A long-term, multicenter, open-label study of risperidone in elderly patients with psychosis. On behalf of the Risperidone Working Group.

RATIONALE: Studies have shown that risperidone is safe and efficacious in young and middle-aged adults with chronic schizophrenia, but considerably fewer data are available on the treatment of elderly patients with schizophrenia or other psychotic disorders, particularly long-term outcomes. OBJECTIVE: A 12-month, open-label study was conducted to assess the effects of risperidone in elderly, chronically ill, psychotic patients. METHODS: This study enrolled 180 elderly, chronically ill, psychotic patients (median age, 72 years [range 54-89]), 97 of whom completed the 12-month study. At endpoint, the mean dose of risperidone was 3.7 mg/day. RESULTS: Clinical improvement (> or =20% reduction in Positive and Negative Syndrome Score [PANSS] total score) was achieved by 54% of patients at endpoint. There were significant reductions in PANSS total, subscale (positive, negative, and general psychopathology), and cognition cluster scores at endpoint (p<0.001). Clinical Global Impressions severity of illness scores showed continued improvement through month 12 (p<0.001). In contrast, PANSS data from a historical comparable control group of patients receiving conventional antipsychotic agents showed no symptom improvement over a 12-month treatment period. The severity of preexisting extrapyramidal symptoms (EPS) in patients treated with risperidone decreased significantly from baseline to endpoint (p<0.001), and the use of antiparkinsonian medication decreased from 41.1% of patients before the trial to 25.6% during the trial. There were no spontaneous reports of tardive dyskinesia (TD) and the incidence of assessed TD was 4.3% in contrast to the expected 26% reported in middle-aged and elderly patients receiving conventional antipsychotic agents for 1 year. CONCLUSIONS: Long-term treatment with risperidone was associated with continued symptom improvement, a decrease in the severity of preexising EPS, and a low incidence of TD in elderly psychotic patients.

Long-term treatment of chronic schizophrenia with risperidone: an open-label, multicenter study of 386 patients.

An open-label, multicentre study was conducted to assess the long-term efficacy and safety of risperidone in patients with chronic schizophrenia. Three hundred and eighty-six patients at 70 centres in 11 countries received risperidone (2-16 mg/day) for up to 57 weeks; 247 patients were treated for at least 1 year. All but 48 patients had been treated with antipsychotic agents before entering the trial. The mean (+/- SD) daily risperidone dose at endpoint was 8.6 +/- 4.4 mg. The mean total Positive and Negative Syndrome Scale (PANSS) scores were reduced significantly from 76.7 at baseline to 67.4 at endpoint (p < 0.001). Even though no patients had acutely exacerbated symptoms at the start of the trial, mean scores on each of the PANSS positive, negative, and general psychopathology subscales were significantly reduced during the first month of open treatment, and these mean scores continued to improve over the course of the trial. At endpoint, 64% of patients were rated as improved on the Clinical Global Impression change scale. Extrapyramidal symptoms (scores on the Extrapyramidal Symptom Rating Scale) tended to decrease in severity or remained unchanged over the course of risperidone treatment; 27.7% of patients required antiparkinsonian medication during the study. The results demonstrate that risperidone's efficacy against the positive and negative symptoms of chronic schizophrenia can be maintained in long-term treatment with a low incidence of adverse experiences; moreover, the drug reduces preexisting extrapyramidal symptoms over time.

Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive offsodes.

A 6-week, randomised, double-blind, multicentre study in 256 patients with a DSM-III-R diagnosis of major depression was carried out to compare the selective noradrenaline reuptake inhibitor (NARI), reboxetine, with the reference standard tricyclic antidepressant, imipramine. The efficacy of reboxetine, as measured by the extent of improvement of Hamilton Depression Rating Scale. Montgomery and Asberg Depression Rating Scale and the Clinical Global Impression Scale, was similar to that of imipramine. The improvement was observed in the overall population and in severely depressed and melancholic patients. Reboxetine tolerability compared favourably with that of imipramine. Frequency of discontinuation due to adverse events was lower in the reboxetine-treated group (10.0%) than in the imipramine-treated group (14.3%), and the cumulative risk of development (Kaplan-Meier analysis) of dry mouth, hypotension and/or related symptoms and tremor was significantly higher on imipramine than on reboxetine.

