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At least 19 recordsLinked to original sources

PubMed1987

Alprazolam: an antidepressant? Alprazolam, desipramine, and an alprazolam-desipramine combination in the treatment of adult depressed outpatients.

The antidepressant efficacy of alprazolam (ALP) was tested in a double-blind controlled comparison with desipramine (DMI) and an ALP-DMI combination in outpatients 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 endpoint 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 standard 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.

Adolescent↗

PubMed1992

Mechanism of immunosuppressive effect of alprazolam: alprazolam suppresses T-cell proliferation by selectively inhibiting the production of IL2 but not acquisition of IL2 receptor.

The purpose of this study was to elucidate the mechanism of action of alprazolam on concanavalin A (Con A)-induced murine T-cell proliferation. Splenic cells of BALB/c mice were first cultured with an optimum dose of Con A in the presence or absence of varying doses of alprazolam to assess effects of alprazolam on T-cell proliferation, interleukin 2 (IL2) production and IL2 receptor (IL2R) expression. Then, Con A-induced T-blast cells from BALB/c mice were cultured with an excess dose of human recombinant IL2 (rIL2) or crude rat IL2 supernate in the presence or absence of alprazolam to assess the effects of alprazolam on the interaction of IL2 and IL2R. The results of these studies clearly demonstrated that alprazolam can inhibit the T-cell proliferation in response to Con A but not to IL2. Alprazolam also reduced the production of IL2 by splenic T-cells, but did not alter the expression of IL2R on Con A-induced T-blast cells. Furthermore, the results also showed that (a) alprazolam did not inhibit the proliferative response of splenic T-cells to a combination of phorbol 12-myristate-13-acetate (PMA) and ionomycin, and (b) the addition of exogenous IL2 reversed the inhibitory effect of alprazolam on T-cell proliferation. Finally, the addition of alprazolam produced a time-dependent inhibiting effect on T-cell proliferation. However, this inhibitory effect of alprazolam was abolished when the drug was added to the cultures of competent cells that fully expressed IL2R. Taken together, these results suggest that alprazolam inhibits murine T-cell proliferation by affecting the mitogenic receptor-mediated events (initiation) rather than the IL2R-mediated events (progression) of ligand-activated T-cells through the cell cycle.

Alprazolam↗

PubMed1992

A fixed-dose study of alprazolam 2 mg, alprazolam 6 mg, and placebo in panic disorder.

A recently reported multinational, 8-week double-blind, placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam. We now report the results of a three-site, 6-week, double-blind, fixed-dose study comparing alprazolam 2 mg, alprazolam 6 mg, and placebo in 94 patients with panic disorder with or without agoraphobia. Both alprazolam treatment groups (6 mg and 2 mg) improved significantly more than did the placebo treatment group on most outcome measures. Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned, although the pattern of treatment response across measures suggested a dose effect. Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects, which may have contributed to the limited differences between groups at study end. The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder.

Adolescent↗

PubMed1990

In vitro and in vivo effects of the triazolobenzodiazepine alprazolam on hypothalamic-pituitary-adrenal function: pharmacological and clinical implications.

