Venlafaxine is a serotonin-noradrenaline reuptake inhibitor (SNRI) that has no affinity for muscarinic, adrenergic or histaminergic receptors. In short-term trials, the adverse effects that occurred more often with venlafaxine than with placebo included nausea, somnolence, dizziness, dry mouth, and sweating. Rapid titration of the dose of venlafaxine to higher levels appeared, not unexpectedly, to be associated with an increased incidence of side effects. Side effects that appeared to be dose related included insomnia, nausea and sexual dysfunction. The incidence of nausea and dizziness was highest during the first 2 or 3 weeks of therapy and decreased rapidly thereafter. Somnolence also decreased over time. At high doses blood pressure increases were reported in a small percent of patients on venlafaxine and antidepressant drugs but were uncommon at the venlafaxine dose of 75–150 mg daily. Studies with venlafaxine in healthy volunteers indicate a low potential for drug-drug interactions. Overdoses have been reported in 14 of 3,082 patients administered venlafaxine in clinical trials, and no deaths were reported among these patients. Overdoses of venlafaxine induced mainly drowsiness and lethargy.

The present study describes the results of neuropsychiatric consultations in 70 institutionalized mentally retarded patients. On the basis of their major complaint, patients were assigned to eight overlapping categories. Diagnoses of a certain probability were established during multidisciplinary consensus meetings and classification was achieved according to ICD-10 criteria. In ten patients mental retardation was related to a specific syndrome; seizures or somatic comorbidity were present in 40 patients. The most frequent psychiatric diagnoses were: unspecified bipolar affective disorder (n = 14), depressive disorder (n = 6), impulse control disorder (n = 12), cycloid, transient, or schizoaffective psychotic disorder (n = 14), and (atypical) autism (n = 7). Recent history revealed a high occurrence of serious side effects of psychotropics or pharmacokinetic interactions. Appropriate pharmacological intervention resulted in an amelioration of the behavioural condition in about half of the patients. It is emphasized that psychiatric disorders frequently present with an atypical psychopathology and that stress- and anxiety-related disorders are most probably underdiagnosed.

All the HIV-infected patients having referred to our Liaison Psychiatry Service between October 1992 and June 1994 were considered in this study. Seventy patients underwent psychiatric assessment and medical/neurological evaluation. Forty-seven of these patients were also subjected to cognitive/neuropsychological examination by means of the Milan Overall Dementia Assessment (MODA). Depressive episodes, adjustment disorders and substance abuse were the most frequently encountered diagnoses. Taking into account neuropsychological data, we found that symptomatic patients performed worse on tests than did asymptomatic ones.

The different aspects of general safety of zolpidem are reviewed after analysing the safety data obtained in adults as well as in elderly patients. The low incidence of reported adverse events during the first three years of utilisation of zolpidem have corroborated the results of the clinical studies. The most frequent adverse effects are central nervous system (CNS) related but they can be largely prevented by respecting the recommended doses and prescription rules. In cases of acute overdoses, no severe complications have been attributed to zolpidem taken alone. In most of the studies carried out within the recommended treatment duration, abrupt treatment discontinuation was not associated with clinically significant rebound insomnia, and the available pre-clinical and clinical data indicate that the risk of abuse or dependence is minimal when prescribed according to the recommended doses of 10 mg in adults and 5 mg in elderly. Thus, with now well-established arguments on a large patient basis going in the same direction, the safety of zolpidem can authorise and justify its wide prescription in the short-term treatment of insomnia.

The aim of this study was to identify possible peripheral biological markers (both lipidic and hormonal) which can be easily used for the early detection of parasuicidal behaviour and to propose a predictive biological model of such behaviour. A case-control analytical study was undertaken at least 3 months after attempted suicide. Study was made of 128 patients who presented at the University General Hospital of Oviedo (Spain) with signs of self-intoxication. Lipidic and hormonal profiles were measured under basal conditions and comparison was made with a control group of healthy volunteer donors obtained from the Oviedo General Hospital blood bank. A discriminant analysis was later made with the aim of establishing a predictive biological model. This included the following variables: cholesterol, HDL-C, LDL-C and cortisol. Sensitivity and specificity were 62.5% and 65.6%, respectively. Replication and improvement of this model, through other prospective studies, could lead to the use of serum cholesterol and cortisol levels as inexpensive and readily available markers of suicide risk.

