Panic, hyperventilation and perpetuation of anxiety.

1. Studies on the pathogenesis of panic disorder (PD) have concentrated on panic attacks. However, PD runs a chronic or episodic course and panic patients remain clinically unwell between attacks. Panic patients chronically hyperventilate, but the implications of this are unclear. 2. Provocation of panic experimentally has indicated that several biological mechanisms may be involved in the onset of panic symptoms. Evidence from provocation studies using lactate, but particularly carbon dioxide (CO2) mixtures, suggests that panic patients may have hypersensitive CO2 chemoreceptors. Klein proposed that PD may be due to a dysfunctional brain's suffocation alarm and that panic patients hyperventilate to keep pCO2 low. 3. Studies of panic patients in the non-panic state have shown EEG abnormalities in this patient group, as well as abnormalities in cerebral blood flow and cerebral glucose metabolism. These abnormalities can be interpreted as signs of cerebral hypoxia that may have resulted from hyperventilation. 4. Cerebral hypoxia is probably involved in the causation of symptoms of anxiety in sufferers of chronic obstructive pulmonary diseases. By chronically hyperventilating, panic patients may likewise be at risk of exposure to prolonged periods of cerebral hypoxia which, in turn, may contribute to the chronicity of their panic and anxiety symptoms. 5. Chronic hyperventilation may engender a self-perpetuating mechanism within the pathophysiology of PD, a hypothesis which warrants further studies of panic patients in the non-panic state.

"Saturday night fever": ecstasy related problems in a London accident and emergency department.

OBJECTIVES: To report on the extent and nature of acute MDMA (ecstasy) related problems presenting to a large London hospital's accident and emergency (A&E) department. METHOD: The computerised attendance records for all patients attending the A&E department over a 15 month period were retrospectively screened. Potential cases thus identified had their case notes systematically reviewed to confirm the history of MDMA use and to extract other relevant data. RESULTS: Forty eight consecutive MDMA related cases were identified. All were in the 15-30 year age group with the majority presenting in the early hours at weekends and having consumed the drug at a night club. The mean number of tablets consumed was two and almost 40% had taken MDMA before. Polydrug use was common with half of the sample having concurrently taken another illicit substance--most commonly other stimulants (amphetamines and cocaine). A wide range of adverse clinical features was found. The most common symptoms were vague and non-specific such as feeling strange or unwell, however many patients had collapsed or lost consciousness. The most common signs elicited were related to sympathetic overactivity, agitation/disturbed behaviour, and increased temperature. The more serious complications of delirium, seizures, and profound unconsciousness (coma) were commoner when MDMA was used in combination with other substances. CONCLUSIONS: For young adults presenting late at night at weekends and exhibiting symptoms of sympathetic overactivity, disturbed behaviour, and increased temperature ("Saturday night fever") the use of stimulant dance drugs especially MDMA should be suspected. As MDMA use does not appear to occur in isolation, the clinical picture is likely to be complicated by multiple rather than single drug ingestion. This poses increased diagnostic and management challenges for A&E staff who typically represent the front line response to dance drug related problems.

Panic patients in the non-panic state: physiological and cognitive dysfunction.

Panic attacks and the antipanic effect of antidepressants are claimed to distinguish panic disorder (PD) from generalised anxiety disorder. However, most studies showing neurochemical disturbances in PD overlook the non-panic state. We compared panic patients in the non-panic state with controls on biochemical, psychological and physiological measures. There were no differences on the neuroendocrine tests. Self-ratings of bodily and psychological symptoms of anxiety were significantly higher in patients and they scored worse on word recall. Patients had significantly more skin conductance fluctuations and slow wave activity in the electroencephalogram, a sign of hyperventilation which may have implications for brain activity. Discrepancies between patients' self-ratings and objective measures of pulse rate and psychomotor performance indicated that panic patients have distorted perceptions of both physical and mental functioning. Hyperventilation and cognitive distortions in the non-panic state may facilitate panic attacks and are part of the pathophysiology of PD.