We report here a study of the effects of alprazolam on in vivo pituitary-adrenal function in jacketed nonrestrained nonhuman primates and on in vitro CRH release from rat hypothalami and ACTH release from rat dispersed anterior pituicytes. We undertook this study because alprazolam is the only benzodiazepine effective in treating both major depressive and anxiety disorders, and recent data suggest that the hypercortisolism of major depression reflects hypersecretion of CRH. Moreover, the intracerebroventricular administration of CRH can reproduce many of the components of the symptom complex of major depression, including not only hypercortisolism, but also hypothalamic hypogonadism, decreased libido, anorexia, and intense anxiety. As a comparison, we also assessed the effects of diazepam on in vitro CRH release, because in contrast to alprazolam, diazepam is effective in anxiety states but not in depression. Alprazolam (0.01-0.3 mg/kg, iv) produced a dose-dependent inhibition of both plasma ACTH and cortisol secretion in non-restrained adult male rhesus monkeys. Our in vitro studies showed that alprazolam significantly inhibited serotonin (5HT)-induced CRH release in a dose-dependent fashion (10(-10)-10(-5) M). Diazepam also inhibited 5HT-induced CRH release, but was 40 times less potent than alprazolam. Alprazolam was ineffective in blocking basal or CRH-induced ACTH release from rat dispersed anterior pituicytes, suggesting that its in vivo effects are through inhibition of CRH secretion. As expected, the inactive benzodiazepine ligand Ro 15-1788 inhibited the effects of alprazolam on 5HT-induced CRH release, but this occurred only at doses below 10(-7) M. Interestingly, when incubated alone in higher doses with our rat hypothalamic organ culture, Ro 15-1788, like alprazolam, produced a dose-dependent inhibition of 5HT-induced CRH release (10(-7)-10(-5) M), suggesting an agonistic action of Ro 15-1788 at the benzodiazepine receptor at higher concentrations. We conclude that alprazolam is capable of suppressing the primate pituitary-adrenal axis, and that this suppression most likely reflects suppression of the CRH neuron rather than of the pituitary corticotroph cell. We speculate that the enhanced capacity of alprazolam to suppress the CRH neuron relative to other benzodiazepines may contribute to its unique efficacy among this class of drugs in the treatment of major depression. The capacity of Ro 15-1788 to reverse alprazolam-induced suppression of the CRH neuron indicates that the effects of alprazolam are mediated at least in part via its interaction with the benzodiazepine component of the gamma-aminobutyric acidA macromolecular complex.

Adrenocorticotropic Hormone↗

PubMed1989

Intravenous alprazolam challenge in normal subjects. Biochemical, cardiovascular, and behavioral effects.

Alprazolam, a novel benzodiazepine derivative is thought to be effective in the treatment of anxiety, panic, and depressive disorders. There is considerable interest in alprazolam's mechanism of action, particularly whether its profile of actions might resemble that of the alpha 2 adrenoreceptor agonist, clonidine. The present study assessed the biochemical, cardiovascular, and behavioral responses of healthy volunteers to acute intravenous infusions of alprazolam and placebo. Alprazolam reduced ACTH and cortisol while increasing growth hormone. There was a transient reduction in plasma norepinephrine and only modest effects on cardiovascular parameters. Subjects became quite sedated after intravenous alprazolam. This pharmacodynamic profile resembles that previously reported for traditional benzodiazepines, although alprazolam may be a more potent stimulator of growth hormone release. Alprazolam's effects on growth hormone resemble those of clonidine, but unlike clonidine, alprazolam has relatively little effect on plasma catecholamine and cardiovascular parameters. This suggests that alpha 2 mechanisms do not play a primary role in alprazolam's mode of action. Since alprazolam infusion affects three different measures (ACTH/cortisol, growth hormone, and plasma norepinephrine) thought to be dysregulated in depression, challenge with intravenous alprazolam may prove to be a useful "probe" in affective disorders.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Urinary screening for alprazolam and its major metabolites by the Abbott ADx and TDx analyzers with confirmation by GC/MS.

Alprazolam is a short-acting triazolobenzodiazepine with anxiolytic and antidepressant properties. It has a half-life of 10-15 hours after multiple oral doses. Approximately 20% of an oral dose is excreted unchanged in the urine. The major urinary metabolites are alpha-OH alprazolam glucuronide and 3-HMB benzophenone glucuronide. The objective of this study was to characterize the reactivity of alprazolam and three metabolites in the Abbott ADx and TDx urinary benzodiazepine assays compared with the EMIT d.a.u. benzodiazepine assay. Alprazolam (at 300 ng/mL) gave an equivalent response as the 300 ng/mL low control (nordiazepam). alpha-OH alprazolam gave an equivalent response to this control between 300-500 ng/mL and 4-OH alprazolam between 500-1000 ng/mL. The 3-HMB benzophenone was not positive even at 10,000 ng/mL. The ADx screening assay was positive in 26 of 31 urine specimens collected from alprazolam-treated patients. All 31 of these specimens were confirmed positive for alpha-OH alprazolam by GC/MS after enzymatic hydrolysis and formation of a TMS derivative. For the TDx, 27 of 31 specimens were positive for benzodiazepines and all 31 were confirmed by GC/MS. All 5 of the negative ADx specimens and 4 of 5 TDx specimens contained 150-400 ng/mL of alpha-OH alprazolam. In conclusion, both the ADx and TDx urine benzodiazepine assays are acceptable screening assays for alprazolam use when the alpha-OH alprazolam concentration is greater than 400 ng/mL.

