Hypnotic and Benzodiazepine Policy: prescribing and withdrawal
Indications
Benzodiazepines are all controlled drugs and therefore covered by relevant legislation, licensed indications include (check product summary of product characteristics for individual licensed indications): • The short-term relief (2-4 weeks only) of anxiety that is severe, disabling or causing the patient unacceptable distress, occurring alone or in association with insomnia or short- term psychosomatic, organic or psychotic illness. The use of benzodiazepines to treat short term ‘mild’ anxiety is inappropriate • Treatment of insomnia only when it is severe, disabling or causing the patient extreme distress.
Benzodiazepines may also be used for muscle spasm, epilepsy and alcohol withdrawal depending on individual product licenses (see Appendix 1).
The “Z” drugs (a group of non- benzodiazepine type hypnotics) are controlled drugs and therefore covered by relevant legislation. They are indicated for:
Short-term treatment of insomnia in adults in situations where the insomnia is debilitating or is causing severe distress for the patient.
As there is no compelling evidence to distinguish between the effects of different ‘z’ drugs the drug with the lowest purchase price should normally be used (NICE TA 77). If patients fail to respond to one of these drugs a second ‘z’ drug should NOT be prescribed. These drugs have addictive potential and there is evidence of misuse. Dosages should be within licensed/BNF dosage only. Benzodiazepines:
Benzodiazepines should only be used for the short term management of a specific, one off circumstance e.g. air travel, pre-procedural use. Benzodiazepines should not be used for the treatment of generalised anxiety disorder (GAD) in primary or secondary care except as a short-term measure during crises Benzodiazepines should never be used long term to manage anxiety For mild to moderate anxiety refer patients to ‘Improving Access to Psychological Therapies’ (IAPT). For patients with severe anxiety refer to ‘Essex Partnership University Foundation Trust’ (EPUT) via the Clinical Triage Service (CTS).
Hypnotics:
Before a hypnotic is prescribed the cause of the insomnia should be established and where possible underlying causes should be treated. This may include conditions such as depressive illness, pain, pruritus, dyspnoea or use of prescribed or OTC medications (including sympathomimetics, SSRIs, β blockers, thyroid hormones, statins, theophylline and corticosteroids). It is important to consider the following before prescribing: • The BNF states any medication for short-term insomnia should be given for no more than three weeks (preferably one week). • Management of unrealistic sleep expectations- five to six hours sleep a night is normal for older people, especially if the individual ‘cat naps’ during the day • Avoidance of tea, coffee and alcohol 6 hours before going to bed (consider eliminating caffeine from the diet). N.B. Patients may understate their alcohol consumption which is often the cause of insomnia • Use of ‘sleep hygiene’ strategies; o Establish fixed times for going to bed and waking up (avoid sleeping in after a poor night’s sleep). o Don't use back-lit devices shortly before going to bed, including televisions, phones, tablets and computers. If possible create a bedtime routine such as taking a bath and drinking a warm, milky drink every night. o Try to relax before going to bed o Maintain a comfortable sleeping environment, not too hot, cold, noisy or bright. The bedroom should be dark, quiet and a relaxing place. o Avoid napping during the day o Avoid nicotine and alcohol late at night both are stimulants o Avoid exercise within 4 hours of bedtime (however exercise earlier in the day such as 30 minutes of walking is beneficial) o Avoid eating a heavy meal late at night o Avoid regularly using over-the-counter sleeping tablets. o Avoid watching or checking the clock throughout the night o If sleep is not achieved after 30 minutes, get up and go into another room and try to do something else (light reading or listening to relaxing music) until feeling sleepy, then return to bed. o Write a list of worries and any ideas to solve them then put to one side and try to forget until the morning o A good sleep pattern can take weeks to become established • For insomnia lasting longer than 4 weeks a referral to IAPT services should be considered for a cognitive or behavioural intervention
Cautions to hypnotics and benzodiazepines
Tolerance and dependence to the effects of hypnotics and ‘z’ drugs develops within 3- 14 days of continuous use. Prolonged high level use of benzodiazepines may be associated with adverse effects e.g. memory loss and confusion, accidents and falls, low mood and insomnia. A paradoxical increase in anxiety, hostility and aggression may occur in patients taking benzodiazepines. Hypnotics and anxiolytics may impair judgement and increase reaction time, and so affect ability to drive or operate machinery. Hangover effects of a night dose may impair driving on the next day, patients should be made aware of the change in law relating to driving whilst taking medication (http://www.gov.uk/government/collections/drug-driving) When taken with alcohol the sedative effect increases. Benzodiazepines should be avoided in the elderly as they are at greater risk of memory impairment, impaired cognitive function, poor psychomotor performance increasing the risk of falls, and behaviour disinhibition (often manifested as irritability and argumentativeness). Avoid in pregnant and lactating women. Avoid concurrent prescribing with: other hypnotics, sedative tricyclic anti-depressants, antihistamines, opioids, clozapine and some antifungal drugs (e.g. fluconazole). Do not prescribe to unfamiliar patients (e.g. temporary residents), without checks.
Contra-indications to hypnotics and benzodiazepines Avoid all benzodiazepines and ‘z’ drugs in patients with pulmonary insufficiency, significant respiratory depression, obstructive sleep apnoea or severe hepatic impairment. Benzodiazepines should be avoided in those with a history of substance abuse or with personality disorders.
