhere to good sleep habits, most will return to normal sleep once the precipitating factor has resolved or diminished.106

Chronic insomnia was previously viewed as a sleep disturbance that was secondary to a medical condition, psychiatric illness, sleep disorder or medication, and would improve with treatment of the underlying disorder.107,108 However, evidence over the last 20 years indicates this view is incorrect. It is now recognised that insomnia may be an independent disorder.108110 The understanding of chronic insomnia continues to evolve. Insomnia may have some similarities with depression in that they both represent long-term disorders for which many patients require maintenance treatment.

Chronic insomnia may occur in the absence of coexisting conditions. When coexisting conditions exist, insomnia may persist despite successful treatment of the coexisting condition. Treatment directed at the insomnia, rather than the comorbidity, may be necessary. Since insomnia can precipitate, exacerbate or prolong comorbid conditions, treatment of insomnia may in turn improve comorbidities.

Chronic insomnia is unlikely to resolve spontaneously.111

Management of insomnia in general practice

When patients present with insomnia to GPs in Australia, few (0.8%) receive a referral for specific non-drug therapy.112 All guidelines strongly recommend psychological and behavioural management.68,102,108,113

Assessment and diagnosis

Assessment and diagnosis of insomnia requires:111

  • understanding the patient’s typical sleep pattern over an extended time frame (weeks to months) – a sleep diary can help assessment
  • identifying contributing lifestyle factors (eg caffeine, nicotine, pets in the bedroom)
  • understanding the patient’s beliefs and concerns about sleep
  • determining the effects of poor sleep on the patient (eg poor memory, fatigue, work absence, accidents)
  • identifying comorbid conditions – this may be aided by the Auckland Sleep Questionnaire, which is a validated screening tool.114

Acute insomnia

Treatment is focused on avoiding or withdrawing the precipitant, if possible. All patients should receive basic behavioural counselling on sleep hygiene and stimulus control.

Drug treatment may be indicated as an adjuvant to non-drug therapies for acute insomnia that is severe, disabling and causing distress. Benzodiazepines and Z drugs are the most effective drugs.25 The short-term use of benzodiazepines as hypnotic agents should only be one aspect of general management,25 with a clear endpoint of drug cessation once sleep patterns return to normal.

Chronic insomnia

Management of chronic insomnia starts with addressing any relevant, underlying problems that are present, such as:

  • pharmacological – prescribed drugs (eg some antidepressants, withdrawal of sedatives) and non-prescribed drugs (eg caffeine, alcohol)
  • physical (eg pain, respiratory and cardiovascular disorders, neurological disorders, movement disorders, restless leg syndrome and other sleep disorders)
  • psychiatric disorders (eg depression, anxiety, dementia and substance misuse)
  • disruption of circadian rhythm (eg shift work).

Non-drug interventions

First-line therapy for chronic insomnia should be non-drug interventions that are supported by evidence in achieving sustained improvements in sleep parameters.115,116 Interventions include:

  • CBTs18,117 (eg stimulus control, sleep restriction therapy, relaxation techniques, cognitive therapy and sleep hygiene education)111
  • brief behavioural therapy (ie modification of waking behaviours that affect the physiological systems regulating sleep)118121
  • exercise.122

Psychological and behavioural treatments administered weekly over a 4–8– week period have shown robust and stable improvements in sleep continuity for up to 2 years.123 These therapies are now available online, which has vastly improved access.

Refer to Resource G for a GP guide to behavioural therapies for insomnia.

Drug therapy

For patients who continue to have insomnia that is sufficiently burdensome to warrant other interventions, reasonable approaches include continued behavioural therapies, medication or both.108

Recommendations in guideline on the use of medication for chronic insomnia vary. This is primarily due to the lack of evidence from extended trials that adequately compare long-term risks and harms of these medications. Some guidelines suggest avoidance of hypnotic drugs as far as possible,102 while others make a considered judgement on the risks and benefits.68,108,113

The decision to treat chronic insomnia must weigh any potential serious side effects associated with pharmacologic therapy against potential health risks of not providing treatment. This includes decreased quality of life, increased risk for psychiatric comorbidities and SUD, and decreased performance. The approach should be individualised according to the patient’s values and preferences, the availability of advanced behavioural therapies, the severity and impact of the insomnia, and the potential benefits versus the risks, costs and inconveniences.108

Pharmacological treatment should be accompanied by specific patient education, regular review and continued effort to employ the lowest effective maintenance dosage of medication, and to taper medication when conditions allow.113

  • Benzodiazepines – May have a place in the treatment of severe acute insomnia or treatment-resistant chronic insomnia. For patients with sleep onset insomnia, a short-acting medication is a reasonable choice for an initial trial of pharmacologic therapy. This may improve the insomnia with less residual somnolence the following morning. For patients with sleep maintenance insomnia, a longer-acting medication is preferable for an initial trial of pharmacological therapy.108
  • Z drugs – Have been shown to be effective in the treatment of insomnia in the short term. However, there is very limited evidence that they retain their efficacy during long-term treatment.123 Z drugs are associated with issues relating to adverse events, rebound insomnia, development of tolerance and SUD, and need to be carefully monitored in individual patients.123 Zolpidem’s black box warning states, ‘Zolpidem may be associated with potentially dangerous complex sleep-related behaviours which may include sleep walking, sleep driving and other bizarre behaviours. Zolpidem is not to be taken with alcohol. Caution is needed with other CNS depressant drugs. Limit use to four weeks maximum under close medical supervision’.124
    Psychological and behavioural treatments produce comparable outcomes to Z drugs during active treatment and have better durability beyond the active administration of treatment.123
    Prescription of zolpidem and zopiclone should be treated with the same precautions and patient management as benzodiazepines.102
  • Melatonin – An endogenous hormone associated with the control of circadian rhythms and sleep regulation. Melatonin levels may be reduced in middle-aged and elderly patients with insomnia. Supplementation with melatonin has been shown to improve limited aspects of sleep in 30–50% of patients over 55 years of age.106,125,126 Data from clinical trials are variable. Some showed that some patients gain clinically significant improvements in quality of sleep and morning alertness with prolonged-release melatonin, but many patients in the clinical trials did not respond to treatment.35 Melatonin does not appear to be addictive or cause withdrawal effects when stopped.125 There are a lack of long-term study data.

     

    At the time of writing, melatonin is available in Australia as a prolonged-release formulation for short-term treatment of primary insomnia, characterised by poor sleep quality in patients aged 55 years or older.35 The recommended dose is 2 mg orally at bedtime, and at present, there is insufficient evidence to support treatment beyond 3 weeks.35
    In a European campaign to reduce benzodiazepine and Z drug usage, the availability of prolonged-release melatonin was shown to positively contribute to success.127
 
  • Other prescription medications – Includes antipsychotics (eg quetiapine, olanzepine). Studies demonstrating the usefulness of these medications for either short- or long-term management of insomnia are lacking. Furthermore, these agents have significant risks and therefore, their use in the treatment of chronic insomnia (without a relevant comorbid condition) cannot be recommended.107 Numerous other medications have a sedating effect, but are not recommended for routine use in patients with insomnia. These include antidepressants, diphenhydramine and antipsychotics.108
  • Over-the-counter (OTC) medications – Such as antihistamines or antihistamine/analgesic type drugs, and herbal and nutritional substances (eg valerian) are not recommended in the treatment of chronic insomnia due to the relative lack of efficacy and safety data.

Resources

Key points

  • Anxiety disorders are common and exist as a spectrum of conditions that vary from mild to severe.
  • Comprehensive clinical assessment is the first step in management. Effective management requires obtaining a diagnosis, and recognising that patients may not present with a single disorder (eg patients may experience generalised anxiety, panic disorder as well as depression).
  • Where treatment is indicated:
    • First-line therapy for generalised anxiety disorder (GAD), panic disorder, and panic attacks should include CBT (due to its effectiveness at reducing the symptoms of anxiety in the short and long term.
    • SSRI and SNRI medications are effective across the range of anxiety disorders and generally suitable for first-line pharmacological treatment of anxiety.
    • Short-term benzodiazepines as occasional adjunctive therapy may be effective at reducing worsening of symptoms that can occur in the first days to weeks of initiating antidepressant medication, and therefore aid adherence
    • Benzodiazepine use in anxiety disorders is mostly limited to severe or treatment-resistant cases.
    • Patients who use two or more psychoactive drugs in combination (polydrug use) may be more vulnerable to major harms.