Alprazolam↗

PubMed1991

Efficacy and safety of alprazolam, imipramine and placebo in treating panic disorder. A Scandinavian multicenter study.

As part of the cross-national collaborative panic study, a double-blind comparison of alprazolam, imipramine and placebo was performed in Scandinavian outpatients with panic disorder according to DSM-III; 41 patients were randomly allocated to each drug. Doses were increased for 3 weeks to an average of about 6 mg alprazolam, 150 mg imipramine and a corresponding number of placebo capsules, which were then given for 5 weeks. No more than supportive psychotherapy was given. Key symptoms were rated weekly. The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months. Compliance at 3 weeks was 95% for alprazolam, 83% for imipramine and 88% for placebo; at 8 weeks 95% for alprazolam, 73% for imipramine and 46% for placebo. At 3 weeks plasma determination showed that the proportion taking diazepam outside the protocol was 0% for alprazolam, 19% for imipramine and 31% for placebo; at 8 weeks the corresponding proportions were 3%, 11% and 16%. Intention-to-treat analysis showed that freedom from panic attacks was obtained for 68% with alprazolam, 61% with imipramine and 34% with placebo. Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms. Globally rated by physicians and patients, about 60% had complete remission with alprazolam and imipramine and 30% on placebo. At least partial remission was obtained in about 85% with alprazolam, 70% with imipramine and 40% with placebo. Alprazolam had a more rapid onset of action than imipramine on all symptoms. Side effects were generally mild, with a preponderance of drowsiness for alprazolam and anticholinergic effects for imipramine. Tapering was uneventful without significant discontinuation phenomena. During taper and follow-up, several patients in remission relapsed, leaving approximately 30% patients in complete remission in all groups. To obtain more stable improvement, either long-term drug treatment or combinations of drug treatment and psychotherapy should be evaluated.

Adolescent↗

PubMed1992

Alprazolam in end-stage renal disease. II. Pharmacodynamics.

The sensitivity to the psychomotor and memory effects of alprazolam was evaluated in 12 normal subjects and 12 dialysis patients (seven patients receiving hemodialysis and five patients receiving continuous ambulatory peritoneal dialysis). Subjects received a single oral dose of 0.5 mg alprazolam, 2 mg alprazolam, and placebo in a double-blind, placebo-controlled, balanced, three-way crossover study with a Latin square design. After administration of the test drug, blood was obtained for alprazolam concentration and protein-binding determinations, and psychomotor performance, memory, and sedation were assessed. The maximum psychomotor impairment corrected for free alprazolam concentration was 5.0%, 8.2%, and 10.1% per nanogram per milliliter in normal subjects, patients receiving hemodialysis, and patients receiving continuous ambulatory peritoneal dialysis, respectively (p less than 0.01), after administration of 2 mg alprazolam. Free alprazolam concentrations at which 50% of maximum effect is elicited for psychomotor impairment were 10, 7.40, and 5.31 ng/ml in normal subjects, patients receiving hemodialysis, and patients receiving continuous ambulatory peritoneal dialysis, respectively. The maximum memory impairment corrected for the maximum free alprazolam concentration was 4.4%, 7.2%, and 8.9% per nanogram per milliliter, respectively (p less than 0.09), after administration of 2 mg alprazolam. Thus our group of patients receiving dialysis showed enhanced sensitivity to some psychomotor and memory effects of alprazolam.

Adult↗

PubMed1990

Evaluation of the interaction of lithium and alprazolam.

