Loprazolam - Tolerance, Dependence and Withdrawal

Tolerance, Dependence and Withdrawal

Loprazolam, like all other benzodiazepines, is recommended only for the short term management of insomnia in the UK, owing to the risk of serious adverse effects such as tolerance, dependence and withdrawal, as well as adverse effects on mood and cognition. Benzodiazepines can become less effective over time and patients can develop increasing physical and psychological adverse effects, e.g., agorophobia, gastrointestinal complaints, and peripheral nerve abnormalities such as burning and tingling sensations.

Loprazolam has a low risk of physical dependence and withdrawal if it is used for less than 4 weeks or very occasionally. However, one placebo controlled study comparing 3 weeks of treatment for insomnia with either loprazolam or triazolam showed rebound anxiety and insomnia occurring 3 days after discontinuing loprazolam therapy, whereas with triazolam the rebound anxiety and insomnia was seen the next day. The differences between the two are likely due to the differing elimination half-lives of the two drugs. These results would suggest that loprazolam and possibly other benzodiazepines should be prescribed for 1 – 2 weeks rather than 2 – 4 weeks to reduce the risk of physical dependence, withdrawal, and rebound phenomenon.

Withdrawal symptoms

Slow reduction of the dosage over a period of months at a rate that the individual can tolerate greatly minimizes the severity of the withdrawal symptoms. Individuals who are benzodiazepine dependent often cross to an equivalent dose of diazepam to taper gradually, as diazepam has a longer half-life and small dose reductions can be achieved more easily.

• anxiety and panic attacks
• sweating
• nightmares
• insomnia
• headache
• tremor
• nausea and vomiting
• feelings of unreality
• abnormal sensation of movement
• hypersensitivity to stimuli
• hyperventilation
• flushing
• sweating
• palpitations
• dimensional distortions of rooms and television pictures
• paranoid thoughts and feelings of persecution
• depersonalization
• fears of going mad
• heightened perception of taste, smell, sound, and light; photophobia
• agoraphobia
• clinical depression
• poor memory and concentration
• aggression
• excitability
• Somatic Symptoms
• numbness
• altered sensations of the skin
• pain
• stiffness
• weakness in the neck, head, jaw, and limbs
• muscle fasciculation, ranging from twitches to jerks, affecting the legs or shoulders
• ataxia
• paraesthesia
• influenza-like symptoms
• blurred double vision
• menorrhagia
• loss of or dramatic gain in appetite
• thirst with polyuria
• urinary incontinence
• dysphagia
• abdominal pain
• diarrhoea
• constipation

Major complications can occur after abrupt or rapid withdrawal, especially from high doses, producing symptoms such as:

• psychosis
• confusion
• visual and auditory hallucinations
• delusions
• epileptic seizures (which may be fatal)

It has been estimated that between 30% and 50% of long term users of benzodiazepines will experience withdrawal symptoms. However, up to 90% of patients withdrawing from benzodiazepines experienced withdrawal symptoms in one study, but the rate of taper was very fast at 25% of dose per week. Withdrawal symptoms tend to last between 3 weeks to 3 months, although 10 - 15% of people may experience a protracted benzodiazepine withdrawal syndrome with symptoms persisting and gradually declining over a period of many months and occasionally several years.