Göran Eberhard

Efficacy and safety of risperidone in the long-term treatment of patients with schizophrenia

The long-term efficacy and safety of risperidone were evaluated in patients with chronic schizophrenia in an open-label study. Thirty-two patients received risperidone for 1 year and 19 of the 32 received risperidone for 2 years. The mean dose of risperidone was 9.4 mg/d in the 1-year follow-up. At the end of 1 and 2 years, improvements were found in total scores on the Positive and Negative Syndrome Scale (PANSS), on four PANSS factors (positive, negative, excited, and cognitive), and the Clinical Global Impression scale. Severity of extrapyramidal symptoms (based on scores on the Extrapyramidal Symptom Rating Scale) was also reduced. Clinical improvement (defined as a 20% or more reduction in total PANSS scores) was shown by 54% of the patients at end point. Social functioning (as assessed by using the modified Strauss/Carpenter scale) was significantly improved after 2 years. Number of days spent in hospitals was significantly reduced during the 2 years of treatment, and the number of days in treatment (group) homes significantly increased. It is concluded that treatment with risperidone for 1 and 2 years is associated with significant reductions in symptoms of schizophrenia, improved social functioning, and reduction in days spent in the hospital.

A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice.

The purpose of this double-blind, multicenter trial was to compare the efficacy and safety of sertraline (50–150 ing/day) with those of citalopram (20–60 mg/day) in patients with major depression in general practice during 24 weeks of treatment. The patients were assessed using the Montgomery-Åsberg Depression Rating Scale and the Clinical Global Impressions of severity and improvement scales. Observed and spontaneously reported adverse events were recorded and side-effects were assessed by means of the UKU Side-Effect Scale. Altogether 400 patients were randomized into the study. A total of 308 patients completed the 24-week study in accordance with the protocol. A significant reduction in the total Montgomery-Åsberg Depression Rating Scale scores was observed in both treatment groups as early as 2 weeks, with no statistically significant differences between the drugs. In the intention to treat-lust observation carried forward analysis 76% responded to treatment in the sertraline and 81% in the citalopram group. The final mean doses were 82 mg/day (64% higher than baseline) in the sertraline group and 34 mg/day (70% higher than baseline) in the citalopram group. The response rate in completers in accordance with protocol was 90% in the sertraline group and 93% in the citalopram group. The side-effects were those usually seen, and both sertraline and citalopram were considered to be well tolerated. It was concluded that patients with major depression in general practice respond well to 24 weeks of treatment with sertraline or citalopram. With regard to efficacy, no statistically significant differences were found between the drugs.

A Double-Blind Randomized Study of Clomipramine versus Maprotiline in Patients with Idiopathic Pain Syndromes

Seventy patients with idiopathic syndromes were treated with maprotiline, a noradrenaline reuptake inhibitor, or clomipramine, a serotonin reuptake inhibitor in a 6-week, double-blind, randomized, multicenter trial. Fifty-two patients completed the double-blind phase. Overall, 50% of the patients improved. Significant decreases were seen not only in the levels of pain but also in bodily discomfort, sadness an inner tension (determined by visual analogue scales, VAS). A decrease was also found in the frequency of sleep disturbances, intellectual and emotional inhibition, irritability, guilt feelings, retardation, sadness and suicidal ideas (observed ratings). Sixty-three percent of the subjects showed an overall improvement during treatment with clomipramine as compared to 36% during treatment with maprotiline (p less than 0.05). During clomipramine treatment significant decreases were seen on all the six VAS: sadness, bodily discomfort, inner tension, concentration difficulties, memory disturbances and pain. Bodily discomfort and pain were significantly reduced during maprotiline treatment. The effects produced by clomipramine were also significantly greater than the effects caused by maprotiline as concerns psychic anxiety and inhibition (VAS). The overall reduction in VAS was significantly greater with clomipramine when compared to maprotiline. The most important side effects were dry mouth (both drugs) and sweating (clomipramine). However, in the clomipramine group, 8 patients were excluded due to side effects as compared to 1 patient in the maprotiline group. Thus, the results indicate that antidepressants reduce not only pain but are also of clinical value in the treatment of patients with idiopathic pain syndromes. Drugs with pronounced effects on the serotonin reuptake are to be preferred.

A multinational study of the relationships between nighttime urinary melatonin production, age, gender, body size, and latitude.

Abstract Overnight urines were collected each month for 12–16 months from 321 normal subjects at 19 medical centers in 14 countries distributed on 5 continents at latitudes from 31 01 South to 77 00 North. Mean melatonin concentration was found to negatively correlate with age, weight, and height. When the sexes were considered separately melatonin only correlated with age for female and with age and weight for males. A weak correlation with latitude, but not longitude, was also found.

