Benzodiazepines adverse effects

Once the first dose of benzodiazepine is given, an antiepileptic drug must be started to prevent further seizures from occurring. AEDs must not be given as first-line therapy since they must be infused relatively slowly to avoid adverse effects, delaying their onset of action. 

Electroconvulsive therapy (ECT) is used for severe mania or depression during pregnancy and for mixed episodes prior to treatment, anticonvulsants, lithium, and benzodiazepines should be tapered off to maximize therapy and minimize adverse effects. 

Evaluate patients for symptom improvement frequently (e.g., weekly) during the first 4 weeks of therapy. The goal is to alleviate panic attacks and reduce anticipatory anxiety and phobic avoidance with resumption of normal activities. Alter the therapy of patients who do not achieve a significant reduction in panic symptoms after 6 to 8 weeks of an adequate dose of antidepressant or 3 weeks of a benzodiazepine. Regularly evaluate patients for adverse effects, and educate them about appropriate expectations of drug therapy. 

Marketed compounds display well-known efficacy in inducing sleep onset, but many fail in the maintenance of sleep throughout the night due to short half-lives. On the other hand, longer acting compounds, such as the benzodiazepines, elicited significant next-day adverse effects. Therefore, the balance between sustained efficacy and adequate pharmacokinetic profile remains to be solved. 

Benzodiazepines are addictive and associated with high risk of adverse effects... 

When treating anxiety one should of course first treat any reversible medical condition. When pharmacological treatment is necessary SSRI is most often drug of choice. Selective serotonin reuptake inhibitors are both effective and safe. Benzodiazepines that have been widely used are drugs with a relative high risk of adverse effects (see Chapter 4). Risks for dependence and abuse must always be considered for benzodiazepines. 

With regard to the structural relationship of WEB 2086 to triazolo-diazepines, it is interesting to note that up to the highest dose tested (400 mg) no diazepine-characteristic central nervous adverse effects were observed, confirming in man the dissociation of PAF- and benzodiazepine-like effects reported in animals. 

No health hazards are known with the proper use of kava (Gruenwald et al. 1998). Kava has been approved by the German Commission E for treatment of anxiety and insomnia. In clinical studies of kava for anxiety, adverse effects were uncommon and did not differ across placebo and kava groups. There do not appear to be any studies published on the effects of acute overdosage with kava. Given its CNS depressant effects, it should not be taken with other similar drugs, including benzodiazepines, barbiturates. 

There have been no formal studies of the toxicity of passionflower, but adverse effects have not been reported. There is one report of a case of inflammatory vasculitis associated with a preparation of passionflower (Smith et al. 1993). Like other herbs in this category, its putative benzodiazepine action contraindicates its combined use with other CNS depressants. 

However, adverse effects also include dependence and thus drug abuse. Tolerance develops within 3 months for anxiety. However considerable interindividual variability exists for the development of this tolerance. Benzodiazepines have very little effect on respiration which is not seen with sedative doses. In cases involving benzodiazepine intoxication, respiratory assistance has only been needed in patients who had also taken another CNS depressants. 

There is no cross-tolerance of buspirone with benzodiazepines or other sedative medications. Withdrawal symptoms, occurring for example after stopping benzodiazepine use are influenced by buspirone only to a minor extend. Adverse effects include dizziness, light-headiness, agitation, headache, tinnitus and nausea but those reactions are generally mild. 

In anesthesia drugs from several groups are used as premedication. Pre-anesthetic medication can decrease the anesthetic doses which otherwise would be required to induce anesthesia and so decrease the risk for adverse effects. Pre-anesthetic medication will increase the rate of induction of anesthesia and can reduce pre-operative pain and anxiety. Drugs include benzodiazepines for sedation and their muscle relaxant properties, opiates for pain relieve and anticholinergics or histamine Hi receptor antagonists against nausea and vomiting. Neuroleptics are also used as premedication for their antiemetic effects. 

Less common adverse effects include blurred vision, hallucinations, and paradoxical reactions consisting of excitement, stimulation, and hyperactivity. Also, a variety of gastrointestinal complaints occur, and blood dyscrasias have been reported, but these are rare. Benzodiazepine administration during pregnancy, delivery, or lactation has the potential to have adverse effects on the fetus or newborn. 

Mirtazapine has been found to have synergistic depressant effects on motor and cognitive performance when used in conjunction with benzodiazepines or alcohol (Kuitunen, 1994). Somnolence and increased appetite accompanied by weight gain are common adverse effects. Lower doses are clearly associated with more sedative effects than those with higher doses. It is unclear if a similar pattern is noted for appetite and weight gain. 

Tropisetron. The 5-FIT3 antagonist tropisetron has also been reported to be effective in the treatment of patients with generalized anxiety disorder [Lecrubier et al. 1993). The anxiolytic effect of tropisetron develops quickly, is dose dependent, and is accompanied by satisfactory tolerability and safety. The incidence of adverse events, including headache, nausea, constipation, and nervousness, is low and the severity is generally mild. The most typical adverse effects of benzodiazepine anxiolytics, such as fatigue, muscle relax-... 

The Y -aminobutyric acid-A receptor (GABAjJ is a macromolecular complex through which a variety of ligands act. Our understanding of this receptor complex and the mechanism of action of these ligands has expanded rapidly over recent years. This is as a consequence of substantial developments in the fields of molecular biology and immunochemistry and has been fueled by the as yet elusive quest for effective anxiolytics that do not have the problems associated with the benzodiazepines, that is, adverse effects, interaction with alcohol, and the related issues of tolerance, dependency, and problems on withdrawal. 

This section describes the partial agonists and the nonbenzodiazepine drugs that act at the benzodiazepine receptor. What these drugs have in common is that their development has been driven by the search for effective anxiolytics that do not have the adverse effects of sedation, amnesia, ataxia, interaction with alcohol, or the problems of tolerance, dependency, and withdrawal seen with classic benzodiazepines. These problems have been addressed by the development of partial agonists, subtype-selective ligands, and other drugs, the cyclopyrrolones, which do not seem to cause these problems. 

Alpidem. Alpidem is an imidazopyridine partial agonist that also shows relative selectivity for the type I benzodiazepine receptor. Studies have shown an anxiolytic effect comparable with the classic benzodiazepines, but with an improved adverse effect profile [Pancheri et al. 1993). It has also been compared with buspirone in patients with generalized anxiety disorder and shown to be more rapidly effective and again to have a more favorable adverse effect profile [Legris et al. 1993). Longer-term studies with alpidem have shown that tolerance does not occur, and no significant problems of withdrawal on discontinuation were found [Chevalier et al. 1993). Alpidem was licensed in France for the treatment of anxiety but has now been suspended because of recent reports of alpidem-induced hepatic dysfunction. The reason for this is unclear, but it may be a reflection of the fact that alpidem also binds to peripheral benzodiazepine receptors, which are present in high density in the liver. 

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