The aim of this study was to investigate for the effects of valpromide on heart rate circadian rhythm in remitted recurrent unipolar and bipolar disorders (DSM-III-R). It consisted of a comparative, randomized, double-blind, repeated cross-over study of valpromide versus placebo over four four-week periods. The primary evaluation criteria was heart rate (HR). Secondary criteria comprised motor activity (MA) and the Bech and Rafaelsen mania assessment scale, Horne and Ostberg questionnaire, Montgomery and Asberg depression rating scale, Spiegel questionnaire, a sleep diary, and Clinical Global Impression. Fifteen patients were included, giving 60 one-month periods (30 valpromide periods and 30 placebo periods).

Cosinor analysis of HR and MA data revealed a difference in amplitude (P = 0.037, analysis of variance, one-tailed test).

The clinical sleep study shows that the duration of sleep was greater with valpromide than with placebo (P = 0.007, one-tailed test). Similarly, evaluation of the quality of sleep by patients themselves showed valpromide to be superior to placebo (P = 0.045, one-tailed test). The results of analysis of the Spiegel questionnaire also confirm the superiority of valpromide over placebo. Safety and compliance were comparable for the active drug and the placebo.

In conclusion, the relatively small sample size requires cautious interpretation of this study. Nevertheless, these initial results show a definite effect of valpromide on a biological rhythm that leads one to suppose that it may be effective through a ‘synchronizing’ effect.

The investigation of biological correlates of suicidal behavior is important for identifying high-risk subjects. The objective of this study was to examine the neurochemical variables' platelet MAO activity and urinary MHPG, 5HIAA and HVA, the main metabolites of noradrenaline, serotonin and dopamine, neurotransmitters that are considered to be involved in the pathophysiology of suicidal behavior, as well as plasma cortisol, in a group of subjects with adjustment disorder after a suicide attempt. Fifty-three patients, 42 females and 11 males, were included in the study and were compared to a group of 50 healthy controls, 25 females and 25 males. Platelet MAO activity was found to be significantly lower in both male and female patients compared to controls of the same sex (P < 0.001 for both comparisons). 5HIAA and HVA were not different between patients and controls, but MHPG was significantly higher in the patients group (P = 0.008). Moreover, plasma levels of cortisol were significantly higher in the patients compared to the controls (P < 0.001). Our results confirm the hypothesis of low platelet MAO activity as a biological characteristic of patients who attempt suicide. They also point to a possible parallel activation of the noradrenergic system.

P300 is an event-related brain potential (ERP) particularly interesting to the study of cognitive processes in normal subjects and in psychopathology. P300 has been applied in depression with controversial results. A major source for these controversial results could result from the diversity of depressed patients included in the different studies. Supporting this assumption, impulsivity, blunted affect, suicidal behavior and psychotic features significantly influence P300 amplitude. However, no data are available on the possible influences of the personality of depressed patients on P300. Since personality is related to P300 in normal subjects, the aim of the present study is to investigate the relationship between ERPs (P200, N200, and P300) and the Temperament and Character Inventory (TCI) in 54 depressed patients. The main results of the study concern the absence of major correlations between personality dimensions as assessed by the TCI and ERP parameters among depressed patients. Only weak partial positive correlations relate N200 latency with harm avoidance, and P300 amplitude (Pz) with the self-directedness dimension. N200 amplitude is also negatively correlated to persistence. However, the preliminary nature of the presented results with respect to the weak statistical significance should be underlined.

Certain studies on measures related to central neurotransmitter activity have demonstrated that in delusional (psychotic) depression there is a dopaminergic dysregulation which distinguishes it from non-psychotic depression. A neuroendocrinologic method to check the degree of DA receptor responsivity is by measuring the prolactin responses to acute intramuscular administration of haloperidol. We studied this possibility by applying the haloperidol test in seven delusional and ten non-delusional depressed patients. All patients met DSM-IV criteria for a major depressive episode, single or recurrent, with or without psychotic features. After a three-week washout period, 5 mg of haloperidol were injected i.m. and blood samples were taken at 0, 30, 60, 90 and 120 minutes. In both trials, significant time effects were observed (elevated prolactin levels, F = 11.36, P = 0.000). However, the prolactin responses to haloperidol did not differ significantly between the two patient groups (F = 0.12, P = 0.97). These data do not show a difference in D2 receptor responsivity, at least at the hypothalamus-pituitary level, between psychotic and non-psychotic depression.

In this multicentre study the two-year outcome of two groups of consecutive patients (total N = 106) with first-episode functional non-affective psychosis, both treated according to the ‘need-specific Finnish model’, which stresses teamwork, patient and family participation and basic psychotherapeutic attitudes, was compared. No alternative treatment facilities were available in the study sites. The two study groups differed in the use of neuroleptics: three of the sites (the experimental group) used a minimal neuroleptic regime whilst the other three (the control group) used neuroleptics according to the usual practice. Total time spent in hospital, occurrence of psychotic symptoms during the last follow-up year, employment, GAS score and the Grip on Life assessment were used as outcome measures. In the experimental group 42.9% of the patients did not receive neuroleptics at all during the whole two-year period, while the corresponding proportion in the control group was 5.9%. The overall outcome of the whole group could be seen as rather favourable. The main result was that the outcome of the experimental group was equal or even somewhat better than that of the control group, also after controlling for age, gender and diagnosis. This indicates that an integrated approach, stressing intensive psychosocial measures, is recommended in the treatment of acute first-episode psychosis.

Addiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.

Spontaneous remarks to the author concerning the experience of brief depressive episodes prompted an enquiry into the experience of these in the general population. The finding that a high proportion of subjects admitting to the experience of recurring brief depression, that the episodes were generally of less than 24 hours' duration, suggests that allowance should be made for such very brief episodes in future enquiry of the topic, as these would not be recognised by the criteria for recurrent brief depression in the ICD and DSM definitions. There was no association of duration of episode with either age or gender. There did not appear to be an association of episode duration with possible precipitants of stress, climatic conditions, season of year or dietary factors.

The objectives of the study were to assess lifetime prevalence of specific anxiety disorders, and their age of onset relative to that of eating disorders (ED), in a French sample of patients with anorexia nervosa (AN) or bulimia nervosa (BN). We assessed frequencies of seven anxiety disorders and childhood histories of separation anxiety disorder among 63 subjects with a current DSM-IV diagnosis of an ED, using the Composite International Diagnostic Interview (CIDI). Eighty-three percent of subjects with AN and 71% of those with BN had at least one lifetime diagnosis of an anxiety disorder. By far, the most frequent was social phobia (55% of the anorexics and 59% of the bulimics). When present, the co-morbid anxiety disorder had predated the onset of the ED in 75% of subjects with AN, and 88% of subjects with BN. Our results are consistent with those of studies conducted in other countries, and show that an anxiety disorder frequently exists before an ED. This has to be taken in consideration for successful treatment of patients with AN or BN.

Epidemiologic surveys show a high lifetime co-morbidity with psychiatric disorders (e.g., depression and anxiety) in alcoholics. However, alcoholics frequently complained about psychopathologic symptoms, particularly during alcohol withdrawal. There is some evidence that symptomatology decreases spontaneously with prolonged abstinence. Thus, the question arises whether high levels of psychopathology could be accounted for by withdrawal effects. This study was aimed at examining the impact of the alcohol withdrawal severity (assessed by the AWS scale) on psychopathologic symptoms. The psychopathologic profile of 110 alcoholics as measured by the Symptom Checklist-90 revised (SCL-90-R) was compared to that of 253 patients with adjustment, anxiety or depressive disorders (according to ICD-10 criteria). No relationship between the severity of alcohol withdrawal and psychopathology could be found which might hint at two different neurobiological processes underlying these phenomena. The comparison with patients suffering from depression or anxiety disorders revealed that the global symptom severity of alcoholics undergoing withdrawal was similar, but recovery was achieved more rapidly than in the other groups. On the other hand, the self-rated psychopathologic symptom profile of alcoholics was rather similar to that of patients with adjustment disorders. While about one-quarter of the alcoholics reported severe psychopathology on admission, only about 10% showed symptomatology at discharge about three weeks later, predominantly depression or anxiety. These results underline the notion that much of the psychopathology described by alcoholics decreases within 2–3 weeks after withdrawal without specific treatment.

Identifying the burden of care on relatives of the mentally ill remains an integral part of research in community psychiatric services. The present study aimed to assess the level and extent of burden on relatives in South Verona (northeast Italy). The South Verona catchment area provides a comprehensive, community-based psychiatric service with minimal reliance on the hospital. Patients were selected from the South Verona Psychiatric Case Register and 40 of their relatives were interviewed using structured assessments measuring objective burden, patient behaviour, coping strategies, satisfaction and needs for services. Both positive and negative aspects of burden were apparent, 92% of relatives continued to maintain contact with friends/relatives, 72% had no change to their family income, and 52% could manage any household disruptions during a crisis. The main negative effects for relatives included reduced leisure activities (57%) and psychological problems (67%). The greatest burden was on relatives of patients who were male (P = 0.016), unemployed (P = 0.013) and diagnosed with psychosis (P = 0.041). The implications of employment for patients and its association with lower levels of caregiver burden are discussed.

This study examines the relationship between duration of untreated psychosis (DUP) and long-term symptomatic and social outcome in 205 patients with schizophrenia, whose parents are member of a consumer organisation. We found only a tendency that longer DUP was related to negative symptoms, but no relation to other outcome domains. The results of this study do not support antipsychotic intervention at the earliest sign of psychosis in order to ‘protect the brain’.

