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The Cochrane Database of Systematic... Jul 2012The 'off-label' effect of alprazolam on depression has not been systematically evaluated. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The 'off-label' effect of alprazolam on depression has not been systematically evaluated.
OBJECTIVES
To determine the antidepressant effect, including tolerability and acceptability, of alprazolam as monotherapy for major depression, when compared to placebo and conventional antidepressants in outpatients and patients in primary care.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register, which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years to February 2012); EMBASE (1970 to February 2012); MEDLINE (1950 to February 2012) and PsycINFO (1960 to February 2012). Two review authors identified relevant trials by assessing the abstracts of all possible studies. We applied no language restrictions.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) of alprazolam versus placebo or conventional antidepressants for depression in adults, excluding studies with inpatients only.
DATA COLLECTION AND ANALYSIS
Two review authors performed the data extraction and 'Risk of bias' assessment independently with disagreements resolved through discussion with a third review author. Primary outcomes included the mean difference (MD) in reduction of depression on a continuous measure of depression symptoms, and the risk ratio (RR) of the clinical response based on a dichotomous measure, with 95% confidence intervals (CI).
MAIN RESULTS
We identified 21 alprazolam studies (22 reports) with a total of 2693 participants. Seven studies used a placebo (n = 771) and 20 used cyclic antidepressants (n = 1765). The typical duration of the studies was four to six weeks. We considered six studies to have a high risk of bias.When alprazolam was compared with placebo for reduction in symptoms all estimates indicated a positive effect for alprazolam. Pooled estimates of efficacy data showed a moderately large continuous mean difference (MD) at the end of trial (-5.34, 95% CI -7.48 to -3.20; I(2) = 68%). The risk difference (RD) for the dichotomous measure of clinical response (50% improvement) was 0.32 in favour of alprazolam (95% CI 0.22 to 0.42; I(2) = 0%), with a number needed to treat to benefit (NNTB) of 3 (95% CI 2 to 5). The RD of all-cause withdrawals did not differ between alprazolam and placebo.When depression severity was measured as a continuum the effect of alprazolam did not differ statistically or clinically from the effects of any of the conventional antidepressants combined (MD 0.25, 95% CI -0.93 to 1.43; I(2) = 55%). However, for dichotomised depression severity, alprazolam had less effect than antidepressants (RR 0.86, 95% CI 0.75 to 0.99; I(2) = 37%; RD -0.11, 95% CI -0.24 to 0.01; I(2) = 58%; NNTB 9, 95% CI 4 to 100). The RD of all-cause withdrawals was -0.04 (95% CI -0.07 to 0.00; I(2) = 35%), in favour of alprazolam.
AUTHORS' CONCLUSIONS
Alprazolam appears to reduce depressive symptoms more effectively than placebo and as effectively as tricyclic antidepressants. However, the studies included in the review were heterogeneous, of poor quality and only addressed short-term effects, thus limiting our confidence in the findings. Whilst the rate of all-cause withdrawals did not appear to differ between alprazolam and placebo, and withdrawals were less frequent in the alprazolam group than in any of the conventional antidepressants combined group, these findings should be interpreted with caution, given the dependency properties of benzodiazepines.
Topics: Adult; Aged; Alprazolam; Antidepressive Agents; Depression; Humans; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 22786504
DOI: 10.1002/14651858.CD007139.pub2 -
The Cochrane Database of Systematic... Oct 2009Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies... (Review)
Review
BACKGROUND
Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies have been unclear, with some suggesting that benzodiazepines may be useful in controlling non-alcohol related delirium.
OBJECTIVES
To determine the effectiveness and incidence of adverse effects of benzodiazapines in the treatment of non-alcohol withdrawal related delirium.
SEARCH STRATEGY
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 February 2008 using the search terms: (deliri* or confusion) and (benzo* or lorazepam," or "alprazolam" or "ativan" or diazepam or valium or chlordiazepam).The CDCIG Specialized Register contains records from major health databases (including MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, LILACS) as well as many ongoing trial databases and grey literature sources.
SELECTION CRITERIA
Trials had to be unconfounded, randomized and with concealed allocation of subjects. Additionally, selected trials had to have assessed patients pre- and post-treatment. Where crossover design was present, only data from the first part of the trial were to be examined.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data from included trials. Data were pooled where possible, and were to be analysed using appropriate statistical methods. Odd ratios or average differences were to be calculated. Only "intention to treat" data were to be included.
MAIN RESULTS
Only one trial satisfying the selection criteria could be identified. In this trial, comparing the effect of the benzodiazepine, lorazepam, with dexmedetomidine, a selective alpha-2-adrenergic receptor agonist, on delirium among mechanically ventilated intensive care unit patients, dexmedetomidine treatment was associated with an increased number of delirium- and coma-free days compared with lorazepam treated patients (dexmedetomidine patients, average seven days; lorazepam patients, average three days; P = 0.01). One partially controlled study showed no advantage of a benzodiazepine (alprazolam) compared with neuroleptics in treating agitation associated with delirium, and another partially controlled study showed decreased effectiveness of a benzodiazepine (lorazepam), and increased adverse effects, compared with neuroleptics (haloperidol, chlorpromazine) for the treatment of acute confusion.
AUTHORS' CONCLUSIONS
No adequately controlled trials could be found to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients, and at this time benzodiazepines cannot be recommended for the control of this condition. Because of the scarcity of trials with randomization of patients, placebo control, and adequate concealment of allocation of subjects, it is clear that further research is required to determine the role of benzodiazepines in the treatment of non-alcohol withdrawal related delirium.
Topics: Benzodiazepines; Delirium; Dexmedetomidine; Humans; Lorazepam
PubMed: 19821364
DOI: 10.1002/14651858.CD006379.pub3