Benzodiazepine dependence: reduce the risk

• Benzodiazepines are not recommended as first-line therapy for insomnia, panic disorders, and anxiety (including anxiety with depression).
  
• Consider other treatment options, including non-pharmacological measures, for the respective indication.
  
• Treatment duration should be limited to the shortest period of time.
  
• Use patient-focused treatment plans to help educate patients about the risks and benefits of benzodiazepines.
  
• Consider a multidisciplinary care model to achieve the best health outcome for your patient.
  

In Australia benzodiazepines are indicated for a range of conditions, including anxiety, sleep and panic disorders, epilepsy, muscle spasms and alcohol dependence.

Common adverse events include over-sedation, drowsiness, slurred speech and dependence.¹

International and national guidelines recommend short-term use of benzodiazepines of 2–4 weeks, and as part of a broader management plan that includes other pharmacological or non-pharmacological measures for the treatment of these conditions.^{2, 3}

Continued use of benzodiazepines contributes to a significant risk of dependence and abuse.^{4, 5} These drugs are commonly implicated in overdose incidents and in drug-related suicide attempts leading to hospital and emergency department admissions.⁴

They are also present in about one-half to two-thirds of drug deaths, either in motor vehicle accidents, in which they are the most prevalent prescription drug, or in combination with other depressants such as opiates and/or alcohol.^{6, 7}

While the total number of prescriptions of benzodiazepines dispensed through the PBS/RPBS declined from 1992 to 2011,⁸ the increase in dispensed quantity per script⁸ and the large number of scripts written annually Australia-wide indicates that most prescriptions relate to long-term use.⁴

Although benzodiazepines in some cases are prescribed long-term, particularly in the elderly and in complex clinical situations, these drugs should be prescribed with caution as they can be associated with physical and psychological dependence and tolerance often leading to misuse.¹

The WHO defines dependence as including a strong desire or sense of compulsion to take a substance, difficulty in controlling its use, tolerance and the presence of a withdrawal state.^{9, 10}

The development of dependence with benzodiazepines appears to be similar to that of other classes of addictive drugs. The mechanism of dependence is associated with the disinhibition of dopaminergic neurons located in the midbrain, known as the ventral tegmental area, leading to dopamine surges causing pleasurable sensations.¹¹

These surges also change the expression of glutamatergic receptors, which makes the cells in the midbrain more susceptible to stimulation by glutamate. As a result, the cells respond to future drug exposures with larger dopamine surges that produce more intense pleasure.^{2, 11}

Benzodiazepine use for longer than 4 weeks, particularly at high doses, risks development of dependence that increases with duration of treatment.³ It can also lead to cognitive impairment, delirium, falls and fall-related injuries such as hip fractures, motor vehicle crashes and death.¹²

Stopping benzodiazepine use can be relatively easy for some patients but may be difficult for others. Estimates suggest that 30% to 40% of patients on benzodiazepine treatment for longer than 1 month will experience significant withdrawal symptoms on abrupt cessation.^{2, 3, 13}

When judiciously used, benzodiazepines are therapeutically effective; however, health professionals and patients should be aware of the risk of addiction and dependence associated with long-term use.¹⁴

To reduce the risk of benzodiazepine dependence and misuse:

• use only for appropriate indications¹
  
• seek specialist advice before considering prescribing a benzodiazepine for panic disorder¹⁵
  
• consider managing underlying causes and use of behavioural and/or psychological interventions for insomnia and anxiety disorders^{1, 15}
  
• reserve for short-term use only for a duration of up to 2–4 weeks
  
• assess efficacy at one week^{1, 5, 13}
  
• only prescribe to well-known patients
  
• assess the risk–benefit ratio of long-term use of benzodiazepines and openly discuss withdrawing from benzodiazepines if appropriate¹³
  
• identify patients who take large doses of benzodiazepines to achieve an intoxicated effect and refer them to a specialist drug and alcohol service.^13,16
  

Encourage collaborative decision making

Maintaining a patient focus ensures that care, including the prescribing or non-prescribing of drugs of dependence, is provided in collaboration with patients and their families and/or carers.¹⁶

When discussing dependence with patients, adopt a non-judgemental approach and be empathetic to the individual circumstances.¹⁶

Explore issues surrounding the starting or continuing of a benzodiazepine and provide open and honest information with continuing support to help patients make an informed decision.^{13, 16}

A useful tool for managing expectations and providing education is a written management plan to document:¹⁶

• patient and doctor responsibilities, goals and expectations
  
• desired outcomes in behavioural terms (ie, obtaining scripts from only one doctor and one pharmacy, attending appointments regularly, consequences of inappropriate patient behaviour such as verbal threats or manipulative behaviour, etc).
  

For a patient who has been using benzodiazepines long term and has signs of dependence, consider determining a score of withdrawal symptoms using the CIWA-B Benzodiazepine Withdrawal Scale.¹⁷

The score can be used to start an open discussion on gradual withdrawal of the benzodiazepine, leading to a more patient-focused management plan.

Refer to Therapeutic Guidelines³ or the Victorian Government Alcohol and Other Drug Withdrawal Practice Guidelines¹⁸ for further information on withdrawal regimens.

Consider a shared care approach

Pharmacists and nurses can also contribute to reducing the risk of benzodiazepine dependence and misuse by considering the following practice points:

• reinforce the importance of short-term use and tapering of benzodiazepine dose
  
• inform patients about side effects and withdrawal symptoms when supplying the medicine
  
• counsel on the use of the medicine and the context of its use
  
• advise of the possibility of tolerance and dependence associated with long-term use
  
• monitor for signs of dependence (ie, drug-seeking behaviour, need for increased dose, unwillingness to withdraw from treatment)
  
• refer the patient to the doctor if signs of dependence are identified
  
• provide details of patient support groups, for example, Reconnexion.
  

Additionally, in developing a withdrawal management plan, prescribers can enlist the help of the patient's pharmacist to dispense the medication at regular intervals as staged supply.¹³

Offering fact sheets will help educate patients, particularly when a benzodiazepine is not appropriate, or in those seeking repeat prescriptions. Fact sheet examples include:

• RACGP fact sheet for patients (page 55–56 of the Clinical Governance framework)
  
• SA Health fact sheet 'Reasons to Stop'
  
• NPS MedicineWise mediated treatment plan: Reduction plan for your sleeping tablets.