Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers.

OBJECTIVE: Fasedienol (PH94B) is a pherine compound formulated as a nasal spray that is hypothesized to regulate olfactory-amygdala circuits of fear and anxiety. Fasedienol's effect on the local electrogram of nasal chemosensory neurons (EGNR) and autonomic nervous system (ANS) responses versus steroidal hormones and controls in healthy adults is reported. METHODS: Eight males and 8 females randomly received aerosolized control (propylene glycol) and study drugs (fasedienol, 17ß-estradiol, progesterone, cortisol, and testosterone, 0.4 µg each in propylene glycol) onto the nasal septum mucosal lining at 30-min intervals over 2 sessions. EGNR was continuously monitored; autonomic parameters were recorded before and after administration. RESULTS: Fasedienol significantly increased EGNR amplitude (males: 5.0 vs. 0.6 mV, p < 0.001; females:5.7 vs. 0.6 mV, p < 0.001), and rapidly reduced respiratory rate (p < 0.05), heart rate (p < 0.01), and electrodermal activity (p < 0.05) versus control. EGNR and ANS responses after steroidal hormone administration were similar to control. 81% reported feeling less tense/more relaxed after receiving fasedienol, but not after receiving either control or steroidal hormones. CONCLUSIONS: Intranasal fasedienol, but not control or steroidal hormones, activated EGNR and rapidly reduced ANS responses, consistent with sympatholytic effects. Combined with subjective reports, results suggest fasedienol may provide acute relief in anxiety conditions.

Effect of an acute intranasal aerosol dose of PH94B on social and performance anxiety in women with social anxiety disorder.

OBJECTIVE: Although social anxiety disorder is a common and sometimes disabling condition, there are no approved treatments that can be used on an as-needed basis. The authors examined the acute use of PH94B, an intranasally administered neurosteroidal aerosol, for the acute management of the symptoms of social anxiety disorder. METHOD: The authors conducted a phase 2, multicenter, randomized, double-blind, placebo-controlled, single-dose study of PH94B. Ninety-one women 19-60 years of age with generalized social anxiety disorder received placebo intranasal spray (single-blind) 15 minutes before laboratory-simulated public speaking and social interaction challenges. Patients who experienced significant distress during at least one challenge returned 1 week later to receive either intranasal PH94B or placebo aerosol spray (double-blind) before repeat challenges. RESULTS: Patients who received PH94B during the second set of challenges had a significantly greater decrease in mean Subjective Units of Distress scores during the public speaking and social interaction challenges compared with the first set of challenges, than did patients who received placebo for both sets of challenges. A significantly greater proportion of the PH94B group were much or very much improved from the first to the second sets of challenges compared with the placebo group (75% and 37%, respectively). The side effects of PH94B were benign. CONCLUSIONS: PH94B may be a novel, effective, and well-tolerated acute treatment for performance and social anxiety in women with social anxiety disorder.

Ziprasidone monotherapy in bipolar II depression: an open trial.

BACKGROUND: The use of atypical neuroleptics for bipolar depression is currently being studied extensively. Given ziprasidone's favorable side effect profile as compared to other atypical neuroleptics, and the dearth of studies of this drug in depressed bipolar patients, we initiated an 8 week open monotherapy trial in bipolar II patients suffering major depressive episodes. METHOD: Patients met DSM IV criteria for bipolar II disorder, were in a major depressive episode, and had a 17 item HAM-D score of 18 or greater. Ziprasidone was begun at 20 mg bid and raised step wise to 60 mg bid if needed and tolerated. Change was assessed on the HAM-D (primary outcome measure), HAM-A, MADRS, YMRS, CGI-S, CGI-I, BDI and Q-LES-Q scales. Safety and tolerability were assessed. The study was approved by Asentral IRB and all patients gave written informed consent. RESULTS: Thirty patients (including 6 early terminators) completed the study. Significant improvement was seen at all visits on HAM-D, CGI-S and BDI (beginning week 1), and on MADRS and HAM-A (beginning week 2). Nine patients (30%) were responders and 5 (17%) remitters at week 1; 18 (60%) were responders and 13 (43%) remitters by the end of treatment. There was one serious AE's that was not study drug related, and no patient became manic. Occasional mild hypomania responded to dosage reduction. Mean end of study dose was 58 mg/day. LIMITATIONS: Given the small sample size and lack of placebo control, the results must be considered preliminary. CONCLUSIONS: Ziprasidone at a relatively low dose appears to be a rapid, effective and generally well tolerated treatment for bipolar II patients experiencing major depression. However, larger, placebo-controlled trials are needed to confirm these findings.

Comparative phenomenology of ataques de nervios, panic attacks, and panic disorder.

This article examines a clinical sample of 66 Dominican and Puerto Rican subjects who reported ataques de nervios and also psychiatric disorder, and disentangles the phenomenological experiences of ataque de nervios, panic attacks, and panic disorder. In-depth cultural interviews assessed the symptomatic phenomenology of ataque episodes from the local perspective as well as in terms of key panic features, such as recurrence, rapid peaking of symptoms, and lack of provocation. Independent diagnostic assessments of panic attacks and disorder were also used to establish the phenomenological overlap between ataque and panic. Our findings indicate that 36 percent of ataques de nervios fulfill criteria for panic attacks and between 17 percent and 33 percent for panic disorder, depending on the overlap method used. The main features distinguishing ataques that fulfill panic criteria from ataques that do not include whether the episodes were provoked by an upsetting event in the person's life and the rapidity of crescendo of the actual attack. A key finding is that ataques often share individual phenomenological features with panic episodes, but that these features usually do not "run together" during the ataque experience. This confirms previous findings that ataque is a more inclusive construct than panic disorder. The importance of these findings for the clinical diagnosis and treatment of persons with ataques is discussed.