Clinical Pharmacist Intervention to Engage Older Adults in Reducing Use of Alprazolam.

OBJECTIVE: To assess whether a letter explaining the risks of alprazolam can engage older adults to call a clinical pharmacist (CP) to initiate reduction in alprazolam use. DESIGN: Randomized, controlled study. SETTING: Integrated health care delivery system. PATIENTS: Patients 65 years of age and older who resided at home, had a current supply of alprazolam as of December 15, 2016, and had four outpatient dispensings of alprazolam during the previous 12 months. INTERVENTION: Patients were randomized to receive an educational outreach regarding alprazolam use reduction via a mailed letter (intervention group) or receive usual care (control group). Intervention patients/caregivers were requested to call the CP to discuss reduction of alprazolam use. For intervention patients who called and consented to participate, alternative treatment options were discussed on a case-by-case basis. MAIN OUTCOME MEASURES: Composite rate of 1) no alprazolam dispensing, 2) an alprazolam dose reduction, or 3) interchange to an alternative medication during the six-month follow-up. RESULTS: 153 and 173 patients were and were not, respectively, sent a letter. The mean age was 73 years and patients primarily were female. Thirty (19.6%) intervention patients called the CP. The composite rate was equivalent between the intervention (34.0%) and control (35.3%) groups (P = 0.822). In subanalyses, the composite rate was higher among intervention patients who did vs. those who did not call the CP (77.8% vs. 27.6%; P < 0.001). CONCLUSION: A low-cost patient educational outreach coupled with CP care efficiently engaged older adults in benzodiazepine use reduction process; however, alprazolam continues to be a challenging medication for patients to discontinue.

[Family malediction in the background of panic disorder -- case report]. / Családi átok a pánikzavar hátterében. Esetismertetés.

The author reports the combined treatment with pharmacotherapy and psychotherapy of a patient suffering from recurrent panic disorder. Respected the patient's subjective aspects, at the beginning there was only supportive therapy supplemented with autogenic training. At this time the treatment was aimed at anxiety reducing directly. Later, when the panic disorder returned, the therapy was completed with shorter periods of cognitive behavioral therapy. During these sessions the patient learned that the underlying, hidden causes of her mental disorders could be revealed, understood and coped with, thereby more permanent periods without symptoms could be achieved. During the last sessions of the treatment the patient herself recognised the main cause of her recurrent panic disorder: it was a sentence she was told by her relatives when she was 18, which acted as a malediction-sentence. After the identification and modification of the dysfunctional attitudes and basic assumptions related to the malediction-sentence the patient had no panic symptoms anymore and she gradually stopped taking her medication. This case report demonstrates that the underlying, deep-rooted psychic cause of panic disorder can be revealed and understood and by this way permanent asymptomatic state can be achieved. This case also strengthens the common knowledge that panic disorder can be treated most successfully if pharmacotherapy is combined with psychotherapy.

Efficacy of CBT for benzodiazepine discontinuation in patients with panic disorder: Further evaluation.

Despite its acute efficacy for the treatment of panic disorder, benzodiazepines (BZs) are associated with a withdrawal syndrome that closely mimics anxiety sensations, leading to difficulty with treatment discontinuation and often disorder relapse. An exposure-based cognitive-behavioral treatment for BZ discontinuation, Panic Control Treatment for BZ Discontinuation (CBT) targets the fear of these sensations and has demonstrated efficacy in preventing disorder relapse and facilitating successful BZ discontinuation among patients with panic disorder. In this randomized controlled trial, CBT was compared to taper alone and a taper plus a relaxation condition to control for the effect of therapist contact and support among 47 patients with panic disorder seeking taper from BZs. Based on the primary outcome of successful discontinuation of BZ use, results indicate that adjunctive CBT provided additive benefits above both taper alone and taper plus relaxation, with consistently medium and large effect sizes over time that reached significance at the six month follow-up evaluation. The efficacy of CBT relative to either of the other taper conditions reflected very large and significant effect sizes at that time. These findings suggest that CBT provides specific efficacy for the successful discontinuation from BZs, even when controlling for therapist contact and relaxation training.

[The withdrawal syndrome in benzodiazepine dependence and its management]. / Managementul sindromului de abstinenta in dependenta la benzodiazepine.

