title: Comparison of alprazolam, imipramine, and placebo in the treatment of depression. Alprazolam and oxazepam in the treatment of anxious out-patients with depressive symptoms: a double-blind multicenter study. Alprazolam versus imipramine in depressed out-patients with neurovegetative signs. Double-blind clinical study comparing alprazolam and doxepin in primary unipolar depression. Influence of depression on the treatment of panic disorder with imipramine, alprazolam and placebo. Anxiety psychopathology predictive of outcome in patients with panic disorder and depression treated with imipramine, alprazolam and placebo. A double-blind clinical trial of alprazolam, imipramine, or placebo in the depressed elderly. Alprazolam and amitriptyline in the treatment of major depressive disorder: a double-blind clinical and sleep EEG study. A double-blind comparative study of alprazolam and dothiepin hydrochloride in the treatment of anxiety associated with depression. A DOUBLE-BLIND EVALUATION OF ALPRAZOLAM AND IMIPRAMINE IN THE TREATMENT OF MAJOR DEPRESSION Alprazolam and amitriptyline in the treatment of moderate depression Identification and treatment of masked depression in a general medical practice. New evidence on benzodiazepine use and falls: the time factor. Alprazolam compared to amitriptyline in the treatment of major depression Treatment of depressive outpatients with lorazepam, alprazolam, amytriptyline and placebo A comparison of alprazolam with amitriptyline in the treatment of patients with neurotic or reactive depression Alprazolam vs amitriptyline in depressions with reduced REM latencies. Alprazolam: An Antidepressant? Alprazolam, Desipramine, and an Alprazolam‐Desipramine Combination in the Treatment of Adult Depressed Outpatients A Comparison of the Safety and Efficacy of Alprazolam and Desipramine in Moderately Severe Depression * Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation. Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Comparative efficacy of alprazolam, imipramine, and placebo administered once a day in treating depressed patients. A Comparison of the Efficacy and Safety of Alprazolam and Desipramine in Depressed Outpatients Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper. Issues in clinical trials with the depressed elderly. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision Comparison of alprazolam and imipramine for treatment of outpatient depression. A Double Blind Comparison of Alprazolam and Amitriptyline Hydrochloride in the Treatment of Nonpsychotic Depression Antidepressant or antianxiety? A study of the efficacy of antidepressant medication An evaluation of alprazolam in the treatment of reactive or neurotic (secondary) depression. Differential response to chlorpromazine, imipramine, and placebo. A study of subgroups of hospitalized depressed patients.
abstract: 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 In a four-week double-blind study comparing alprazolam with oxazepam , 62 out patients suffering from anxiety with depressive symptoms were evaluated . The average daily doses of alprazolam and oxazepam were 1.48 mg and 44.4 mg , respectively . According to all rating scales applied , both alprazolam and oxazepam were effective in relieving anxiety associated with mild depression ( p less than 0.01 ) . Alprazolam proved somewhat more effective than oxazepam especially with regard to overall performance ( p less than 0.05 ) . Treatment-emergent adverse effects were few and mild for both compounds tested 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 r and omly 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 therapeutic effect and safety of alprazolam and doxepin were studied in 126 out patients suffering from primary unipolar depression . The 6-week study was double-blind with a r and om allocation of treatment . Patients were treated with a flexible dose of 1.0 - 4.5 mg of alprazolam and 50 - 225 mg of doxepin per day . The mean final doses were 2.7 mg for alprazolam and 137.5 mg for doxepin . The results indicate that alprazolam and doxepin were equally efficacious . The incidence of side-effects was lower in the alprazolam treatment group 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 This study examines clinical predictors of outcome for patients with panic disorder and depression in a 16 week , placebo-controlled trial of alprazolam and imipramine  ( n = 126 ) . Baseline global severity of illness and phobic avoidance were differentially predictive of acute response to treatment . Patients in the mild to moderate range of global distress experienced smaller degrees of improvement on alprazolam than on imipramine at week 4 . At endpoint , the relative effectiveness of the active medication versus placebo was diminished in patients with higher levels of phobic avoidance . This relationship was not evident for completers , suggesting that the adverse effects of avoidance on outcome after sustained treatment was reduced 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 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 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 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 