Background

Anxiety disorders include GAD, panic disorder, OCD, PTSD, phobias and SAD.

In 2007, anxiety disorders were the most common self-reported mental disorder in Australia, affecting 14% of people aged 16–85 years.129 Anxiety disorders may be prominent in depressive conditions and other chronic health diseases. Anxiety and related disorders often become chronic.

Not all patients with anxiety symptoms require treatment. Anxiety symptoms exist on a continuum and many people with milder degrees of anxiety, particularly recent onset and association with stressful situations will recover without intervention.89 The need for treatment is determined by the severity and persistence of symptoms, the presence of comorbid mental or physical illness, the level of disability and the impact on social functioning. Treatment should aim to achieve full remission of symptoms and return of function, rather than just symptom improvement and distress reduction.130

Randomised controlled trials across a range of anxiety disorders often demonstrate a high placebo response, which indicates that non-specific effects can play a large part in improvement.128

Approaching anxiety disorders systematically involves identifying and treating any comorbidities, providing patient education and appropriate psychological and pharmacological interventions. These should be evidence-based and patients should receive ongoing monitoring to determine whether treatment aims are being achieved.130

Management of anxiety in general practice

For a comprehensive review of management of anxiety disorders, GPs are advised to review individual clinical guidelines.

Benzodiazepine use in anxiety disorders is mostly limited to severe, or treatment-resistant, cases. Patients with a history of significant mental illness who use two or more psychoactive drugs (polydrug use) may be more vulnerable to major harms. Significant caution should be taken if prescribing benzodiazepines to patients with comorbid alcohol or SUDs, or polydrug use. GPs should consider seeking specialist opinion in the management of these patients.

Assessment and diagnosis

Comprehensive clinical assessment is the first step to developing a diagnosis and determining the patient’s level of disability. In milder, recent onset anxiety disorders, consider ‘watchful waiting’ (support, addressing social factors and monitoring).89

It is important to detect comorbid depression. Depression should be treated if depressive symptoms are moderate or severe.

Most guidelines recommend CBT as first-line non-drug therapy, while SSRIs and SNRIs are the drugs of first choice. Benzodiazepine recommendations are generally limited to severe or treatment-resistant cases. However, the efficacy of psychological and pharmacological approaches is similar in the acute treatment of mild to moderate anxiety disorders.89,94,131

The selection of an initial treatment modality should be guided by considerations including the patient’s needs and preferences, the risks and benefits for the patient, the patient’s past treatment history, the presence of comorbid general medical and other psychiatric conditions, cost and the local availability of evidence-based psychological interventions.

Where appropriate and available, patients should be offered a choice of evidence-based treatment approaches.

Cognitive behavioural therapy

All major guidelines recommend CBT as the first-line intervention for anxiety disorders.64,89,94,130

CBT is a multimodal intervention. Specific techniques used in the therapy include education, self-monitoring, relaxation training, cognitive restructuring, exposure to imagery and anxiety-producing situations, and relapse prevention. CBT has been shown to be an effective stand-alone treatment for GAD.132 Comorbidity does not decrease the treatment effects of CBT.

CBT for most anxiety, and related disorders, can be delivered effectively in individual or group therapy formats.130 There are also an increasing number of self-directed formats that require minimal or no therapist contact, which have been shown to be effective.130 These include bibliotherapy (self-help books) and internet or computer-based programs.133,134

A combination of medication and cognitive behaviour or exposure therapy has been shown to be a clinically desired treatment strategy.94 However, combination therapy results have been conflicting,135,136 and results vary for different anxiety disorders. While current evidence does not support the routine combination of CBT and pharmacotherapy as initial treatment for all anxiety disorders, there is support for combined use in panic disorders, with or without agoraphobia.137,138

Benzodiazepines are generally avoided in patients with anxiety disorders who are undergoing CBT. This is due to their potential interference with motivation and learning, which are required for CBT to be effective. Some authors are now challenging this,73 however there is sparse trial evidence to support a conclusion. More research is needed to ascertain if these treatment modalities can be combined effectively.

CBT protocols for anxiety usually involve 10–14 weekly sessions, but briefer strategies of 6–7 sessions have been shown to be as effective. Unfortunately, a lack of access to trained clinicians may be an issue in some areas and therefore lead to the majority of patients with anxiety being treated with medications.139 Online CBT programs have shown efficacy, and may be suitable for patients who cannot access face-to-face therapy, or who prefer treatment in their own homes, in their own time.

Antidepressants

Note that anxiety disorders show a strong placebo response, especially at mild to moderate levels of symptom severity.89 If pharmacotherapy is indicated, the SSRIs and SNRIs are preferred agents.140 Tricylic antidepressants (TCAs) and monoamine oxidase inhibitors (MOAI) are other alternatives.

Although preferred over benzodiazepines, there are limited studies comparing head-to-head effectiveness with antidepressants. Reviews of the studies performed suggest comparative effectiveness of benzodiazepines to older and new antidepressants.141–142

In trials of benzodiazepines and newer antidepressants, benzodiazepines have demonstrated comparable or greater improvements with fewer adverse events in patients suffering from GAD or panic disorder.141 Efficacy of benzodiazepines for panic disorder is comparable to SSRIs, SNRIs and TCAs.143 Similarly, the incidence of withdrawal symptoms from antidepressants seems to occur at similar levels to benzodiazepines.96

Reviewers have suggested the major change in prescribing pattern from benzodiazepines to newer antidepressants in anxiety disorders has occurred in the absence of comparative data of high-level of proof.141,144

However, SSRIs and SNRIs remain recommended first-line treatments by international guidelines for anxiety disorders.143

Short-term benzodiazepines as occasional adjunctive therapy may be effective at reducing worsening of symptoms that can occur in the first days to weeks of initiating antidepressant medication.

Benzodiazepines

Benzodiazepines are not indicated for ‘mild’ anxiety.

Benzodiazepines may be used (as monotherapy or in combination with antidepressants) for patients with very distressing or impairing symptoms whom rapid symptom control is critical.143

Benzodiazepines have evidence of benefit for GAD, social anxiety disorder and panic disorder, but not for OCD or PTSD.64,94 Trials have been conducted with clonazepam, diazepam and lorazepam, which have demonstrated the efficacy of these compounds in managing panic disorder clonazepam for SAD, diazepam and bromazepam for GAD.3

The benefit of a more rapid response to benzodiazepines must be balanced against the possibilities of troublesome side effects (eg sedation) and physiological dependence that may lead to difficulty discontinuing the medication.143 Note that:

  • Due to its rapid onset and offset of action, alprazolam is the benzodiazepine most commonly prescribed for panic disorders. However, in a meta-analysis, it has not been shown to have better efficacy than other benzodiazepines for panic disorders, and it does have a greater risk of dependence, problematic use and withdrawal.145
  • Although tolerance is less of an issue with anxiety, patients are at risk of dependence and other harms (eg depression, increased anxiety, accidents).

When benzodiazepines are prescribed short term for severe anxiety, they are generally used in conjunction with other interventions including counselling or antidepressants (where appropriate), to reduce the risk of symptom recurrence89 or to alleviate and prevent the worsening of anxiety130 that may occur at the start of antidepressant therapy.146

Rarely, ongoing therapy with benzodiazepines may be necessary in patients with severe, treatment-resistant anxiety. Although concerns have surrounded the risks of tolerance and SUD with long-term use of benzodiazepines, there is little evidence of tolerance to their anxiolytic effects.35 Problematic use is a risk in those with a history of SUD, but is otherwise uncommon.147

The decision to treat chronic anxiety with benzodiazepines must weigh the risks and benefits of benzodiazepine therapy. Concerns about potential problems in long-term use should not prevent their use in patients with persistent, severe, distressing and impairing anxiety symptoms,147 or in patients who are resistant to, or cannot tolerate, multiple first-line therapies.130 Ongoing supervision is required.