A potential pharmacokinetic interaction between lithium and alprazolam was studied in 10 normal subjects. Pharmacokinetic parameters were determined from the following regimens: single-dose alprazolam, multiple-dose lithium, and multiple-dose alprazolam with lithium. Steady-state alprazolam clearance during multiple dosing with lithium was not different from that with the single dose of alprazolam. Lithium renal clearance decreased when it was coadministered with alprazolam (31.2 vs. 22.4 ml/minute, p less than 0.05). There was a small but significant increase in the steady-state area under the curve for lithium in the presence of alprazolam (10.3 vs. 11.1 mEq/hour/liter). The small increase in the serum lithium concentrations and decrease in lithium renal clearance was probably the result of lower urine flow rates (1.46 vs. 0.98 ml/minute, p less than 0.05) with the combination of the drugs. This is supported by a weak but significant linear relationship between urine flow rates and lithium renal clearance (N = 57, r = 0.353, p = 0.007). The percent of daily lithium dose recovered at steady-state from the 24-hour urine collection decreased significantly from 93.6% to 78.2% in the presence of alprazolam. This suggests that alprazolam may decrease lithium absorption. The results of this study do not support a definitive interaction of lithium and alprazolam and there is little clinical significance to the small rise in serum lithium concentrations.

Adult↗

PubMed1988

Alprazolam augmentation of the antipsychotic effects of fluphenazine in schizophrenic patients. Preliminary results.

Alprazolam was added, under double-blind conditions, to stable fluphenazine hydrochloride regimens in 12 symptomatic, chronically ill inpatients with schizophrenia. The addition of alprazolam was associated with significant, albeit modest, reductions in global psychosis, thought disorder, and paranoia ratings, with a return to pretreatment levels on discontinuation of alprazolam treatment. Improvement in "negative symptoms" such as emotional withdrawal paralleled the changes in "positive symptoms" but did not, in itself, reach statistical significance. There were no significant changes in group mean plasma levels of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol during alprazolam treatment, although group mean serum cortisol levels were significantly decreased by alprazolam treatment. Patients who responded favorably to alprazolam treatment were significantly more psychotic or anxious before treatment, were older, showed significant alprazolam-associated reductions in plasma levels of homovanillic acid, and had significantly more prominent prefrontal cortex atrophy on computed tomographic scans than patients in whom alprazolam was without therapeutic effect. These preliminary data, based on a small sample, suggest that some patients with schizophrenia who are only partially responsive to standard neuroleptic treatment may benefit from the addition of triazolobenzodiazepines, such as alprazolam.

Adult↗

PubMed1991

Alprazolam in end-stage renal disease: I. Pharmacokinetics.

In a double-blind, randomized, placebo-controlled study, the pharmacokinetics of alprazolam and its active metabolite, alpha-hydroxyalprazolam, were determined in 12 normal subjects and 12 dialysis patients [7 hemodialysis (HD) patients and 5 continuous ambulatory peritoneal dialysis (CAPD) patients]. Blood samples were collected over 48 hours after alprazolam 0.5 mg and alprazolam 2 mg administration. Alprazolam and alpha-hydroxyalprazolam concentrations and alprazolam free fraction were determined. The pharmacokinetics of alprazolam were similar in normal subjects and HD patients with the exception of higher free fraction in HD patients. Differences were detected, however, in the pharmacokinetics of alprazolam in CAPD patients when compared with normal subjects and HD patients. These differences included a higher free fraction and a lower apparent oral clearance and free clearance in CAPD patients than in normal subjects or in HD patients. There was also a tendency for a later Tmax and a longer elimination half-life in CAPD patients than in normal subjects or HD patients. Alpha-hydroxyalprazolam concentrations were less than 15% of corresponding alprazolam concentrations in normal subjects and dialysis patients. Thus, end-stage renal disease is associated with changes in absorption, distribution, and/or elimination of alprazolam.

Adult↗

PubMed1991

Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine.

