Quality prescribing for Benzodiazepines and z-drugs: guide for improvement 2024 to 2027

Appendix 8: National Therapeutic Indicators for mental health conditions

NTI: Hypnotic and anxiolytic (excluding melatonin) defined daily doses (DDDs) per 1,000 list size per day (all age groups included)

Benzodiazepines and z-drugs (B-Z) demonstrate limited therapeutic effects for the short-term (e.g. less than two weeks) treatment of insomnia and some anxiety disorders (e.g. generalised anxiety disorder, panic disorder). For the vast majority, long-term use of B-Z raises the risk of harm and is contrary to current clinical guidelines and drug licensing, as B-Z are licensed for a maximum of four weeks. B-Z use is associated with tolerance, dependence and avoidable drug-related harms. These harms include but are not limited to:

• cognitive dysfunction (confusion, impaired concentration, memory impairment, impaired ability to drive and increased accidents)
• falls, and associated increased risk of hip fractures
• depressive symptoms
• paradoxical effects i.e. disinhibition, anxiety and impulsivity

Therefore B-Z should generally be limited to short courses with regular review.

There should be a low level of prescribing of hypnotics and anxiolytics for this indicator.

Actions:

• Health boards and prescribers to ensure appropriate use of B-Z; promoting person-centred reviews, and appropriate continuation, reduction and stopping of them
• The 'What matters to you' approach can assist the individual to achieve goals which have been identified and developed in partnership with clinicians
• Non-pharmacological options, including psychosocial and/or psychological interventions, should be encouraged and pursued where appropriate, e.g. regular physical activity, cognitive behavioural therapy
• Review effectiveness, tolerability and compliance on an ongoing basis
• Any reduction/stop should be gradual to minimise discontinuation effects
• The 7-Steps review process should be used for all medication reviews
• Individuals can be identified using the Scottish Therapeutics Utility (STU) in GP practice

Notes:

• This indicator includes all medicines in BNF legacy sub section 4.1.1 and 4.1.2 including benzodiazepines, z-drugs, buspirone and meprobamate but excluding melatonin.
• Formulations excluded from NTI: injectables, suppositories, enemas.

NTI: Melatonin defined daily doses (DDDs) per 1,000 list size population per day (all age groups)

This indicator is intended to support health boards and prescribers to ensure appropriate use of melatonin. Melatonin is currently licensed for:

• short term use for insomnia in adults 55yrs and over, for up to 13 weeks
• jet lag for up to five days duration
• insomnia in individuals with learning difficulties and behaviour that challenges (where sleep hygiene measures have been insufficient), initiated under specialist supervision

Prescribing has been increasing within board regions in both adults and children prescribing.

Actions:

• Health boards and prescribers to ensure appropriate use of melatonin, considering licensed indications and duration of therapy
• Promote person-centred reviews, with appropriate continuation, reduction or stopping of melatonin
• The 'What matters to you' approach should assist the individual to achieve goals which have been identified and developed in partnership with clinicians.
• Non-pharmacological options, e.g. regular physical activity, cognitive behavioural therapy, sleep hygiene measures
• NHS Inform: Sleep problems and insomnia self-help guide
• Review effectiveness, tolerability and compliance on an ongoing basis
• The 7-Steps review process should be used for all medication reviews
• Individuals can be identified using the Scottish Therapeutics Utility (STU) in GP practices.

Notes:

1. Formulations excluded from NTI: injectables, suppositories, enemas.

2. Identifying different age groups;

a. STU allows sorting by age to allow review of appropriate duration of therapy and formulation choice.