We have analysed the trial results obtained in two placebo and imipramine controlled double blind studies with a new psychotropic compound. Statistical analysis as outlined in the protocol showed a rather meagre therapeutic effect of imipramine of 1.53 points difference on HAMD-17 total score in comparison to placebo. In order to increase the discriminative power of the analysis we performed a post hoc analysis selecting centres that were able to detect a difference of at least two centres points between imipramine and placebo on HAMD-17 total score at week 6 (selective centres). All other were called nonselective. The analysis revealed that there were no statistically significant differences between the two types of centres concerning patient characteristics except that the nonselective centres recruited less patients with previous good response to antidepressant treatment. There was also some difference in drop out rates in the active treatment group wich might indicate different treatment strategies in the two groups of centres that participated in this trials.

The aim of this study was to determine whether schizophrenic patients' impairment in semantic verbal fluency tasks is due to difficulties in organizing their search or, in other words, in organizing output in terms of clusters of meaningfully related words. Consecutive association of words belonging to subcategories of the semantic task was defined as semantic clustering. A categorical verbal fluency task was first administered to 100 healthy subjects and then to 22 schizophrenic patients and 22 healthy subjects matched for sex, age and education. In the normal population, semantic clustering was found to be involved in word generation. A large number of semantic clusters indicated efficient organization of semantic knowledge and led to better word production. Schizophrenic patients showed impaired verbal fluency and generated a smaller number of semantic clusters than the control subjects. These findings point to a defect in self-initiation of semantic categorization in schizophrenia.

This study concerns the state of physical health and the availability of somatic care for 3,470 adult patients diagnosed as schizophrenic according to the research criteria established by the International Classification of Diseases (ICD-10 F20) and treated in public institutions. These institutions volunteered to participate in the study, whereas the patients were selected at random. Data concerning demographic characteristics, physical health, and access to somatic care are compared to that of a public health survey of a sample of the French population. The present study allows the estimation of ratios for a large number of diseases and of some risk factors among the target group. Heavy smokers and overweight individuals are more numerous among schizophrenics. Pathologies such as epilepsy, diabetes and AIDS infection are overrepresented. Patients' access to somatic care is more prevalent than that of the general population overall, similar to that of the less qualified workers or unemployed group. In this study, gender does not appear to allow prediction of care use for schizophrenics in contrast to the general population.

Mental health service delivery in the general health care sector is restricted with regard to understanding the magnitude and impact of mental illness in the medically ill (co-morbidity), as well as the significance of current mental health service delivery. A new model in development in the framework of a Biomed2 grant is presented. It consists of case-finding through complexity of hospital care prediction (COMPRI) followed by an integral health service needs assessment (INTERMED). It might serve to develop a more structural relation with the general health care sector for the management of mentally co-morbid high utilizing patients.

Is the onset of efficacy of antidepressants always delayed and which early clinical signs predict final outcome of therapy ? Our analyses show that strict response criteria produce necessarily later onset estimations rather than less strict ones. In two large-scale clinical samples we compared different estimation methods of the day of onset. Patients' direct ratings produced the earliest onset estimations. Because of the strong dependency of onset estimations on measurement methods, we argue that it is still open to debate, in which degree drug response is delayed. Concerning early clinical signs of final outcome we compared early changes of the Hamilton Rating Scale for Depression (HAM-D) items with several measures of final outcome. From the data we analyzed, there are no sufficiently precise signs of final outcome within the first 2 weeks of therapy.

A study of 128 consecutive patients with thromboembolic stroke in a rehabilitation hospital from July 1988 to September 1990 found a prevalence of major depression of 17%. The patient population was described according to the principles of the World Health Organization's (WHO) International Classification of Impairments, Disabilities and Handicaps (ICIDH) according to biological impairment, measured by computerized tomography (CT) scanning of the brain and side of hemiparesis and physical disability, measured by functional movement and activities of daily living. Handicap, referring to the interaction between disability and the environmental situation, often defined as the subjective disadvantage of being ill, was not measured in this study. A stroke index with four items was generated from the parameters describing biological impairment and physical disability. The psychiatric rating scales (the 17-item Hamilton Scale for Depression (HAM-D), the Melancholia Scale [MES]and the Newcastle Diagnostic Depression Scale), and the new stroke-index showed adequate coefficients of Cronbach's alpha and Loevinger, suggesting that these scales have both adequate item correlation and homogeneity (adequate hierarchical structure). The impairment disability index of stroke thus seems to be a meaningful measurement of the specific factors of this disease. There was no correlation between the stroke-index and the psychiatric rating scales measuring the emotional dimension of disability caused by the disease expressed as depression. The results suggest that the depression found among stroke patients is not a simple reaction to the physical disability of the stroke.