The pharmacokinetic and pharmacodynamic effects of concomitant administration of alprazolam and fluoxetine were studied in this double-blind parallel study in 80 healthy, male volunteers. Subjects were randomly assigned to one of four treatment groups. Drug treatments consisted of 4-day regimens of 1 mg alprazolam four times daily, 60 mg fluoxetine every morning, 1 mg alprazolam four times daily and 60 mg fluoxetine every morning, and placebo four times daily. Psychomotor performance, mood status, and degree of sedation were evaluated at designated times. Combined administration of alprazolam and fluoxetine resulted in an approximate 30% increase in plasma alprazolam concentrations relative to plasma concentrations following the administration of alprazolam alone. There were no significant differences in fluoxetine or norfluoxetine plasma concentrations between the alprazolam/fluoxetine and fluoxetine treatments. Psychomotor decrements increased when fluoxetine was administered with alprazolam relative to alprazolam administration alone. Psychomotor performance of the fluoxetine treatment group was not significantly different from that of the placebo group. No significant changes were observed in mood status, and sedation was minimal in all treatment groups. As when any two psychoactive drugs are administered together, increased patient monitoring and patient education is recommended when alprazolam and fluoxetine are prescribed concurrently.

Adult↗

PubMed1987

Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects.

The relationships between alprazolam and metabolite concentrations and CNS effects were determined in a double-blind placebo controlled four-way crossover trial in 16 normal male volunteers. Active drug treatments consisted of 4-day regimens of 4 mg alprazolam PO daily as 2 mg bid., 1 mg qid, and 0.25 mg each hour. On days 1 and 4, the kinetics, sedative and psychomotor effects were evaluated. Plasma concentrations of the 4- and alpha-hydroxy metabolites of alprazolam were less than 10% of unchanged alprazolam levels on both days. Accumulation of these metabolites and alprazolam was dependent on alprazolam half-life (11.6 h). Acute and chronic tolerance to the sedative and psychomotor effects was observed with all active drug treatments. All alprazolam treatments resulted in significantly greater sedation than placebo on days 1 and 4. However, on day 4, sedation was 16-36% less than observed on day 1, despite plasma concentrations 1.4-2.76 times the day 1 concentrations. Sedation from alprazolam was reduced in each successive study phase, suggesting a tolerance which was sustained during the 10-day washout between phases. By day 4, psychomotor performance was not different from placebo, indicating more complete development of tolerance than occurred for the sedative effect. Sedation and psychomotor impairment on day 1 were greatest with 2 mg alprazolam bid. During the initiation of therapy, the patient will likely experience less sedation and psychomotor impairment with smaller, more frequent doses. Since tolerance develops to these effects, the advantage of more frequent dosing regimen dissipates by the 4th day.

Adult↗

PubMed1992

Antidepressant and anxiolytic effects of alprazolam versus the conventional antidepressant desipramine and the anxiolytic diazepam in the forced swim test in rats.

The antidepressant and anxiolytic effects of alprazolam were compared to those of desipramine, diazepam and buspirone in the forced swim test. Subchronic alprazolam induced a reduction in immobility similar to that of desipramine in 'non-pretested' and 'pretested' rats. In 'non-pretested' rats, the anti-immobility effect of desipramine was potentiated by diazepam and alprazolam, given before subchronic desipramine, while the anti-immobility effect of subchronic alprazolam was counteracted by diazepam. Diazepam, administered before the pretest session, counteracted, 24 h later, the anti-immobility effect of subchronic desipramine and alprazolam; alprazolam counteracted the anti-immobility effect of alprazolam but not of desipramine, buspirone at the highest doses tested potentiated the anti-immobility effect of subchronic desipramine but not of alprazolam. These data provide further support for the hypothesis that the GABA/benzodiazepine/Cl complex is directly implicated in the action of antidepressants and that systems other than the GABA system are involved in the antidepressant and anxiolytic effects of alprazolam.

Alprazolam↗

PubMed1985

A comparison of the safety and efficacy of alprazolam and desipramine in moderately severe depression.

Fifty-four patients (34 outpatients, 20 inpatients) 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 outpatients and inpatients, 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 (outpatients, inpatients, or both groups combined) on any of the subjective or objective psychometrics used in this study. Clinically, only twelve of thirty-four outpatients (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 outpatients 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 inpatients. Alprazolam appeared well-tolerated by most subjects although drowsiness was a common--and at times serious--medication side effect.

Adult↗

PubMedDate not supplied

The pharmacology of alprazolam: a review.