Moclobemide twice daily in the treatment of major depressive episode: a double-blind, multicenter comparison with different three times daily dosage schedules.

The data on a twice-daily dosage schedule with moclobemide in the treatment of a major depressive episode (MDE) is limited. In this randomized, double-blind, multicenter study, moclobemide, 150 mg twice daily, was compared with two different three times daily regimens with total daily dosages of 300 and 450 mg, respectively, over a 6-week period. Two hundred seventy patients were included, of whom 237 completed the study. The treatment groups were comparable with respect to demographic parameters and severity of depression at baseline. No clear differences between the treatment groups could be shown with respect to response on the Hamilton Rating Scale for Depression (HAM-D), the Zung Self Rating Scale, or the Clinical Global Impression of efficacy and severity. There was, however, a slightly higher response rate with respect to the anxiety/agitation subscale of the HAM-D in the 150-mg twice-daily group. In all groups, there was a marked and comparable response with respect to suicide ideation. There were no marked differences between the groups with respect to the type and frequency of adverse events. Tolerability was rated "good" or "excellent" in 93% of patients, and there was no appreciable change in blood pressure, pulse rate, or body weight in any of the treatment groups over the study period. The three dosage schedules of moclobemide studied are effective and well tolerated in the treatment of patients with MDE. Moclobemide, 150 mg twice daily, is the optimal initial daily dosage schedule.

Moclobemide in continuation treatment of major depressive episodes: an open follow-up study over six months.

This was an open study of moclobemide, 300 to 450 mg daily, as continuation treatment for 18 weeks, after a 6-week randomized, double-blind acute treatment period with moclobemide administered in three different dosage regimens. The primary antidepressant efficacy criterion was the total score on the Hamilton Rating Scale for Depression. Secondary efficacy criteria were the total scores on the Hamilton Rating Scale for Anxiety and the clinical global impression of illness, severity, and efficacy. The safety of moclobemide was assessed by the type, incidence, and severity of adverse events, as well as changes from baseline in vital signs. Moclobemide as continuation treatment of patients with major depressive episodes and comorbid anxiety was efficacious over a 6-month period. There was some additional antidepressant effect after 6 weeks of acute treatment, especially with respect to treatment response rates. Moclobemide was well tolerated, and no patient's treatment was terminated as the result of adverse events.

Identification of depression in a rural general practice.

Major depression is underdiagnosed by general practitioners, but the reasons for this are not clear. This study aimed to establish the prevalence of major depression and coexisting generalised anxiety disorder in a rural general practice in the Orange Free State. It also assessed the predictive value of a screening questionnaire for use by general practitioners. The two practitioners evaluated 858 patients over a 4-week period. Those who met the screening criteria, together with a random sample of 60 patients who did not, were re-evaluated by a registrar in psychiatry who was unaware of the findings of his colleagues. Of the patients studied, 134 (15.6%) had major depression; 59 of these (44.0%) also had coexisting generalised anxiety disorder. The general practitioners had correctly diagnosed major depression in 32 patients (3.7%) before the study started. The screening questionnaire had a 42% chance of correctly identifying a patient with depression and a 97% chance of correctly identifying a patient who did not have major depression. Both practitioners were equally capable at identifying major depression. The study confirmed both the high prevalence of depression in a rural general practice and its low identification rate. It also showed the advantage of using a screening questionnaire to alert practitioners to the possibility of depression in their patients.

[Masked depression]. / Gemaskerde depressie.

