Alprazolam comparative studies

Finally, it should be stressed again that certainly not all benzodiazepine prescribing to opioid maintenance patients need be long term. McDuff et al. (1993) reported on detoxification from alprazolam, the benzodiazepine most commonly used by their methadone subjects. With methadone dosage usually remaining the same, patients were offered a set reducing course of alprazolam over 11 weeks. Of 22 patients, four refused the treatment and 12 out of 18 subsequently completed detoxification, although timescales in practice proved variable. In a comparative study by Weizman et al. (2003) just over a quarter of benzodiazepine-dependent methadone maintenance patients remained free of benzodiazepines... 

Several controlled studies of IMI involved less homogeneous samples of anxious children. Neither IMI nor alprazolam (a BZ) was superior to placebo in an 8-week study of 24 children (ages 7-18 years) with school refusal, which included subjects with anxiety and depression (Bernstein et ah, 1990). A more recent placebo-controlled study of IMI -I- CBT for 47 adolescents (ages 12-18 years) with school refusal, anxiety, and/or depression was designed to address the limitations of previous studies of TCA treatment for pediatric anxiety disorders (Bernstein et ah, 2000). Accordingly, sample size was based on proposed power analysis IMI dose and serum level were monitored to ensure adequate exposure (mean IMI dose 180 mg/day mean serum IMI180 pg/L and mean IMI -I- DMI 250 pg/L at week 3 and week 8) and CBT was manual based and closely monitored. Fifty-four percent of subjects treated with IMI -I- CBT met remission criteria (defined as > 75% school attendance at the end of the study), compared to 17% of subjects treated with placebo -I- CBT. No between-group differences were noted... 

Gelernter et al. (1991) compared phenelzine, alprazolam, placebo, and cognitive-behavior therapy in social phobia. In those patients receiving alprazolam, only 38% improved, based on the Marks Fear Questionnaire [Marks and Matthews 1982) scores. In this study, the mean daily dose for alprazolam was 4.2 mg. At 2-month follow-up, after discontinuation of the drug, the improvement in the alprazolam group was no longer measurable. 

American Psychiatric Association Benzodiazepine Dependence, Toxicity, and Abuse A Task Force Report of the American Psychiatric Association. Washington, DC, American Psychiatric Association, 1990 Cohn JB, Wilcox CS Low-sedation potential of buspirone compared with alprazolam and lorazepam in the treatment of anxious patients a double-blind study. J Clin Psychiatry 47 409 12, 1986 Dolovich LR, Addis A, Vaillancourt JM, et al Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and case-control studies. BMJ 317 839-843, 1998 Goldberg HL, Finnerty RJ The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry 136 1184—1187, 1979 Kupfer DJ, Reynolds CF 111 Management of insomnia. N Engl J Med 336 341-346, 1997... 

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). 

Short-Term Efficacy Although at least one study found no difference between alprazolam and placebo, several short-term studies have reported that alprazolam reduces the frequency and intensity of panic attacks (19, 20, 21, 22, 23, 24, 25, 26 and 27) (Table 13-2). In phase I of a cross-national collaborative study, including approximately 500 patients at eight sites, alprazolam was superior to placebo at the end of week 1 in improving spontaneous and situational panic attacks, anxiety, and secondary disability ( 23). At week 4, 50% of alprazolam patients and 28% of placebo patients were free of panic attacks. At week 8, however, 50% of those on placebo were also free of panic attacks, compared with 59% of those receiving alprazolam. These data reflect group efficacy and not individual responses over time. Furthermore, there was considerable variability and, at times, instability of response in individual patients. Explanations offered for the high rate of placebo response in this and other studies include ... 

Alprazolam was also compared with imipramine and placebo in a sample of 1,168 randomly assigned subjects in the Cross-National Collaborative Panic Study, Phase Two. This study was conducted at 12 centers and assessed clinical change over 8 weeks of double-blind treatment. Improvement occurred with alprazolam by weeks 1 and 2 and with imipramine by week 4. By the end of week 8, the effects of the two active drugs were similar and both were superior to placebo for most outcome measures (31). 