NTI: All people prescribed an antidepressant (all) in combination with a long-term benzodiazepine or z-drug (>8 weeks) as a proportion of people prescribed an antidepressant (BNF section 4.3)

Benzodiazepines and/or z-drugs (B-Z) are sometimes prescribed to treat:

• anxiety and/or insomnia symptoms prior to starting an antidepressant for depression or anxiety
• symptoms of poorly controlled depression, anxiety or back pain
• agitation, anxiety or insomnia symptoms associated with starting a selective serotonin reuptake inhibitor (SSRI)
• avoidable adverse drug effects such as insomnia and/or agitation caused by higher SSRIs doses

This can lead to regular long-term (≥8 weeks) B-Z use, sometimes lasting for years.

B-Z only demonstrate marginal benefits for short-term relief of insomnia and some anxiety disorders.

Long-term chronic use is:

• contrary to good practice, guidance, and terms of the licence
• known to worsen depressive symptoms, cause cognitive dysfunction and other avoidable adverse effects
• known to reduce the efficacy of some psychological therapies

Therefore the prescribing of B-Z should generally be limited to short-term use with regular review.

There should be a low level of prescribing for this indicator.

Actions:

• Health boards and prescribers to ensure appropriate use of B-Z in conjunction with antidepressants; promoting person-centred reviews, and appropriate continuation, reduction and stopping of them
• The 'What matters to you' approach should assist the individual to achieve goals which have been identified and developed in partnership with clinicians
• The long-term B-Z should be reviewed first
• where appropriate gradually withdraw using an agreed structured and planned reduction schedule
• a small minority of individuals may require longer-term B-Z treatment with regular review to optimise care and minimise street/illicit B-Z use
• Non-pharmacological options, including psychosocial and/or psychological interventions, should be encouraged and pursued where appropriate, e.g. regular physical activity, cognitive behavioural therapy
• Any reduction/stop should be gradual to minimise discontinuation effects
• Review effectiveness, tolerability and compliance on an ongoing basis
• The 7-Steps review process should be used for all medication reviews
• Individuals can be identified using the Scottish Therapeutics Utility (STU) in GP practices

Notes:

1. Formulations excluded from NTI: injectables, suppositories, enemas

2. For tools (NTI) using more than eight weeks avoids 56-day prescribing

3. BNF section 4.3 includes tricyclic and related antidepressants, monoamine-oxidase inhibitors, SSRIs, other antidepressant medication

4. This indicator may trigger individuals prescribed low dose amitriptyline which may be indicated for pain. However these individuals should still be reviewed due to the duration of the B-Z prescribing, especially if prescribed to manage symptoms associated with back pain.

NTI: Adults (18+) prescribed a benzodiazepine or z-drug (B-Z) long term (>8 weeks) as a proportion of people prescribed a benzodiazepine or z-drug

Benzodiazepines and/or z-drugs (B-Z) demonstrate limited therapeutic effects for the short-term (e.g. less than two weeks) treatment of insomnia and some anxiety disorders (e.g. generalised anxiety disorder, panic disorder). For the vast majority, long-term use of B-Z raises the risk of harm and is contrary to current clinical guidelines and drug licensing, as B-Z are licensed for a maximum of four weeks only. B-Z use is associated with tolerance, dependence and avoidable drug-related harms. These harms include but are not limited to:

• cognitive dysfunction (confusion, impaired concentration, memory impairment, impaired ability to drive and increased accidents)
• falls, and associated increased risk of hip fractures
• depressive symptoms
• paradoxical effects i.e. disinhibition, anxiety and impulsivity

Therefore the prescribing of B-Z should generally be limited to short-term use with regular review.

There should be a low level of prescribing of hypnotics and anxiolytics for this indicator.

Actions:

• Health boards and prescribers to ensure appropriate use of B-Z; promoting person-centred reviews, and appropriate continuation, reduction and stopping of them
• The 'What matters to you' approach should assist the individual to achieve goals which have been identified and developed in partnership with clinicians
• Non-pharmacological options, including psychosocial and/or psychological interventions, should be encouraged and pursued where appropriate, e.g. regular physical activity, cognitive behavioural therapy
• Review effectiveness, tolerability and compliance on an ongoing basis
• Any reduction/stop should be gradual to minimise discontinuation effects
• The 7-Steps review process should be used for all medication reviews
• Individuals can be identified using the Scottish Therapeutics Utility (STU) in GP practices

Notes:

Formulations excluded from NTI: injectables, suppositories, enemas.