Valid information on the early course of schizophrenia is necessary for clinical and research purposes, for example, to determine the onset of the disorder. Since reports given by psychotic patients are questionable, relatives are often asked about their observations. In order to test the quality of these reports, the recollections of emerging symptomatology were assessed systematically from 30 recent onset, postpsychotic schizophrenic patients and from 69 informants (mostly their close relatives) by means of the Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS). Patient-informant agreement rates like kappa were compared between the relatives of every single case. Multiple regression analyses demonstrated that personality and attributional factors, particularly causal attributions and the image the informant has about him/herself and about the patient, determine the quality of the informants' reports. Highest kappas over all symptoms, for instance, were reached by relatives who described the patient as “dominant” and themselves as “reserved”, and who attributed the disease to current psychosocial stress. Long and close contact to the patient tends to impair the quality of reports.

Venlafaxine is a selective serotonin norepinephrine reuptake inhibitor with no activity at muscarinic, histaminergic or adrenergic receptors. The antidepressant activity of venlafaxine has been demonstrated in placebo-controlled and active comparator-controlled clinical trials. Venlafaxine was effective in outpatients and hospitalized patients with major depression and in those with melancholia, agitated or retarded symptoms, and refractory or treatment-resistant depression. Venlafaxine was at least as effective as comparative antidepressants and was more effective than fluoxetine or imipramine in some trials. A positive dose-response relationship has been shown with venlafaxine. When doses of venlafaxine are titrated rapidly upward, an onset of antidepressant action has been detected within one week in some studies. Venlafaxine is well tolerated during short- and long-term treatment. The most common adverse effects are nausea, somnolence and dry mouth. The overall tolerability of venlafaxine appears to exceed that of tricyclic antidepressants and compares favorably with that of selective serotonin reuptake inhibitors. Venlafaxine is a novel antidepressant that is appropriate for first-line therapy in patients with major depression.

The allergic reactivity of atopic type was investigated in 54 patients with mood disorders in the course of depressive episode and in 39 patients with schizophrenia. The assessment was done by three methods: intradermal tests, determination of IgE concentration and determination of specific immunoglobulin E (IgE) antibodies. The hypersensitivity to three or more allergens on intradermal tests was found in 40% of depressive and in 27% of schizophrenic patients. The concentration of IgE > 100 IU/mL was found in 45% of patients with depression and in 46% of patients with schizophrenia, more frequently in subjects with hyperactivity of hypothalamic-pituitary-adrenal axis, and in depression, in patients with higher intensity of symptoms. The positive results of the Phadiatop test which detects specific antibodies for inhalatory antigens, were found in 46% of depressive and in 40% of schizophrenic patients The indices of atopy for all three tests were higher in males than in females in both mood disorders and in schizophrenia. However, these indices were similar for unipolar and bipolar depressed patients as well as for patients with paranoid or residual schizophrenia.

Dysthymia clinical trials raise several methodological issues. The validity of the concept remains a matter of concern, as does the need for specific instruments, the difficulties in assessment of change and long-term assessments. Diagnostic criteria for inclusion should be used in a polydiagnostic approach. This paper summarises the main assessment tools and diagnostic criteria used in clinical trials on dysthymia. Severity criterion for inclusion could be a Hamilton Depression Rating Scale score (HAMD-17) between 13 and 17. The main response criteria should be a decrease of at least 50% of the total score on this scale and a final score under a predetermined limit. However, other response criteria may be useful: depression self-ratings, global assessments, general psychopathology assessments, personality and defense mechanisms, quality of life, psychosocial and functional impairment, diagnostic criteria (presence or absence) and side-effect assessment.

