A DOUBLE-BLIND EVALUATION OF ALPRAZOLAM AND IMIPRAMINE IN THE TREATMENT OF MAJOR DEPRESSION Alprazolam and amitriptyline in the treatment of major depressive disorder: a double-blind clinical and sleep EEG study. Treatment of depressive outpatients with lorazepam, alprazolam, amytriptyline and placebo Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. An evaluation of alprazolam in the treatment of reactive or neurotic (secondary) depression. Comparison of alprazolam, imipramine, and placebo in the treatment of depression. Influence of depression on the treatment of panic disorder with imipramine, alprazolam and placebo. Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. A double-blind clinical trial of alprazolam, imipramine, or placebo in the depressed elderly. Alprazolam and amitriptyline in the treatment of moderate depression A Comparison of the Efficacy and Safety of Alprazolam and Desipramine in Depressed Outpatients A Comparison of the Safety and Efficacy of Alprazolam and Desipramine in Moderately Severe Depression * Depression Treatment in Patients With General Medical Conditions: Results From the CO-MED Trial Patients with panic disorder unaccompanied by depression improve with alprazolam and imipramine treatment. Alprazolam compared to amitriptyline in the treatment of major depression Alprazolam: An Antidepressant? Alprazolam, Desipramine, and an Alprazolam‐Desipramine Combination in the Treatment of Adult Depressed Outpatients A double-blind comparative study of alprazolam and dothiepin hydrochloride in the treatment of anxiety associated with depression.
SUMMARY This report describes the results of a multicentre collaborative study comparing the safety and efficacy of alprazolam with imipramine in patients suffering from major depressive disorder . Two hundred and eight patients diagnosed as major depression as per DSM-III criteria were r and omly allocated to alprazolam ( N= 105 ) or imipramine ( N = 103 ) in a double-blind fashion . Detailed assessment s were carried out for a period of six weeks . Results revealed that alprazolam was as effective as imipramine as an antidepressant . Side effects were less frequently reported with alprazolam This study was design ed to compare the antidepressant effects of alprazolam and amitriptyline in a group of 30 in patients suffering from a severe major endogenous depression , diagnosed by Research Diagnostic Criteria and the Newcastle Rating scale , and to examine the effects of alprazolam and amitriptyline on two biological markers of depression , the dexamethasone suppression test and sleep EEG parameters . The 6-week study was double-blind with a r and om allocation of treatment . Patients were treated with flexible doses of 4 - 9 mg of alprazolam and 100 - 225 mg of amitriptyline . After 4 weeks of treatment the antidepressant effects of amitriptyline significantly exceeded those of alprazolam , as measured on the Hamilton Rating Scale for Depression . There was a high drop-out rate in the alprazolam group because of ineffectiveness of treatment . Alprazolam showed similar effects on sleep parameters as amitriptyline : lengthening of the REM latency and a tendency to shorten stages 3 and 4 and stage REM . These negative clinical results should be interpreted with caution , because of the severity of our selection criteria , and should not be extended to all depressive disorders This r and omized double-blind study in 342 mildly to moderately depressive out patients 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 Two hundred forty-one out patients with a DSM-III diagnosis of major depressive disorder participated in a six-week double-blind therapeutic trial of alprazolam , diazepam , imipramine hydrochloride , and placebo .  Side effects were given as a major reason for attrition by patients taking the three active compounds and ineffectiveness was the reason given by patients taking placebo . Imipramine-treated patients reported the most and placebo patients the least number of adverse effects .  Imipramine and alprazolam , but not diazepam , produced significantly more improvement in depressed symptomatology than did placebo . Mean diazepam scores frequently assumed an intermediate position between those of imipramine or alprazolam and placebo . These treatment differences were found to be independent of initial severity levels of anxiety and depression 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 design ed 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 Alprazolam is the first of the triazolobenzodiazepines to be studied in a large population of depressed patients . In a six-week , double-blind multicenter comparison of alprazolam , imipramine hydrochloride , and placebo in the treatment of 723 patients with depression , the two active drugs were statistically more effective than placebo . Alprazolam was at least as effective as imipramine in relieving depressive symptoms , significantly more effective in relieving somatic symptoms , and showed an earlier onset of activity in some measurements . Anticholinergic side effects were reported most often by patients receiving imipramine , while drowsiness was the only side effect reported most often in the alprazolam group . The Feighner Diagnostic Criteria and pre study and post study intercenter conferences with videotaped patient interviews ensured interrater reliability This paper presents findings from a multisite study of 126 subjects meeting DSM-III-R criteria for Panic Disorder who also met criteria for a concurrent Major Depressive Episode , Dysthymia , or Depressive Disorder NOS . The study 's primary aim was to discern the influence of varying degrees of depression on the comparative efficacy of alprazolam , imipramine and placebo on anxiety outcomes . A placebo-controlled , double-blind , parallel r and om assignment design was utilized over a total of 16 weeks . There was no medication effect on panic outcomes . At endpoint , percent of anticipatory anxiety ( i.e. , time spent worrying about having an anxiety attack ) was significantly lower in the patients taking active medications vs. placebo .  