NTI: People resident in a care home aged 50 years and over prescribed a benzodiazepine or z-drug as a proportion of people resident in a care home aged 50+ in receipt of any medication

Up to one in eight older adults in Scotland receive one or more benzodiazepines and/or z-drugs (B-Z) prescription annually, and care home residents are twice as likely to receive these medicines than non-care home residents.

Older adults and/or those with frailty are more susceptible to the adverse effects and harms of B-Z:

• cognitive dysfunction (i.e. confusion, impaired concentration, memory impairment, impaired ability to drive, increased accidents)
• falls and associated increased risk of hip fractures and hospitalisation
• depressive symptoms
• paradoxical effects i.e. disinhibition, anxiety and impulsivity

They may also experience liver impairment and/or reduced kidney function which can reduce B-Z excretion, increasing the effective dose, which may increase the risk of adverse effects.

Therefore proactively reviewing, reducing and stopping B-Z will help to reduce avoidable B-Z-related harms.

This indicator should have a low percentage, indicating alignment with current best practice prescribing guidance.

Actions:

• Health boards and prescribers to ensure appropriate use of B-Z; promoting person-centred reviews, and appropriate continuation, reduction and stopping of them
• The 'What matters to you' approach should assist the individual to achieve goals which have been identified and developed in partnership with clinicians
• Non-pharmacological options, including psychosocial and/or psychological interventions, may be less suitable for some care home residents, however there should be awareness of stress and distress in dementia - symptoms of anxiety and agitation which may be precipitated by physical conditions, e.g. constipation, pain, infection. (See Alzheimer Scotland report ‘Understanding stress and distress in dementia’^[89]
• Review effectiveness, tolerability and compliance on an ongoing basis.
• Any reduction/stop should be gradual to minimise discontinuation effects.
• The 7-Steps review process should be used for all medication reviews.
• Individuals can be identified using the Scottish Therapeutics Utility (STU) in GP practices

Notes:

• Formulations excluded from NTI: injectables, suppositories, enemas.
• There is no care home flag in STU. Accurate results rely on practice coding.

NTI: Mental Health Triple Whammy – All people in receipt of three or more of benzo/ z-drug, strong opioid (including tramadol), gabapentinoid, antidepressant, antipsychotics (excluding levomepromazine 6mg tabs or injections) per 1,000 list size

The combination of three or more of these medications increases the risks of medicine related harm. Prescribers should consider the ‘benzo-burden’ – the total benzodiazepine-type drug load prescribed per day – as benzodiazepines, z-drugs and gabapentinoids have similar synergistic effects: sedation, respiratory depression, etc. These may interact with an individual’s conditions to cause more adverse effects and avoidable medicine related harms e.g. increased breathlessness, fatigue, respiratory depression which can be potentially fatal.

• Opioids: The effects of B-Z and the ‘benzo-burden’ can be further be exacerbated by the addition of a range of opioids, and even reduce the protective ceiling effects of buprenorphine. MHRA advice is only prescribe B-Z and opioids together if there is no alternative and closely monitor individuals for signs of respiratory depression.
• B-Z use with antipsychotics is associated with a higher mortality risk for people with schizophrenia.
• B-Z use with antidepressants: the use of SSRIs, and particularly high dose SSRIs for the treatment of depression. This may cause more avoidable adverse effects and harms such as anxiety, agitation and insomnia. However, B-Z is also associated with an increased incidence of depressive symptoms, so reviewing and reducing B-Z use may help to optimise care and recovery.

People who report/present with street/non-prescribed B-Z use, often set within the context of polysubstance use, are arguably at greatest risk of combination effects.

