Search

Aims and methodThere is very little research into the challenges of training in intellectual disability psychiatry or into interventions which may address these challenges. Using focus groups, we explored the experiences of intellectual disability psychiatry trainees, and evaluated a leaderless trainee support group developed in Bristol.ResultsFive distinct themes were identified via framework analysis: that trainees felt unprepared for the difference from previous posts; the need for support; the value of the group; that trainees were concerned about judgement in supervision; that the group structure was valued.Clinical implicationsOur findings highlight the support needs specific to intellectual disability psychiatry trainees. Leaderless peer support groups may be a valued resource to address such issues, and may be a useful model to be considered by other training schemes.

ur understanding of the natur eof anxiety has incr eased gr eatlydue to advances in research in thefields of neuroscience and psychol-ogy. It has been possible to distin-guish several different anxietydisorders each having distinct pat-terns of symptoms, such as panicdisorder, social anxiety disorder,post-traumatic stress disorder andgeneralised anxiety disorder. Effective treatments for anxietydisorders have been available forsome time, and in recent yearsadvances, both in drug researchand psychological therapies, haveallowed a range of treatmentoptions to be developed that can betailored to the individual patient. Panic disorder is the mostextensively studied of the anxietydisorders. It was first described inthe 1960s when it was observed thatpatients with panic attacksresponded to treatment withimipramine, while other anxiouspatients did not. Experimental models and par-adigms in animals and humanshave allowed the importantprocesses occurring during a panicattack to be identified. Evidencepointing to a role for brain chemi-cals such as serotonin, GABA andnoradrenaline has accumulated,and manipulation of these neuro-transmitter systems provides thebasis for drug therapy. For the patient pr esenting withpanic anxiety it should be possibleto provide a diagnosis, under-standing and ef fective treatment.

BackgroundThe importance of the neurotransmitter serotonin (5-HT) in the pathophysiology of anxiety is well known. A key role for postsynaptic 5-HT1A receptors has recently been suggested in studies of genetic knockout mice.AimsTo measure 5-HT1A receptor binding in patients with panic disorder in the untreated state and after recovery on treatment with selective serotonin reuptake inhibitors (SSRIs).MethodNine symptomatic untreated patients with panic disorder, seven patients recovered on SSRI medication and nineteen healthy volunteers underwent a single positron emission tomography (PET) scan using the 5-HT1A tracer [11C]WAY-100635.ResultsIn comparison with controls, both presynaptic and postsynaptic 5-HT1A receptor binding was reduced in untreated patients, with the most significant reductions being in the raphe, orbitofrontal cortex, temporal cortex and amygdala. In recovered patients presynaptic binding was reduced, but there was no significant reduction in postsynaptic binding.ConclusionsPanic disorder is associated with reduced 5-HT1A receptor availability, which is also known to have a key role in depression.

The long and sometimes controversial history of the use of drugs for the treatment of anxiety is at an interesting stage. As scientific advances develop our understanding of human anxiety, public interest in the field is growing and the range of therapeutic options is increasing. Long-standing controversies such as the relative merits of psychological therapies versus medication continue to be debated, and the role of medication is still challenged from some quarters (Nutt, 2003), but current practice guidelines draw on a solid research base and substantial clinical experience. This enables psychiatrists confidently to justify the treatment options they offer to their patients. This contribution describes the place of prescribing in the management of the anxious patient, outlines the main classes of anxiolytic drugs and summarizes prescribing guidance for the major anxiety disorders.

Studies of the correlation of subjective and objective sleep measures in depressed patients have produced mixed results so far. Further, they were carried out in sleep laboratories and tended to obtain one-off assessments, thus not taking into account the effect of treatment. We investigated forty (40) patients over the course of 8-week treatment of depression with either paroxetine or nefazodone. We used home polysomnography at baseline, nights 3 and 10, and week 8 of treatment, with extensive assessments of subjective sleep, the morning after each sleep recording. The patients were able to judge accurately their total sleep time and sleep onset latency, both before and during treatment. However, they were inaccurate in estimating the number of times they woke up during the night. Sleep satisfaction correlated negatively with Stage 1 sleep at baseline. Sleep quality was represented by a combination of subjective parameters measuring the ease of initiation and maintenance of sleep, and it appeared to derive from slow wave sleep and sleep continuity as seen in polysomnography. The partial discrepancy between subjective and objective measures suggests that a cognitive element is combined with the biological element to produce the sleep problems reported by depressed patients.