Resources

Key points

  • Benzodiazepines are an important component of alcohol withdrawal programs, but not every patient requires medication.
  • Benzodiazepines are generally only used as first-line options for acute treatment in a controlled environment for alcohol withdrawal.

Background

Alcohol dependence is characterised by craving, tolerance, preoccupation with alcohol and continued drinking in spite of harmful consequences (eg liver disease). From a clinical perspective, alcohol dependence can be subdivided into mild, moderate or severe categories. People with mild dependence (based on alcohol dependence assessment tools) usually do not need assisted alcohol withdrawal. People with moderate dependence usually need assisted withdrawal, which can be managed in a community setting. People who are severely alcohol dependent need assisted alcohol withdrawal, typically in an in-patient or residential setting.149

The onset of alcohol withdrawal is usually 6–24 hours after the last drink. In some severely dependent drinkers, withdrawal can occur while the patient is still intoxicated due to drops in blood alcohol level.30

About 95% of people with alcohol dependence can stop drinking without major withdrawal symptoms (ie delirium, seizures).30 Supportive care alone is often effective in minor alcohol withdrawal. Medication may not be necessary with lower daily alcohol consumption or for periodic drinkers. Seizures (usually a single episode) occur in approximately 5% of people with alcohol dependence when withdrawing from alcohol, and delirium tremens are typically seen in the most severe forms of alcohol withdrawal.30

Management of alcohol withdrawal in general practice

Alcohol dependence may require complex multidisciplinary therapy, including social support systems.

Assessment

Formal assessment tools can help determine if the patient is best suited to alcohol withdrawal in the primary care or specialist alcohol services setting.

The routine screening tool is the Alcohol Use Disorders Identification Tool (AUDIT or AUDIT-C) (refer to Resource F in the PDF version). Other tools include Severity of Alcohol Dependence Questionnaire (SADQ) to assess the severity of dependence; and the Clinical Institute Withdrawal Assessment of Alcohol State, revised (CIWA-Ar) or Alcohol Withdrawal Scale (AWS) for severity of withdrawal.

Patients may be suitable for home alcohol withdrawal if they:

  • have no history of seizures or delirium tremens
  • do not pose a suicide risk
  • have social support
  • show no significant polydrug misuse
  • are not dependent on benzodiazepines.149

Assisted withdrawal approaches

When conducting an assisted withdrawal from alcohol, there are three commonly used approaches:30

  • benzodiazepine loading – involves giving a large dose (up to 80 mg of diazepam) on day one in an in-patient setting, and then no further benzodiazepines
  • tapering dose regimes – a predetermined (fixed) dose of benzodiazepine is administered in tapering doses over 2–6 days
  • symptom-triggered sedation – doses of benzodiazepine are administered according to the severity of withdrawal symptoms.

There is limited evidence for selecting one approach over another, however, the first approach is more suited to an in-patient setting. In a comparison of fixed schedule and symptom triggered regimens, the latter two approaches were favoured.150

Benzodiazepines

Benzodiazepines have been shown to be one of the most effective drug classes in the management of alcohol withdrawal syndrome. The rationale of the use of benzodiazepines is to modulate CNS hyperactivity due to the alcohol withdrawal, by interacting with GABA receptors.150

A 2010 systematic review found benzodiazepines have a protective benefit against alcohol withdrawal symptoms, in particular seizures (when compared to placebo), and have a potentially protective benefit for many outcomes when compared with other drugs. This review did not find a statistical significance among the performance of different benzodiazepines.150

Avoid prescribing benzodiazepines to patients who are dependent on alcohol before enrolling them in, or referring them to, community withdrawal. Prescribing a ‘small dose of diazepam’ to help patients who claim to have stopped or reduced their alcohol consumption should also be avoided. Benzodiazepines can increase alcohol cravings and relapse rates.151

Baclofen and carbamazepine

Baclofen has been used to rapidly reduce symptoms of severe alcohol withdrawal syndrome. However, the evidence for recommending baclofen is insufficient to support its use in most situations.152 Carbamazepine has been effective in trials, but its role is as yet unclear.153 These, and several other drugs, may be useful adjuncts but cannot currently be recommended for clinical monotherapy.

Key points
Benzodiazepines can be used to calm or sedate and control aggressive, overactive or disturbed behaviour in manic episodes until a mood stabiliser takes effect.

Background

Bipolar disorder is a recurrent, disabling condition. Patients experience periods of mania or hypomania, depression and mixed episodes or ‘dysphoric mania’ (both manic and depressive symptoms). Bipolar disorder is commonly subdivided into bipolar disorder I (at least one manic episode) and bipolar disorder II (hypomania and depression only).154

Bipolar disorder has a lifetime prevalence of up to 1.6%.154

Management of manic episodes in general practice

For acutely manic patients, referral to a specialist psychiatric service for in- or out-patient care is recommended.154

There are two components to managing acute mania with medication:154

  • mood stabilisation with drugs (eg lithium, sodium valproate, carbamazepine) or one of the new second-generation antipsychotics
  • adjunct therapy to control acute agitation while mood stabilisers start to take effect (about 1 week for most patients).

Adjunct therapy usually consists of an antipsychotic or benzodiazepine (or a combination). This calms or sedates the person with mania as a temporary measure, until the mood stabiliser starts to be effective.154

In most cases, the benzodiazepine or antipsychotic would be withdrawn once the acute episode has resolved, and then only the mood stabiliser continued. It is common practice to taper down and discontinue benzodiazepines within 2–3 weeks of achieving adequate symptom control in mania.154

Background

Epilepsy affects approximately 224,000 Australians (1 in 100) and is the most common chronic brain disorder. Nearly 10% of Australians will have a seizure during their lifetime, and one-third of those will be diagnosed with epilepsy.156

Management of epilepsy in general practice

In acute epilepsy, diazepam, lorazepam and midazolam are the drugs most commonly used to control prolonged seizures.155

In chronic epilepsy, the use of benzodiazepines is now rare. They have limited usefulness in long-term management due to the rapid development of tolerance to anticonvulsant effects and the associated side effects (eg sedation and psychomotor slowing).155

Benzodiazepines are considered adjunct to standard antiepileptic drugs, and used when these have failed to achieve acceptable control.155

Benzodiazepines for seizure prophylaxis should only be used on advice from a specialist neurologist or paediatrician.

Prescription of benzodiazepines for epilepsy within Australia requires an authority prescription. Take care with monitoring and detecting problematic use.