This indicator should have a high percentage, indicating alignment with current best practice prescribing guidance.

Actions:

• Health boards and prescribers to ensure appropriate use of B-Z in conjunction with other medication; promoting person-centred reviews, and appropriate continuation, reduction and stopping
• The 'What matters to you' approach should assist the individual to achieve goals which have been identified and developed in partnership with clinicians
• The long-term B-Z should be reviewed.
• where appropriate gradually withdraw using an agreed structured and planned reduction schedule
• a small minority of individuals may require longer-term B-Z treatment with regular review to optimise care and minimise street/illicit B-Z use
• Consider pain management and ensure valid indication for analgesia, e.g. neuropathic pain, nociceptive pain. If no ongoing indication for opioid or gabapentinoids, reduce gradually to prevent withdrawal
• Review duration of treatment for depression, and if ongoing need. If none, reduce gradually to prevent discontinuation effects
• Non-pharmacological options, including psychosocial and/or psychological interventions, should be encouraged and pursued where appropriate, e.g. regular physical activity, cognitive behavioural therapy
• Review effectiveness, tolerability and compliance on an ongoing basis
• The 7-Steps review process should be used for all medication reviews
• The Scottish Drug Deaths Taskforce and Public Health Scotland’s: Medication Assisted Treatment (MAT) standards informed response for benzodiazepine harm reduction guidance:
• highlights that everyone has a responsibility to respond to B-Z related harms and to have supportive, collaborative conversations regarding B-Z
• supports a comprehensive, holistic assessment of need to develop a psychological formulation of the presenting issues to inform highly intensive, flexible and individualised care plans
• supports addition of psychological components of care, to support harm reduction and stabilisation
  • Individuals can be identified using the Scottish Therapeutics Utility (STU) in GP practices

Notes:

1. Levomepromazine not included as generally used in palliative care.

2. Opioids include: buprenorphine, fentanyl, morphine, oxycodone (with/without naloxone), pentazocine, tapentadol, hydromorphone, pethidine, methadone, tramadol (with/without paracetamol)

3. Benzodiazepines and z-drugs include: Diazepam, Chlordiazepoxide, clonazepam, loprazolam, lorazepam, lormetazepam, oxazepam, nitrazepam, temazepam, alprazolam, clobazam, flurazepam, zolpidem, zopiclone, zaleplon

Formulations excluded: injectables (B-Z and opiate pain medicines), suppositories and enemas (benzodiazepines).

NTI: Diazepam tablet 2mg items as a proportion of all diazepam tablet items

Historically 5mg and 10mg tablets have enabled people to take higher doses with fewer tablets and have been desirable for those using substances illicitly. Due in part to these issues the National Therapeutic Indicators for Scotland advise that where diazepam is required that the 2mg tablets are the preferred choice when prescribing. Do not prescribe 5mg or 10mg strength of diazepam tablets due to their black-market value.

This indicator should have a high percentage, indicating alignment with current best practice prescribing guidance.

Actions:

• Health boards and prescribers to ensure appropriate use of B-Z; promoting person-centred reviews, and appropriate continuation, reduction and stopping of them
• The 'What matters to you' approach should assist the individual to achieve goals which have been identified and developed in partnership with clinicians
• Non-pharmacological options, including psychosocial and/or psychological interventions, should be encouraged and pursued where appropriate, e.g. regular physical activity, cognitive behavioural therapy
• Review effectiveness, tolerability and compliance on an ongoing basis
• Where continued prescribing of diazepam is necessary, where possible convert to equivalent dose in 2mg tablets
• Any reduction/stop should be gradual to minimise discontinuation effects
• The 7-Steps review process should be used for all medication reviews
• Individuals can be identified using the Scottish Therapeutics Utility (STU) in GP practices

Notes:

• Formulations only include tablets, and exclude injectables, suppositories, enemas