- Toxicity in Overdose - The acute toxicity of benzodiazepines is extremely low; even large overdoses taken alone rarely cause death, although risks are increased in the presence of obstructive pulmonary disease.
- Oversedation - Oversedation is a dose-related extension of the sedative-hypnotic effects of benzodiazepines. Symptoms include drowsiness, poor concentration and vigilance, ataxia, dysarthria, motor inco-ordination, diplopia, muscle weakness, vertigo, and mental confusion.
- Drug Interactions - Benzodiazepines have additive effects with other CNS depressants, including other hypnotics, sedative antidepressants, neuroleptics, anticonvulsants, sedative antihistamines, and alcohol. The combined disinhibitory effects of alcohol and benzodiazepines (see below) may also be additive and contribute to aggressive behaviour. Patients prescribed benzodiazepines should be warned of these interactions.
- Impairment of Memory - Benzodiazepines have long been known to induce anterograde amnesia. This action is utilised when the drugs are administered as premedication before major surgery and for minor surgical procedures. Loss of memory for unpleasant events is here a welcome therapeutic effect.
- Paradoxical Stimulant Effects - Benzodiazepines occasionally cause paradoxical excitement with increased anxiety, insomnia, nightmares, hypnogogic hallucinations at sleep onset, irritability, hyperactive or aggressive behaviour, and exacerbation of seizures in epileptics. Increased aggression, hostility, and impulsivity occur in some subjects and may result in attacks of rage and violent behaviour.
- Depression, Emotional Blunting - Long-term benzodiazepine users, like alcoholics and barbiturate-dependent patients, are often depressed, and the depression may first appear during prolonged benzodiazepine use.
- Adverse Effects in Pregnancy - Benzodiazepines cross the placenta, and if taken regularly by the mother in late pregnancy, even in therapeutic doses, can cause neonatal complications.
- Tolerance - Tolerance can develop to all the actions of benzodiazepines, although at variable rates and to different degrees. Tolerance to hypnotic effects develops rapidly: sleep latency, Stage 2 sleep, slow wave sleep, dreaming, and intrasleep awakenings all tend to return to pretreatment levels after a few weeks of regular hypnotic use, and daytime anxiolytic users no longer feel sleepy after a few days.
- Dependence - Benzodiazepines are potentially addictive drugs. They can provide positive reinforcement in some individuals and negative reinforcement in many. They can give rise to both psychological and pharmacological dependence, and dependent individuals show varying degrees of drug-seeking behaviour, develop tolerance, and suffer withdrawal effects on drug cessation or dosage reduction.
- Therapeutic Dose Dependence
- Prescribed High-Dose Dependence - A minority of patients who start on prescribed benzodiazepines begin to "require" larger and larger doses.
- Recreational Benzodiazepine Abuse
- Withdrawal Symptoms - Abrupt withdrawal from high doses can cause a severe reaction, including convulsions and psychotic episodes. Withdrawal symptoms from therapeutic doses are mainly those of anxiety, both psychological and somatic, but certain symptoms such as sensory hypersensitivity and perceptual distortion may be especially prominent, and depression may sometimes be a prominent feature.
- Structural Brain Damage