Several open trials have reported significant improvement or remission of panic attacks in patients given clonazepam ( 60, 61, 62, 63, 64, 65 and 66). One double-blind, placebo-controlled study comparing the efficacy of alprazolam, clonazepam, and placebo found both drugs superior to placebo and comparable with each other (67). Because favorable response to clonazepam usually occurs early in treatment, lack of initial improvement may predict treatment failure ( 42, 61, 68). Interdose and morning rebound anxiety have not been reported. Clonazepam is not approved by the FDA for panic attacks, and because there are only a few controlled studies, there is only limited knowledge about its efficacy for this indication. 

There is some evidence that higher than usual doses of lower potency BZDs may also be effective in treating PD ( 17, 25, 43, 81, 82, 83 and 84). For example, studies comparing alprazolam with lorazepam or diazepam indicate approximately equal efficacy ( 25, 43, 84, 85). In addition, there is evidence that higher than usual doses of diazepam, lorazepam, bromazepam, or clobazam may also block panic attacks. 

Results from studies comparing TCAs, SSRIs, and MAOIs with placebo in the treatment of PD are summarized in Table 13-5, Table 13-6, and Table 13-7. The results of studies comparing alprazolam or SSRIs with standard TCAs are summarized in Table 13-8 and Table 13-9. All drugs were superior to placebo, although no significant differences in efficacy were noted among them. 

Most studies comparing imipramine and alprazolam indicate that both drugs produce a comparable reduction of symptoms, although onset of action is considerably slower with a TCA, requiring 2 weeks to as long as 12 weeks (21,24, 26, 37, 85, 92). 

Cross-National Collaborative Panic Study, Second Phase Investigators. Drug treatment of panic disorder. Comparative efficacy of alprazolam, imipramine, and placebo. BrJ Psychiatry 1992 160 191-202. 

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. 

In another study, Malsch and Kieser (2001) investigated the anxiolytic effects of WS 1490 compared to placebo in patients previously treated with a benzodiazepine. They evaluated the potential of the kava preparation as a replacement for the benzodiazepine, as well as the ability of the kava preparation to reduce benzodiazepine withdrawal symptoms. This was a five-week randomized, double blind placebo-controlled study in outpatients with non-psychotic anxiety (e.g., generalized anxiety disorder, social phobia, and simple phobia). Forty patients were included, and all had been on benzodiazepines (i.e., lorazepam, bromazepam, oxazepam, or alprazolam) for a mean duration of 20 months prior to entering the study. Of the 40 patients, 25 were males, and the mean age of the total sample was 40 years (range 21—75 years). 

It is very difficult to assess and compare the results of the very many studies of this interaction because of the differences between the tests, their duration, the dosages of the benzodiazepines and alcohol, whether given chronically or acutely, and a number of other variables. However, the overall picture seems to be that benzodiazepines and related drugs including diazepam, " alprazolam,bromazepam, brotizolam, chlo-rdiazepoxide, " clobazam, dipotassium clorazepate, flunitrazepam, flurazepam, loprazolam, " lorazepam, lormetazepam, medazepam, midazolam, nitrazepam, " " oxazepam, temazepam, " triazolam, and zopiclone enhance the effects of alcohol i.e. cause increased drowsiness, impaired performance and driving skills. 

In an analysis of phase HI studies, changes in vital signs did not differ between patients given linezolid and comparator drugs (i.e. antibiotics) when either were used with drugs known to interact with MAOIs, including unnamed cyclic antidepressants. A case report describes the serotonin syndrome in an elderly patient treated with linezolid 600 mg every 12 hours, 21 days after amitriptyline 10 mg daily, paroxetine 20 mg daily and alprazolam 500 micrograms daily were started. ... 

The initial studies with heterologously expressed P450 3A43 (in E. coli) showed only low testosterone 6jff-hydroxylation activity (a marker for other 3A subfamily members) [1531], Agarwal et al. [1254] reported different catalytic specificity in alprazolam oxidation compared to P450 3A4 and a relatively high level of activity, con-... 

Drag formulations Conventional and sublingual tablets of alprazolam 0.5 mg have been compared in a randomized multicenter study in the acute phase of panic disorders with and without agoraphobia [3 ]. Somnolence and sedation were the principal adverse events (25%), and there were no differences between the two formulations of alprazolam. 

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