Epidemiologic studies in the general population and those based on the clinical assessment of schizophrenic populations have revealed a high degree of overlap between schizophrenia and addictive disorders. The abuse of psychoactive substances (including alcohol) throughout life is so frequent (50%) that the possibility of a specific link inevitably arises. Various hypotheses have been suggested to explain the high co-morbidity between schizophrenia and addiction: 1) The social-environmental hypothesis has been developed but studies have provided poor evidence to validate it. 2) The possible shared biological vulnerability between schizophrenia and addictions led researchers to explore common genetic determinants and study the involvement of the dopaminergic and opioid systems in the aetiology of both schizophrenia and the abuse of and dependence on psychoactive drugs. 3) Finally, the theory of self-medication suggests that schizophrenics may be attempting to counter the deficit linked to their disorders by using the substances they take or their dependency-type behaviour to cope with their emotional problems. The clinical profile of schizophrenic addicts does seem to display some distinctive features, such as the high level of depressive co-morbidity, very high nicotine and alcohol dependence, with a very poor prognosis. These patients are difficult to manage; the possibility of pharmacologic interactions between the substances they are taking and neuroleptic medication calls for prudence, and their compliance is also poor. Addictive disorders in schizophrenics are currently a topic of active research intended to lead to identifying specific treatments. The early identification of addictive disorders in schizophrenics should make it possible to limit their development and improve the prognosis.

This study modelled the economic impact of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in the UK, as well as the costs related to discontinuation of antidepressant treatment.

Decision models of the management of moderate and severe depression were developed from clinical trial data, resource use obtained from interviews with general practitioners and psychiatrists, and published literature, and were used to estimate the expected direct National Health Service (NHS) costs of managing a patient with moderate or severe depression.

The expected cost of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment, irrespective of the initial treatment, was estimated to be £206 (range £50 to £504) over five months.

Using mirtazapine instead of amitriptyline for seven months increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%) and reduces the expected direct NHS cost by £35 per patient (from £448 to £413). Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for an additional cost to the NHS of £27 per patient (from £394 to £420).

In conclusion, this study suggests that mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine in the management of moderate and severe depression in the UK.

In a multicentre, double-blind, flexible-dose study, 199 patients with paranoid schizophrenia or schizophreniform disorders received haloperidol (10–30 mg/d) or amisulpride (400–1200 mg/d) for four months. More patients in the haloperidol group withdrew prematurely (44% vs 26%; P = 0.0077) due to a higher incidence of adverse events. Amisulpride was at least as effective as haloperidol in reducing the Brief Psychiatric Rating Scale (BPRS) total score (–27.3 vs –21.9) (non-inferiority test; P < 0.001). The PANSS positive score improved to a similar extent in both groups whilst improvement in the PANSS negative score was significantly greater with amisulpride (–10.5 vs –7.2; P = 0.01). The percentage of responders on the Clinical Global Impression scale was also significantly greater with amisulpride (71% vs 47%; P < 0.001). Both the Quality of Life Scale (QLS) and the Functional Status Questionnaire (FSQ) improved to a significantly greater extent under amisulpride. Haloperidol was associated with a greater incidence in extrapyramidal symptoms and with a greater increase in the Simpson-Angus score than was seen with amisulpride (0.32 vs 0.02; P < 0.001). In conclusion, amisulpride is globally superior to haloperidol in the treatment of acute exacerbations of schizophrenia and significantly improves patients’ quality of life and social adjustment.

Social phobia is increasingly recognized as a prevalent and socially impairing mental disorder. However, little data is available regarding the general and disease-specific impairments and disabilities associated with social phobia. Furthermore, most studies have not controlled for the confounding effects of comorbid conditions.

This study investigates: (a) the generic quality of life; (b) work productivity; and, (c) various other disorder-specific social impairments in current cases with pure (n = 65), comorbid (n = 51) and subthreshold (n = 34) DSM-IV social phobia as compared to controls with no social phobia (subjects with a history of herpes infections).

Social phobia cases reported a mean illness duration of 22.9 years with onset in childhood or adolescence. Current quality of life, as assessed by the SF-36, was significantly reduced in all social phobia groups, particularly in the scales measuring vitality, general health, mental health, role limitations due to emotional health, and social functioning. Comorbid cases revealed more severe reductions than pure and subthreshold social phobics. Findings from the Liebowitz self-rated disability scale indicated that: (a) social phobia affects most areas of life, but in particular education, career, and romantic relationship; (b) the presence of past and current comorbid conditions increases the frequency and severity of disease-specific impairments; and, (c) subthreshold social phobia revealed slightly lower overall impairments than comorbid social phobics. Past-week work productivity of social phobics was significantly diminished as indicated by: (a) a three-fold higher rate of unemployed cases; (b) elevated rates of work hours missed due to social phobia problems; and (c) a reduced work performance.

Overall, these findings underline that social phobia in our sample of adults, whether comorbid, subthreshold, or pure was a persisting and impairing condition, resulting in considerable subjective suffering and negative impact on work performance and social relationships. The current disabilities and impairments were usually less pronounced than in the past, presumably due to adaptive behaviors in life style of the respondents. Data also confirmed that social phobia is poorly recognized and rarely treated by the mental health system.