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Biomedical subjects

Lieuwe de Haan

Publications and source records attributed to Lieuwe de Haan.

25 records · Page 2Linked to original sources

Suicide risk in placebo vs active treatment in placebo-controlled trials for schizophrenia.

BACKGROUND: If there is an increased risk of suicide in the placebo arms of placebo-controlled studies in patients with schizophrenia, it would be a strong ethical argument against the conduct of placebo-controlled studies in this patient population. We tested whether the risk of suicide and attempted suicide in the placebo arms of placebo-controlled studies among patients with schizophrenia is higher than in the active treatment arms of such studies. METHODS: All placebo-controlled double-blind studies that were part of a registration dossier for the indication schizophrenia, and that were submitted to the regulatory authority of the Netherlands from January 1, 1992, through December 31, 2002, were reviewed for suicide and attempted suicide. RESULTS: In 31 studies, 7152 patients were included: 1888 in placebo groups (398.2 person-years) and 5264 in active compound groups (981.3 person-years). One suicide occurred in the placebo groups (0.05%, or an incidence rate of 251 per 100,000 years of exposure) and 1 in the active compound groups (0.02%, or an incidence rate of 102 per 100,000 years of exposure). This difference was not statistically significant. Two attempted suicides occurred in the placebo groups (0.11%, or an incidence rate of 502 per 100,000 years of exposure) and 11 in the active compound groups (0.21%, or an incidence rate of 1121 per 100,000 years of exposure). This difference was also not statistically significant. CONCLUSION: Concern about increased risk of suicide or attempted suicide in the placebo group should not be an argument against the conduct of placebo-controlled trials in schizophrenia, provided that appropriate precautions are taken.

Ambulatory Care↗

Duration of untreated psychosis and outcome of schizophrenia: delay in intensive psychosocial treatment versus delay in treatment with antipsychotic medication.

Duration of untreated psychosis (DUP), defined as delay in treatment with antipsychotic medication, was found to be associated with an unfavorable course of schizophrenia. Delay in intensive psychosocial treatment (DIPT) may also be related to outcome. We examined the relationship of DUP and DIPT with several outcome domains 6 years after onset in a cohort of 88 consecutively admitted patients with early-onset schizophrenia and related disorders. Patients and their parents completed an inventory concerning DUP, DIPT, and various aspects of outcome. Psychotic relapse during the first year after hospitalization was assessed with a chart review. Both DUP and DIPT were found to be associated with negative symptoms at outcome; mode of onset was not. DUP was associated with mild psychotic relapse. DIPT was associated with months of rehospitalization. There was no relation between DUP or DIPT and other aspects of outcome. When we controlled for age at onset, gender, and duration of treated first psychotic episode, only DIPT was associated with negative symptoms at outcome. DIPT may be a more important predictor of negative symptoms at outcome than is delay in starting antipsychotic medication alone.

Adult↗

Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study.

OBJECTIVE: The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol. METHOD: Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography. RESULTS: The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group. CONCLUSIONS: A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.

Adolescent↗

Attitudes of patients toward the first psychotic episode and the start of treatment.

Consecutively admitted patients with recent-onset schizophrenia disorders (n = 56) were interviewed about their awareness of mental disorder at first occurrence of psychotic symptoms, their views about the necessity of psychiatric treatment, their perception of the role of others in initiating psychiatric treatment, and suggestions they might have about getting treatment started at an earlier point in time. About 57 percent of the patients had at least some awareness of having a mental disorder at onset of psychotic symptoms, and 61 percent of the sample believed psychiatric help was unnecessary prior to the start of psychiatric treatment. A majority of the patients (91%) perceived others to be essential in initiating treatment. Most patients (82%) thought that no change is needed on the part of professional caregivers in order to facilitate early treatment. Some awareness of mental disorder at onset was related to a shorter duration of untreated psychosis (DUP). Delaying treatment until patients themselves become aware of the need for treatment may enlarge DUP.

Adolescent↗

Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders.

OBJECTIVE: To determine whether severity of obsessive-compulsive symptoms (OCS) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS. METHOD: We conducted a prospective study of consecutively hospitalized young patients (mean age = 22.4 years) with DSM-IV schizophrenia or related disorders (N = 113) who were treated with olanzapine or risperidone. Olanzapine or risperidone was randomly prescribed for patients who were drug-naive or were treated with typical antipsychotics before admission (N = 36). Patients who had started olanzapine (N = 39) or risperidone treatment (N = 23) prior to admission continued with that medication if they showed initial clinical response. Patients who prior to admission started olanzapine (N = 6) or risperidone (N = 9) but showed no response or suffered from adverse effects switched at admission to risperidone or olanzapine, respectively. Medical records, parents, and patients revealed information on duration of treatment and compliance with olanzapine or risperidone prior to admission. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was administered at admission and 6 weeks thereafter. RESULTS: At baseline and 6-week assessments, OCS were found in about 30% of 106 evaluable cases and 15% met DSM-IV criteria for obsessive-compulsive disorder. No differences in OCS were found in the patients randomly assigned to olanzapine or risperidone. The 35 subjects treated with olanzapine at both assessments had significantly (p = .01) more severe OCS at week 6 than the 20 subjects treated with risperidone at both assessments. Duration of treatment with olanzapine was significantly (p < .01) related to severity of OCS. CONCLUSION: There are no differences in the short-term propensity of olanzapine or risperidone to induce or exacerbate OCS. However, severity of OCS was associated with duration of treatment with olanzapine.

Acute Disease↗