Masked depression is a condition in which the classic affective and cognitive symptoms of depression are hidden behind a variety of somatic complaints or behavioural problems. Patients suffering from masked depression are usually incorrectly diagnosed and treated symptomatically with little success. The condition is often encountered in the medical literature from the late 1960s to the early 1980s, but little has been published about it in recent years. This review discusses the changing ideas and approach with regard to masked depression and examines whether they are still relevant today. The literature published in each of the previous decades is studied and specific attention is given to cultural differences in a South African context. Although little has been published on masked depression in the past few years, somatic complaints in depression are still regularly examined in the literature. A significant number of patients with depression are still not correctly diagnosed and masked depression therefore remains relevant. Doctors should be aware of the presenting complaints in these patients and should understand the reasons for somatisation.

Possible reasons why certain epileptics commit unlawful acts during or directly after seizures.

Courts have accepted that epileptics sometimes commit unlawful acts as a result of an epileptic seizure. Reasons for this unlawful behaviour may be found in the interictal, ictal and post-ictal phases of the seizure. Interictal aspects which are relevant to the form of epileptic automatism may be the person's natural tendencies, the same psychodynamic factors which determine the contents of dreams, the person's social background of violence and the contents of a person's thoughts immediately before a seizure. Ictal aspects include the specific part of the brain from which the seizure originates, the loss of integration of incoming sensorial stimuli with motor-emotional output, the loss of higher control associated with a reversion to primitive automatic behaviour and the emergence of repressed feelings and aggressive instincts. Post-ictal violent behaviour may stem from the epileptic's misinterpretation of well-meant attempts by bystanders to protect him or her against the consequences of his or her confused conduct--and is usually characterized by a clouded consciousness, paranoid ideas and hallucinations.

Moclobemide twice daily in the treatment of major depressive episode: a double-blind, multicenter comparison with different three-times-daily dosage schedules.

Data on a twice-daily dosage schedule with moclobemide in the treatment of depression is limited. In this study, moclobemide 150 mg twice daily (b.i.d.) was compared to two different three-times-daily (t.i.d.) regimens with total daily dosages of 300 and 450 mg, respectively, over a 6-week period. The study was randomized, double-blind, and conducted at three university centers. Efficacy was measured on the Hamilton Depression and Anxiety Rating Scales, on the Zung Scale, and on clinical global impression. Tolerability and safety were assessed through adverse events and vital signs and on clinical global impression. One hundred seventy-eight depressed outpatients were included, and 158 completed the study. The treatment groups were comparable at baseline. No clear differences between the treatment groups could be shown with respect to efficacy. There was, however, a slightly larger decrease in the total HAM-A score in the groups receiving 150 mg b.i.d. and t.i.d. than in the third group. There were no marked differences between the groups with respect to tolerability and safety. Tolerability was rated "good" or "excellent" in 94% of patients, and there was no appreciable change in vital signs in any of the treatment groups. Moclobemide 150 mg b.i.d. is the optimal initial schedule for treatment of depression.

Psychiatric disorders in internal medicine.

All patients admitted to one firm of the Department of Medicine were psychiatrically evaluated in terms of Diagnostic and Statistical Manual of Mental Disorders (DSM III, 1980) criteria. Thirty-three per cent of the patients had treatable psychiatric disorders while only 3.5% of admissions to a comparable firm of the same department were referred for psychiatric consultation (P < 0.05). These data support the need for a more comprehensive liaison psychiatric service than a mere consultation service in the general hospital.

[Psychiatric nursing. The ideal and the practice]. / Psigiatriese verpleging. Die ideaal en die praktyk.

Psychiatric services at primary health care level are far from ideal. Under present conditions the PHCN is relatively uninvolved. This state of affairs will change when a new model proposed by the authors is implemented. This model involves primary prevention programmes; training of PHCNs in the classification and diagnostic criteria of psychiatric illnesses; developing skills in crisis management, therapeutic intervention and behaviour modification; knowledge of drugs and their side-effects; multi-professional team planning implemented by the PHCN; and 24-hour consultation services by specialists.

