Pharmacology, Toxicology and Addiction MedicineTier 1Disease (DEADMAN)

Acute and chronic effects, including overdose, from the use of - benzodiazepines and Z-drugs

Description

Benzodiazepines and Z-drugs (zolpidem, zopiclone)
Acute: sedation, anterograde amnesia, ataxia, disinhibition (paradoxical agitation esp. in elderly/children) - overdose alone rarely fatal (see toxidromes-sedative-hypnotic)
Chronic: tolerance, dependence, cognitive impairment, falls - risk rises sharply with duration of use

Epidemiology

Commonly prescribed for insomnia/anxiety but guidelines recommend short-term use only (2-4 weeks) given dependence risk with longer use
High rates of co-prescription with opioids - a major driver of polydrug overdose deaths

Aetiopathogenesis

GABA-A receptor potentiation -> sedation, anxiolysis, anticonvulsant and muscle relaxant effects
Chronic use -> receptor downregulation/tolerance -> withdrawal on cessation (see toxidromes-withdrawal) -> reinforces continued use
Elderly - reduced clearance + inc CNS sensitivity -> disproportionate sedation, falls, cognitive impairment even at "normal" doses

Diagnosis

Clinical - assess for dependence features (tolerance, unsuccessful attempts to cut down, use despite harm)
Cognitive screening in long-term users, esp. elderly, presenting with falls or confusion
Urine drug screen for use/co-ingestion where relevant

Management

Acute overdose

Supportive care - see toxidromes-sedative-hypnotic and poisoning-from-sedatives (flumazenil generally avoided)

Dependence/long-term use

Gradual dose taper (not abrupt cessation) - risk of seizure/delirium with abrupt withdrawal after prolonged use
Switch to a long-acting agent (diazepam) to facilitate a smooth taper
Address the underlying insomnia/anxiety with non-pharmacological strategies (CBT-I) in parallel

Associations

Falls and hip fracture in the elderly
Cognitive impairment - controversial association with longer-term dementia risk
Respiratory depression when combined with opioids or alcohol - major contributor to polydrug overdose deaths

Natural history & complications

Dependence can develop within weeks of regular use, even at prescribed doses
Cognitive effects often improve, though not always completely, with prolonged abstinence

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