Background Sleep effects of antidepressants are important clinically and for elucidating mechanism of action: selective serotonin reuptake inhibitors disturb sleep and 5-HT2 receptor-blocking compounds may enhance sleep quality. Aims To compare the objective and subjective effects on sleep of paroxetine and nefazodone in patients with moderate to severe depression. Method Forty patients with depression were randomised to take paroxetine 20-40 mg/day or nefazodone 400–600 mg/day for 8 weeks. Objective and subjective quality of sleep and depression measures were assessed throughout. Results Nefazodone significantly increased objective sleep efficiency and total sleep time, and improved subjective sleep on days 3 and 10. Paroxetine decreased sleep efficiency early in treatment and some sleep disruption remained at week 8. Paroxetine but not nefazodone produced marked suppression of rapid eye movement (REM) sleep. Conclusions Nefazodone improves sleep in early treatment compared with paroxetine in patients with moderate to severe depression. These effects are seen within the first 2 weeks of treatment and diminish thereafter.

The aim of this study was to examine the effect of rapid tryptophan depletion (RTD) combined with a panicogenic challenge in patients with panic disorder who had responded to treatment with cognitive behavioural therapy (CBT). We hypothesised that RTD (compared with the control drink) would result in an increase in anxiety symptoms when provoked by a panicogenic challenge with the benzodiazepine antagonist, flumazenil. Nine patients with panic disorder who had responded to CBT received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design. In addition, they received flumazenil and placebo infusions on each day. Our hypothesis regarding the effects of RTD was supported by findings of a significant interaction between RTD and flumazenil on measures from visual analogues scales (total) and the Spielberger State Anxiety inventory. A somewhat unexpected finding was that in this group of CBT responders, the panicogenic effect of flumazenil was not completely blocked by treatment. This meant that although four of the nine subjects (44%) reported a panicogenic effect of flumazenil on the RTD day, this was not significantly different from the rate of panic attacks in response to flumazenil on the control day. We suggest that the partial return of symptoms in response to flumazenil reflects a vulnerability to RTD in this group of panic disorder patients who had responded to treatment with CBT.

Aim: The aim of this study was to measure GABAA benzodiazepine receptor (GBzR) sensitivity in alcohol-dependent patients and compare with matched non-dependent drinkers. Methods: Nine abstinent alcohol-dependent male patients, age matched with nine male non-dependent social drinkers, received an intravenous infusion of midazolam. Objective (saccadic eye movement slowing) and subjective (visual analogue scales) measurements were recorded at 15-min intervals for 2 h. Results: There were no differences in objective or subjective measures. Conclusions: Our hypothesis that patients with alcohol dependence would have less slowing of their eye movements in response to this challenge, reflecting reduced GBzR sensitivity, was not confirmed. The reasons for this could mean that GBzR function returns to normal with abstinence, or that this paradigm is unable to measure the subtle subtype-specific changes in GBzR sensitivity that occur following dependent alcohol use.

The psychometric tools used for the assessment of generalized anxiety disorder (GAD) either do not conform to the current concept of the condition or have important limitations. We aimed to develop and validate a new questionnaire for the assessment of symptom profile and severity of GAD. An original pool of potential scale items was subjected to a series of studies in non-clinical and clinical populations, in order to determine the final composition of the scale. The psychometric properties of the new scale, the Generalized Anxiety Disorder Inventory (GADI), were evaluated using a factor analytic model suitable for ordinal data and the Graded Response Model. The precision of measurement of the GADI was quantified through the item information functions. A total of 197 outpatients and 522 non-clinical subjects participated in four studies and completed the GADI. The final 18-item scale was derived from an original pool of 30 potential items. The GADI showed good reliability, convergent and divergent validity. The scale comprises three factors, relating to cognitive, somatic and sleep symptoms. It accurately distinguished GAD patients from non-patient controls. The cognitive factor also distinguished GAD from other anxiety disorders and depression. The GADI is a useful tool in the assessment of the breadth of symptoms and the severity of generalized anxiety disorder in clinical settings.