  1. Mehdi T. Benzodiazepines revisited. BJMP 2012;5(1):a501.
  2. Ashton H. The diagnosis and management of benzodiazepine dependence. Curr Opin Psychiatry 2005;18(3):249–55.
  3. Dell’osso B, Lader M. Do benzodiazepines still deserve a major role in the treatment of psychiatric disorders? A critical reappraisal. Eur Psychiatry 2013;28(1):7–20
  4. Committee on Safety of Medicines. Current problems – Benzodiazepines, dependence and withdrawal symptoms. London: Committee on Safety of Medicines, 1988. [Accessed 12 June 2015]
  5. Islam MM, Conigrave KM, Day CA, Nguyen Y, Haber PS. Twenty-year trends in benzodiazepine dispensing in the Australian population. Intern Med J 2014;44(1):57–64. [Accessed 12 June 2015]
  6. Nicholas R, Lee N, Roche A. Pharmaceutical drug misuse in Australia: Complex issues, balanced responses. Adelaide: National Centre for Education and Training on Addiction (NCETA); 2011. [Accessed 12 June 2015]
  7. Drugs and Crime Prevention Committee (DCPC). Inquiry into the misuse/abuse of benzodiazepines and other forms of pharmaceutical drugs in Victoria – Final report. Melbourne: DCPC; 2007. [Accessed 12 June 2015]
  8. Sirdifield C, Anthierens S, Creupelandt H, et al. General practitioners’ experiences and perceptions of benzodiazepine prescribing: Systematic review and meta-synthesis. BMC Fam Pract 2013;14:191. [Accessed 12 June 2015]
  9. Balon R. Benzodiazepines revisited. Psychother Psychosom. 2013;82(6):353–54. [Accessed 12 June 2015]
  10. Haw C, Stubbs J. Benzodiazepines – A necessary evil? A survey of prescribing at a specialist UK psychiatric hospital. J Psychopharmacol 2007;21(6):645–9. [Accessed 12 June 2015]
  11. Medicare Australia Statistics. Pharmaceutical Benefits Schedule Item Reports [internet]. [Accessed 4 April 2014].
  12. Coroners Court of Victoria. Coroners Prevention Unit – Pharmaceutical drugs in fatal overdose: A coroner’s perspective. Melbourne: Coroners Court of Victoria; 2015. [internet]. [Accessed 4 April 2014].
  13. Hollingworth SA, Siskind DJ, Nissen LM, Robinson M, Hall WD. Patterns of antipsychotic medication use in Australia 2002–2007. Aust N Z J Psychiatry 2010;44(4):372–7 [internet]. [Accessed 4 April 2014].
  14. Britt HC, Miller GC, Henderson J, et al. A decade of Australian general practice activity 2003–04 to 2012–13. Sydney: Sydney University Press; 2013 [internet]. [Accessed 4 April 2014].
  15. Rintoul AC, Dobbin MD, Nielsen S, Degenhardt L, Drummer OH. Recent increase in detection of alprazolam in Victorian heroin-related deaths. Med J Aust 2013;198(4):206–09. [internet]. [Accessed 4 April 2014].
  16. Australian Institute of Health and Welfare. 2010 National Drug Strategy Household Survey report. Cat. no. PHE 145. Canberra: AIHW; 2011. [internet]. [Accessed 4 April 2014].
  17. McGregor C, Gately N, Flemming J. Prescription drug use among detainees: Prevalence, sources and links to crime. Trends and issues in crime and criminal justice no.423. Canberra: Australian Institute of Criminology; 2011. [internet]. [Accessed 4 April 2014].
  18. Mitchell MD, Gehrman P, Perlis M, Umscheid CA. Comparative effectiveness of cognitive behavioral therapy for insomnia: A systematic review. BMC Fam Pract 2012;13:40. [internet]. [Accessed 4 April 2014].
  19. Nielsen S, Bruno R, Degenhardt L, et al. The sources of pharmaceuticals for problematic users of benzodiazepines and prescription opioids. Med J Aust 2013;199(10):696–99 [internet]. [Accessed 4 April 2014].
  20. Alcohol and other Drugs Council of Australia (ADCA). Misuse of prescription drugs. Canberra: ADCA; 2003. [internet]. [Accessed 4 April 2014].
  21. Mental Health and Drug and Alcohol Office (MHDAO). NSW Opioid Treatment Program: Clinical guidelines for methadone and buprenorphine treatment. Sydney: MHDAO; 2006 [internet]. [Accessed 4 April 2014].
  22. Pilgrim JL, McDonough M, Drummer OH. A review of methadone deaths between 2001 and 2005 in Victoria, Australia. Forensic Sci Int 2013;226(1–3):216–22. [internet]. [Accessed 4 April 2014].
  23. Ross J, Darke S. The nature of benzodiazepine dependence among heroin users in Sydney, Australia. Addiction 2000;95(12):1785–93 [internet]. [Accessed 4 April 2014].
  24. Kirwan A, Dietze P, Lloyd B. Victorian drug trends 2011: findings from the Illicit Drug Reporting System (IDRS). Sydney: National Drug and Alcohol Reseach Centre, University of New South Wales; 2012. [internet]. [Accessed 4 April 2014].
  25. Baldwin DS, Aitchison K, Bateson A, et al. Benzodiazepines: risks and benefits. A reconsideration. J Psychopharmacol 2013;27(11):967–71. [internet]. [Accessed 4 April 2014].
  26. Quaglio G, Lugoboni F, Fornasiero A, et al. Dependence on zolpidem: two case reports of detoxification with flumazenil infusion. Int Clin Psychopharmacol 2005;20(5):285–87 [internet]. [Accessed 4 April 2014].
  27. Sethi PK, Khandelwal DC. Zolpidem at supratherapeutic doses can cause drug abuse, dependence and withdrawal seizure. J Assoc Physicians India 2005;53:139–40. [internet]. [Accessed 4 April 2014].
  28. Harter C, Piffl-Boniolo E, Rave-Schwank M. Development of drug withdrawal delirium after dependence on zolpidem and zoplicone. Psychiatr Prax 1999;26(6):309. [internet]. [Accessed 4 April 2014].
  29. Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, Siriwardena AN. Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration. BMJ 2012;345:e8343 [internet]. [Accessed 4 April 2014].
  30. Mental Health and Drug and Alcohol Office (MHDAO). NSW Drug and Alcohol Withdrawal Clinical Practice Guidelines. Sydney: MHDAO; 2008. [internet]. [Accessed 4 April 2014].
  31. World Health Organization. Lexicon of alcohol and drug terms published by the World Health Organization. Geneva: WHO; 2014 [Accessed 14 January 2014]. [internet]. [Accessed 4 April 2014].
  32. Vinkers CH, Olivier B. Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective GABA(A) Receptor Modulators? Adv Pharmacol Sci 2012;2012:416864. [internet]. [Accessed 4 April 2014].
  33. Longo LP, Johnson B. Addiction: Part I. Benzodiazepines – Side effects, abuse risk and alternatives. Am Fam Physician 2000;61(7):2121–28 [internet]. [Accessed 4 April 2014].
  34. Argyropoulos SV, Nutt DJ. The use of benzodiazepines in anxiety and other disorders. Eur Neuropsychopharmacol 1999;9 Suppl 6:S407–12 [internet]. [Accessed 4 April 2014].
  35. Therapeutic Guidelines. eTG complete [internet.] Melbourne: Therapeutic Guidelines Limited; 2013 [Accessed 26 Decemeber 2013] [internet]. [Accessed 4 April 2014].
  36. Soldatos CR, Dikeos DG, Whitehead A. Tolerance and rebound insomnia with rapidly eliminated hypnotics: A meta-analysis of sleep laboratory studies. Int Clin Psychopharmacol 1999;14(5):287–303. [internet]. [Accessed 4 April 2014].
  37. Ashton H. Benzodiazepine withdrawal: outcome in 50 patients. Br J Addict 1987;82(6):665–71. [internet]. [Accessed 4 April 2014].
  38. Ford C, Law F. Guidance for the use and reduction of misuse of benzodiazepines and other hypnotics and anxiolytics in general practice. London: SMMGP; 2014. [internet]. [Accessed 4 April 2014].
  39. Smith DE, Wesson DR. Benzodiazepine dependency syndromes. J Psychoactive Drugs 1983;15(1–2):85–95 [internet]. [Accessed 4 April 2014].
  40. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th edn. Arlington VA: American Psychiatric Publishing; 2013. [internet]. [Accessed 4 April 2014].
  41. Willems IA, Gorgels WJ, Oude Voshaar RC, Mulder J, Lucassen PL. Tolerance to benzodiazepines among long-term users in primary care. Fam Pract 2013;30(4):404–10. [internet]. [Accessed 4 April 2014].
  42. Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J 2013;13(2):214–23. [internet]. [Accessed 4 April 2014].
  43. Roche. Valium (diazepam) Product Information. Date of first TGA inclusion 1994. Date of most recent amendment 2012. Sydney: Roche Products Pty Ltd; 2012. [internet]. [Accessed 4 April 2014].
