Anxiolytics and memory: a comparison of lorazepam and alprazolam

Thirty healthy male volunteers participated in a double-blind, placebo-controlled study to investigate whether mild anterograde memory impairment is found after lorazepam has been taken for 5 days. The study compares the amnestic properties of lorazepam and alprazolam on immediate and delayed recall of word lists under the same conditions. Results suggest that individuals who take benzodiazepines will perform less well on an anterograde memory delayed recall task completed after dosing on the sixth day of treatment, but no similar difference will be found in performance on a similar task completed just before dosing on the sixth day. In addition, results suggest there is no significant difference between alprazolam and lorazepam on anterograde memory task effect. The chronic use of lorazepam 1 mg and alprazolam 0.5 mg had no effect on immediate recall of word lists, on the long-term recall of a word list already committed to memory, or on hand-eye coordination as measured in a standard way.     

Double-blind, placebo-controlled comparison of clonazepam and alprazolam for panic disorder

To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.     

Lactate vulnerability after alprazolam versus placebo treatment of panic disorder

Thirty-six patients with panic disorder underwent sodium lactate infusion before and after 8 weeks of treatment with alprazolam or placebo. With reinfusion, those patients panic-free with chronic alprazolam treatment displayed significantly decreased reactivity to lactate, as measured by subjective symptom ratings, duration of infusion before developing peak lactate-induced symptoms, and the proportion of patients experiencing lactate-induced anxiety or panic. Patients panic-free on placebo, as well as nonresponders to alprazolam treatment, displayed some, although less striking, decreases in reactivity to lactate with reinfusion. As a group, patients clinically unchanged with placebo treatment showed no systematic change in lactate response with reinfusion. Although the small numbers of patients in each treatment outcome group prohibit drawing definitive conclusions, these findings suggest that decreases in lactate-induced panic after successful alprazolam treatment of panic may result from a combination of changes in clinical state and direct effects of the medication.     

Psychopharmacological treatment of panic disorder and related states: a placebo controlled study of alprazolam

The paper consists of two parts. A review of the relationship of panic disorder to the phobic states and the treatment of these disorders by means of tricyclic antidepressants, MAOIs, beta blocking drugs and benzodiazepines. A double blind study of alprazolam and placebo in 118 patients with agoraphobia and panic is presented. In an eight week study alprazolam was found to be significantly superior to placebo in the treatment of panic attacks, phobic avoidance, anticipatory anxiety and general anxiety.     

Lorazepam vs. alprazolam in the treatment of panic disorder

Sixty-seven patients with panic disorder were treated with single-blind placebo for one week before being randomized to 6 weeks of double-blind treatment with either lorazepam or alprazolam. Both drugs showed significant and comparable antipanic efficacy throughout the course of the study. With the exception of sedative effects, both drugs were well-tolerated at a mean daily dose of 7 mg for lorazepam and 3 mg for alprazolam. Lorazepam appeared to be as effective as alprazolam in the acute treatment of panic disorder.     

Effect of alprazolam and diazepam on anxiety and panic attacks in panic disorder: a controlled study

Forty-eight patients currently experiencing panic attacks were randomly assigned to double-blind treatment with alprazolam, diazepam, or placebo. Efficacy was assessed using the Hamilton Rating Scale for Anxiety and a panic attack frequency rating scale. Results indicate that the two active treatments appeared equally effective in reducing both the frequency of panic attacks and the severity of generalized anxiety when compared with placebo. Overall, these data support the use of benzodiazepines in the treatment of panic disorder.     

Monoamine oxidase inhibitors and alprazolam in the treatment of panic disorder and agoraphobia

This article reviews the evidence on the efficacy of monoamine oxidase inhibitors (MAOIs) and of alprazolam in the treatment of panic disorder and agoraphobia. It also presents guidelines to the clinician on how to implement these treatments in practice.     

Patients with panic disorder unaccompanied by depression improve with alprazolam and imipramine treatment

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 subsample (N = 312) defined by multiple criteria to ensure the absence of depression and dysphoria. In both the overall sample and the nondepressed subsample, 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.     

