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Home , Zolpidem, Zopiclone

, and : problem use

Introduction Problems arising from the use of benzodiazepines are insidious and diverse. These include overdose, particularly from the use of benzodiazepines together with other drugs, and dependence as a result of long-term use.

Zopiclone and zolpidem also attach to the binding site of the GABAA receptor and have most of the same adverse effects. Benzodiazepine consumption exceeding 1 month, particularly at high doses, risks development of dependence. The risk increases with the duration of treatment. About a third of patients who have been prescribed benzodiazepines long term may have difficulty in reducing or stopping them. There is little, if any, justification for prescribing benzodiazepines beyond a few days. Clinicians encountering patients taking benzodiazepines long term should encourage them to slowly reduce the dose to zero. Severe benzodiazepine dependence is seen in some polydrug-dependent patients. Their pattern of drug use tends to be chaotic, with benzodiazepines used to augment or substitute for intoxication with other drugs, notably . Benzodiazepines may also be used to terminate a stimulant binge. An escalation in ‘doctor shopping’ in the years before overdose death has been noted in this group. Every effort should be made to engage these patients in treatment for drug dependence. Direct or oblique requests for benzodiazepines should be treated with caution and, as a general rule, prescriptions should not be issued to patients not well known to the clinician. Clinicians can specify when prescribing that dispensing is to be supervised by a pharmacist, partner or parent and that there is frequent urine drug testing to monitor other drug use. Benzodiazepines may also be prescribed for daily pick up to provide an opportunity for ongoing patient monitoring. Among benzodiazepines, only can be individually identified on urine drug testing. Thus, although clobazam is more expensive, it provides a means of checking whether the patient is taking other benzodiazepines. Patients on long-term prescribed benzodiazepines are likely to be dependent even if the dose is stable and they are not at risk from consuming other psychoactive drugs. The highest rate of benzodiazepine use is in the older population despite this being the group of patients that is most at risk of harm from adverse effects of benzodiazepines (eg falls, cognitive impairment). Clinicians should discuss the problem with the patient and encourage them to become abstinent over a couple of months. Patients with current or previous and drug problems are at increased risk of developing benzodiazepine dependence. The safety of zolpidem and zopiclone is uncertain; some patients may be at risk of bizarre and sometimes dangerous -related behaviours after taking these drugs. Benzodiazepine withdrawal The benzodiazepine withdrawal (discontinuation) syndrome is highly variable. Common symptoms include , , irritability, myoclonic jerks, palpitations, and sensory disturbances such as hyperacusis and photophobia. Abrupt discontinuation in patients taking high doses (eg greater than 50 mg daily or equivalent) may be accompanied by seizures. After short-term use, benzodiazepines can usually be stopped without problem. When a person has been consuming a benzodiazepine within or only slightly above the therapeutic dose range for several months or more, reduction of the dose at a rate of 15% of the starting dose per week is likely to be well tolerated. However, there is considerable variability in withdrawal symptom severity. The rate of decrease should be titrated against symptoms.

Adapted with permission from Psychotropic Expert Group. Benzodiazepines, zolpidem and zopiclone: problem use [revised 2013 June]. In: eTG complete. Melbourne: Therapeutic Guidelines Limited; 2013 Nov. www.tg.org.au. Page 1 of 2 Published in eTG complete, July 2013. ©Therapeutic Guidelines Ltd Benzodiazepines, zolpidem and zopiclone: problem use

For those people using higher doses, stabilisation on an equivalent dose of diazepam is recommended before dose reduction (see Table 8.2). If several different benzodiazepines are being used concurrently, sum the various diazepam equivalents to obtain the stabilisation dose. This diazepam stabilisation dose should not normally exceed 80 mg daily. Sometimes patients overestimate their unsanctioned consumption hoping to obtain higher prescribed doses. It is common practice to prescribe 40% of the stated dose of unsanctioned benzodiazepines. The diazepam equivalent should be given in divided daily doses. Following a few days stabilisation, dose reduction should occur at a rate determined by symptom severity. Reductions of 10% of the diazepam dose per day can be achieved in inpatient settings, but much slower reductions, often over a period of 2 months, are more common in the outpatient environment. Patients who present in severe benzodiazepine withdrawal should be treated in an inpatient setting with diazepam, using a dose equivalent to their total daily benzodiazepine consumption (see Table 8.2). If this is not known, use: diazepam 20 mg orally, every 2 hours until withdrawal symptoms are controlled. Gradually taper dose over subsequent days. Supportive care, including a low-stimulus environment and reassurance, is helpful.

Comparative oral doses of benzodiazepines (Table 8.2)

Drug Approximate equivalent dose (mg) [NB1] to diazepam 5 mg 0.5 3 clobazam 10 0.25 [NB2] diazepam 5 0.5 1 [NB3] 5 15 10 NB1: the widely varying half-lives and receptor-binding characteristics of these drugs make exact dose equivalents difficult to establish NB2: particular care is needed if changing from clonazepam to a different benzodiazepine because there is a wide variety of reported equivalences NB3: lorazepam may be relatively more potent at higher doses

Adapted with permission from Psychotropic Expert Group. Benzodiazepines, zolpidem and zopiclone: problem use [revised 2013 June]. In: eTG complete. Melbourne: Therapeutic Guidelines Limited; 2013 Nov. www.tg.org.au. Page 2 of 2 Published in eTG complete, July 2013. ©Therapeutic Guidelines Ltd