In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. Common * Sedation * Motor impairment Less common * Confusion * Irritability and aggression * Psychomotor agitation * Lack of motivation * Loss of libido * Impaired motor function * Impaired coordination * Impaired balance * Dizziness * Cognitive impairments * Hallucinations. * Short-term memory loss * Anterograde amnesia (common with higher doses) * Some users report hangover-like symptoms of drowsiness, headaches, sluggishness, and irritability upon waking up if the medication was taken before sleep. This is likely the result of the medication's long half-life, which continues to affect the user after waking up. While benzodiazepines induce sleep, they tend to reduce the quality of sleep by suppressing or disrupting REM sleep. After regular use, rebound insomnia may occur when discontinuing<unk> . * Benzodiazepines may cause or worsen depression. Occasional * Dysphoria * Induction of seizures or increased frequency of seizures * Personality changes * Behavioural disturbances * Ataxia Rare * Suicide through disinhibition * Psychosis * Incontinence * Liver damage * Paradoxical behavioural disinhibition (most frequently in children, the elderly, and in persons with developmental disabilities) * Rage * Excitement * Impulsivity The long-term effects of<unk>  can include depression, disinhibition, and sexual dysfunction. Drowsiness<unk> , like other benzodiazepines, may impair a person's ability to drive or operate machinery. The central nervous system depressing effects of the drug can be intensified by alcohol consumption, and therefore alcohol should be avoided while taking this medication. Benzodiazepines have been shown to cause dependence. Patients dependent on<unk>  should be slowly titrated off under the supervision of a qualified healthcare professional to reduce the intensity of withdrawal or rebound symptoms. Withdrawal-related * Anxiety * Irritability * Insomnia * Tremors * Headaches * Stomach pain * Nausea * Hallucinations * Suicidal thoughts or urges * Depression * Fatigue * Dizziness * Sweating * Confusion * Potential to exacerbate existing panic disorder upon discontinuation * Seizures similar to delirium tremens (with long-term use of excessive doses) Benzodiazepines such as<unk>  can be very effective in controlling status epilepticus, but, when used for longer periods of time, some potentially serious side-effects may develop, such as interference with cognitive functions and behavior. Many individuals treated on a long-term basis develop a dependence. Physiological dependence was demonstrated by flumazenil-precipitated withdrawal. Use of alcohol or other CNS depressants while taking<unk>  greatly intensifies the effects (and side effects) of the drug. A recurrence of symptoms of the underlying disease should be separated from withdrawal symptoms. Tolerance and withdrawal Like all benzodiazepines,<unk>  is a GABA-positive allosteric modulator. One-third of individuals treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. A gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome. Due to the risks of tolerance and withdrawal seizures,<unk>  is generally not recommended for the long-term management of epilepsies. Increasing the dose can overcome the effects of tolerance, but tolerance to the higher dose may occur and adverse effects may intensify. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit composition and in gene transcription coding. Tolerance to the anticonvulsant effects of<unk>  occurs in both animals and humans. In humans, tolerance to the anticonvulsant effects of<unk>  occurs frequently. Chronic use of benzodiazepines can lead to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with<unk>  than with chlordiazepoxide. In general, short-term therapy is more effective than long-term therapy with<unk>  for the treatment of epilepsy. Many studies have found that tolerance develops to the anticonvulsant properties of<unk>  with chronic use, which limits its long-term effectiveness as an anticonvulsant. Abrupt or over-rapid withdrawal from<unk>  may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations. Sudden withdrawal may also induce the potentially life-threatening condition, status epilepticus. Anti-epileptic drugs, benzodiazepines such as<unk>  in particular, should be reduced in dose slowly and gradually when discontinuing the drug to mitigate withdrawal effects. Carbamazepine has been tested in the treatment of<unk>  withdrawal but was found to be ineffective in preventing<unk>  withdrawal-induced status epilepticus from occurring. Overdose Excess doses may result in: * Difficulty staying awake * Mental confusion * Nausea * Impaired motor functions * Impaired reflexes * Impaired coordination * Impaired balance * Dizziness * Respiratory depression * Low blood pressure * Coma Coma can be cyclic, with the individual alternating from a comatose state to a hyper-alert state of consciousness, which occurred in a four-year-old boy who suffered an overdose of<unk> . The combination of<unk>  and certain barbiturates (for example, amobarbital), at prescribed doses has resulted in a synergistic potentiation of the effects of each drug, leading to serious respiratory depression. Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, and fainting. Detection in biological fluids<unk>  and 7-aminoclonazepam may be quantified in plasma, serum, or whole blood in order to monitor compliance in those receiving the drug therapeutically. Results from such tests can be used to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. Both the parent drug and 7-aminoclonazepam are unstable in biofluids, and therefore specimens should be preserved with sodium fluoride, stored at the lowest possible temperature and analyzed quickly to minimize losses. Special precautions The elderly metabolize benzodiazepines more slowly than younger people and are also more sensitive to the effects of benzodiazepines, even at similar blood plasma levels. Doses for the elderly are recommended to be about half of that given to younger adults and are to be administered for no longer than two weeks. Long-acting benzodiazepines such as<unk>  are not generally recommended for the elderly due to the risk of drug accumulation. The elderly are especially susceptible to increased risk of harm from motor impairments and drug accumulation side effects. Benzodiazepines also require special precaution if used by individuals that may be pregnant, alcohol- or drug-dependent, or may have comorbid psychiatric disorders.<unk>  is generally not recommended for use in elderly people for insomnia due to its high potency relative to other benzodiazepines.<unk>  is not recommended for use in those under 18. Use in very young children may be especially hazardous. Of anticonvulsant drugs, behavioural disturbances occur most frequently with<unk>  and phenobarbital. Doses higher than 0.5–1 mg per day are associated with significant sedation.<unk>  may aggravate hepatic porphyria.<unk>  is not recommended for patients with chronic schizophrenia. A 1982 double-blinded, placebo-controlled study found<unk>  increases violent behavior in individuals with chronic schizophrenia.<unk>  has similar effectiveness to other benzodiazepines at often a lower dose.
Clonazepam
Diclazepam
Halazepam
Clotiazepam
Phenazepam
Oxazepam
Medazepam
Gidazepam