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 The usefulness of the  Zung Self-Rating Depression Scale  as a screening instrument to uncover masked depression , and the benefits of early identification and treatment with alprazolam , were evaluated in a general medical practice population . There was a 95 % scale acceptance by patients and a 12 % overall prevalence of depression based on SDS results . Patients who scored in the depressed range on the SDS were , on a r and omized basis , either identified immediately to their physicians and treated with alprazolam ( N = 21 ) or identified after 4 weeks ( natural history controls , N = 20 ) . Treatment result ed in improvement in 66 % of the identified group versus a 35 % spontaneous improvement in the control group ( p less than .05 ) The objectives of this prospect i ve study were to calculate incidence rates for fall-related hospitalization , to compare the effect of risk factors among  benzodiazepine ( BZD ) users and unexposed controls , and to examine variations in risks according to length of time following a BZD prescription . Data were derived from Saskatchewan Health linked data bases , leading to information on 468 hospitalizations for injury due to falls among a study population of 321422 .  Incidence rates per 10000 within 28 days of the prescription fill date were 26.2 , 12.1 and 9.0 for BZD sedative users , BZD tranquillizer users and for unexposed controls , respectively . Incidence rates increased with age , and were higher for women than for men . Results from multivariate logistic regression models also showed a greater risk of falling for BZD users but the odds ratio was higher for men than for women . A history of treatment for alcohol abuse was a very strong risk factor for falls among both men ( odds ratio , 10.7 ) and women ( odds ratio , 4.3 ) . The highest risk of serious injury due to falls was within 15 days of filling the prescription , with an odds ratio of 3.6 for BZD sedatives and 2.6 for BZD tranquillizers . Risk decreased with further increase of time after the BZD fill date . For the individual BZD , flurazepam and triazolam showed the highest increase in risk with odds ratios of 3.4 and 2.7 , respectively , while oxazepam , lorazepam and diazepam showed odds ratios of 2.2 , 2.0 and 1.8 ( all odds ratios mentioned are statistically significant at p < 0.05 ) 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 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 Summary 104 patients suffering from neurotic or reactive depressioDDn were treated with either alprazolam or amitriptyline in r and omised , double-blind fashion . Seventeen patients were either lost to follow-up3 or withdrawn before week 2 ( 13 due to side effects and 1 because she was feeling better ) . A further 7 patients did not comply with the protocol , giving a total of 24 patients whose data were not considered suitable for inclusion in the analysis of therapeutic assessment s . Evaluation of the 80 patients ( 40 in each group ) who completed at least 2 weeks of the 4-week study demonstrate that both treatments produced a statistically significant response rate . There was a more rapid effect in those patients who received amitriptyline , but there was no significant difference in response between the treatment groups after 4 weeks treatment . Analysis of safety and side effect data on 101 patients ( 50 treated with alprazolam and 51 with amitriptyline ) shows no statistically significant difference in the overall number of side effects experienced in each group , although 11 of those patients who received amitriptyline withdrew because of adverse reactions before completing the study compared to 6 in the alprazolam group . These results suggest that alprazolam may be a useful treatment for patients with neurotic or reactive depression not requiring hospitalisation This study was design ed 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 in patients . 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 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 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 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 We compared the effect of abrupt discontinuation of therapeutic doses of short half-life and long half-life benzodiazepines in 57 benzodiazepine-dependent patients ( daily use , greater than 1 year ) . Despite the use of a mean daily dose of 14.1 mg of diazepam equivalents , there were notable residual symptoms of anxiety and depression present at intake ( Hamilton Rating Scale for Anxiety score , 17.0 ; Hamilton Rating Scale for Depression score , 14.0 ) . Benzodiazepine intake was stabilized for 3 weeks before double-blind assignment to placebo ( n = 47 ) , or continued benzodiazepine use ( n = 10 ) . Clinical assessment s were performed daily , including  benzodiazepine plasma levels . Depending on the outcome criteria used , anywhere from 58 % to 100 % of patients were judged to have experienced a withdrawal reaction , with a peak severity at 2 days for short half-life and 4 to 7 days for long half-life benzodiazepines .  