  44. Alphapharm. Kalma (alprazolam) Product Information. Date of first TGA inclusion 1998. Most recent amendment 2014. Sydney: Alphapharm Pty Ltd; 2014. [internet]. [Accessed 4 April 2014].
  45. Alphapharm. Temaze (temazepam) Product Information. Date of first TGA inclusion 1998. Date of most recent amendment 2014. Sydney: Alphapharm Pty Ltd; 2014. [internet]. [Accessed 4 April 2014].
  46. Aspen. Ativan (lorazepam) Product Information. Date of first TGA inclusion 1993. Date of most recent amendment 2013. Sydney: Aspen Pharma Pty Ltd; 2013. [internet]. [Accessed 4 April 2014].
  47. Tiplady B, Bowness E, Stien L, Drummond G. Selective effects of clonidine and temazepam on attention and memory. J Psychopharmaco 2005;19(3):259–65. [internet]. [Accessed 4 April 2014].
  48. Buffett-Jerrott SE, Stewart SH. Cognitive and sedative effects of benzodiazepine use. Curr Pharm Des 2002;8(1):45–58. [internet]. [Accessed 4 April 2014].
  49. Barker MJ, Greenwood KM, Jackson M, Crowe SF. Cognitive effects of long-term benzodiazepine use: A meta-analysis. CNS Drugs 2004;18(1):37–48. [internet]. [Accessed 4 April 2014].
  50. Billioti de Gage S, Begaud B, Bazin F, et al. Benzodiazepine use and risk of dementia: Prospective population based study. BMJ 2012;345:e6231. [internet]. [Accessed 4 April 2014].
  51. Wu CS, Wang SC, Chang IS, Lin KM. The association between dementia and long-term use of benzodiazepine in the elderly: Nested casecontrol study using claims data. Am J Geriatr Psychiatry 2009;17(7):614–20. [internet]. [Accessed 4 April 2014].
  52. Gallacher J, Elwood P, Pickering J, et al. Benzodiazepine use and risk of dementia: Evidence from the Caerphilly Prospective Study (CaPS). J Epidemiol Community Health 2012;66(10):869–73. [internet]. [Accessed 4 April 2014].
  53. Amieva H, Le Goff M, Millet X, et al. Prodromal Alzheimer’s disease: Successive emergence of the clinical symptoms. Ann Neurol 2008;64(5):492–98. [internet]. [Accessed 4 April 2014].
  54. Mura T, Proust-Lima C, Akbaraly T, et al. Chronic use of benzodiazepines and latent cognitive decline in the elderly: Results from the Threecity study. Eur Neuropsychopharmacol 2013;23(3):212–23. [internet]. [Accessed 4 April 2014].
  55. Dassanayake T, Michie P, Carter G, Jones A. Effects of benzodiazepines, antidepressants and opioids on driving: A systematic review and meta-analysis of epidemiological and experimental evidence. Drug Saf 2011;34(2):125–56. [internet]. [Accessed 4 April 2014].
  56. Chouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004;65 Suppl 5:7–12. [internet]. [Accessed 4 April 2014].
  57. Ashton H. Benzodiazepines: How they work and how to withdraw. Newcastle: The Ashton Manual; 2002. [internet]. [Accessed 4 April 2014].
  58. Nielsen M, Hansen EH, Gotzsche PC. What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors. Addiction 2012;107(5):900–08. [internet]. [Accessed 4 April 2014].
  59. Ashton H. Protracted withdrawal syndromes from benzodiazepines. J Subst Abuse Treat 1991;8(1–2):19–28. [internet]. [Accessed 4 April 2014].
  60. Schweizer E, Rickels K. Benzodiazepine dependence and withdrawal: a review of the syndrome and its clinical management. Acta Psychiatr Scand Suppl 1998;393:95–101. [internet]. [Accessed 4 April 2014].
  61. McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in Alzheimer’s disease. Cochrane Database Syst Rev 2014;3:Cd009178. [internet]. [Accessed 4 April 2014].
  62. Olsen Y. Clinical Guidelines for the use of benzodiazepines among patients receiving medication assissted treatment for opioid dependence. Baltimore: Baltimore Sustance Abuse Systems; 2013. [internet]. [Accessed 4 April 2014].
  63. van Marwijk H, Allick G, Wegman F, Bax A, Riphagen, II. Alprazolam for depression. Cochrane Database Syst Rev. 2012;7:CD007139. [internet]. [Accessed 4 April 2014].
  64. Guideline Working Group for the Treatment of Patients with Anxiety Disorders in Primary Care. Clinical Practice Guideline for Treatment of Patients with Anxiety Disorders in Primary Care. UETS no 2006/10 ed. Madrid: National Plan for the NHS of the MSC. Health Technology Assessment Unit; 2008. [internet]. [Accessed 4 April 2014].
  65. Busto U, Sellers EM, Naranjo CA, et al. Withdrawal reaction after long-term therapeutic use of benzodiazepines. N Engl J Med 1986;315(14):854–59. [internet]. [Accessed 4 April 2014].
  66. Paquin AM, Zimmerman K, Rudolph JL. Risk versus risk: a review of benzodiazepine reduction in older adults. Expert Opin Drug Saf 2014;13(7):919–34. [internet]. [Accessed 4 April 2014].
  67. Kenny P, Swan A, Berends L, et al. Alcohol and other drug withdrawal: Practice guidelines 2009. Melbourne: Turning Point Alcohol and Drug Centre; 2009. [internet]. [Accessed 4 April 2014].
  68. Psychotropic Drugs Committee. Practice Guideline 5: Guidelines for use of benzodiazepines in psychiatric practice: Royal Australian and New Zealand College of Psychiatrists. Melbourne 2008 (update, first issued 1991). [internet]. [Accessed 4 April 2014].
  69. Reconnexion. Beyond benzodiazepines: Helping people recover from benzodiazepine dependence and withdrawal – For health practitioners. Redman T, Cannard G, editors. Melbourne: Reconnexion Inc; 2010. [internet]. [Accessed 4 April 2014].
  70. Lader M. Withdrawal reactions after stopping hypnotics in patients with insomnia. CNS Drugs1998;10(6):425–40. [internet]. [Accessed 4 April 2014].
  71. Ashton H. Benzodiazepine dependency. In: Baum A, Newman S, Weinman J, West R, McManus C, editors. Cambridge Handbook of Psychology and Medicine. Cambridge: Cambridge University Press; 1997. [internet]. [Accessed 4 April 2014].
  72. Balter MB, Ban TA, Uhlenhuth EH. International study of expert judgment on therapeutic use of benzodiazepines and other pyschotherapeutic medications: I. Current concerns. Hum Psychopharmacol Clin Exp 1993;8:253–61. [internet]. [Accessed 4 April 2014].
  73. Starcevic V. The reappraisal of benzodiazepines in the treatment of anxiety and related disorders. Expert Rev Neurother 2014:1–12. [internet]. [Accessed 4 April 2014].
  74. American Psychiatric Association Task Force on Benzodiazepine Dependency. Benzodiazepine dependence, toxicity, and abuse. Washington, DC: AMA; 1990. [internet]. [Accessed 4 April 2014].
  75. Sheehan D, Raj A. Benzodiazepines. In: Shatzberg A, Nemeroff C, editors. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th edn. Arlington, VA: American Psychiatric Publishing; 2009. [internet]. [Accessed 4 April 2014].
  76. Tvete IF, Bjorner T, Aursnes IA, Skomedal T. A 3-year survey quantifying the risk of dose escalation of benzodiazepines and congeners to identify risk factors to aid doctors to more rationale prescribing. BMJ Open 2013;3(10):e003296. [internet]. [Accessed 4 April 2014].
  77. Longo LP, Parran T, Jr., Johnson B, Kinsey W. Addiction: Part II. Identification and management of the drug-seeking patient. Am Fam Physician 2000;61(8):2401–08. [internet]. [Accessed 4 April 2014].
  78. Oster G, Huse DM, Adams SF, Imbimbo J, Russell MW. Benzodiazepine tranquilizers and the risk of accidental injury. Am J Public Health 1990;80(12):1467–70. [internet]. [Accessed 4 April 2014].
  79. Lloyd B. Trends in alcohol and drug related ambulance attendences in Melbourne 2010–11. Melbourne: Turning Point Alcohol and Drug Centre; 2012. [internet]. [Accessed 4 April 2014].
  80. Lloyd B. Ambo Project: Alcohol and drug related ambulance attendance in Victoria 2011–12. Melbourne: Turning Point Alcohol and Drug Centre and Ambulance Victoria; 2013. [internet]. [Accessed 4 April 2014].
  81. Tinetti ME. Clinical practice. Preventing falls in elderly persons. N Engl J Med 2003;348(1):42–49. [internet]. [Accessed 4 April 2014].
  82. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988;319(26):1701–07. [internet]. [Accessed 4 April 2014].
  83. Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med 2009;169(21):1952–60. [internet]. [Accessed 4 April 2014].
