Sleep disorders are common in the general population and even more so in clinical practice, yet are relatively poorly understood by doctors and other health care practitioners. These British Association for Psychopharmacology guidelines are designed to address this problem by providing an accessible up-to-date and evidence-based outline of the major issues, especially those relating to reliable diagnosis and appropriate treatment. A consensus meeting was held in London in May 2009. Those invited to attend included BAP members, representative clinicians with a strong interest in sleep disorders and recognized experts and advocates in the field, including a representative from mainland Europe and the USA. Presenters were asked to provide a review of the literature and identification of the standard of evidence in their area, with an emphasis on meta-analyses, systematic reviews and randomized controlled trials where available, plus updates on current clinical practice. Each presentation was followed by discussion, aimed to reach consensus where the evidence and/or clinical experience was considered adequate or otherwise to flag the area as a direction for future research. A draft of the proceedings was then circulated to all participants for comment. Key subsequent publications were added by the writer and speakers at draft stage. All comments were incorporated as far as possible in the final document, which represents the views of all participants although the authors take final responsibility for the document.

The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic-like response to the gas either using the single or double breath 35% CO2 inhalation or 5-7% CO2 inhaled for 15-20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers. For this reason we have studied the effects of a higher concentration of CO2, 7.5%, given over 20 min. Twenty healthy volunteers were recruited to a double blind, placebo-controlled study where air and 7.5% CO2 were inhaled for 20 min. Cardiovascular measures and subjective ratings were obtained. When compared to air, inhaling 7.5% CO2 for 20 min increases systolic blood pressure and heart rate, indicating increased autonomic arousal. It also increases ratings of anxiety and fear and other subjective symptoms associated with an anxiety state. The inhalation of 7.5% CO2 for 20 min is safe for use in healthy volunteers and produces robust subjective and objective effects. It seems promising as an anxiety provocation test that could be beneficial in the study of the effects of anxiety on sustained performance, the discovery of novel anxiolytic agents, and the study of brain circuits and mechanisms of anxiety.

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The monoamine neurotransmitter serotonin (5-HT) has an important role in both the pathophysiology and treatment of anxiety and panic attacks.1,2 The strongest evidence that a specific abnormality of the serotonin system predisposes or contributes to anxiety comes from studies of the 5-HT 1A receptor. 'Knockout' mice bred without 5-HT 1A receptors in the cerebral cortex and limbic system show increased anxiety behaviours 3 and patients with panic disorder have been shown by challenge testing to have subsensitivity of these receptors. 4 Furthermore, the azapirone 5-HT 1A agonist buspirone is licensed for the treatment of generalised anxiety disorder in the UK. In a systematic review of 36 trials of patients treated for generalised anxiety disorder azapirones, including buspirone, were found to be superior to placebo in short-term studies (4-9 weeks). 5The development of select radiotracers for the 5-HT 1A receptor now allows a direct examination of this receptor system in living patients with panic disorder. Neumeister et al 6 reported the first full positron emission tomography (PET) study of 5-HT 1A binding in 16 unmedicated patients with panic disorder and 15 healthy controls. Regions of interest examined were limited to the anterior cingulate cortex, posterior cingulate cortex, anterior insula, mesiotemporal cortex, anterior temporopolar cortex and midbrain raphe -all areas of high 5-HT 1A binding. Lower 5-HT 1A binding occurred in anterior cingulate, posterior cingulate and raphe only in patients with panic disorder. Seven of the 16 patients with panic disorder had comorbid depression, although there was no difference in 5-HT 1A binding between the patients with panic disorder with comorbid depression and those without. The radiotracer used for Neumeister et al's study [18 F]-FCWAY, gives a reliable signal subcortically, but quantification in cortical areas is limited because of retained fluoride signal in bone. 7A further recent PET study using [11 C]WAY-100635 found reduced 5-HT 1A binding in social anxiety disorder. 8 That study compared 12 unmedicated male patients with social anxiety disorder with 18 healthy controls. Six of these patients had comorbid agoraphobia. Six regions of interest were examined a priorireduction of 5-HT 1A binding was found in the amygdala, anterior cingulate, insula, medial orbitofrontal cortex and raphe. After Bonferroni correction only the differences in the amygdala and anterior cingulate cortex remained significant. There was no significant correlation between state or trait anxiety scores and regional 5-HT 1A binding potential in both groups.In this study, we used the PET tracer [ 11 C]WAY-100635 which allows in vivo quantification of 5-HT 1A receptors with exquisite delineation and precision.9,10 Specifically, we wished to confirm the findings of Neumeister et al, 6 extend the findings to look at more regions of interest and finally examine the effect of SSRI treatment. Our specific hypothesis was that patients with panic disorder would have reductions in 5-HT 1A receptor ...

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