Benzodiazepines general adverse effects

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. 

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-... 

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. 

Abecarnil is a partial agonist at the benzodiazepine -GABA receptor complex, and is used in generalized anxiety disorder. Its pharmacology suggests that it may be less likely to produce sedation and tolerance, but data thus far have not shown clear differences in its adverse effects from those of classical benzodiazepines, such as alprazolam, diazepam, and lorazepam. As expected, both acute adverse effects and tolerance are dose-related. 

Alprazolam, a triazolobenzodiazepine, has been marketed as an anxiolytic with additional antidepressant properties an analogue, adinazolam, also has partial antidepressant activity (1) and is useful in panic disorder. Like other benzodiazepines, alprazolam is effective in acute and generalized anxiety its efficacy in panic disorder (2,3), premenstrual syndrome (4), and chronic pain (5) is complicated by high rates of adverse effects (6). On the other hand, low-dose alprazolam (1.4 mg/day) is useful and well tolerated in the treatment of anxiety associated with schizophrenia (SEDA-19, 34). 

The SSRIs (paroxetine, fluoxetine, sertraline, fluvoxamine, citalopram) and SNRI (ven-lafaxine) have an impressive side-effect profile, and this has contributed to their widespread use. Possible adverse effects include nausea, insomnia, and agitation, but these are generally manageable and diminish over time. More significant is the association of the SSRIs with sexual dysfunction, in both men and women. These effects are longer lasting, and can occur in up to 40% of patients (79). A withdrawal syndrome has also been observed with the SSRIs, characterized by dizziness, headache, and irritability upon abrupt discontinuation. This is much less serious than that observed with benzodiazepines. 

Because of the lack of dependency and tolerable adverse effect profile, antidepressants have emerged as the treatment of choice for the long-term management of chronic anxiety, especially in the presence of comorbid depressive symptoms. Buspirone is an additional anxiolytic option (Table 69-7) in patients without comorbid depression or other anxiety disorders (e.g., panic disorder and SAD). Because of the high risk of adverse effects and toxicity, barbiturates, antipsychotics, antipsychotic-antidepressant combinations, and antihistamines generally are not indicated in the treatment of GAD. The benzodiazepines are more effective in treating the somatic and autonomic symptoms of GAD as opposed to the psychic symptoms (e.g., apprehension and worry), which are reduced by antidepressants. ... 

Benzodiazepines are prescribed commonly for SAD. Clonazepam is the most extensively studied benzodiazepine for the treatment of generalized SAD. " Clonazepam improved fear and phobic avoidance, interpersonal sensitivity, fears of negative evaluation, and disability measures. " Adverse effects included sexual dysfunction, unsteadiness, dizziness, and poor concentration. " Clonazepam is often prescribed in conjunction with an antidepressant, psychotherapy, or both for initial symptom relief. Comorbid alcohol or substance abuse are contraindications to the use of benzodiazepines. Other limitations of clonazepam therapy include lack of efficacy in depression and difficulty with discontinuation. Because of the risk of dependency, benzodiazepines should be reserved for patients at a low risk of substance abuse, those who require rapid relief of symptoms, or those who have not responded to other therapies. 

Clobazam has similar effects on anxiety to other benzodiazepines, but may be better tolerated (SEDA-20, 31). Used as an anticonvulsant, clobazam is generally well tolerated in epileptic patients, many showing little evidence of tolerance (5). On the other hand, children with epilepsy appear unusually prone to adverse behavioral reactions when taking clobazam (SEDA-19, 34). 

Evidence of an adverse interaetion between valproate and the benzodiazepines and related hypnoties is sparse, and concurrent use is generally beneficial. However, on rare occasions potentially clinically significant effects have been seen. It has been suggested that the combination of clonazepam and sodium valproate should be avoided. However, a very brief letter points out that neither drug affects the serum concentrations of the other and that clonazepam and valproate can be given together in patients with absence seizures since some patients have an excellent response to the combination. ... 

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