Subtypes in major depression without melancholia.

Using the Diagnostic and Statistical Manual of Mental Disorders (DSM III, 1980) criteria to diagnose major depression without melancholia, 70 adult patients were selected for further detailed clinical and neuro-endocrinological evaluation. Two subtypes emerged; changes in sleeping patterns, body mass and thyrotrophin response to thyrotrophin-releasing hormone constituted the distinguishing features between the two categories (P = 0.012).

[A modern community psychiatric service in the Orange Free State]. / 'n Moderne psigiatriese gemeenskapsdiens in die Oranje-Vrystaat.

The number of patients with psychiatric syndromes in the community may be as high as 15% at any time. The concept of institutionalisation has gradually changed to the concept of community psychiatry. The main aim of community psychiatric service is to treat the patient in the community. Such a service should be within reach of all the patients in the community. A psychiatric community service has been developed in the Orange Free State over the past 2 years. This has resulted in a reduction of 48% in the chemotherapy budget. Comparing the results with a similar study in Stockholm the reduction of 19% in neuroclinic admissions in Oranje Hospital compares favourably with the 22% reduction in Stockholm. The increase of 90% in the outpatient numbers for the Orange Free State is below the 170% increase reported for Stockholm. A further increase can be expected within the next few years in the Orange Free State.

Noradrenergic function and hypothalamic-pituitary-adrenal axis activity in primary unipolar major depressive disorder.

Plasma levels of cortisol, norepinephrine (NE), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were found to be significantly higher in 16 drug-free patients with primary, unipolar major depressive disorder than in 20 controls. Plasma free MHPG and basal cortisol levels showed a significant positive correlation in the controls, but not in the patients. There were, however, significant positive correlations between cortisol and NE, as well as between NE and free MHPG levels in the patients. No correlations were observed between patient plasma NE levels and platelet alpha 2-adrenoceptor or lymphocyte beta-adrenoceptor Kd or Bmax values. These peripheral measures of noradrenergic function are proposed as useful markers for patients with primary, unipolar major depressive disorder with melancholia.

Beta-adrenoceptors on lymphocytes of patients with major depressive disorder.

3H-Dihydroalprenolol binding to lymphocyte membranes of patients with primary, unipolar major depressive disorder was compared to that of a normal, healthy control population. No significant difference could be demonstrated between the Kd values of the two different groups, but the Bmax values of the depressed patients were significantly lower than those of the controls. Positive correlations were observed between the lymphocyte beta-adrenoceptor Bmax values of the patients and their Beck self-evaluation and Hamilton depression ratings. We propose that decreased lymphocyte beta-adrenoceptor Bmax values may be used as a biological marker for major depressive disorder.

Endocrine responses after thyrotrophin-releasing hormone stimulation and dexamethasone suppression tests in the major depressive syndrome.

The effects of dexamethasone 1 mg on plasma cortisol levels and of thyrotrophin-releasing hormone (TRH) 200 micrograms on thyrotrophin (TSH), growth hormone and prolactin levels in 107 patients with a major depressive disorder (MDD) were compared with those in 87 healthy subjects. Individual hormonal responses and combinations of hormonal responses after administration of dexamethasone and TRH were evaluated as diagnostic aids for MDD by calculating sensitivity, specificity and efficiency for single and multiple hormonal abnormalities. In patients suffering from MDD, 65% of men, 74% of reproductive women and 71% of menopausal or hysterectomized (H/M) women had abnormal responses (sensitivity) to a dexamethasone suppression test (DST). When the DST and TSH responses to TRH were combined, 85% of men, 87% of reproductive women and 84% of H/M women had abnormal results. If the efficiency of the different combinations of hormone responses is calculated, a totally different picture emerges.