Faculty Bibliography

OBJECTIVE: The authors summarize two special sessions focused on the teaching of psychopharmacology at the 2003 and 2004 annual meeting of the American College of Neuropsychopharmacology (ACNP). The focus was on whether "improving the teaching-learning process" in psychiatric residency programs could improve clinical practice. METHOD: Problems of strategies and pedagogic techniques that have been used were presented from multiple perspectives (e.g., from a dean, department chair, training director, and former students). CONCLUSIONS: There was a consensus that action involving psychopharmacology organizations and the American Association of Directors of Residency Training in Psychiatry (AADPRT) was necessary to improve "evidence-based" competencies before graduation and to follow prescribing patterns into clinical practice to determine whether the standards of care could be improved.

BACKGROUND: We report here a study examining the relationships between insight and psychopathology, cognitive performance, brain volume and co-morbid depression in 251 patients experiencing a first episode of psychosis, who were then randomly assigned to 2 years of double-blind treatment with either olanzapine or haloperidol. METHOD: Repeated measures of insight were obtained at baseline and 12, 24, 52 and 104 weeks by the Insight and Treatment Attitudes Questionnaire (ITAQ). RESULTS: Older age, female gender and white ethnicity were associated with more insight. Higher total, positive, negative and general psychopathology scores on the Positive and Negative Syndromes Scale (PANSS) were associated with less insight. Higher depression scores were associated with more insight. Better neurocognitive function and large brain volumes were associated with more insight. More insight throughout the study was associated with longer time to medication non-adherence. However, baseline insight was not significantly related to the probability of discontinuing the study before 2 years. Insight improved significantly over the course of the study, but the improvement in insight was not significantly different between the two antipsychotic treatment groups. CONCLUSIONS: Multiple factors contribute to insight. Patients experiencing a first episode of psychosis who have little insight are at increased risk of discontinuing their medication.

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study was undertaken to provide a valid assessment of the differences between conventional and atypical antipsychotics and among the atypicals themselves in patients with schizophrenia. The CATIE investigators reported that while none of the study medications were ideal, olanzapine was the most effective in terms of treatment discontinuation, and there were no significant differences in effectiveness between the conventional antipsychotic perphenazine and the atypicals quetiapine, risperidone, and ziprasidone. Each drug differed slightly in rates of side effects, with more patients discontinuing perphenazine due to extrapyramidal side effects and more patients discontinuing olanzapine due to weight gain and metabolic effects. In order for data from phase 1 of the CATIE study to be interpreted within the appropriate context, physicians must understand how aspects of study design and statistical methods affect interpretation, and how this trial weighs against other data in the literature. This article enumerates the factors that complicate our understanding of the CATIE results and compares these findings with those from previously published meta-analyses. It is clear that therapeutic and side effects of antipsychotics vary from person to person. The goal of schizophrenia management is to maintain pharmacotherapeutic efficacy and tolerability over the long-term in order to maximize treatment adherence and benefits. What should emerge from CATIE is a renewed commitment to tailor schizophrenia treatment to the individual patient for long-term management.

OBJECTIVE: This study examined the prevalence and correlates of concomitant psychotropic medications and use of anticholinergic drugs to treat schizophrenia. METHODS: Concomitant medication use was studied at baseline for participants in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial. RESULTS: Of the 1,380 patients with baseline medication data, 82 percent were taking psychotropic medications. Of this group, 6 percent were taking two antipsychotics (one first generation and one second generation); 38 percent, antidepressants; 22 percent, anxiolytics; 4 percent, lithium, and 15 percent, other mood stabilizers. The strongest predictors of taking several medications were having anxiety or depression, being female, and taking second-generation antipsychotics. Conversely, African Americans and those with better neurocognitive functioning were less likely to be taking several concomitant psychotropic medications. In some cases symptoms that were likely targets of polypharmacy, such as depression, remained prominent, suggesting only partial response. CONCLUSIONS: Concomitant use of psychotropic medications to treat people with schizophrenia is common. Empirical data demonstrating the effectiveness of many of these agents for this population are lacking.

BACKGROUND: There are virtually no controlled data suggesting that concomitant psychotropic medications (CPMs) improve outcome in schizophrenia after the acute phase. Despite that, polypharmacy (with all of its disadvantages) is far more common than monotherapy. To our knowledge, there have been no published reports of prospective systematic investigations of the efficacy of unrestricted CPM use in nonacute schizophrenia. METHOD: This was a naturalistic, systematic study using a sample of 53 stabilized patients with DSM-IV-TR schizophrenia from 1 clinical practice setting including both private patients and patients from controlled research studies of the effectiveness of antipsychotics. Since there are meager controlled or systematic data on the effectiveness of CPM use with antipsychotics in nonacute schizophrenia, we tested the clinical strategy of CPM use by gradually tapering all CPMs (except antianxiety agents). The aim was to determine if the CPM improved outcome, had no effect, or worsened outcome using the Clinical Global Impressions-Improvement scale before and after taper, over at least 3 months and in some cases up to 18 months after discontinuation. Data were gathered from July 2002 to June 2005. RESULTS: For 21 patients undergoing 22 antidepressant tapers, no change was noted in 18 of 22 tapers, while in 3 improvement was noted and in 1 worsening was noted. For the 12 patients on treatment with mood stabilizers, no change was noted in 10 of 13 discontinuations, while in 3 mild worsening was noted. One patient was on treatment with both modafinil and trazodone and reported no change after tapering each in separate discontinuation trials, while another 3 patients were taking sleeping medications and also noted no change after discontinuation. CONCLUSION: For most stabilized, chronic patients with schizophrenia, tapering adjunctive medications did not change outcome. This naturalistic study further defines the limits of efficacy of some concomitant classes of medications in patients with chronic schizophrenia who are already receiving adequate antipsychotic therapy.

Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study. Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse effects that are more likely with olanzapine.