Prescribers should consider the ‘benzo-burden’ – the total benzodiazepine-type medicine load prescribed per day – as benzodiazepines, z-drugs and gabapentinoids provide synergistic effects such as sedation and respiratory depression.13 All may interact with the individual's conditions to cause more adverse effects and avoidable drug-related harms e.g. increased breathlessness, fatigue, respiratory depression, which can be potentially fatal.
People receiving B-Z and opioids e.g. oxycodone, morphine, tramadol etc.
The effects of B-Z and the ‘benzo-burden’ can be further exacerbated by the addition of a range of opioids, and even reduce the protective ceiling effects of buprenorphine.72 In line with the Medicines and Healthcare products Regulatory Agency advice, only prescribe B-Z and opioids together if there is no alternative and closely monitor individuals for signs of respiratory depression.
People who report/present with street/non-prescribed B-Z use
People who report street/non-prescribed B-Z use, often within the context of polysubstance use, are arguably at greatest risk of combination effects. To respond to what is recognised as a public health crisis, recent guidance, including key principles of care, are outlined in the Scottish Drug Deaths Taskforce and Public Health Scotland’s Medication Assisted Treatment (MAT) standards informed response for benzodiazepine harm reduction.73
The MAT standards highlight that we all have a responsibility to respond to B-Z-related harms which is underpinned by a willingness to have supportive, collaborative conversations regarding B-Z. This guidance supports a comprehensive, holistic assessment of need, to inform highly intensive, flexible and individualised care plans. This may include prescribing interventions (e.g. a small minority of individuals may require longer-term B-Z treatment to optimise care and minimise street B-Z use). This is in addition to psychological components of care to support harm reduction and stabilisation.
Again for this patient group, the 7-Steps process should be used to determine the appropriateness of prescribing medication and to minimise harm. This allows consideration of the risks and benefits of treatment, in particular at point of initiation.
People receiving other psychotropic medicines e.g. antidepressants, antipsychotics, gabapentinoids etc.
Antidepressants
B-Z use is associated with the use of selective serotonin re-uptake inhibitors (SSRIs), and the use of higher SSRI doses for the treatment of depression.74,75 In part this may be due to higher SSRI doses causing more avoidable adverse effects such as anxiety, agitation and insomnia.76-78 However, B-Z are also associated with an increased incidence of depressive symptoms.20,21 Therefore, person-centred review and reducing B-Z using the 7-Steps process may help to optimise care and recovery.
Antipsychotics
B-Z use is associated with a higher mortality risk for people with schizophrenia.18 Although some have argued that B-Z provide antipsychotic sparing effects,79 this is not supported by current evidence.80
People receiving high dose B-Z combinations: >30mg per day diazepam equivalent
As highlighted above the use of more than one B-Z will increase the ‘benzo-burden’ and provide synergistic effects which may lead to avoidable adverse effects and harms. Minimising the use of such combinations and high doses of B-Z will help to minimise adverse drug effects, see Reduction schedules. It is important to consider if benzodiazepines are being bought alongside those that are being prescribed.
People receiving diazepam 10mg tablets – ‘blues’
Historically these have enabled people to take higher doses with fewer tablets and have been desirable for those using substances illicitly.19 Due in part to these issues, where diazepam is required, multiples of 2mg tablets should be prescribed as the preferred choice.81
Psychological therapies
B-Z may limit the efficacy of psychological therapies such as CBT due to negative effects on cognitive function; impairing memory function and amnesia.22