Oxazepam long-term effects

Long-term effects of oxazepam in children/adolescents are unknown... 

The use of benzodiazepines should be avoided. There are other safer pharmacological alternatives. Benzodiazepine withdrawal may play a role in the occurrence of delirium in the elderly. Other withdrawal symptoms include tremor, agitation, insomnia and seizures (Turnheim 2003). Thus, when there is long-term use of benzodiazepines abrupt discontinuation might be difficult. Discontinuation should however not be withheld but done slowly and step-wise. If benzodiazepines are used in the elderly, short-acting benzodiazepines such as oxazepam are preferred, because they do not accumulate in the elderly to the same extent (Kompoliti and Goetz 1998). If short-acting benzodiazepines are used they should be prescribed with caution, at low doses, and for short periods. As with all pharmacotherapy the effects should be evaluated. Benzodiazepines are sometimes used as a behavioural control. One should always ask if this use is for the benefit of staff or the benefit of the patient. The presence of staff may be sufficient for behavioural control. 

The speciflc clinical use of the numerous available benzodiazepines depends on their individual pharmacokinetic and pharmacodynamic properties. Drugs with a high affinity for the GABAa receptor (alprazolam, clonazepam, lorazepam) have high anxiolytic efficacy drugs with a short duration of action (temazepam) are used as hypnotics to minimise daytime sedative effects. Diazepam has a long half-life and duration of action and may be favoured for long-term use or when there is a history of withdrawal problems oxazepam has a slow onset of action and may be less susceptible to abuse. 

Although short half-life BZDs are usually recommended for the elderly patient because they are less likely to accumulate and are rapidly eliminated, few comparisons have been made of their effects on performance in the elderly population. In one study of nonanxious elderly volunteers, both diazepam (long half-life, oxidation) and oxazepam (short half-life, conjugation) produced comparable self-rated sedation and fatigue during long-term administration ( 303). These effects persisted in diazepam subjects during a 2-week washout period, but rapidly returned to baseline in the oxazepam subjects. 

Additional doses of benzodiazepines in long-term users are commonly needed, but it is unknown whether these additional doses have any effect. The effects of an additional 20 mg dose of oxazepam has been assessed in a double-bhnd, balanced-order, crossover, randomized study in 16 long-term users of oxazepam and 18 benzodiazepine-naive controls (5). The effects of oxazepam 10 and 30 mg were assessed on (a) saccadic eye movements as a proxy for the sedative effect (b) the acoustic startle response as a proxy for the anxiolytic effects (c) memory (d) reaction time tasks (e) subjective measurements. There were dose-related effects on the peak velocity of saccadic eye movement and response probability and on the peak amplitude of the acoustic startle response. Comparison with the controls suggested that the sedative effects might be confounded with the suppression of sedative withdrawal symptoms, whereas the patients were as sensitive as the controls to the effects of an additional dose of oxazepam on the acoustic startle response. 

Neither 10 mg nor 30 mg of oxazepam affected the reaction time tasks in the patients, whereas the controls had dose-related impairment. The memory impairing effects did not differ significantly. In contrast to the controls, the patients could not discriminate between a 10 mg and a 30 mg dose, as assessed by visual analogue scales and the Spielberger State-Trait Anxiety Inventory Version 1, which might indicate a placebo effect of 10 mg in patients. The authors concluded that additional doses of oxazepam during long-term treatment have pronounced effects, even after daily use for more than 10 years. 

Oude Voshaar RC, Verkes R-J, van Luijtelaar GLJM, Edelbroek PM, Zitman FG. Effects of additional oxazepam in long-term users of oxazepam. J Clin Psychopharmacol 2005 25(l) 42-50. 

---