Alprazolam adverse effects

Pregabalin produced anxiolytic effects similar to lorazepam, alprazolam, and venlafaxine in acute trials. Sedation and dizziness were the most common adverse effects, and the dose should be tapered over 1 week upon discontinuation. 

Anxiolytics and Sedative-Hypnotics. Because of their large therapeutic index, measurement of anxiolytic or sedative-hypnotic serum concentrations is not usually necessary in clinical practice, unless abuse, overdose, or inadvertent toxicity are suspected. Some data indicate that plasma alprazolam levels of 40 ng/mL may be required to manage panic disorder ( 51) (see the sections Adverse Effects of Anxiolytics and Adverse Effects of Sedative-Hypnotics in Chapter 12). 

Compared with TCAs and MAOIs, BZDs have a rapid onset of action, have fewer unpleasant adverse effects, and are considerably less toxic. Despite these advantages, however, BZDs (with the possible exception of alprazolam, discussed later) generally appear devoid of true antidepressant effects. When the results of several well-controlled studies totalling 1,275 patients were summarized, the overall response to BZDs was 51% versus 73% for standard antidepressants. This generated a highly significant difference (p < 10 ) on the Mantel-Haenzsel test in favor of the antidepressants (Table 7-15). 

Alprazolam has no significant anticholinergic or cardiovascular effects, but in almost all studies reporting adverse effects, alprazolam-induced sedation was comparable with or greater than that of the tertiary amine TCA. In one comparison with desipramine, drowsiness led to motor vehicle accidents in 2 of 16 outpatients taking alprazolam and required discontinuation in another 3 (212, 213). 

Wells BG, Evans RL, Ereshefsky L, et al. Clinical outcome and adverse effect profile associated with concurrent administration of alprazolam and imipramine. J Clin Psychiatry 1988 49 394-399. 

Adverse Effects Sedation, ataxia, and fatigue are the most common adverse effects reported with acute use of alprazolam in PD (39). Although tolerance to the sedative effect may develop within a few days of treatment initiation, this adaptation may be only partial. At weeks 4 and 8 in the Cross-National Collaborative study, many patients still showed signs of sedation (48% and 39%, respectively), ataxia (25% and 16%, respectively), and fatigue (19% and 16%, respectively) ( 23). 

Alprazolam has been shown to be effective in alleviating the jitteriness syndrome ( 94). A patient s inability to tolerate these adverse effects may be the most important treatment-limiting factor with these drugs. Alternatively, short-term combination with another BZD may be helpful until the full impact of the antidepressant is realized. 

The experience of pregnancy itself is often anxiety provoking, and symptoms sufficient to warrant drug therapy are common in this group ( 16). Although this discussion primarily focuses on the benzodiazepines (BZDs), antidepressants and buspirone may also be used for women of childbearing age with certain anxiety-related disorders. Perhaps the best-documented adverse effect of the BZDs is a neonatal withdrawal syndrome, which has been reported to occur with several of the agents (e.g., diazepam, alprazolam, and triazolam). In addition, there is a weak positive relationship between diazepam exposure and oral clefts ( 17). 

Comparison of common adverse effects of buspirone and alprazolam. Results are expressed as percent of patients showing each symptom. 

Clozapine has been used to treat benign essential tremor refractory to the usual drugs (propranolol, primidone, alprazolam, phenobarbital, and botulinum toxin) in a randomized, double-blind, crossover study in 15 patients with essential tremor (58). Responders with more than 50% improvement after a single dose of clozapine 12.5 mg, compared with placebo, subsequently received 39-50 mg unblinded for a mean of 16 months. Tremor was effectively reduced by a single dose of clozapine in 13 of 15 patients sedation was the only adverse effect reported. 

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). 

Rapid and sometimes serious mood swings to mania or depression, and other adverse effects, including enuresis, aggression, impaired memory, sedation, and ataxia, can occur in patients with panic disorder treated with alprazolam (SEDA-19, 34 SEDA-20, 31). 

ALPRAZOLAM, DIAZEPAM, MIDAZOLAM-ORAL GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects, e.g. sedation, CNS depression Possibly t bioavailability, 1 presystemic metabolism. Constituents of grapefruit juice irreversibly inhibit intestinal CYP3A4. Transport via P-gp and MRP-2 efflux pumps is also inhibited Avoid concomitant use. Be particularly vigilant in elderly patients or those with impaired liver function. Consider alternative, e.g. temazepam... 

Alosetron 1 mg twice daily for 2 days had no significant effect on the pharmacokinetics of a singie 1-mg dose of alprazolam in 12 heaithy subjects. No increase in adverse effects was noted with the combination. No speciai precautions therefore seem necessary on concurrent use. 

---