Lorazepam long-term effects

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

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. 

Other than slow taper, no consistently effective treatment to alleviate withdrawal symptoms has been reported. Although several compounds have been studied (e.g., b-blockers, clonidine, carbamazepine, abercamil, ondansetron), results have been contradictory ( 250). Carbamazepine, however, may be useful in seizure-prone patients (251). Valproate (VPA) has also been reported to benefit patients undergoing BZD discontinuation after long-term dependence ( 252), which may be related to VPA s potential anxiolytic properties, its ability to alleviate withdrawal phenomena, or both. The azaspirone anxiolytic buspirone has been reported ineffective in suppressing withdrawal symptoms, particularly in long-term BZD users (253, 254). Hydroxyzine has also been found beneficial in treating patients for lorazepam withdrawal (255). 

Long half-life BZDs may increase the risk of daytime sedation, lethargy, cognitive impairment, and delirium, as well as falls and hip fractures ( 309, 310 and 311). Long-term use of flurazepam (30 mg per day) has been associated with an increased incidence of ataxia and hallucinations ( 312). However, short half-life BZDs also may cause serious adverse effects. Ataxia, depression, confusion, amnestic syndromes, and oversedation have been reported in elderly lorazepam users, and there is some evidence that short-acting BZDs may also increase the risk of falls (313, 314, 315, 316 and 317). 

Several members of the benzodiazepine group are effective in treating epilepsy, but most are limited because of problems with sedation and tolerance. Some agents such as diazepam (Valium) and lorazepam (Ativan) are used in the acute treatment of status epilepti-cus (see Treatment of Status Epilepticus ), but only a few are used in the long-term treatment of epilepsy. Clonazepam (Klonopin) is recommended in specific forms of absence seizures (e.g., the Lennox-Gastaut variant) and may also be useful in minor generalized seizures such as akinetic spells and myoclonic jerks. Clorazepate (Tranxene) is another benzodiazepine that is occasionally used as an adjunct in certain partial seizures. 

Lorazepam (la) in 2 or 4 mg doses showed hypnotic activity in insomniacs and good sedation in surgical premedication.41 Flurazepam (2h) is useful in the long term treatment of insomnia42 and shows no rebound effect after withdrawal.43 Flunitrazepam (2 ) has hypnotic activity in man at 2.5 mg, but does not induce physiological sleep.44 Fosazepam (2j) at 60-80 mg decreased sleep onset and awakening in healthy subjects.45 Quazepam (Sch 16134 2k) has been entered in the USAN listing as a sedative, hypnotic.46 Clobazam (9a) at 10—20 mg, but not triflubazam (9b) was useful for limited sleep difficulties in healthy males.47... 

A general and persistent anxiety with nervousness and other symptoms is termed generalized anxiety disorder (GAD). It can lead to a chronic condition exacerbated by stressful events. Benzodiazepines are commonly used in treatment but they cause sedation, and long-term use may induce dependence or abuse. A second study (Woelk and Schlafke, 2010) compared the effects of Silexan with lorazepam in 78 patients with GAD. Over a 6-week period, they were administered daily either one Silexan capsule with a lorazepam placebo or a 0.5 mg lorazepam capsule and a Silexan placebo. Assessments were based on HAMA, HSQ, SAS, CGI, and the Penn State Worry Questionnaire. Results showed that the total HAMA score decreased by 45% and 46% in the Silexan and lorazepam groups, respectively. Other assessment scores improved to a similar extent for both groups. It was concluded that both Silexan and lorazepam had comparable positive effects in adults with GAD (Woelk and Schlafke, 2010). 

Evaluation of the safety and therapeutie effects of lorazepam on long term use. Curr. therapeut. Res., 18, 163. 

Diazepam produces less sedation in cigarette smokers, and higher (not lower, as stated in SEDA-20) doses may be required for the same sedative or anxiolytic effect. Owing in part to its continued widespread use, several unusual adverse effects of diazepam continue to be reported. These include cases of urinary retention and compartment syndrome, which are not explicable by its pharmacology. On the other hand, accumulation of diazepam and attendant complications of obtundation and respiratory depression may be understood in terms of its long half-life, particularly in elderly people and medically ill patients. Caution about the intravenous use of diazepam comes from a study that showed cardiac dysrhythmias (mainly ventricular extra beats) in a quarter of oral surgery patients midazolam and lorazepam were much safer (1). 

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