Some biochemical correlates of panic attacks with agoraphobia and their response to a new treatment.
ABSTRACT Thirty-two patients with chronic debilitating agoraphobia and panic attacks participated in a comparative study of the triazolobenzodiazepine alprazolam and the anti-inflammatory agent ibuprofen. After a 2-week placebo washout period, patients were randomly assigned to 8 weeks of treatment with alprazolam (2 to 6 mg/day) or ibuprofen (0.8 to 2.4 g/day). Medication was identically packaged and patients were blind to the treatment condition, but investigators were aware of which medication was dispensed. Alprazolam recipients (mean daily dose: 5.4 mg) improved markedly with respect to physician and patient global rating of disease severity, frequency and severity of panic attacks, and phobic anxiety target symptoms on the 90-Item Hopkins Symptom Check List. Ibuprofen recipients (mean daily dose: 2.13 g) experienced significantly less clinical improvement than patients on alprazolam. After 8 weeks of treatment, ibuprofen patients were crossed over to alprazolam, while the original alprazolam group continued on that drug. The daily dosage ceiling was increased to 10 mg. In the ensuing 4 weeks (mean daily alprazolam dose: 6.3 mg), all patients achieved comparably marked clinical improvement relative to baseline. Pretreatment plasma concentrations of platelet factor 4 and beta-thromboglobulin--two measures of platelet turnover and release--were significantly elevated in patients relative to normal controls. The elevated platelet factor 4 and beta-thromboglobulin normalized during treatment with both drugs. Alprazolam appears to produce rapid and specific clinical improvement in patients with severe agoraphobia and panic attacks and deserves further evaluation under double-blind conditions.
Archives of General Psychiatry 05/1988; 45(5):413. DOI:10.1001/archpsyc.1988.01800290027004 · 13.75 Impact Factor
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ABSTRACT: Summary Putative interactions between the specific a2-adrenoceptor antagonist idazoxan and benzodiazepines (BDZs) were examined in two different rat conflict models; Vogel's drinking conflict test (VT) and Montgomery's conflict test (MT) (the elevated +-maze). In the MT, idazoxan (0.031mg/kg) produced anxiogenic-like effects, which were counteracted both by the triazolo-BDZ alprazolam (APZ; 0.2mg/kg) and the conventional BDZ diazepam (DIZ; 0.2mg/ kg). In fact, the anxiolytic-like effects of APZ were significantly potentiated when co-administering idazoxan. A tendency to such a phenomenon was seen also in rats treated with DIZ and idazoxan. In the VT, the anxiolytic-like effects both of APZ (1.0 mg/kg) and DIZ (4.0 mg/kg) were significantly enhanced when co-administering idazoxan (1.0 mg/kg) in a dose not affecting the behaviorper se. Similar potentiating phenomena by behaviorally inert doses of a2-adrenoceptor antagonists (idazoxan 1.0 mg/kg; yohimbine 2.0 mg/kg) were seen with regard to the ataxic/sedative effects of the BDZs (APZ 0.25 mg/kg; DIZ 1.5 mg/ kg). The present results provide further support for the notion that the anxiolytic-like effects of BDZs are not related to attenuation of Locus Coeruleus activity. In addition, it is suggested that the potentiation caused by the a2-adrenoceptor antagonist is mediated via a noradrenaline induced increase in signal-to-noise ratio in target neurons of the brain noradrenergic system.Journal of Neural Transmission 01/1989; 76(3):191-204. DOI:10.1007/BF01260504 · 2.87 Impact Factor
Article: Optimum Treatment of Panic Disorder[Show abstract] [Hide abstract]
ABSTRACT: Panic disorder is characterised by the recurrence of acute, unpredictable panic attacks, with associated fear and physiological arousal. The disorder is very common among the general population and has a high rate of associated morbidity and mortality when not treated. Both pharmacological and psychological treatment approaches are effective in alleviating symptoms of panic attacks. Various psychological treatment approaches have been advocated, with cognitive-behavioural treatment the most systematically studied and applied. A wide range of pharmacological agents are useful in treating attacks, and differ primarily in adverse effect profile, latency of onset and potential for abuse or addiction. Available agents include tricyclic anti-depressants, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors and benzodiazepines. We consider long term use of SSRIs, in conjunction with benzodiazepines for the short term relief of symptoms, to be the optimum pharmacological management of panic disorder.CNS Drugs 01/1994; 2(3):208-215. DOI:10.2165/00023210-199402030-00005 · 4.38 Impact Factor