The aim of this study was to compare the efficacy, safety, and tolerability of sertraline and clomipramine in the treatment of obsessive-compulsive disorder (OCD). Outpatients with DSM-III-R defined OCD for 1 year or longer and scores of ≥ 20 on the YaleBrown Obsessive Compulsive Scale (Y-BOCS), ≥ 7 on the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH-OC), ≥ 4 on the Clinical Global Impression Severity of Illness Scale (CGI-S) and ≤17 on the Hamilton Depression Scale (17 item HAMD) were randomized to sertraline (n = 86) or clomipramine (n = 82) once daily for 16 weeks. Initial daily doses of sertraline and clomipramine were 50 mg. After a minimum of 4 weeks, these doses could be increased by 50 mg increments every 2 weeks to a maximum of 200 mg daily if the response was thought inadequate. Efficacy was assessed at the end of 1, 2, 4, 6, 8, 12 and 16 weeks of therapy using the Y-BOCS, NIMH-OC, CGI-S, CGI Improvement Scale (CGI-I) and Clinical Anxiety Scale (CAS). One hundred sixty-eight patients were randomized and received at least one dose of double-blind medication; 86 received sertraline and 82 clomipramine. Mean final daily doses at final visit were clomipramine 90 mg (efficacy evaluable patients 101 mg, completers 110 mg), and sertraline 129 mg (efficacy evaluable patients 132 mg, completers 136 mg). Mean baseline Y-BOCS, NIMH-OC and CGI-S totals were 27.7, 10.1 and 5.5, respectively, for sertraline and 27.4, 9.9 and 5.5, respectively, for clomipramine. Sertraline demonstrated greater efficacy than clomipramine in the intent-to-treat patient group: mean baseline to final visit changes were 50.8% (Y-BOCS), 41.9% (NIMH-OC) and 37.7% (CGI-S) for sertraline and 42.9% (Y-BOCS), 33.8% (NIMH-OC) and 30.0% (CGI-S) for clomipramine (P < 0.05). The number of patients withdrawing because of adverse events was substantially greater for clomipramine (26%) than sertraline (11%) (P < 0.05). The most frequent adverse events for clomipramine were dry mouth (20%), anxiety (17%), constipation (16%), nausea (15%) and somnolence (11%), and for sertraline, diarrhea (12%) and nausea (12%). In this study, sertraline was more effective than clomipramine in the intent-to-treat analysis. The difference in efficacy between the treatments is almost wholly accounted for by a greater number of clomipramine withdrawals due to the poor patient acceptance of clomipramine. The superior tolerability of sertraline and the lower rate of premature treatment withdrawal relative to clomipramine may offer considerable quality of life and compliance benefits in the long-term management of a chronic disorder such as OCD.

Evidence indicates that clozapine is effective in the management of treatment-resistant schizophrenia and in affective psychoses. To examine whether affective components within the boundaries of the schizophrenia spectrum imply specific psychopathological characteristics of response to treatment, 60 patients with a treatment-resistant schizophrenia spectrum disorder who were treated with clozapine (75–600 mg/d) were evaluated in a naturalistic, open, follow-up study. The group comprised 41 patients with and 19 without bipolar features (43 men and 17 women, mean age 34.3 years). Patients were evaluated with the Brief Psychiatric Rating Scale (BPRS) during the first year of treatment. The results show a significant improvement in scores in both groups (P < 0.001) compared with the baseline evaluation. A higher percentage of responders was seen in the ‘affective’ group. No typical psychopathological characteristic or symptom cluster predicting the response to treatment was identified. During the study, 15 patients discontinued treatment: six for lack of efficacy, five for non-compliance and four for adverse events. The study confirms the efficacy of clozapine in the treatment of schizophrenia spectrum disorders, particularly in patients with bipolar features.

Taking up the Bleulerian view of a clinical description based on a pathogenic model, we propose a rating scale for the assessment of communication disorders in schizophrenic patients. The scale consists of clinical items that could be the direct expression of the three hypotheses of cognitive dysfunction which have been postulated to explain communication dysfunction in these patients. We assessed the frequency of the 16 items in the scale in a total of 80 subjects (43 schizophrenic subjects, ten manic subjects, 17 depressive subjects and ten normal control subjects). The results of this study showed that this item schedule was specific to schizophrenic patients and, in particular, could statistically significantly discriminate schizophrenic patients from psychotic patients with affective disorder. The methodological qualities of the scale were explored and proved accurate, except for the reliability which is too low for some items and the item-to-total correlation which is too low for one item of the scale.

Traditional custodial care in mental hospitals has given way to brief hospitalizations and a variety of active inpatient treatment milieus, eg, therapeutic communities. But can only well-educated patients utilize this kind of complex, even demanding form of psychosocial care? A total of 1,538 patients and their first admissions from 1977 to 1993 at a closed therapeutic community ward at the Department of Psychiatry, University of Oulu (Finland) were assessed to analyze the association of the patient's educational level with some treatment and outcome characteristics. Educational levels were non-professional education (46% of all patients), lower professional (39%) and higher professional education (15%). There were no statistically significant differences in the treatment and outcome variables of patients in any educational level. The result indicates the achievement of one treatment goal on the therapeutic community model, ie, patient equality in spite of different educational status. This result may be especially important for less educated persons.