Influence of single-dose quetiapine on fear network activity - A pharmaco-imaging study.

OBJECTIVE: Anxiety disorders are among the most frequent psychiatric disorders. Current treatment guidelines recommend antidepressants, the calcium modulator gabapentin, and benzodiazepines as pharmacological treatments. However, delayed onset of action precludes the use of antidepressants as an acute treatment, while benzodiazepines can be recommended only as an emergency treatment due to their inherent risk of dependence. Therefore, an alternative pharmacological agent with acute efficacy is needed. Preliminary evidence points towards possible anxiolytic properties of the atypical antipsychotic quetiapine. The goals of this study were to test the acute anxiolytic properties of quetiapine in patients suffering from arachnophobia in a challenge paradigm, and to assess the effects of quetiapine on the central nervous fear network. METHODS: In a randomized, double-blind, placebo-controlled proof-of-concept study, n=58 arachnophobic patients underwent an fMRI scan while looking at phobia-related and neutral stimuli. Subjective anxiety was evaluated retrospectively in questionnaires. RESULTS: The functional imaging data revealed that patients showed stronger amygdala activation to phobia-related than to neutral stimuli. However, no effect of quetiapine on fear network activity was detected. Further, on questionnaire measures, quetiapine significantly reduced somatic anxiety symptoms, but had no effect on general psychological anxiety. CONCLUSION: Viewing phobic pictures resulted in a robust amygdala activation in arachnophobic patients. Quetiapine seems to have no influence on activation in anxiety-related brain areas but appears to reduce acute somatic anxiety symptoms in patients with specific phobia. The central nervous correlates of the anxiolytic effects of quetiapine remain to be clarified in future studies.

Contrast transcranial doppler ultrasound in the detection of right-to-left shunts : time window and threshold in microbubble numbers.

BACKGROUND AND PURPOSE: Cardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound (TCD) with the use of contrast agents and a Valsalva maneuver (VM) as provocation procedure. Currently, data on the appropriate timing of the VM, the use of a diagnostic time window, and a threshold in contrast agent microbubbles detected are insufficient. METHODS: Fifty-eight patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with injections of 10 mL of the commercial galactose-based contrast agent Echovist was applied in a randomized way: (1) no VM, (2) VM for 5 seconds starting 2 seconds after the beginning of contrast injection, (3) VM for 5 seconds starting 5 seconds after the beginning of contrast injection, (4) VM for 5 seconds starting 8 seconds after the beginning of contrast injection, and (5) repetitive short VMs in between 2 and 13 seconds after the beginning of contrast injection. In addition to the single tests, we also tested the sensitivity and specificity of combined results of the tests with VM. RESULTS: In 21 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt positive). Twenty-one patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 16 patients were only positive on at least 1 TCD investigation but negative during TEE. Test 3 was the most appropriate test when combined with the results of 1 of the other tests with VM. The highest sensitivities were achieved with a diagnostic time window of 40 seconds and when the presence of a single microbubble was sufficient for the diagnosis of a shunt. CONCLUSIONS: TCD performed twice with 2 provocation maneuvers with Echovist is a sensitive method to identify TEE-proven cardiac right-to-left shunts. The VM should be performed for 5 seconds starting at 5 seconds after the beginning of contrast injection.