The partial agonist buspirone has a REM (rapid eye movement) suppressing effect on human sleep probably via a 5HT1A receptor in the pontine area. Eptapirone is a new 5HT1A agonist with a greater intrinsic effect than buspirone. The objective of this study was to examine the effects of eptapirone on sleep architecture, particularly REM sleep, in normal volunteers and compare it with buspirone and placebo. This was a randomized, double-blind placebo-controlled four-way crossover study in 12 healthy volunteers. Volunteers were screened to ensure that they had normal overnight sleep EEG (electroencephalogram) and were extensive CYP 2D6 metabolizers. Sleep was recorded on pairs of nights on four occasions, with medication being taken before the second night. Treatments were eptapirone 1.5mg at 10 AM, eptapirone 1.5mg at 11 PM, buspirone 20mg at 11 PM and placebo. Standard measures of sleep were derived and compared among the four treatments using ANOVA. REM sleep was significantly suppressed supporting the proposition that activation of post-synaptic 5HT1A receptors reduces REM sleep. Sleep fragmentation increased by both drugs. REM sleep suppression was significantly greater with morning eptapirone than with buspirone. Wakefulness in sleep was significantly greatest after morning eptapirone. REM sleep effects were greatest after evening eptapirone, suggesting a greater effect on central serotonin receptors than that of buspirone.

The diagnosis and management of anxiety disorders have evolved greatly during the past 50 years. For the clinician, a careful assessment of the patient is critical in formulating an appropriate treatment plan. Once a diagnosis has been made, a range of psychological and medical treatments are available. The authors suggest a structured classification of anxiety disorders according to their symptoms, and of drug therapies according to their mechanism of action. The evidence for effectiveness of medications in each of the major anxiety disorders is reviewed and a series of treatment algorithms are proposed. Likely future developments are considered. Keywords: anxiety; pharmacotherapy; antidepressants; benzodiazepines; serotonin; GABA-A; diagnosis

Background Tryptophan depletion studies have suggested that central serotonin (5-hydroxytryptamine, 5-HT) function mediates the therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) in depression and panic disorder. The present study tested the hypothesis that temporary reduction in central 5-HT transmission, through acute tryptophan depletion, could reverse the therapeutic effect of the SSRIs in social anxiety disorder (SAD) patients. Methods Fourteen patients with SAD who showed sustained clinical improvement with SSRI treatment underwent tryptophan depletion in a double-blind, placebo-controlled, crossover design, over 2 days 1 week apart. At the peak time of depletion, the participants also underwent three behavioral challenges: autobiographical script, verbal task, and neutral script. Psychological outcome was assessed with the Spielberger State Anxiety Inventory (STAI) Form Y-1 and visual analog scales (VAS) measuring anxiety, depression, and somatic symptoms. Results Anxiety was significantly increased on the depletion day compared with the control day, both on the STAI Form Y-1 and composite VAS score. Furthermore, there was a significant depletion × time interaction, explained mainly by the anxiogenic effect of the autobiographical script. In contrast, the verbal and the neutral tasks failed to differentiate between depletion and placebo. Conclusions Tryptophan depletion induced significant increase of anxiety in treated SAD patients, which was more prominent during the recital of an autobiographical script. This finding supports the notion that SSRIs improve social anxiety by increasing 5-HT availability. The autobiographical script seems to be a more robust challenge test for SAD than the stressful verbal task.

