Treatment of depressive outpatients with lorazepam, alprazolam, amytriptyline and placebo. Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Alprazolam vs amitriptyline in depressions with reduced REM latencies. Alprazolam versus imipramine in depressed out-patients with neurovegetative signs. A double-blind clinical trial of alprazolam, imipramine, or placebo in the depressed elderly. An evaluation of alprazolam in the treatment of reactive or neurotic (secondary) depression. Double-blind trial of alprazolam and chlordiazepoxide in the management of the acute ethanol withdrawal syndrome. A double-blind comparative study of alprazolam and dothiepin hydrochloride in the treatment of anxiety associated with depression. Alprazolam and exposure alone and combined in panic disorder with agoraphobia. A controlled study in London and Toronto.
This randomized double-blind study in 342 mildly to moderately depressive outpatients investigated the antidepressant effectiveness and speed of action of lorazepam, alprazolam and amitriptyline versus placebo. Six weeks of drug treatment were followed by a drug taper period, a control period with placebo and a control period without placebo, of 2 weeks duration each. Clinical improvement was assessed by rating scales (Clinical Global Impressions, Hamilton Rating Scales for Depression and Anxiety) and patient's self-ratings (Patient's Global Impressions, Self-rating Depression Scale and Visual Analogue Scale). At the end of week 6 all active drugs showed similar efficacy which was significantly superior to placebo. Compared to placebo, onset of efficacy was earlier on benzodiazepines than on amitriptyline . While tapering by decreasing the dosage, replacing drug with placebo and finally discontinuing placebo, clear withdrawal phenomena were not seen, but 20% of patients, equally distributed to all treatment groups, did not want to stop taking tablets after replacing drug with placebo. Drop-out rate during the treatment period was very low (9%). Significantly interfering adverse effects were seen in 27 patients, without predominance in one of the active drug groups. Five hundred four outpatients suffering from a major depressive episode were randomly assigned to receive either amitriptyline, doxepin, alprazolam, or placebo. The study was conducted in three treatment centers during a six-week period. All three active medications produced significantly more clinical improvement than did placebo, irrespective of the patient's initial anxiety, depression, and psychomotor retardation and irrespective of the patient's assignment to various subtypes of depression, including the DSM-III melancholia subtype. Compared with placebo, sedation was reported more frequently with all three medications, whereas anticholinergic effects were reported more frequently only for the two tricyclic antidepressants, but not for alprazolam. This study was designed to compare the antidepressant effects of alprazolam, a triazolobenzodiazepine, with amitriptyline hydrochloride in a group of patients with nonpsychotic, major depressions diagnosed by Research Diagnostic Criteria. A mean rapid eye movement latency of less than 65 minutes was required to enter this study. Dexamethasone suppression tests were conducted before treatment. By strictly applied Research Diagnostic Criteria, 83.6% of the subjects were endogenous, and 34.7% were inpatients. A significantly greater percentage of alprazolam-treated patients responded within the first seven days of treatment. By the end of this six-week trial, alprazolam was associated with significant reductions in Hamilton, Beck, Covi, Raskin, and Carroll Rating scores (pretreatment to posttreatment). However, by the end of treatment the effects of amitriptyline exceeded those of alprazolam on both the Hamilton and Beck scales. These data indicate that alprazolam is not as effective as amitriptyline in major depressions with a shortened rapid eye movement latency. The purpose of this study was to compare the safety and efficacy of a relatively new antidepressant drug, alprazolam (a triazolobenzodiazepine) with imipramine in the treatment of 60 depressed symptomatic volunteers. Eligible patients were randomly assigned after a 1-week washout to one of the medications and followed for 6 treatment weeks. Contrary to the earlier report of Feighner et al. (1983), who found alprazolam superior to imipramine and placebo, but consistent with Rush et al. (1985) we find imipramine superior in efficacy to alprazolam on a variety of symptoms. Both the present study and Rush's study employed patients with signs indicative of response to tricyclics. Feighner's patients may have been the type who tend to be less responsive to tricyclics but may be more responsive to alprazolam. Some of our data also show that alprazolam may have a more advantageous effect in the early weeks of treatment but is overtaken in subsequent treatment weeks by imipramine. The efficacy and safety of alprazolam as compared to imipramine or a placebo added to weekly interpersonal psychotherapy was compared in a 6-week double-blind randomized clinical trial of 35 ambulatory elderly patients with major depression. The average maximum dosage of alprazolam was 2.2 mg and the average maximum dosage of imipramine was 97.5 