Zopiclone

The safety profile of zopiclone is addressed via the assessment of its rebound insomnia potential, withdrawal and dependence on zopiclone and residual effects and tolerability [1]. Insomnia in North America and the UK is between 5-15% with around 40% also experiencing daytime sleepiness [9]. Z-drugs, including zopiclone, have the potential to cause spontaneous reactions, such as acute excitement, vivid dreams, along with an increase in hostile, anxious and aggressive behaviour [7]. Zopiclone has previously been studied and monitored by the Prescription-Event Monitoring (PEM) in 13,177 patients [18]. 85% of the 13,177 patients were prescribed a zopiclone tablet (pill) of 7.5mg. Comparisons were made with flunitrazepam – in a previously similar study – and results reported 7 cases of possible zopiclone dependence, however overall researchers of the study noted no confirmed dependence to zopiclone [18]. Unfortunately, one patient in the study cohort ingested 28 zopiclone pills along with 100 co-proxamol, and died from this accumulative dose [18]. 37 patients overdosed with other drugs – namely psychotropic drugs – with 3 deaths recorded [18]. Side Effects Rebound insomnia is evident after the termination of hypnotic treatment with benzodiazepines [14]. In the case of misuse or increased intake of zopiclone, one commentary article [15] presented several cases where zopiclone doses were increased. Other cases documented zopiclone dosage have reported no adverse reactions. Table 1 describes each case. Table 1. Data summarised and adapted from Jones et al., 1998. Case Description Outcome Reference 29-year old man Prescribed 7.5mg zopiclone Increased dose to 22.5mg with other tablets mixed. Stopped taking zopiclone after 8 months. Severe anxiety with tachycardia, tremors, sweating and rebound insomnia. Treated: 25mg (3x daily) with amitriptyline. Full recovery [15] 26-year old man Prescribed 7.5mg zopiclone Increased dose to 4x daily Experienced tremors, sweats flushes, palpitations. – 49-year old woman Received 7.5mg zopiclone for insomnia. Increased dose to 15mg and then 22.5mg Attempted to stop dose, twice. Severe rebound insomnia and anxiety – 36-year old woman Bipolar affective disorder. Prescribed 7.5mg zopiclone nightly to treat insomnia. After 1 year: taking 7.5mg 4x daily. Reduction in dose led to sweating, palpitations, tremors and anxiety Dose gradually reduced. – 20-year old man Diagnosed with MDD. Patient started on escitalopram (20mg) daily dose Further prescribed 7.5mg zopiclone at bedtime. Dose increased to 15mg (high dose): symptoms of intractable insomnia, decreased total sleep time Zopiclone reduced to 7.5mg: moderate improvements in sleep Discontinuation of zopiclone: improvement of sleep [5] 42-year old woman Tetrabenazine first administered Followed by clonazepam, and subsequently amantadine. Botulinum was also introduced to address involuntary movements, Zopiclone was introduced to aid in sleeping difficulties. Dose began at 7.5mg once daily, and was increased to 15mg once daily No adverse outcomes [4] 67-year old man DSM IV primary insomnia, depressive disorder and abuse of zopiclone. Initially began treatment using flunitrazepam. Moved onto zolpidem – for half a year using 20mg daily – and zopiclone – 7.5mg daily. Patient increased zopiclone dose to 337.5mg daily. Patient’s zopiclone dose was reduced to 15mg daily. No side effects experienced. No severe problems associated with zopiclone withdrawal Severe problems with reducing zopiclone dose. [16] In general, Z-drugs, such as zopiclone can produce adverse effects such as headaches, stomach upset and dizziness; however, are usually well-tolerated [9]. Physical side effects of zopiclone include a peculiar metallic taste in the mouth along with reduced coordination [11] in simple tasks. According to the WHO, zopiclone has yet to be examined for any euphoric effects in users [17].