A comparison of augmenting central serotonin and noradrenaline function in healthy subjects: implications for studies on the neurochemistry of anxiety.

Biochemical and psychophysiological effects of augmenting serotonergic and noradrenergic function were compared in 12 normal volunteers. Fluvoxamine (100 mg), a serotonin (5-HT) re-uptake inhibitor, maprotiline (75 mg), a noradrenaline re-uptake inhibitor, and placebo were given for 7 days each to each subject. Subjects were tested pre-drug on days 1, 4 and 8 of each treatment. Catecholamines in 24 h urine, 'platelet-rich' plasma 5-HT and hormones, EEG, auditory evoked response, skin conductance, and bodily and psychological responses were monitored. Augmentation of central 5-HT by fluvoxamine was demonstrated by the decrease of 5-HT plasma levels. Fluvoxamine also reduced urinary dopamine, indicating a decrease in dopamine metabolism in response to augmentation of 5-HT function. Decrease in pulse rate, loss of appetite and a mild arousing effect were also detected with administration of fluvoxamine. Thus, further investigations on the neuro chemistry of anxiety disorders should include the study of mechanisms of interaction of neurotransmitters.

Measurement of plasma serotonin by high-performance liquid chromatography with electrochemical detection as an index of the in vivo activity of fluvoxamine.

A reversed-phase high-performance liquid chromatographic method is described for the measurement of plasma serotonin concentrations. Sample preparation is by a simple solid-phase extraction using C18 columns. An isocratic separation is used with electrochemical detection. The application of the method to the measurement of plasma serotonin concentrations following the administration of fluvoxamine (a serotonin re-uptake inhibitor), maprotiline (a noradrenaline re-uptake inhibitor) and placebo to normal subjects for a seven-day period is reported. Fluvoxamine significantly decreases plasma serotonin over this time period in a linear fashion. No effect on plasma serotonin was seen for maprotiline or placebo. Plasma serotonin concentrations can be used to monitor compliance with fluvoxamine therapy.

The dexamethasone suppression test: its relationship to diagnoses, severity of depression and response to treatment.

1. The dexamethasone suppression test (DST) was applied to 40 depressed patients, 40 healthy volunteers and 40 patients with other psychiatric disorders. 2. The post-dexamethasone cortisol level, adopted as the non-suppression criterion and established locally, was 3.0 micrograms/dl. 3. The DST sensitivity in depression was 45%, with a specificity of 95% and a positive predictive value of 90%. 4. There was a significant correlation (r = 0.38, p less than 0.05) between HDRS scores of depressed patients and their post-dexamethasone cortisol levels. 5. A prospective study of the depressed group, which was assessed with three depression rating scales, showed differences between non-suppressors and suppressors regarding to the symptoms severity and response to the treatment. It suggests that an abnormal DST result could have a prognostic value to antidepressant drugs and ECT. 6. The DST specificity in depression was also calculated from its performance in the group with other psychiatric disorders, and their diagnoses as well as the abnormal DST results were critically discussed.

Depression assessment in Brazil. The first application of the Montgomery-Asberg Depression Rating Scale.

Cross-cultural investigation in psychiatry is revealing the need for standardised instruments in diagnosing and assessing depression. Recently, a new instrument was developed to evaluate depressed patients, namely the Montgomery-Asberg Depression Rating Scale (MADRS). The present study introduced the MADRS in Brazil, comparing it to the Hamilton Depression Rating Scale, the Visual Analogue Mood Scale (a self-rating scale), and with the global clinical assessment of independent Brazilian psychiatrists. The results show correlation between MADRS and the three other assessments, indicating that it is a useful and operational instrument to evaluate depressed patients. They also support the application of the MADRS in cross-cultural studies of depression in Brazil and other countries. These results are critically discussed.