Cognitive style, alprazolam plasma levels, and treatment response in panic disorder

This study investigated an anxiety-prone cognitive style (measured by the Anxious Thoughts and Tendencies Questionnaire, AT&T) as a predictor of the acute response to increasing alprazolam plasma levels in panic disorder. Panic disorder patients (n=26) were treated with escalating doses of alprazolam for 4 weeks, then a fixed dose of 1 mg four times a day for 4 weeks. At 0, 1, 2, 3, 4, 6, and 8 weeks, trough alprazolam plasma levels; clinical, self-report, and performance measures; and vital signs were assessed. Panic attack data were from daily diaries. The repeated response measures were analyzed in relation to alprazolam plasma levels using SAS GENMOD, with patients classified as high or low on the baseline AT&T. Panic attacks, anticipatory anxiety, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, and clinicians' global ratings improved with increasing alprazolam plasma levels. Hopkins Symptom Checklist-90 Anger-Hostility; Profile of Mood States Vigor, Confusion, and Friendliness; and speed and accuracy of performance worsened. Patients with high AT&T scores were worse throughout the study on situational panics, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, the Hamilton Rating Scale for Depression, and Clinical Global Improvement; most Hopkins Symptom Checklist-90 clusters; Profile of Mood States Anxiety, Depression, and Confusion; and Continuous Performance Task omissions. We conclude that in panic disorder: (1) alprazolam has a broad spectrum of clinical activity related to plasma levels in individual patients; (2) sedation, disinhibition, and performance deficits may persist for at least a month after dose escalation ends; (3) marked anxiety-prone cognitions predict more symptoms throughout treatment, but do not modify the response to alprazolam and therefore should not influence the choice of alprazolam as treatment.     

Drug treatment of panic disorder: the comparative efficacy of imipramine, alprazolam, and trazodone

Data from 74 patients with panic disorder were evaluated to determine the comparative efficacy of imipramine, alprazolam, and trazodone. All patients were treated with placebo for 3 weeks and were then blindly switched to active treatment for 8 weeks. Both imipramine and alprazolam were highly effective in reducing the symptoms of generalized anxiety, the frequency of panic attacks, and phobic avoidance. However, the time course of these effects differed; alprazolam demonstrated therapeutic properties during the first week, whereas the therapeutic efficacy of imipramine was not clearly apparent until the fourth week of treatment. Relative to imipramine and alprazolam, trazodone was not an effective treatment for panic disorder and was poorly tolerated; only 17 trazodone-treated patients completed at least 4 weeks of treatment, and only 2 patients were considered good or complete responders. These findings support the hypotheses that drugs that are efficacious in the treatment of panic disorders act by altering noradrenergic function and that drugs with primary actions on serotonin function are likely to be less effective treatments. The different time courses of therapeutic action of imipramine and alprazolam indicate that these drugs ameliorate panic anxiety via different mechanisms. The possible therapeutic applications of this observation are discussed.     

Discontinuation of alprazolam treatment in panic patients

Alprazolam treatment was tapered in 17 panic patients at a rate of 10% of the starting dose every 3 days. Only four subjects completed withdrawal on schedule (4-5 weeks); four additional subjects discontinued treatment in 7-13 weeks. During withdrawal 15 patients had recurrent or increased panic attacks and nine had significant new withdrawal symptoms. Most common among the latter were malaise, weakness, insomnia, tachycardia, lightheadedness, and dizziness. None had seizures, psychosis, or significant neurological or EEG abnormalities. Results indicate that relapse and withdrawal are important considerations in the choice of alprazolam treatment for panic attacks.     

Hypochondriacal concerns in panic disorder and major depressive disorder: a comparison

OBJECTIVE: To gain perspective on the relationship between hypochondriasis and panic disorder, we compared the occurrence of hypochondriasis in patients with panic disorder (N= 59) and major depressive disorder (N= 27). METHODS: Patients who participated in separate drug treatment trials were assessed at baseline and eight weeks using the Whiteley Index of Hypochondriasis. RESULTS: At baseline, the Whiteley Index score was greater for patients with panic disorder than for those with major depressive disorder. At eight weeks, a statistically significant reduction in the mean hypochondriasis score was observed in panic patients who had improved but not in major depressive patients who had improved. Modest correlations were observed between hypochondriasis and symptoms of panic and major depressive disorder, but in depressed patients, hypochondriasis was positively correlated with anxiety symptoms as well. CONCLUSION: A unique relationship appears to exist between hypochondriasis and panic disorder. The nature of this relationship and its implications for classification are discussed.