mg. The findings showed a rapid onset of action of alprazolam within 1 week on symptoms of depression and anxiety. The effects for imipramine were seen later in the study. There were no serious side effects that interfered with treatment. The anticholinergic effects of imipramine were the ones that most commonly interfered with treatment. Alprazolam produced the greatest number of symptoms with discontinuation, most of which were alleviated within a week. We conclude that alprazolam may be useful as an antidepressant for the elderly. More clinical trials are needed to test its efficacy in the depressed elderly with concomitant medical problems, using plasma levels. A double-blind discontinuation study of alprazolam is needed to determine the degree of symptom return. To investigate the effectiveness of a new benzodiazepine, alprazolam, and to compare this with amitriptyline (AMT) and with placebo, a trial was undertaken in 65 patients in whom depression was considered to be the dominating feature but not considered to be the primary cause of their condition; it was designed to exclude endogenous depressions. A consistent pattern was found favouring alprazolam over AMT both in rate of response and in total response, as well as significant differences in favour of both alprazolam and AMT over placebo. A comparison of side effects showed a definite trend in favour of alprazolam and placebo over AMT. A sequential sample of 101 patients hospitalized for ethanol withdrawal and requiring sedation for evolving withdrawal syndromes was assigned randomly according to a double-blind protocol to treatment with either alprazolam or chlordiazepoxide administered orally. The data from one patient were unevaluable due to acute bleeding, leaving a sample of 100 (50 in each condition). At discharge, three independent ratings of diaphoresis, tremor, hallucinations, nausea/vomiting, and overall severity of withdrawal were obtained, and the occurrence of delirium tremens and grand mal seizures was noted. Patients also completed the Beck Depression Inventory, and their disposition following discharge was recorded. There were no statistically significant differences between the two treatment groups on any of the dependent variables studied. It was concluded that the choice between alprazolam and chlordiazepoxide for managing ethanol withdrawal should be based on criteria other than efficacy of control. Potential antidepressant effects and drug kinetics were suggested as the basis for rational decision-making. One hundred patients with mixed symptoms of anxiety and depression were enrolled into a prospective, multi-centre, randomized, double-blind study comparing the response to, and the side-effects of, alprazolam and dothiepin hydrochloride over 4 weeks of treatment. Mean daily doses were 2.33 mg alprazolam and 115 mg dothiepin. Data on 96 patients were evaluated for tolerance, and data for 85 patients were analyzed for therapeutic response. In each case, the groups were similar in numbers, mean ages and sex ratios. Both groups experienced satisfactory responses to therapy, with highly statistically significant changes (p less than 0.001) in the means of all efficacy measures within each group. No statistical difference was demonstrated in favour of either treatment group. Both dothiepin and alprazolam exhibited a similar profile of mild minor side-effects, but more patients suffered moderate to severe reactions to dothiepin, leading to a greater drop-out rate in the dothiepin-treated group. It is concluded that, as both treatments produced equally satisfactory responses in this study, alprazolam should be considered for the treatment of anxiety associated with depression in patients for whom tricyclic antidepressant drugs are either contra-indicated or poorly tolerated. A cross-national randomised trial of alprazolam for chronic panic disorder with agoraphobia was run. Compared with previous trials it had three new features: an exposure therapy contrast group, a six-month treatment-free follow-up, and a low rate of early placebo drop-outs ('non-evaluables'). The dose of alprazolam was high (5 mg/day). The 154 patients had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo and exposure; or placebo and relaxation (double placebo). Drug taper was from weeks 8 to 16. Follow-up was to week 43. Results were similar at both sites. Treatment integrity was good. All four treatment groups, including double placebo, improved well on panic throughout. On non-panic measures, by the end of treatment, both alprazolam and exposure were effective, but exposure had twice the effect size of alprazolam. During taper and follow-up, gains after alprazolam were lost, while gains after exposure were maintained. Combining alprazolam with exposure marginally enhanced gains during treatment, but impaired improvement thereafter. The new features put previous trails in a fresh light. By the end of treatment, though gains on alprazolam were largely as in previous studies, on phobias and disability they were half those with exposure. Relapse was usual after alprazolam was stopped, whereas gains persisted to six-month follow-up after exposure ceased. Panic improved as much with placebo as with alprazolam or exposure.
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.