3 The technologies
3.1 Zaleplon, zolpidem and zopiclone (the Z-drugs) are nonbenzodiazepine hypnotics. Although the Z-drugs differ structurally from the benzodiazepines, they are also agonists of the GABA receptor complex and therefore enhance GABA-mediated neuronal inhibition. The Z-drugs were developed with the aim of overcoming some of the disadvantages of benzodiazepines – for example, next day sedation, dependence and withdrawal.
3.2 Zaleplon is a pyrazolopyrimidine with an elimination half-life of 1 hour. It is licensed for "the treatment of patients with insomnia who have difficulty falling asleep". It is indicated only when the disorder is severe, disabling or subjecting the patient to extreme distress. The Summary of Product Characteristics (SPC) specifies that treatment should be as short as possible with a maximum duration of 2 weeks.
3.3 Zolpidem is an imidazopyridine and has an elimination half-life of 2.5 hours. It is licensed for "the short-term treatment of insomnia in situations where the insomnia is debilitating or is causing severe distress for the patient". The SPC states that the duration of treatment should usually vary from a few days to 2 weeks with a maximum of 4 weeks, including tapering off where appropriate.
3.4 Zopiclone is a cyclopyrrolone and has an elimination half-life of 3.5–6.5 hours. It is licensed for "the short-term treatment of insomnia (including difficulties in falling asleep, nocturnal awakening and early awakening, transient, situational or chronic insomnia, and insomnia secondary to psychiatric disturbances) in situations where the insomnia is debilitating or is causing severe distress for the patient". The SPC states that long-term continuous use is not recommended, that a course of treatment should employ the lowest effective dose, and a single period of treatment should not exceed 4 weeks including any tapering off. The SPC also states that the duration of treatment should be 2–5 days for transient insomnia and 2–3 weeks for short-term insomnia.
3.5 In common with the benzodiazepines, the sedative effects of the Z-drugs may persist into the next day. The SPCs for all three Z-drugs carry warnings about their potential to cause tolerance, dependence and withdrawal symptoms. For full details of side effects and contraindications, see the SPCs.
3.6 The current acquisition costs for an adult dose are zaleplon (10 mg) £0.29, zolpidem (10mg) £0.16 and zopiclone (7.5 mg) £0.16 (excluding VAT; BNF 46th edition). Costs may vary in different settings because of negotiated procurement discounts.