There have been numerous studies on the effects of caffeine on behaviour and cardiovascular function. It is now important to clarify the mechanisms that underlie such effects, and the main objective of the present study was to investigate whether changes in central noradrenaline underlie some of the behavioural and cardiovascular effects of caffeine. This was examined using a clonidine challenge paradigm. Twenty-four healthy volunteers were assigned to one of four conditions: (i) clonidine/caffeine; (ii) clonidine/placebo; (iii) placebo/caffeine; (iv) placebo/placebo. Baseline measurements of mood, cognitive performance, saccadic eye movements and cardiovascular function were recorded. Subsequently, volunteers were given either clonidine (200 μg) or placebo and consumed coffee containing caffeine (1.5 mg/kg) or placebo. The test battery was then repeated 30 min, 150 min and 270 min later. A second cup of coffee (with the same amount of caffeine as the first) was consumed 120 min after the first cup. The results showed that clonidine reduced alertness, impaired many aspects of performance and slowed saccadic eye movements; caffeine removed many of these impairments. Both clonidine and caffeine influenced blood pressure (clonidine reduced it, caffeine raised it) but the effects appeared to be independent, suggesting that separate mechanisms were involved. In addition, there were some behavioural effects of caffeine that were independent of the clonidine effect (e.g. effects on speed of encoding of new information) and these may reflect other neurotransmitter systems (e.g cholinergic effects). Overall, the results suggest that caffeine counteracts reductions in the turnover of central noradrenaline. This mechanism may underlie the beneficial effects of caffeine seen in low alertness states.

Background: The hypothalamo–pituitary–adrenal (HPA) axis is a major stress responsive system in humans. Although there are numerous ways of testing responsiveness of the HPA in experimental animals, this is much more difficult in man. Hypercapnea is a very stressful stimulus for humans and has been used as an anxiogenic probe in psychiatric patients. We have now investigated whether the simple challenge of a single 35% inhalation of CO 2 activates the neuroendocrine system as evidenced by changes in HPA activity, as well as cardiovascular and subjective responses, in healthy volunteers. Methods: Fourteen healthy male volunteers were recruited. They underwent single vital capacity inhalation of room air and 35% CO 2 , in a single blind fashion. Neuroendocrine, cardiovascular and subjective fear measures were taken at regular intervals. Results: CO 2 inhalation produced significant activation of the HPA axis in all subjects, as measured with plasma cortisol. Heart rate was decreased and systolic blood pressure was significantly increased shortly after the inhalation of CO 2 . The subjects reported short-lived symptoms of fear with the experimental gas. Conclusions: Single vital capacity inhalation of 35% CO 2 activated the HPA axis in healthy volunteers. It also had a significant cardiovascular and psychological (anxiogenic) effect, as expected from previous published studies. The test is potentially useful in studying the responsivity of the HPA axis in health and disease.

Selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in depression and anxiety disorders. This raises the question of how the single action of serotonin reuptake inhibition can improve several psychiatric conditions. In order to understand this apparent paradox it is necessary to consider where SSRIs act in the pathogenic process underlying depression or anxiety disorders. Tryptophan depletion has been used extensively in research into depression and has shown that, in patients receiving an SSRI whose depression is in remission, depleting serotonin leads to recurrence of the disorder. Similar results have been found for panic disorder. This suggests that increased levels of serotonin are necessary in the synapse for the SSRI to be effective in the treatment of depression and panic disorder. In obsessive compulsive disorder, depletion of serotonin in patients recovered on an SSRI does not cause relapse; receptor adaptation may be more important. Variations within the SSRI drug class, such as the selectivity ratios for serotonin versus noradrenaline uptake, elimination half-life, and affinity for the 5-HT2 receptor have been identified and may be important determinants of efficacy, side effects and clinical use.

The neurobiological basis of panic disorder has not been clearly established, although a role for serotonin (5-HT) has been postulated. It is clear that drugs which increase 5-HT neurotransmission are effective in treating the condition but how they do so remains a point of debate. The aim of this study was to determine if lowering brain serotonin activity using the technique of tryptophan depletion provoked a short-term relapse of panic symptoms in patients with panic disorder who had responded to drug treatment. Fourteen patients with panic disorder who had responded to treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design. In addition, they received an infusion of flumazenil (used as a pharmacological challenge) and placebo on each day. The tryptophan depleted drink produced an 87% reduction in plasma tryptophan concentration. Flumazenil produced a panic attack (defined by changes in the panic inventory) in seven out of 14 patients when tryptophan depleted and one out of 14 on the control day (p < 0.02). Three patients also experienced temporary depressive symptoms when tryptophan depleted, with no mood changes being seen on the control days. We conclude that rapid lowering of brain serotonin function can allow the precipitation of panic symptoms in response to flumazenil in panic disorder patients who have responded to treatment with an SSRI. This implies that in panic disorder increased 5-HT availability is important in maintaining the response to SSRIs.