UNLABELLED: The authors present the result of an observational study about the withdrawal syndrome in benzodiazepine dependence, and the aspect of identifying withdrawal symptoms, effective communication with the patient and the structure of withdrawal programmes. MATERIAL AND METHOD: The study included a number of 22 pacients hospitalised in the Drug-Dependence Clinic of Iasi between January 2006 - December 2008. RESULTS: The present article consists of data covering current issues in the area of withdrawal syndrome in benzodiazepine dependence. The most prescribed benzodiazepines were diazepam (10 cases), followed by alprazolam (5 cases) and nitrazepam (4 cases). The clinical manifestations such as anxiety, insomnia, concentration problems, fatigability were present at all patients.

[Therapeutical strategies for essential tremor]. / Estrategias terapéuticas en el temblor esencial.

Essential tremor is the most common adult movement disorder. Traditionally considered as a benign disease, it can cause an important physical and psychosocial disability. Drug treatment remains poor and often unsatisfactory. Current therapeutical strategies are reviewed according to the level of discomfort caused by tremor: mild tremor, non-pharmacological strategies, alcohol, acute pharmacological therapy; moderate tremor, pharmacological therapies (propranolol, gabapentin, primidone, topiramate, alprazolam and other drugs), and severe tremor, the role of functional surgery is emphasized (thalamic deep brain stimulation, thalamotomy). It is also described the more specific treatment of head tremor with the use botulinum toxin. Finally, several points are exposed to guide the immediate research of this disease in near future.

Combining alprazolam with systematic desensitization therapy for dental injection phobia.

To determine whether a benzodiazepine facilitates systematic desensitization, 144 subjects with dental injection phobia received systematic desensitization in combination with placebo or one of two doses of alprazolam (0.5mg or 0.75mg). Systematic desensitization therapy included computer-controlled presentation of digitized video segments followed by in vivo exposure segments, culminating in an actual dental injection. Subjects advanced to the next hierarchy segment when low anxiety was reported during a segment. Alprazolam and placebo groups progressed at the same rate. The 0.75mg group had elevated heart rates while watching video segments compared with placebo. In a subsequent behavioral avoidance test (during which subjects were randomized to a new drug condition), there was no indication that state-dependent learning had occurred. Dental fear was reduced similarly in all groups for 1 year after study completion. No advantage was found to combining alprazolam with systematic desensitization for dental injection phobia.

Anticipatory anxiety in moderately to highly-anxious oral surgery patients as a screening model for anxiolytics: evaluation of alprazolam.

Alprazolam, a benzodiazepine anxiolytic, was evaluated in anxious patients prior to oral surgery. This population represents a possible acute screening model for novel anxiolytic agents. Healthy subjects, preselected for a moderate to high degree of dental anxiety based upon Corah's Dental Anxiety Scale, were enrolled in a three-arm parallel design study and randomly assigned to receive double-blind placebo (N=15), alprazolam 0.25 mg (N=16) or alprazolam 1 mg (N=16). Subjective self-reported anxiety was rated using the State Anxiety Inventory and visual analog scales. Objective measures included galvanic skin conductance, heart rate variability, blood pressure, pulse rate, and respiration. At 90 minutes after dosing, there were statistically significant (p<0.05) reductions compared with placebo in subjective anxiety and skin conductance mean level for the alprazolam-treated subjects. Changes from pre-dose (mean +/- SEM) at 90 minutes in the placebo, alprazolam 0.25 mg, and alprazolam 1 mg groups were -4.73 +/- 2.79, -13.75 +/- 2.49, and -12.81 +/- 2.32 for the State Anxiety Inventory and 5.44 +/- 6.71, -31.88 +/- 5.88, and -32.34 +/- 5.32 mm for analog anxiety scores. Corresponding skin conductance mean level at 100 minutes in the three groups (respectively) changed 0.64 +/- 0.24, -0.53 +/- 0.21, -0.71 +/- 0.22 microSiemens. The 0.25 mg and 1 mg dosages of alprazolam were not differentiated. Changes in heart rate variability, blood pressure, pulse rate, and respiration did not reflect subjective anxiety. Overall, the oral surgery anticipation anxiety model was found to be a sensitive test for benzodiazepine anxiolytic activity and may represent a potential screening model for evaluation of investigational agents.