Phobic measures were significantly improved by alprazolam , vs. both imipramine and placebo early in the study ; however , by week 8 both active medications were equally superior to placebo in the reduction of phobic symptoms . In addition , both active medications were significantly more effective than placebo in reducing depression . The same efficacy pattern ( i.e. , active medications superior to placebo ) was observed on measures of general functioning . Importantly , there were no significant interactions observed between medication and presence of major depression on the depression measures , indicating that both alprazolam and imipramine were equally efficacious in treating the depression in patients with panic disorder and major depression . Since the patients enrolled in this study suffered from major depressive disorder in the mild to moderate severity range , these results may not be transferrable to patients with panic disorder and severe major depression Five hundred four out patients suffering from a major depressive episode were r and omly 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 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 r and omized 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 Forty-three out- patients with depression of a moderate degree were enrolled in a r and omized , double-blind parallel group study comparing amitriptyline and alprazolam for 6 weeks of treatment . Patients were evaluated at the end of placebo washout and at Weeks 1 , 2 , 3 and 6 of drug therapy using the Hamilton Depression Rating Scale ( HAM-D ) , Hamilton Anxiety Rating Scale ( HAM-A ) , Beck Depression Inventory ( BDI ) and Clinical Global Impression ( CGI ) . Drug dosage was determined in a fixed-flexible design result ing in mean final doses of alprozalam 3.2 mg/day and of amitriptyline 115 mg/day . Although both drug groups improved there were statistically significant differences in favour of amitriptyline at the end of the study on the HAM-D , BDI and HAM-A scales .  Patients on amitriptyline reported more side effects overall than patients taking alprazolam with significantly more reports of dry mouth in the amitriptyline group Fifty-two adult depressed out patients fulfilling Research Diagnostic Criteria for Definite Major Depressive Disorder were enrolled in a double-blind study comparing the antidepressant effects of alprazolam versus desipramine .  Twenty-nine patients completed the seven week ( one week placebo followed by six weeks of active drug ) study . The mean daily dose of alprazolam and desipramine at study termination was 3.34 mg and 192 mg respectively . Based on psychometric ratings of depression ( Hamilton Scale ) and severity of illness ( Clinical Global Impressions ) there was no significant difference between alprazolam and desipramine at the end of six weeks of active drug treatment . Both medications were well tolerated with drowsiness being the most common side effect of alprazolam , and insomnia , dry mouth , and constipation , the complaints most associated with desipramine Fifty-four patients ( 34 out patients , 20 in patients ) fulfilling Research Diagnostic Criteria for Definite Major Depressive Disorder were enrolled in a double-blind study comparing the antidepressant effects of alprazolam versus desipramine . The mean daily dose of alprazolam and desipramine at study termination was 3.78 mg and 208 mg respectively . As there were no significant demographic or clinical differences between out patients and in patients , both groups were combined in data analysis . Using the Hamilton Depression Rating Scale ( HAM-D ) both drug groups showed highly significant improvement beginning with the first week of active drug treatment . HAM-D scores continued to decrease through study termination ( six weeks of active drug ) . There were no significant differences when comparing alprazolam and desipramine ( out patients , in patients , or both groups combined ) on any of the subjective or objective psycho-metrics used in this study . Clinical ly , only twelve of thirty-four out patients ( 35.3 % ) were felt to be “ markedly or moderately ” improved , suggesting that neither the outpatient alprazolam nor desipramine patients did particularly well with drug treatment . In terms of drug safety there was no difference between the alprazolam and desipramine in the number of excessive or serious drug side effects . However , five of twenty-nine alprazolam patients had to discontinue therapy because of excessive drowsiness , and two of the alprazolam out patients had motor vehicle accidents directly related to this adverse event . Alprazolam appeared as effective as desipramine in the pharmacotherapy of this group of depressed outpatient and in patients .  