Quality Prescribing for Antidepressants: A Guide for Improvement 2024-2027

Appendix 6. NTI Indicators

NTI: Adults (18 years and over) prescribed antidepressant medications long-term (two years and more), as a proportion of people in receipt of antidepressant medications (variants excluding tricyclics and showing tricyclics only)

An appropriate course of treatment for depression can be six months for the first episode of depression, or 12 or 24 months of treatment, depending on the number of depressive episodes and relapses. Long-term use is considered as more than two years of treatment and encompasses a growing number of people less likely to have their antidepressant reviewed, than those who have recently been initiated on treatment or receiving a shorter course. The longer an individual receives an antidepressant, the less frequently it, or the condition it is treating, is reviewed. For some they may be ‘lost in the system’ and inadvertently continue treatment that is no longer needed, and in others the antidepressant treatment may be ineffective or causing adverse effects.

Some prescribers may be less comfortable reviewing psychotropic medicines such as antidepressants, and may be apprehensive of reducing or stopping antidepressant therapy. This may be due to concerns about relapse or recurrence of illness, and/or antidepressant discontinuation/withdrawal symptoms, all of which may result in inappropriate long-term use where treatment is no longer required.

Reviewing people receiving the same antidepressant for two years or more can result in one in four people having a change in treatment, reduction, or stopping their antidepressants.

Actions:

• Health boards and prescribers to ensure appropriate use of antidepressants, considering licensed indications and duration of therapy
• The 'What matters to you' approach should assist the individual to achieve goals which have been identified and developed in partnership with clinicians.
• Access to and availability of non-pharmacological options, including psychosocial and/or psychological interventions, should be encouraged and pursued where appropriate
• Review effectiveness, tolerability and compliance on an ongoing basis
• Any reduction/stop should be gradual to minimise discontinuation effects
• Some individuals may be more sensitive to discontinuation than others
• Review and reduce dose every one to four weeks, or as guided by the individual’s needs and/or preferences. See guidance for suggested dose reductions
• 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. Age limited to 18 years and over due to licensing, however there may be some individuals under 18 years who are prescribed off-licence and should have regular follow-up by specialists. These individuals will not be identified in current STU searches.

2. In NTIs, two years or more treatment is assessed as those received more than 10 prescriptions in a 24-month period of the same antidepressant medication, with medicine issued at any point in the first three months and an issue in the last three months. It does not include anyone who may have changed antidepressant during that time. This is measured against the count of people prescribed an antidepressant at the midpoint of the last three months.

3. Antidepressants included are those in BNF legacy section 4.3, including tricyclic and related antidepressants, monoamine-oxidase inhibitors, SSRIs, other antidepressant drugs. Exclusions: injectables

NTI: All people prescribed an SSRI in combination with an antiplatelet, NSAID, DOAC or warfarin without gastro-protection, as a proportion of people prescribed an SSRI

Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of gastrointestinal bleed. This is further increased when they are used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and/or antiplatelets and/or direct oral anticoagulants (DOAC)/warfarin. These individuals should be prescribed gastro-protection such as proton pump inhibitors as advised in local and national guidelines.

This indicator should have a low value to ensure safe prescribing.

Actions:

• Health boards and prescribers to ensure appropriate use of SSRIs in conjunction other medication with may increase the risk of GI bleeds
• Reviewing people in this group will help to ensure appropriate use and help reduce avoidable adverse drug events and harms
• The 'What matters to you' approach should assist the individual to achieve goals which have been identified and developed in partnership with clinicians
• It is appropriate to ensure that there is an ongoing valid indication for all medication, as it may be more appropriate to stop the SSRI, rather than add PPI, if the depression/anxiety has resolved. Any reduction/stop of SSRI should be gradual to minimise discontinuation effects
• If continued SSRI use is required, non-pharmacological options, including psychosocial and/or psychological interventions, should be encouraged and pursued where appropriate, e.g. regular physical activity, cognitive behavioural therapy
• Consider the use of NSAID and whether alternative analgesia, e.g. paracetamol, is more appropriate, or when required topical NSAID
• Ongoing need for SSRI and other medication will require appropriate gastro-protection such as proton pump inhibitors. Note the interaction between clopidogrel and omeprazole/esomeprazole, when selecting PPI
• 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:

NTI searches include:

• SSRI: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, but not dapoxetine as when required use and side effects do not list haemorrhage risk
• Aspirin 75mg considered as antiplatelet dosing
• NSAID preparations exclude those including misoprostol, omeprazole and esomeprazole

Exclusions: injectables

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.
• 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.

where appropriate gradually withdraw using an agreed structured and planned reduction schedule

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: All people prescribed two or more antidepressant medications (excluding low dose nortriptyline 10mg/ amitriptyline 10mg and 25mg) per 1,000 list size

Using more than one antidepressant is not recommended.

• Combining an SSRI or serotonin and noradrenaline re-uptake inhibitor (SNRI) (e.g. venlafaxine) with mirtazapine is sometimes used by specialist services.
  • Non-specialist psychiatry prescribers should not initiate such antidepressant combinations, unless on the advice of specialists.
  • The potential benefits of such combinations are small and may be of questionable clinical value due to the variable response rates.
• Combining an SSRI/SNRI with low dose mirtazapine 15mg daily:
  • Is sometimes undertaken for its short-term sedating antihistamine effects (also seen with trazodone)
  • These additional antidepressants are possibly being used to treat SSRI/SNRI induced insomnia, agitation etc., and as alternative to B-Z.
  • This combination is of questionable benefit, and it may be more appropriate to reduce the dose of the SSRI/SNRI to minimise potential adverse effects and drug-related harms rather than adding extra psychotropics, especially as tolerance can quickly develop to the sedating effect of mirtazapine and trazodone.
• Neuropathic pain plus depression/anxiety treatment may require treatment with two antidepressants:
  • For example, a TCA (e.g. low dose amitriptyline 10mg/25mg or nortriptyline 10mg) for neuropathic pain and another antidepressant for depression, but not two TCAs.
  • Use should be reviewed regularly, considering interactions, adverse and synergistic effects, e.g. TCA dose related QTc interval prolongation, sedating effects.

Prescribing by specialist services can and does influence general practitioners prescribing.

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 antidepressants, considering licensed indications, duration of therapy and combinations
• 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
• Review effectiveness, tolerability and compliance on an ongoing basis
• Any reduction/stop should be gradual to minimise discontinuation effects.
• In managing pain, it may be more appropriate to optimise the dose of one antidepressant or change to duloxetine to manage mood and pain. However the TCA or duloxetine may only be effective for one condition, and not the other. Individuals may not tolerate higher doses of TCAs, or duloxetine which can be more effective for treating depression
• Where mirtazapine was initiated to manage SSRI/SNRI induced insomnia or agitation, review dose of SSRI/SNRI with aim to reduce and then reduce and stop mirtazapine
• 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. Age limited to 18 years and over due to licensing, however there may be some individuals under 18 years who are prescribed off-licence and should have regular follow-up by specialists.

2. In NTIs, count of people dispensed at least two approved names from BNF section 4.3 in the first three months and at least two of the same approved names in the last three months of a six-month period. Note that there may be different strengths prescribed within the same approved (drug) name

Antidepressants included are those in BNF section 4.3, including tricyclic and related antidepressants, monoamine-oxidase inhibitors, SSRIs, other antidepressant drugs. Exclusions: injectables

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 are 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).