  84. Kripke DF Langer RD, Kline LE. Hypnotics’ association with mortality or cancer: A matched cohort study. BMJ Open 2012;2(1):e000850. [internet]. [Accessed 4 April 2014].
  85. Jaussent I, Ancelin ML, Berr C, et al. Hypnotics and mortality in an elderly general population: A 12-year prospective study. BMC Med 2013;11:212. [internet]. [Accessed 4 April 2014].
  86. National Institute on Drug Abuse. Prescription Drugs: Abuse and Addiction: NIDA; 2001, revised 2011. [internet]. [Accessed 4 April 2014].
  87. Heit HA, Lipman AG. Pain: Substance Abuse Issue in the Treatment of Pain. In: Moore RJ, editor. Biobehavioral Approaches to Pain. New York: Springer Science+Business Media, LLC; 2009. [internet]. [Accessed 4 April 2014].
  88. Johnson C, Baxter B, Brough R, Buchanan J. Benzodiazepine prescribing: Lessons from interprofessional dialogue. Aust Fam Physician 2007;36(4):245–46. [internet]. [Accessed 4 April 2014].
  89. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2005;19(6):567–96. [internet]. [Accessed 4 April 2014].
  90. Mugunthan K, McGuire T, Glasziou P. Minimal interventions to decrease long-term use of benzodiazepines in primary care: A systematic review and meta-analysis. Br J Gen Pract 2011;61(590):e573–78. [internet]. [Accessed 4 April 2014].
  91. de Gier NA, Gorgels WJ, Lucassen PL, et al. Discontinuation of long-term benzodiazepine use: 10-year follow-up. Fam Pract 2011;28(3):253–59. [internet]. [Accessed 4 April 2014].
  92. Tannenbaum C, Martin P, Tamblyn R, Benedetti A, Ahmed S. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: The EMPOWER Cluster Randomized Trial. JAMA Intern Med 2014;174(6):890–98. [internet]. [Accessed 4 April 2014].
  93. Spinks A, Bulbeck K, Del Mar C, Glasziou P, Nikles J, Group AcftPBW. Using benzodiazeines: the best evidence. Brisbane: Centre for General Practice, The University of Queensland; 2000. [internet]. [Accessed 4 April 2014].
  94. Bandelow B, Sher L, Bunevicius R, et al. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract 2012;16(2):77–84. [internet]. [Accessed 4 April 2014].
  95. Rogers A, Pilgrim D, Brennan S, et al. Prescribing benzodiazepines in general practice: a new view of an old problem. Health (London) 2007;11(2):181–98. [internet]. [Accessed 4 April 2014].
  96. Fava GA, Gatti A, Belaise C, Guidi J, Offidani E. Withdrawal symptoms after selective serotonin reuptake inhibitor discontinuation: A systematic review. Psychother Psychosom 2015;84(2):72–81. [internet]. [Accessed 4 April 2014].
  97. Nielsen M, Hansen EH, Gotzsche PC. Dependence and withdrawal reactions to benzodiazepines and selective serotonin reuptake inhibitors. How did the health authorities react? Int J Risk Saf Med 2013;25(3):155–68. [internet]. [Accessed 4 April 2014].
  98. Evans EA, Sullivan MA. Abuse and misuse of antidepressants. Subst Abuse Rehabil 2014;5:107–20. [internet]. [Accessed 4 April 2014].
  99. Klein-Schwartz W, Schwartz EK, Anderson BD. Evaluation of quetiapine abuse and misuse reported to poison centers. J Addict Med 2014;8(3):195–98. [internet]. [Accessed 4 April 2014].
  100. Martin P, Tamblyn R, Ahmed S, Tannenbaum C. A drug education tool developed for older adults changes knowledge, beliefs and risk perceptions about inappropriate benzodiazepine prescriptions in the elderly. Patient Educ Couns 2013;92(1):81–7. [internet]. [Accessed 4 April 2014].
  101. Wilson SJ, Nutt DJ, Alford C, et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol 2010;24(11):1577–601. [internet]. [Accessed 4 April 2014].
  102. Ministry of Health Singapore. Prescribing of Benzodiazepines: MOH Clinical Practice Guidelines 2/2008. Singapore: MOH; 2008. [internet]. [Accessed 4 April 2014].
  103. Guideline Working Group for the Treatment of Patients with Insomnia in Primary Care. Clinical Practice Guidelines for the Management of Patients with Insomnia in Primary Care. UETS No 2007/5–1. Madrid: Ministry of Health and Social Policy. Health Technology Assessment Unit; 2009. [internet]. [Accessed 4 April 2014].
  104. Britt HC, Miller GC, Henderson J, et al. General practice activity in Australia 2009–10. Canberra: Australian Institute of Health of Welfare; 2010. [internet]. [Accessed 4 April 2014].
  105. Pagel JF, Parnes BL. Medications for the treatment of sleep disorders: An overview. Prim Care Companion J Clin Psychiatry 2001;3(3):118–25. [internet]. [Accessed 4 April 2014].
  106. Wilson S, Nutt DJ. Recommended diagnosis and management of insomnia. Prescriber 2014. [internet]. [Accessed 4 April 2014].
  107. National Institutes of Health. National Institutes of Health State of the Science Conference statement on Manifestations and Management of Chronic Insomnia in Adults, June 13–15, 2005. Sleep 2005;28(9):1049–57. [internet]. [Accessed 4 April 2014].
  108. Bonnet M, Arand D. Treatment of insomnia [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  109. Katz DA, McHorney CA. Clinical correlates of insomnia in patients with chronic illness. Arch Intern Med 1998;158(10):1099–107. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  110. Krystal AD. Psychiatric comorbidity: the case for treating insomnia. Sleep Med Clin 2006;1:359. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  111. Cunnington D, Junge MF, Fernando AT. Insomnia: prevalence, consequences and effective treatment. Med J Aust 2013;199(8):S36–40. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  112. Cunnington D. Non-benzodiazepine hypnotics: do they work for insomnia? BMJ 2013;346:e8699. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  113. Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med 2008;4(5):487–504. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  114. Arroll B, Fernando A 3rd, Falloon K, Warman G, Goodyear-Smith F. Development, validation (diagnostic accuracy) and audit of the Auckland Sleep Questionnaire: a new tool for diagnosing causes of sleep disorders in primary care. J Prim Health Care 2011;3(2):107–13. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  115. Kierlin L. Sleeping without a pill: non pharmacological treatments for insomnia. J Pscychiatr Pract 2008;14(6):403–07. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  116. Hasora P, Kessmann J. Nonpharmacological management of chronic insomnia. Am Fam Physician 2009;79(2):125–30. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  117. Montgomery P, Dennis J. Cognitive behavioural interventions for sleep problems in adults aged 60+. Cochrane Database Syst Rev 2003(1):CD003161. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  118. Buysse DJ, Germain A, Moul DE, et al. Efficacy of brief behavioral treatment for chronic Insomnia in older adults. Arch Intern Med 2011;171(10):887–95. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  119. Fernando A 3rd, Arroll B, Falloon K. A double-blind randomised controlled study of a brief intervention of bedtime restriction for adult patients with primary insomnia. J Prim Health Care 2013;5(1):5–10. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  120. Troxel WM, Germain A, Buysse DJ. Clinical management of insomnia with brief behavioral treatment (BBTI). Behav Sleep Med 2012;10(4):266–79. [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  121. The Royal Australian College of General Practitioners. Brief behavioural therapy: insomnia in adults. Melbourne: RACGP; 2014. [Accessed 4 October 2014].
  122. Montgomery P, Dennis J. Physical exercise for sleep problems in adults aged 60+. Cochrane Database Syst Rev 2002(4):CD003404. [Accessed 4 October 2014].
  123. Riemann D, Perlis ML. The treatments of chronic insomnia: a review of benzodiazepine receptor agonists and psychological and behavioral therapies. Sleep Med Rev 2009;13(3):205–14. [Accessed 4 October 2014].
  124. Therapeutic Goods Administration (TGA). Zolpidem (Stilnox®) and next day impairment. Canberra: Australian Government Department of Health; 2014 [updated 1 August 2014]. [Accessed 2 September 2014].