Alprazolam appeared well-tolerated by most subjects although drowsiness was a common — and at times serious — medication side effect PURPOSE We studied the effect of 3 antidepressant treatments on outcomes ( depressive severity , medication tolerability , and psychosocial functioning ) in depressed patients having comorbid general medical conditions in the Combining Medications to Enhance Depression Outcomes ( CO-MED ) trial . METHODS Adult out patients who had chronic and /or recurrent major depressive disorder ( MDD ) with and without general medical conditions were r and omly assigned in 1:1:1 ratio to 28 weeks of single-blind , placebo-controlled antidepressant treatment with ( 1 ) escitalopram plus placebo , ( 2 ) bupropion-SR plus escitalopram , or ( 3 ) venlafaxine-XR plus mirtazapine . At weeks 12 and 28 , we compared response and tolerability between participants with 0 , 1 , 2 , and 3 or more general medical conditions . RESULTS Of the 665 evaluable patients , 49.5 % reported having no treated general medical conditions , 23.8 % reported having 1 , 14.8 % reported having 2 , and 11.9 % reported having at least 3 . We found only minimal differences in antidepressant treatment response between these groups having different numbers of conditions ; patients with 3 or more conditions reported higher rates of impairment in social and occupational functioning at week 12 but not at week 28 . Additionally , we found no significant differences between the 3 antidepressant treatments across these groups . CONCLUSIONS Patients with general medical conditions can be safely and effectively treated for MDD with antidepressants with no additional adverse effect or tolerability burden relative to their counterparts without such conditions . Combination therapy is not associated with an increased treatment response beyond that found with traditional monotherapy in patients with MDD , regardless of the presence and number of general medical conditions Patients with panic disorder ( N = 1168 ) were enrolled in a multicenter , 8-week , double-blind clinical trial of imipramine , alprazolam , and placebo to analyze whether the effectiveness of these agents is dependent on the depressive/dysphoric symptomatology which often coexists in panic disorder patients . In addition to analyses performed on the whole sample of patients , the authors conducted analyses on a sub sample ( N = 312 ) defined by multiple criteria to ensure the absence of depression and dysphoria . In both the overall sample and the nondepressed sub sample , the clinical response to imipramine or alprazolam was found to be independent of the presence of depression or dysphoria . In panic disorder patients for whom pharmacotherapy is being considered as treatment , the absence of depression is apparently not a contraindication ABSTRACT — In a double‐blind r and omized study the therapeutic effect and safety of alprazolam was compared with amitriptyline in 81 out patients suffering from major depression . Variable dosages of both drugs were used , the mean final dose of alprazolam being 3.05 and that of amitriptyline 130 mg . Both treatment groups improved steadily , assessed weekly with the use of the Hamilton Rating Scale for Depression , and no significant differences were found between the groups , either on comparison between single items or total scores . On several of the criteria used for assessment of treatment response , however , more patients responded to amitriptyline than to alprazolam . In an analysis of specific subgroups , patients whose depression was accompanied by retardation , those in whom there were no precipitating factors and those with low levels of anxiety , responded better to amitriptyline . Considerably fewer side effects were reported by patients receiving alprazolam . In particular , there was a significantly lower incidence of dry mouth , light‐headedness , tremor and tachycardia in patients receiving alprazolam compared with amitriptyline The antidepressant efficacy of alprazolam ( ALP ) was tested in a double-blind controlled comparison with desipramine ( DMI ) and an ALP-DMI combination in out patients diagnosed with major depressive disorder by Research Diagnostic Criteria ( 90 % met criteria for endogenous subtype ) . Following a placebo period of at least 1 week , subjects who continued to meet severity criteria defined by Hamilton Depression Rating Scale ( HDRS ) scores were administered oral doses of the active medication ( N = 79 ) , in a dose ratio of 1 mg ALP:50 mg DMI:1 mg ALP + 50 mg DMI . Treatment continued for 6 weeks , and all subjects who completed at least 2 weeks ( N = 69 ) were included in endpoint analyses . Following the placebo baseline , symptoms were rated again at day 5 and at the end of weeks 1 , 2 , 4 , and 6 . Final doses averaged 4.6 ± 1.3 mg for the ALP group , 230 ± 61 mg for the DMI group , and 4.6 ± 1.2 mg ALP + 229.5 ± 1.2 mg DMI for the combination group . The final outcome was a comparable degree of improvement at the end-point among the three treatment groups on measures of depression ( HDRS and Beck Depression Inventory ) , anxiety ( Hamilton Anxiety Rating Scale ) , and global improvement ( Global Assessment Scale , and Physician and Patient Global Impressions ) . A similar outcome was found for the subgroup of patients who completed all 6 weeks ( N = 56 ) . Endpoint analyses also showed that ALP-treated subjects responded sooner and continued to show improvement throughout the course of the study on measures of depression , anxiety , and global status . These results suggest that ALP alone is as effective as a st and ard tricyclic for the acute treatment of patients with major depressive disorder and that significant improvement may occur within the first week of medication . Side effect profiles were compared among treatment groups and are discussed , as are other clinical studies that have investigated ALP 's  potential antidepressant efficacy . ( J Clin Psychopharmacol 1987;7:295—310 One hundred patients with mixed symptoms of anxiety and depression were enrolled into a prospect i ve , multi-centre , r and omized , 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
When alprazolam was compared with placebo for reduction in symptoms all estimates indicated a positive effect for alprazolam .
The RD of all-cause withdrawals did not differ between alprazolam and placebo .
Alprazolam appears to reduce depressive symptoms more effectively than placebo and as effectively as tricyclic antidepressants .
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
BACKGROUND The ' off-label ' effect of alprazolam on depression has not been systematic ally 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 out patients and patients in primary care .