Discontinuation of benzodiazepines, even after a relatively short duration of treatment, may result in withdrawal symptoms, which are the main sign of physical dependence. The most frequent symptoms of withdrawal are insomnia, gastric problems, tremors, agitation, fearfulness, and muscle spasms. Less frequent symptoms are irritability, sweating, depersonalization, derealization, hypersensitivity to stimuli, depression, suicidal behavior, psychosis, seizures, and delirium tremens.
Abrupt withdrawal can be dangerous and lead to excitotoxicity, causing damage and even death to nerve cells as a result of excessive levels of the excitatory neurotransmitter glutamate. In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters become pathologically high. Symptoms may also occur during a gradual dosage reduction, but are typically less severe and may persist as part of a protracted withdrawal syndrome for months after cessation of benzodiazepines.
Approximately 10% of patients experience a notable protracted withdrawal syndrome, which can persist for many months or in some cases a year or longer. Protracted symptoms tend to resemble those seen during the first couple of months of withdrawal but usually are of a subacute level of severity. Such symptoms do gradually lessen over time, eventually disappearing altogether.
Benzodiazepines have a reputation for causing a severe and traumatic withdrawal; however, this is due largely to the withdrawal process being poorly managed. A slow and gradual withdrawal is recommended, customized to the individual, with psychological support. The time needed to complete withdrawal ranges from four weeks to several years. Alcohol is also cross tolerant with benzodiazepines and more toxic and caution is advised, in order to avoid replacing one dependence with another.
Withdrawal of benzodiazepines for long-term users leads to improved physical and mental health, particularly in the elderly; although some long term users report continued benefit from taking benzodiazepines, this is likely the result of suppression of withdrawal effects. A number of studies have drawn an association between long-term benzodiazepine use and neuro-degenerative disease, particularly Alzheimer’s disease as well as an increased risk of dementia.