  125. National Precribing Service. Melatonin prolonged-release tablets (Circadin®) for insmonia. Sydney: NPS; 2011. [updated 1 August 2014]. [Accessed 2 September 2014].
  126. Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res 2007;16(4):372–80. [updated 1 August 2014]. [Accessed 2 September 2014].
  127. Clay E, Falissard B, Moore N, Toumi M. Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries. Eur J Clin Pharmacol 2013;69(4):1–10. [updated 1 August 2014]. [Accessed 2 September 2014].
  128. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol 2014;28(5):403–39. [updated 1 August 2014]. [Accessed 2 September 2014].
  129. Mental Health: Australian Bureau of Statistics; 2010 [updated 13 November 2013]. [Accessed 27 December 2013].
  130. Canadian Agency for Drugs and Technologies in Health. Short- and Long-Term Use of Benzodiazepines in Patients with Generalized Anxiety Disorder: A Review of Guidelines. Ottawa: CADTH; 2014. [updated 13 November 2013]. [Accessed 27 December 2013].
  131. National Collaborating Centre for Mental Health. Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults: management in primary, secondary and community care. National Institute for Health and Care Excellence clinical guideline 113. London: NICE; 2011. [updated 13 November 2013]. [Accessed 27 December 2013].
  132. Bystritsky A, Khalsa SS, Cameron ME, Schiffman J. Current diagnosis and treatment of anxiety disorders. P T 2013;38(1):30–57. [updated 13 November 2013]. [Accessed 27 December 2013].
  133. The Royal Australian College of General Practitioners. Depression and anxiety: Internet based or computerised CBT (iCBT or CCBT). Melbourne: RACGP; 2014. [Accessed 4 October 2014].
  134. The Royal Australian college of General Practitioners. Bibliotherapy: Depression. Melbourne: RACGP; 2014. [Accessed 4 October 2014].
  135. Bandelow B, Seidler-Brandler U, Becker A, Wedekind D, Ruther E. Meta-analysis of randomized controlled comparisons of psychopharmacological and psychological treatments for anxiety disorders. World J Biol Psychiatry 2007;8(3):175–87. [Accessed 4 October 2014].
  136. Hofmann SG, Sawyer AT, Korte KJ, Smits JA. Is it Beneficial to Add Pharmacotherapy to Cognitive-Behavioral Therapy when Treating Anxiety Disorders? A Meta-Analytic Review. Int J Cogn Ther 2009;2(2):160–75. [Accessed 4 October 2014].
  137. Furukawa TA, Watanabe N, Churchill R. Psychotherapy plus antidepressant for panic disorder with or without agoraphobia: Systematic review. Br J Psychiatry 2006;188:305–12. [Accessed 4 October 2014].
  138. Furukawa TA, Watanabe N, Churchill R. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev 2007(1):CD004364. [Accessed 4 October 2014].
  139. Tyrer P, Baldwin D. Generalised anxiety disorder. Lancet 2006;368(9553):2156–66. [Accessed 4 October 2014].
  140. Bystritsky A. Pharmacotherapy for generalized anxiety disorder [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  141. Berney P, Halperin D, Tango R, Daeniker-Dayer I, Schulz P. A major change of prescribing pattern in absence of adequate evidence: Benzodiazepines versus newer antidepressants in anxiety disorders. Psychopharmacol Bull 2008;41(3):39–47. [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  142. Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D. Efficacy of treatments for anxiety disorders: a meta-analysis. Int Clin Psychopharmacol. 2015 Apr 29; Epub 2015 Apr 29. [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  143. American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. 2nd edn. Arlington VA: American Psychiatric Publishing, Inc; 2009. [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  144. Offidani E, Guidi J, Tomba E, Fava GA. Efficacy and tolerability of benzodiazepines versus antidepressants in anxiety disorders: A systematic review and meta-analysis. Psychother Psychosom 2013;82(6):355–62. [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  145. Moylan S, Staples J, Ward SA, et al. The efficacy and safety of alprazolam versus other benzodiazepines in the treatment of panic disorder. J Clin Psychopharmacol 2011;31(5):647–52. [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  146. Bostwick JR, Casher MI, Yasugi S. Benzodiazepines: A versatile clinical tool. Curr Psychiatr 2012;11(4). [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  147. Nutt DJ. Overview of diagnosis and drug treatments of anxiety disorders. CNS Spectr 2005;10(1):49–56. [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  148. Scottish Intercollegiate Guidelines Network. The Management of Harmful Drinking and Alcohol Dependence in Primary Care. Guideline No.74. Edinburgh: SIGN, Healthcare Improvement Scotland; 2004. [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  149. National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. London: NICE; 2011. [Accessed April 2015].
  150. Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev 2010(3):CD005063. [Accessed April 2015].
  151. Gitlow S. Substance Use Disorders: A Practical Guide. Philadelphia, PA: Lippincott Williams and Wilkins; 2006. [Accessed April 2015].
  152. Liu J, Wang LN. Baclofen for alcohol withdrawal. Cochrane Database Syst Rev 2013;2:CD008502. [Accessed April 2015].
  153. Lingford-Hughes AR, Welch S, Peters L, Nutt DJ, British Association for Psychopharmacology ERG. BAP updated guidelines: Evidencebased guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: Recommendations from BAP. J Psychopharmacol 2012;26(7):899–952. [Accessed April 2015].
  154. The Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for Bipolar Disorder. Australian and New Zealand clinical practice guidelines for the treatment of bipolar disorder. Aust N Z J Psychiatry 2004;38(5):280–305. [Accessed April 2015].
  155. Scottish Intercollegiate Guidelines Network. Diagnosis and management of epilepsy in adults: A national clinical guideline. Guideline No. 70. Edinburgh: SIGN, Healthcare Improvement Scotland; 2003. [Accessed April 2015].
  156. Walker C, Brown K, Peterson C, et al. A socio-economic longitudinal study of epilepsy: Needs, perceptions and experiences of people with epilepsy. Epilepsy Foundation of Victoria and Epilepsy Australia; 2011. [Accessed April 2015].
  157. Ipser JC, Stein DJ, Hawkridge S, Hoppe L. Pharmacotherapy for anxiety disorders in children and adolescents. Cochrane Database Syst Rev 2009(3):CD005170. [Accessed April 2015].
  158. Witek MW, Rojas V, Alonso C, Minami H, Silva RR. Review of benzodiazepine use in children and adolescents. Psychiatr Q 2005;76(3):283–96. [Accessed April 2015].
  159. Harbord MG, Kyrkou NE, Kyrkou MR, Kay D, Coulthard KP. Use of intranasal midazolam to treat acute seizures in paediatric community settings. J Paediatr Child Health 2004;40(9-10):556–58. [Accessed April 2015].
  160. Humphries LK, Eiland LS. Treatment of acute seizures: is intranasal midazolam a viable option? J Pediatr Pharmacol Ther 2013;18(2):79–87. [Accessed April 2015].
  161. Wikner BN, Stiller CO, Bergman U, Asker C, Kallen B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf 2007;16(11):1203–10. [Accessed April 2015].
  162. Bellantuono C, Tofani S, Di Sciascio G, Santone G. Benzodiazepine exposure in pregnancy and risk of major malformations: a critical overview. Gen Hosp Psychiatry 2013;35(1):3–8. [Accessed April 2015].
  163. Maine Benzodiazepine Study Group. Guidelines for the use of benzodiazepines in office practice in the state of Maine. Maine: Maine Benzodiazepine Study Group; 2008. [Accessed April 2015].
  164. Uzun S, Kozumplik O, Jakovljevic M, Sedic B. Side effects of treatment with benzodiazepines. Psychiatr Danub 2010;22(1):90–93. [Accessed April 2015].
  165. Yoshida K, Smith B, Kumar R. Psychotropic drugs in mothers’ milk: A comprehensive review of assay methods, pharmacokinetics and of safety of breast-feeding. J Psychopharmacol 1999;13(1):64–80. [Accessed April 2015].
