Benzodiazepine withdrawal syndrome

Benzodiazepine withdrawal syndrome (BZD withdrawal) is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines develops a physical dependence on them and then reduces the dose or stops taking them without a safe taper schedule.

Typically, benzodiazepine withdrawal is characterized by sleep disturbance, irritability, increased tension and anxiety, depression, panic attacks, hand tremor, shaking, sweating, difficulty with concentration, confusion and cognitive difficulty, memory problems, dry mouth, nausea and vomiting, diarrhea, loss of appetite and weight loss, burning sensations and pain in the upper spine, palpitations, headache, nightmares, tinnitus, muscular pain and stiffness, depersonalization, restless legs syndrome, seizures, suicidal ideation, and a host of perceptual changes.

Benzodiazepine withdrawal can also lead to disturbances in mental function that persist for several months or years after onset of symptoms (referred to as post-acute-withdrawal syndrome in this form).

Withdrawal symptoms can be managed by educating patients about the nature and expected course of benzodiazepine withdrawal, individualized taper strategies according to withdrawal severity, the addition of alternative strategies such as reassurance, and referral to benzodiazepine withdrawal support groups.

Signs and symptoms

Withdrawal symptoms occur during dose reduction and may include insomnia, anxiety, distress, weight loss, dizziness, night sweats, shaking, muscle twitches, aphasia, panic attacks, depression, numbness, dissociation, paranoia, indigestion, diarrhea, and photophobia. As withdrawal progresses, patients often find their physical and mental health improves with improved mood and improved cognition.

A more complete list of possible symptoms stated in publications:

Rapid discontinuation may result in a more serious syndrome

Mechanism

The neuroadaptive processes involved in tolerance, dependence, and withdrawal mechanisms implicate both the GABAergic and the glutamatergic systems. Gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the central nervous system; roughly one-quarter to one-third of synapses use GABA. GABA mediates the influx of chloride ions through ligand-gated chloride channels called GABAA receptors. When chloride enters the nerve cell, the cell membrane potential hyperpolarizes thereby inhibiting depolarization, or reduction in the firing rate of the post-synaptic nerve cell. Benzodiazepines potentiate the action of GABA, by binding a site between the α and γ subunits of the 5-subunit receptor thereby increasing the frequency of the GABA-gated chloride channel opening in the presence of GABA.

When potentiation is sustained by long-term use, neuroadaptations occur which result in decreased GABAergic response.