Relapse onto benzodiazepines  occurred in 27 % of patients who were receiving long half-life benzodiazepines and in 57 % of patients who were receiving short half-life benzodiazepines . Baseline predictors of relapse were nonpanic diagnoses , a higher  benzodiazepine dose , and a higher Eysenck neuroticism score . A short half-life and higher daily doses were associated with greater withdrawal severity , as were personality traits , such as dependency and neuroticism , less education and higher baseline levels of anxious and depressive symptoms . Patients who were able to remain free of benzodiazepines for at least 5 weeks obtained lower levels of anxiety than before benzodiazepine discontinuation . These results provide a detailed picture of the symptoms , time course , and multidimensional determinants of the benzodiazepine withdrawal syndrome 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 Ninety-eight out patients with major depressive disorder were treated with alprazolam , imipramine , or placebo in a 6-week , double-blind study . Average doses were 3.67 mg of alprazolam and 167 mg of imipramine , given at bedtime . Fifty percent of patients taking alprazolam , 38.2 % taking imipramine , and 17.7 % receiving placebo improved their HAM-D scores by more than 50 % . Eight patients on imipramine , 6 on alprazolam , and 1 on placebo dropped out because of side effects . The most common side effects for imipramine were tachycardia , constipation , light-headedness , and sedation ; common side effects of alprazolam were light-headedness , sedation , and unsteadiness 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 We compared the effect on withdrawal severity and acute outcome of a 25 % per week taper of short half-life vs long half-life benzodiazepines in 63 benzodiazepine-dependent patients . Patients unable to tolerate taper were permitted to slow the taper rate . Ninety percent of patients experienced a withdrawal reaction , but it was rarely more than mild to moderate . Nonetheless , 32 % of long half-life and 42 % of short half-life benzodiazepine-treated patients were unable to achieve a drug-free state . The most difficulty was experienced in the last half of taper . Baseline personality , high Eysenck neuroticism , female sex , and mild-to-moderate alcohol use were found to be more significant predictors of withdrawal severity than the daily benzodiazepine dose or benzodiazepine half-life . These findings suggest that personality factors contribute significantly to the patient 's difficulties with gradual benzodiazepine discontinuation of therapeutic doses of benzodiazepines Despite the fact that there is a high prevalence of depression among the elderly , little research on the efficacy of psychotherapy or pharmacotherapy with the elderly has been reported in the literature . This paper describes a sample of 18 elderly patients who received both psychotherapy and pharmacotherapy for the treatment of depression .  Psychotherapy involved weekly 30 - 50 minutes sessions of interpersonal psychotherapy with a treating psychiatrist . The drug treatment consisted of r and om assignment , double-blind , to either alprazolam , imipramine , or pill-placebo for six weeks . The focus of therapy was on the attendance , compliance , and symptomatic relief in elderly depressed patients , as well as on the major life problems identified by these patients in psychotherapy . Results indicated that elderly patients respond to community publicity regarding a psychotherapy treatment program . However , the majority are inappropriate referrals for diagnostic reasons . If accepted , elderly patients showed good compliance with drugs , and attendance was comparable to that in younger population s. The elderly patients responded well to treatment , with immediate and marked improvement on the Hamilton and Raskin Depression Scales , which was maintained after treatment . Grief and role transitions specific to life changes were frequent antecedents to depression in this elderly population and thus were the major foci in psychotherapy In this report , which is an up date of a guideline published in 2002 ( B and elow et al. 2002 , World J Biol Psychiatry 3:171 ) , recommendations for the pharmacological treatment of anxiety disorder , obsessive-compulsive disorder ( OCD ) and post-traumatic stress disorder ( PTSD ) are presented . Since the publication of the first version of this guideline , a substantial number of new r and omized controlled studies of anxiolytics have been published . In particular , more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs . The recommendations , developed by the World Federation of Societies of Biological Psychiatry ( WFSBP ) Task Force for the Pharmacological Treatment of Anxiety , Obsessive-Compulsive and Post-traumatic Stress Disorders , a consensus panel of 30 international experts , are now based on 510 published r and omized , placebo- or comparator-controlled clinical studies ( RCTs ) and 130 open studies and case reports . First-line treatments for these disorders are selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-noradrenaline reuptake inhibitors ( SNRIs ) and the calcium channel modulator pregabalin . Tricyclic antidepressants ( TCAs ) are equally effective for some disorders , but many are less well tolerated than the SSRIs/SNRIs . In treatment-resistant cases , benzodiazepines may be used when the patient does not have a history of substance abuse disorders . Potential treatment options for patients unresponsive to st and ard treatments are described in this overview . Although these guidelines focus on medications , non-pharmacological were also considered . Cognitive behavioural therapy ( CBT ) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders , OCD , and PTSD to support them being recommended either alone or in combination with the above medicines A 6-week double-blind comparison of the therapeutic efficacy of alprazolam and imipramine in 90 depressed psychiatric out patients revealed a significantly superior response to alprazolam in the first 2 weeks of treatment as measured by total scores on the Hamilton Rating Scale for Depression and the Brief Psychiatric Rating Scale . Further analyses revealed that all significant differences could be accounted for by the superior effect of alprazolam on sleep disturbance . By the end of Weeks 4 and 6 , no significant differences in therapeutic response between the two treatment groups were noted , with patients in both groups evidencing improvement on all measures . A differentially high dropout rate among patients in the imipramine treatment group posed a problem for interpretation of results in the latter weeks of treatment In a six week , double-blind , parallel study of alprazolam and amitriptyline hydrochloride in 130 out patients suffering from moderate to severe nonpsychotic depression , alprazolam was as effective as amitriptyline hydrochloride in relieving depressive symptoms and significantly more effective in relieving symptoms of anxiety and somatization . Alprazolam showed an earlier onset of activity in most measurements of efficacy and produced fewer side effects than amitriptyline hydrochloride .  Anticholinergic side effects were reported more frequently by patients taking amitriptyline hydrochloride , while drowsiness was reported more frequently by patients taking alprazolam . At the end of the study , the average daily doses were 2.4 mg alprazolam and 135 mg amitriptyline hydrochloride . The Hamilton Psychiatric Rating Scale for Depression , Hamilton Anxiety Rating Scale , Physician 's Global Impressions , Patients ’ Global Impressions , Hopkins Self-Rating Symptom Scale , and Symptom and Side Effects Checklist were evaluated at the end of weeks 1 , 2 , 3 and 6 to determine and compare the efficacy and safety of the two study drugs The authors analyzed the relative contributions of improvement in depressive and anxiety symptoms , as measured by the Hamilton Rating Scale for Depression ( HRSD ) and the Hamilton Rating Scale for Anxiety ( HRSA ) , respectively , after 1 week of treatment to the prediction of improvement in HRSD score after 6 weeks of antidepressant pharmacotherapy .  Fifty-six subjects completed 6 weeks of treatment with either desipramine ( n = 20 ) , alprazolam ( n = 18 ) , or a desipramine-alprazolam combination ( n = 18 ) . The results showed that early improvement in the HRSD was a moderately strong predictor of the total 6-week improvement in HRSD score , and a better predictor than early improvement in the HRSA . Partial correlations showed that early HRSD improvement was significantly related to total HRSD improvement within the alprazolam group . This pattern of response differed from those observed for the other treatment groups . Desipramine-treated subjects showed gradual improvement over the course of the study , and the improvement in week 1 was not so strongly predictive of overall improvement . The relationship between early and total HRSD improvement for the combination treatment group was intermediate to the other two groups . These findings are discussed in the context of the relationship between depression and anxiety , and potential implication s for the treatment of these overlapping and often mixed syndromes 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 A MAJOR aim of the present study was to examine the differential effects of chlorpromazine and imipramine among various depression subgroups . Tests were made of differential drug effects among Overall et al 's 1 three empirically derived depressive subtypes , ie , anxious , hostile , and withdrawn-retarded depressives . These investigators found a tranquilizer , thioridazine , best for their anxious depressives and imipramine best for the withdrawn-retarded depressives . An examination was also made of differential drug effects among psychotic depressives , neurotic depressives , and schizophrenics with depression . As there is a tendency in this country to equate psychotic depression with endogenous depression , study findings may have some relevance for the endogenous-neurotic distinction . Proponents of this distinction have reported that imipramine is especially efficacious for endogenous depression and of little value in neurotic depressions . 2 - 12 Finally , tests were made of differential drug effects among depressed patients categorized on the basis of sex and age ( below 40 and 40
target: 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: 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 .