  166. Pons G, Rey E, Matheson I. Excretion of psychoactive drugs into breast milk. Pharmacokinetic principles and recommendations. Clin Pharmacokinet 1994;27(4):270–89. [Accessed April 2015].
  167. Glass J, Lanctot KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: Meta-analysis of risks and benefits. BMJ 2005;331(7526):1169. [Accessed April 2015].
  168. Windle A, Elliot E, Duszynski K, Moore V. Benzodiazepine prescribing in elderly Australian general practice patients. Aust N Z J Public Health 2007;31(4):379–81. [Accessed April 2015].
  169. Takkouche B, Montes-Martinez A, Gill SS, Etminan M. Psychotropic medications and the risk of fracture: a meta-analysis. Drug Saf 2007;30(2):171–84. [Accessed April 2015].
  170. Council of the College of Psychiatry Ireland. A consensus statement on the use of benzodiazepines in specialist mental health services: EAP03/2012 Position Paper; 2012. [Accessed April 2015].
  171. Levy HB. Non-benzodiazepine hypnotics and older adults: what are we learning about zolpidem? Expert Rev Clin Pharmacol 2014;7(1):5–8. [Accessed April 2015].
  172. Bourgeois J, Elseviers MM, Van Bortel L, Petrovic M, Vander Stichele RH. Sleep quality of benzodiazepine users in nursing homes: A comparative study with nonusers. Sleep Med 2013;14(7):614–21. [Accessed April 2015].
  173. Iliffe S, Curran HV, Collins R, et al. Attitudes to long-term use of benzodiazepine hypnotics by older people in general practice: Findings from interviews with service users and providers. Aging Ment Health 2004;8(3):242–48. [Accessed April 2015].
  174. Gilbert A, Owen N, Innes JM, Sansom L. Trial of an intervention to reduce chronic benzodiazepine use among residents of aged-care accommodation. Aust N Z J Med 1993;23(4):343–47. [Accessed April 2015].
  175. Jones KA, Nielsen S, Bruno R, Frei M, Lubman DI. Benzodiazepines – their role in aggression and why GPs should prescribe with caution. Aust Fam Physician 2011;40(11):862–65. [Accessed April 2015].
  176. Briesacher BA, Soumerai SB, Field TS, Fouayzi H, Gurwitz JH. Medicare part D’s exclusion of benzodiazepines and fracture risk in nursing homes. Arch Intern Med 2010;170(8):693–98. [Accessed April 2015].
  177. NSW Department of Health. NSW Clinical Guidelines: For the care of persons with comorbid mental illness and substance use disorders in acute care settings. Sydney: NSW Department of Health; 2009. [Accessed April 2015].
  178. Boscarino JA, Rukstalis M, Hoffman SN, et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US healthcare system. Addiction 2010;105(10):1776–82. [Accessed April 2015].
  179. Brennan MJ, Lieberman JA 3rd. Sleep disturbances in patients with chronic pain: effectively managing opioid analgesia to improve outcomes. Curr Med Res Opin. 2009 May;25(5):1045-55. [Accessed April 2015].
  180. Mills K, Deady M, Proudfoot H, et al. Guidelines on the management of co-occuring alcohol and other drug and mental health conditions in alcohol and other drug treatment settings. Sydney: National Drug and Alcohol Research Centre, University of New South Wales; 2010. [Accessed April 2015].
  181. Darke S, Ross J. The use of antidepressants among injecting drug users in Sydney, Australia. Addiction 2000;95(3):407–17. [Accessed April 2015].
  182. Darke S, Hall W, Ross M, Wodak A. Benzodiazepine use and HIV risk-taking behaviour among injecting drug users. Drug Alcohol Depend 1992;31(1):31–36. [Accessed April 2015].
  183. Darke S, Ross J, Mills K, Teesson M, Williamson A, Havard A. Benzodiazepine use among heroin users: baseline use, current use and clinical outcome. Drug Alcohol Rev 2010;29(3):250–55. [Accessed April 2015].
  184. Austroads. Assessing fitness to drive for commercial and private vehicle drivers. 4th edn. Sydney: Austroads; 2013. [Accessed April 2015].
  185. Bond A, Lader M. Anxiolytics and sedatives. In: Verster JC, Brady K, Galanter M, Conrod P, editors. Drug abuse and addiction in medical illness: Causes, consequences and treatment. New York: Springer; 2012. [Accessed April 2015].
  186. Krystal AD. The treatment of primary insomnia. CNS Spectr 2009;14(12 Suppl 13):6–10. [Accessed April 2015].
  187. Howard P, Twycross R, Shuster J, Mihalyo M, Wilcock A. Benzodiazepines. J Pain Symptom Manage 2014;47(5):955–64. [Accessed April 2015].
  188. National Prescribing Service (NPS). NPS News: Which treatment for what anxiety disorder? Sydney: NPS; 2009. [Accessed April 2015].
  189. Lader M, Tylee A, Donoghue J. Withdrawing benzodiazepines in primary care. CNS Drugs 2009;23(1):19–34. [Accessed April 2015].
  190. Joint National Formulary Committee. British National Formulary. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2011. [Accessed April 2015].
  191. Parr JM, Kavanagh DJ, Cahill L, Mitchell G, Mc DYR. Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta-analysis. Addiction 2009;104(1):13–24. [Accessed April 2015].
  192. Vicens C, Bejarano F, Sempere E, et al. Comparative efficacy of two interventions to discontinue long-term benzodiazepine use: Cluster randomised controlled trial in primary care. Br J Psychiatry 2014;204(6):471–79. [Accessed April 2015].
  193. Denis C, Fatseas M, Lavie E, Auriacombe M. Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. Cochrane Database Syst Rev 2006(3):CD005194. [Accessed April 2015].
  194. Kunz D, Bineau S, Maman K, Milea D, Toumi M. Benzodiazepine discontinuation with prolonged-release melatonin: Hints from a German longitudinal prescription database. Expert Opin Pharmacother 2012;13(1):9–16. [Accessed April 2015].
  195. Falloon K, Arroll B, Elley CR, Fernando A 3rd. The assessment and management of insomnia in primary care. BMJ 2011;342:d2899. [Accessed April 2015].
  196. Stepanski EJ, Wyatt JK. Use of sleep hygiene in the treatment of insomnia. Sleep Med Rev. 2003;7(3):215–25. [Accessed April 2015].
  197. Bootzin RR, Perlis ML. Nonpharmacologic treatments of insomnia. J Clin Psychiatry 1992;53 Suppl:37–41. [Accessed April 2015].
  198. Spielman AJ, Yang P. Insomnia: Sleep restriction therapy. In: Sateia M, Buysse D, editors. Insomnia Diagnosis and Treatment. London: Informa UK Ltd; 2010. p. 277. [Accessed April 2015].
  199. Smith MT, Neubauer DN. Cognitive behavior therapy for chronic insomnia. Clin Cornerstone 2003;5(3):28–40. [Accessed April 2015].
  200. Morin CM. Insomnia Psychological Assessment and Management. New York: The Guilford Press; 1993. [Accessed April 2015].
  201. Espie CA, MacMahon KM, Kelly HL, et al. Randomized clinical effectiveness trial of nurse-administered small-group cognitive behavior therapy for persistent insomnia in general practice. Sleep 2007;30(5):574–84. [Accessed April 2015].
  202. Cran A. Misuse of opioid drugs: Melbourne: MDA National; 2013. [Accessed 4 January 2014].
  203. 203. O’Regan R. Drug Seeking Behaviour: Identifying and dealing with the issues. Perth: North Metro Community Drug Service; 2012. [Accessed 4 January 2014].
  204. Medicare Australia. Prescription Shopping Information Service; 2014. [Accessed 19 January 2014].
  205. Morden NE, Schwartz LM, Fisher ES, Woloshin S. Accountable prescribing. N Engl J Med 2013;369(4):299–302. [Accessed 19 January 2014].
  206. The Royal Australasian College of Physicians. Precription Opioid Policy: Improving management of chronic non-malignant pain and prevention of problems associated with prescription opioid use. Sydney: RACP; 2009. [Accessed 19 January 2014].
  207. Pharmacy Society of Australia. Staged supply: frequently asked questions; 2014. [Accessed 7 September 2014].
  208. Agency for Healthcare Research and Quality. Guideline Summary NGC 8660: Generalised anxiety disorder and Panic Disorder (with or without agoraphobia) in adults. Management in primary, secondary and community care. Rockville, MD: AHRQ; 2011. [Accessed 7 September 2014].
This event attracts CPD points and can be self recorded

Did you know you can now log your CPD with a click of a button?

Create Quick log