Withdrawal:
• Tolerance of these drugs progressively reduces their effectiveness in the treatment of insomnia or anxiety. • Tolerance to the hypnotic effects of benzodiazepine may be rapid, and may occur within a few days or weeks of regular use. • Tolerance to the anxiolytic effects is slower and appears over a few months of use • In contrast, little tolerance develops to the amnesic effects or other cognitive impairments caused by benzodiazepines. • Dependence may develop, and continuing treatment may serve only to prevent withdrawal symptoms. • Dependence is more likely to develop with long-term use, high dose, more potent or shorter- acting benzodiazepines, and in patients with a history of anxiety problems.
Patients on long-term benzodiazepines or related drugs, such as ‘z’ drugs, should be advised to gradually stop. The chances of success are improved when a person's physical and psychological health and personal circumstances are stable. In some circumstances it may be more appropriate to wait until other problems (such as depression, anxiety or other medical problems which may be causing significant distress) are resolved or improved before starting drug withdrawal.
Suggested protocol for benzodiazepine withdrawal:
• Transfer patients step wise, one dose at a time over about a week, to an equivalent daily dose of diazepam preferably taken at night (see equivalents below). Diazepam has several advantages over other benzodiazepines in that it has a relatively long half-life and is available in a range of tablet strengths (2, 5 and 10mg). • Seek specialist advice (preferably from a hepatic specialist) before switching to diazepam in people with hepatic dysfunction as diazepam may accumulate to a toxic level in these individuals. • Reduce diazepam dose, usually by 1-2mg every 2-4 weeks (in patients taking high doses of benzodiazepines, initially it may be appropriate to withdraw the dose by up to one-tenth every 1-2 weeks). If uncomfortable withdrawal symptoms occur maintain this dose until symptoms lessen. • Reduce diazepam dose further, if necessary in smaller steps; steps of 0.5mg may be appropriate towards the end of withdrawal (liquid formulations may be helpful to achieve these small dose reductions). Then stop completely. • For long term patients, the period needed for complete withdrawal may vary from several months to a year or more. It is better to reduce too slowly than too quickly. • The use of beta-blockers, antidepressants and antipsychotics to control withdrawal symptoms should be avoided where possible
Patients should be warned about benzodiazepine withdrawal syndrome which can develop at any time up to 3 weeks after stopping a long acting benzodiazepine, but may occur within a day in the case of shorter acting agents. It is characterised by insomnia, anxiety, loss of appetite and of body weight, tremor, perspiration, tinnitus, and perceptual disturbances. Symptoms may be similar to the original complaint and encourage further prescribing. Some symptoms may continue for weeks or months after stopping benzodiazepines.
Approximate equivalent doses, diazepam 5mg =
alprazolam 0.25mg chlordiazepoxide 12.5mg loprazolam 0.5-1mg lorazepam 0.5mg lormetazepam 0.5-1mg nitrazepam 5mg oxazepam 10mg temazepam 10mg
Suggested protocol for withdrawal of ‘z’ drugs Gradual drug withdrawal is also recommended for people dependent on z-drugs as the manufacturers of these drugs warn that abrupt termination of treatment can lead to withdrawal symptoms, particularly in people taking high doses. Dosage should be withdrawn gradually on an individual patient basis. Dose reductions should be made at not less than 2 week intervals. If the patient suffers from withdrawal symptoms/problems maintain their current dose until symptoms improve. Then continue the withdrawal regime - in smaller steps if necessary.
If patients do not succeed on their first withdrawal attempt, they should be encouraged to try again Remind the patient that reducing benzodiazepine/hypnotic dosage, even if it falls short of complete drug withdrawal, can still be beneficial. If another attempt is considered, the patient should be reassessed and any underlying problems managed (such as depression) before a further attempt is made. Maintain patients at the dose withdrawal symptoms appeared - NOT the original dose.
Appendix 1 Comparison of Benzodiazepines and Z-drugs Adapted from Ipswich and East Suffolk CCG Guidelines for the Prescribing of Benzodiazepines and Z- drugs (Dec 2016)
Approximate equivalent Licensed Indications Duration of Drug dose to (with regards to their use for action diazepam insomnia/anxiety) 5mg Alprazolam Intermediate acting 0.25mg Anxiety (short term use) Chlordiazepoxide Long acting 12.5mg Anxiety (short term use) Clonazepam Long acting 0.25mg Epilepsy NOT licensed in anxiety or insomnia Diazepam Long acting 5mg Insomnia & anxiety (short term use) Loprazolam Intermediate acting 0.5 – 1mg Insomnia (short term use) Lorazepam Intermediate acting 0.5mg Insomnia & anxiety (short term use) Lormetazepam Intermediate acting 0.5 – 1mg Insomnia (short term use) Nitrazepam Long acting 5mg Insomnia (short term use) Oxazepam Short acting 10mg Anxiety (short term use) Temazepam Intermediate acting 10mg Insomnia (short term use) Zaleplon Short acting 10mg Insomnia (short term use) Zolpidem Short acting 10mg Insomnia (short term use) Zopiclone Short acting 7.5mg Insomnia (short term use)
References 1. British Medical Association and Royal Pharmaceutical Society. British National Formulary (BNF) 72, September 2016. 2. NICE clinical knowledge summaries. Benzodiazepine and z-drug withdrawal. April 2015. https://cks.nice.org.uk/benzodiazepine-and-z-drug-withdrawal 3. NICE TA77. Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia. April 2004. https://www.nice.org.uk/Guidance/TA77 4. NHS Choices. Insomnia. Accessed 30th March 2017. http://www.nhs.uk/Conditions/Insomnia/Pages/Prevention.aspx