Alprazolam is the product of the incorporation of the triazolo ring into the benzodiazepine structure. More than 90% of alprazolam is absorbed after an oral dose; the absorption rate is dose independent. After a single oral dose of 0.5 to 3 mg of alprazolam, peak plasma concentrations of 7 to 40 ng/ml are reached at 0.7 to 2.1 hours after administration. Factors such as liver and kidney disease, smoking, age, sex, and obesity have minimal effects on alprazolam pharmacokinetics. A review of alprazolam-drug interactions revealed few that were clinically significant, except that cimetidine and oral contraceptives reduce alprazolam clearance and increase its half-life. The mechanisms of action of alprazolam are reviewed. Its anxiolytic effect is similar to that of other benzodiazepines, but the basis of its other effects is less clear. Like other benzodiazepines, it has a good ratio of efficacy to side effects; its most common side effect, mild sedation, occurs early in treatment. The potential of dependence to and abuse of alprazolam and its toxicity are similar to that of other benzodiazepines. Finally, alprazolam's therapeutic role as an anxiolytic and anti-depressant and its use in the management of panic attacks, agoraphobia, schizophrenia, cancer, the premenstrual syndrome, and anxiety and as a cardioprotective agent are assessed.

Agoraphobia↗

PubMed1990

Unusual behavioral profile of alprazolam in squirrel monkeys.

Alprazolam was studied for its effects on schedule-controlled behavior of squirrel monkeys. Monkeys responded by pressing a lever under fixed-ratio or two separate fixed-interval (FI) schedules. Responding was maintained by the presentation of food under all three schedules and was suppressed under one of the FI schedules by electric shock. Unlike lorazepam, alprazolam did not increase rates of either suppressed or nonsuppressed responding under the two FI schedules after acute administration. When given for 3 (at 0.03 mg/kg) or 11 (at 0.1 mg/kg) consecutive days immediately before test sessions, alprazolam also did not increase suppressed responding. Under all three schedules, alprazolam (0.03-3.0 mg/kg) produced dose-dependent decreases in response rate. The rate-decreasing effects of alprazolam were attenuated by drugs known to have benzodiazepine (BZ) antagonist action: Ro 15-1788 (0.01 and 0.3 mg/kg), Ro 15-4513 (0.01 and 0.1 mg/kg) and 3-(methoxycarbonyl)amino-beta-carboline (10.0 and 30.0 mg/kg). These latter drugs alone either had no effect on or decreased fixed-ratio responding. Alprazolam also was tested in combination with lorazepam under the two FI schedules. In general, low doses of lorazepam, equal to or less than those having little effect on response rate when given alone, increased suppressed and nonsuppressed responding when combined with low to moderate doses of alprazolam. The results show that although the rate-decreasing effects of alprazolam probably are due to actions at BZ recognition sites, alprazolam alone does not have typical BZ-like agonist effects on FI responding; it did, however, potentiate the behavioral effects of lorazepam.

Alprazolam↗

PubMed1988

Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. III. Discontinuation effects.

Preliminary reports of discontinuation of alprazolam therapy in patients with panic disorder have revealed worsening of symptoms despite gradual withdrawal of medication. In this study, 126 patients with panic disorder and phobic avoidance received either alprazolam or placebo in doses of 2 to 10 mg daily for eight weeks. The medication was tapered over a period of four weeks, and patients were observed for another two weeks after all medication was discontinued. Sixty of the 63 alprazolam-treated patients and 49 of the 63 placebo-treated patients entered the taper and discontinuation study. After improvement in the active treatment period, the alprazolam-treated group had significant relapse between the first and last week of taper. However, during the second postdiscontinuation week, outcome scores were not significantly different from those of the placebo-treated group who did not deteriorate during taper. Twenty-seven percent of the alprazolam-treated group reported a rebound of panic attacks during taper and 13% reported a rebound of anxiety on the Hamilton Anxiety Scale. No serious or life-threatening withdrawal symptoms were reported, but distinct, transient, mild to moderate withdrawal syndrome occurred in 35% of the alprazolam-treated group and in none of the placebo-treated group. The coexistence of symptom rebound and a withdrawal syndrome occurred in 10% of the alprazolam-treated group, but both subsided by the end of the second week without alprazolam. We recommend that patients with panic disorder be treated for a longer period, at least six months, and that medication be tapered over a more prolonged period, at least eight weeks, especially where high doses are employed.

Adult↗