Plasma prostaglandin E2 metabolite—measured as 11 -deoxy-15 -keto-13,14-dihydro-11 β, 16ξ-cyclo-PGE2—in twins with schizophrenic disorder

Blood samples were obtained from 18 twin pairs, and the major prostaglandin E2 (PGE2) plasma metabolite 15-keto-13,14-dihydro-PGE2 was measured by RIA after its conversion to 11-deoxy-15-keto-13,14-dihydro-11 beta,16 xi-cyclo-PGE2. Significant positive correlations were found in all the twin pairs, in 11 pairs diagnosed as DSM-III schizophrenic disorder and schizoid/schizotypal personality disorder, and in the 5 nonschizophrenic pairs. These results indicate that synthesis of prostaglandins (PGs) is in part genetically determined. With regard to absolute PGE2 metabolite levels, the data did not support the hypothesis of increased PGE2 in schizophrenia. Thus, seven of eight schizophrenic probands had lower metabolite concentrations than their healthy twin siblings, and in one pair they were similar. Furthermore, schizophrenic probands and their healthy sibling controls, taken as a group, had lower PGE2 metabolite levels than the group comprised of affective disorder probands and their respective controls. These findings raise the possibility that a change in PGE2 may be associated with schizophrenic and also possibly with affective disorders.

Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison.

ABSTRACT Thirty‐two schizophrenic patients, previously treated with antipsychotics, were treated with haloperidol decanoate and flupenthixol decanoate in a double‐blind cross‐over study. The drugs were given for 24 weeks each at an individually adapted dose. The last three injections of either drug were given at fixed 4‐week intervals. The mean dose over the two treatment periods changed from 131 mg (start) to 151 mg (week 24) in the haloperidol decanoate group and from 56 mg to 66 mg in the flupenthixol decanoate group, the inter‐drug ratio being 2.3:1. During the first study period, the patients’ condition remained rather stable with both drugs. After crossing‐over, the symptoms were further reduced with haloperidol decanoate but increased with flupenthixol decanoate. Side effects of the two drugs were comparable and were generally few and mild. It was concluded that 4‐week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals.

Evaluation of postgraduate medical education given by the Swedish PTD Committee

The Swedish Committee for the Prevention and Treatment of Depression (the Swedish PTD committee) has created a series of educational programmes to be used in post-graduate education of general practitioners; they deal with the etiology, pathogenesis, diagnosis and treatment of depression. The separate chapters were presented to general practitioners on the island of Gotland in two separate educational programmes with one year in between. Before, in between and after the last educational programme, information was collected regarding number of suicides, number of attempted suicides, number of referrals to the Dept. of Psychiatry, number of emergency admissions, number of subjects on sickleave due to depression and number of prescriptions for antidepressants and minor tranquillizers. The general practitioners completed a questionnaire concerning knowledge about etiology, pathogenesis, diagnosis and treatment of depression, attitudes towards depressed patients and their treatment, current practice and person...

The Influence of Age, Sex, Height, Weight, Urine Volume and Latitude on Melatonin Concentrations in Urine from Normal Subjects: A Multinational Study

Publisher Summary This chapter reviews the influence of age, sex, height, weight, urine volume, and latitude on melatonin concentrations in urine from normal subjects. Because melatonin formation involves the stimulated metabolism of one monoamine by the transmitter actions of another in accordance with the coupling between an endogenous, free-running pacemaker and light, it has been studied in a number of clinical conditions as a possible marker for endogenous rhythmicity and for noradrenergic activity. Age and sex distributions in these populations often differ from that in the general population and defining the influences of sex and age on melatonin metabolism and distribution is of obvious importance to study design and data interpretation. A recent worldwide multinational study on seasonal and geographic influences on human melatonin production provided multiple urine samples from a large population of geographically dispersed normal subjects. The inverse relationship between melatonin concentration and overnight urine volume was expected as a natural consequence of the free passage of melatonin from blood into the renal tubule.

Predictors for the outcome of treatment with antidepressants in patients with idiopathic pain syndromes

In a double-blind, randomized study of clomipramine (x=97.2 mg/day) versus maprotiline (x=100.0 mg/day) in patients with idiopathic pain syndromes, 50% of the patients improved. 63% showed an overall improvement during treatment with clomipramine (p<0.05). The present analysis was undertaken to determine if only patients with coexisting pain and depression responded to treatment with antidepressants or if all patients with idiopathic pain syndromes responded regardless of the presence of depressive symptomatology. Patients improved and not improved, respectively, did not differ significantly in age, sex, duration of the pain syndrome, the presence of periodic course, heredity for depressive disorders or pretreatment presence of single depressive symptoms, except that improved patients had a significantly lower degree of memory disturbances than the patients who did not improve. Cortisol in plasma at 4 pm after dexamethasone and the degree of 3H-imipramine receptor binding was also about the same in both i...

Psychoses in twins: A 10 year clinical and biochemical follow-up study

An unbiased sample of monozygotic and dizygotic twins with psychotic or pre-psychotic symptoms has been followed during a 10 year period. The sample was based on 9000 patients, both born in 1930-1946, and hospitalized in Scania, Sweden, during the 1960s. 23 complete pairs were examined in 1972 with regard to a variety of clinical, genetic, and biochemical parameters. A fairly young sample was chosen in order to include a sufficient number of discordant pairs to be followed prospectively, thus making it possible to study a group of individuals with a very high risk of developing psychosis. 18 of the 23 pairs were re-examined by the same clinician 10 years later. The biochemical methods were both partly the same as those used 10 years earlier and partly extended. Very few changes in the clinical diagnoses of the twins were noted during the follow-up period. A highly significant correlation was found between 1972 and 1982 activity both for catechol O-methyltransferase (COMT) and for monoamine oxidase (MAO). The basal levels of MAO, COMT, dopamine beta-hydroxylase (DBH) and serotonin (5-HT) did not show correlations to the presence of pre-psychotic or psychotic symptoms.