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Jan Volavka

Publications and source records attributed to Jan Volavka.

43 records · Page 3Linked to original sources
PubMed2002

Managing treatment-resistant schizophrenia: evidence from randomized clinical trials.

Clozapine was the first antipsychotic medication to be approved for the indication of treatment-refractory schizophrenia. This followed rigorous testing in patients who retrospectively and prospectively failed treatment trials of relatively high doses of conventional antipsychotics. In the past decade, other atypical antipsychotics have been approved, but they have not been designated specifically for patients with a history of prior poor treatment response. Better tolerated than clozapine, these new agents have been used with varying success in patients who would have otherwise received clozapine. Up until very recently there has not been a head-to-head controlled clinical trial comparing the two most commonly used atypical antipsychotics, risperidone and olanzapine, with clozapine in patients considered to have a suboptimal response to typical antipsychotics. This review summarizes the current advances made in the pharmacological management of these patients by examining recently published randomized controlled clinical trials that have measured psychopathology and cognition.

Journal Article↗
PubMed2002

Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder.

OBJECTIVE: The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder. METHOD: In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period). RESULTS: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain. CONCLUSIONS: The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.

Adolescent↗
PubMed2002

Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder.

OBJECTIVE: Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia, but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents, particularly in patients who have had suboptimal response to prior treatments. METHOD: The authors examined the effects of clozapine, olanzapine, risperidone, and haloperidol on 16 measures of neurocognitive functioning in a double-blind, 14-week trial involving 101 patients. A global score was computed along with scores in four neurocognitive domains: memory, attention, motor function, and general executive and perceptual organization. RESULTS: Global neurocognitive function improved with olanzapine and risperidone treatment, and these improvements were superior to those seen with haloperidol. Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments. Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol. Clozapine yielded improvement in motor function but not more than in other groups. Average effect sizes for change were in the small to medium range. More than half of the patients treated with olanzapine and risperidone experienced "clinically significant" improvement (changes in score of at least one-half standard deviation relative to baseline). These findings did not appear to be mediated by changes in symptoms, side effects, or blood levels of medications. CONCLUSIONS: Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects.

Adult↗
PubMed2002

Olanzapine in refractory schizophrenia after failure of typical or atypical antipsychotic treatment: an open-label switch study.

BACKGROUND: When patients with schizophrenia fail to respond to an atypical antipsychotic, they are sometimes switched to another atypical compound. However, the benefits of such a switch have not been adequately studied. We present an open-label prospective 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder whose treatment resistance to clozapine, olanzapine, risperidone, and haloperidol had been determined prospectively. METHOD: The subjects were 45 inpatients with DSM-IV schizophrenia or schizoaffective disorder who failed to respond to treatment during a 14-week double-blind trial comparing clozapine, olanzapine, risperidone, and haloperidol. The patients had been selected for participation in the double-blind trial on the basis of a history of suboptimal response to previous treatment. Inclusion criteria for the present study were (1) completion of at least 8 weeks of the 14-week double-blind trial, (2) treatment resistance to 1 of the 4 compounds tested as evidenced by a decrease in total PANSS score of less than 20%, and (3) total PANSS score > or = 60. Subjects were cross-titrated from the previous double-blind treatment to open-label olanzapine, 10 to 40 mg/day, and were treated for 14 weeks without concomitant psychotropic medication. Patients were evaluated weekly with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions scale, and Extrapyramidal Symptom Rating Scale. RESULTS: Open-label olanzapine treatment yielded no significant change in PANSS total, positive subscale, or negative subscale scores. There was a significant improvement for the PANSS cognitive factor (mean +/- SD change = 0.92 +/- 2.27; F = 7.5, df = 1,44; p <.009) and a marginally significant worsening for the excitement factor (mean change = -1.36 +/- 4.64; F = 4.0, df = 1,44; p < .053). Nine percent of patients (N = 4) were classified as responders using the Kane et al. criteria. The worsening in the PANSS excitement factor was significantly associated with the length of illness (t = -2.10, df = 44, p < .04). There was a nonsignificant decrease in extrapyramidal side effects and a significant increase in weight (mean increase = 3.5 +/- 6.2 kg [7.8 +/- 13.8 lb]; F = 5.29, df = 1,42; p <.0005). CONCLUSION: Our results indicate that in patients with treatment-resistant schizophrenia, a switch to olanzapine after treatment failure with an atypical agent or haloperidol may not reduce psychopathology in general, but may improve symptoms related to cognitive function.

Adult↗
PubMedDate not supplied

Optimal dosing of atypical antipsychotics in adults: a review of the current evidence.

This review describes dosing strategies used to optimize the beneficial effects of atypical antipsychotic medications. Differences between manufacturers' recommended dosing and actual clinical practice are reconciled using evidence from pivotal double-blind randomized registration studies, other randomized clinical trials, case series, and case reports. With clozapine and perhaps olanzapine, plasma levels are correlated with therapeutic response; with risperidone, plasma levels are not correlated with therapeutic response but may be related to the occurrence of extrapyramidal symptoms. Information related to optimal dosing of quetiapine and ziprasidone is more limited. In clinical practice, the mean daily dose of risperidone has decreased, whereas that for olanzapine is increasing. The percentage of patients receiving quetiapine at doses above the manufacturer's recommended maximum is higher than would be expected, further illustrating that dosing ranges established during registration studies may not reflect the needs of day-to-day practice.

Adult↗