New alternative agents in essential tremor therapy: double-blind placebo-controlled study of alprazolam and acetazolamide.

Propranolol and primidone are widely used, effective agents in essential tremor although they are not tolerated by all patients. In the present study, the effectiveness of alprazolam, a triazole analog of benzodiazapine class, and acetazolamide, a carbonic anhydrase inhibitor, were investigated as symptomatic treatments for essential tremor. We studied 22 patients with essential tremor in a double-blind, cross-over, placebo-controlled design. The patients received in random order alprazolam, acetazolamide, primidone and placebo for four weeks, each separated by a two-week washout period. The study demonstrated that alprazolam was superior to placebo and equipotent to primidone, whereas there was no statistically significant difference between acetazolamide and placebo. The mean effective daily dose of alprazolam was 0.75 mg and there was not any troublesome side effect reported by the patients on alprazolam. Alprazolam can be used as an alternative agent in elderly essential tremor patients who can not tolerate primidone or propranolol.

Double-blindness procedures, rater blindness, and ratings of outcome. Observations from a controlled trial.

BACKGROUND: We determined whether blindness in a double-blind randomized controlled trial of alprazolam and exposure therapies in patients with panic disorder and agoraphobia was maintained in assessors and patients, what were the factors related to "unblinding," and whether unblinding was associated with clinical outcome. METHOD: In 129 patients with panic disorder and agoraphobia who were randomized to alprazolam-exposure, placebo-exposure, alprazolam-relaxation, or placebo-relaxation conditions, blindness was tested at the end of treatment by the independent assessors' and patients' classification of the treatment condition. RESULTS: Assessors' classifications were correct in 82% of the alprazolam group and 78% of the placebo group; corresponding figures for patients' classifications were 73% and 70%, respectively. Factors associated with unblinding included drug side effects but not assessors' ratings of treatment outcome. CONCLUSION: Judgment of the validity of the outcome of a randomized controlled trial is easier if the report notes not only the use of a double-blindness procedure but also details how blind the raters remained and how any unblinding affected their ratings of clinical outcome.

Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder.

BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.

The role of personality factors and suggestion in placebo effect during mental stress test.

The aims of this study were first of all to document a placebo effect on systolic blood pressure and heart rate during mental arithmetic induced stress and secondly to assess the role of suggestion in producing this effect. Two types of placebo were used, a simple placebo and a placebo with an implied therapeutic action. Both were compared with alprazolam. A placebo response was seen in just over half of the volunteers when the cardiovascular changes to mental arithmetic induced stress in healthy volunteers were measured. This response appeared to be unaffected by the suggested therapeutic effect. Dominant, independent subjects, identified using the Cattell 16 PF personality test were less likely to respond to placebo. Alprazolam (0.5 mg) did not prevent, to a significantly greater degree than placebo, the systolic blood pressure or heart rate increases provoked by the mental stress.

Chronic benzodiazepine administration. IX. Attenuation of alprazolam discontinuation effects by carbamazepine.

Clinical studies suggest that carbamazepine may attenuate effects of alprazolam discontinuation. Since discontinuation of chronic alprazolam in a mouse model is associated with behavioral alterations and upregulation at the gamma-aminobutyric acidA (GABAA) receptor, we studied the effects of carbamazepine administration after alprazolam (2 mg/kg/day) discontinuation. Open-field activity was increased in mice 4 days after alprazolam discontinuation, but this effect was reduced significantly by continuous infusion of carbamazepine, 25 or 100 mg/kg/day. Benzodiazepine receptor binding in vivo was increased in cortex at 2 and 4 days after alprazolam discontinuation, and in hypothalamus at 4 days; with carbamazepine, 100 mg/kg/day, binding in both regions at these time points was similar to control values. Similar results were observed in cortex with benzodiazepine receptor binding in vitro. GABA-dependent chloride uptake was also increased at 4 days alprazolam administration. Treatment with carbamazepine attenuated (P less than 0.10) this increase. Carbamazepine alone after vehicle did not alter benzodiazepine binding or GABA-dependent chloride uptake. These results indicate that carbamazepine administration after alprazolam discontinuation attenuates behavioral and neurochemical alterations associated with discontinuation.