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Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication.

Objective: The authors previously reported a relationship between an allele encoding the low activity variant of catechol O-methyltransferase (COMT) and aggressive behavior in schizophrenic patients. This study replicates and extends these findings by using more direct measures of violent behavior. Method: Fifty-five white patients (34 men, 21 women) with DSM-IV diagnoses of schizophrenia or schizoaffective disorder were selected to form two groups (violent and nonviolent) on the basis of history of aggressive behavior. COMT genotypes were determined by restriction fragment length polymorphism analysis. Results: A significant association was found between COMT genotype and history of violent behavior. Sixty-four percent of patients homozygous for the low-activity COMT allele were violent; 80% of patients homozygous for the high-activity allele were nonviolent. Conclusions: The gene determining the activity of an important regulatory enzyme in catecholamine inactivation is associated with violent behavior in patients with schizophrenia and schizoaffective disorder.

No established treatment algorithm exists for patients with schizophrenia. Whether switching antipsychotics or early use of clozapine improves outcome in (first-episode) schizophrenia is unknown.

Purpose.To evaluate the effectiveness of the Information Technology-Aided Program of Re lapse Prevention in Schizophrenia (ITAREPS). Methods.Relapse-prone outpatients with schizophrenia or schizoaffective disorder were randomized to the active (n=75) or control group (n=71). In the active arm, according to the protocol, investigators were prompted to increase the antipsychotic dose upon occurrence of a pharmacological inter vention requiring event (PIRE) detected by ITAREPS. Results.Intention-to-treat (ITT) analysis found no between-group difference in the hospitalization-free survival rate at 12 months. However, the trial suffered from high non-adherence of investigators in the active group, with no antipsychotic dose increase in 61 of PIREs. Furthermore, Cox regression analysis showed a 11-fold increased risk of hospitalization in the absence of pharmacological intervention following a PIRE (hazard ratio HR=10.8; 95 confidence interval CI 1.4–80.0; p=0.002). Therefore, a post-hoc as-treated analysis was performed, which demonstrated a nine-fold reduction in the risk of hospitalization in ITAREPS Algorithm-Adherers (IAAs, n=25) compared with the ITAREPS Non-interventional group (INIs, n=70; Kaplan-Meier survival analysis, HR=0.11, 95 CI 0.05–0.28, p=0.009; number needed to treat NNT=4, 95 CI 3–10). A significant difference in favor of the IAA group was seen in the number of inpatient days (p<0.05) and costs (p<0.05). Conclusion.Future ITAREPS trials should target the underlying mechanisms that cause low investigator adherence to the program. Trial registration: Clinical Trials NCT00712660 (Journal of Psychiatric Practice2012;18:269–280)

Psychiatrists and other physicians sometimes read publications superficially, relying excessively on abstracts. The authors addressed this problem by teaching critical appraisal of individual articles. The authors developed a 23-item appraisal instrument to assess articles in the area of psychopharmacology. The results were collected with an electronic voting system. A discussion of each of the item followed; tutors shared their views and provided key ratings. Six publications were evaluated in the course of three workshops by a total of 58 trainees. Evaluation of the papers yielded varying results, reflecting variations of the participants’ theoretical background as well as varied quality of the publications. The authors present detailed analysis of one paper as an illustrative example. The discussion format and voting stimulated active participation of the trainees. Active involvement, facilitated by the structured assessment tool, followed by feedback with discussion, may enhance the learning process.

It has been suggested that inclusion of a placebo treatment arm in controlled clinical trials might bias the selection of study subjects. Presumably, patients in the placebo-controlled studies are more stable, but there are no data available to support such an assumption. The authors tested the hypothesis in a set of randomized trials of neuroleptics in treating schizophrenia by comparing placebo-controlled (PCTs) and comparator-controlled trials (CCTs) in terms of basic patient characteristics. The results, based on a total of 296 studies, showed that the patients in PCTs, compared with those in CCTs, were older (p< 0.002), had a longer duration of illness (p< 0.001), and a lower initial symptom severity (p< 0.02). No difference was found in the number of subjects per treatment arm or in the proportion of female subjects. However, investigation of studies which used same-gender study subjects revealed that female-only populations were more likely to be tested in PCTs (p< 0.03) than in CCTs. To investigate current trends in psychopharmacologic research, the authors tested separately a subset of trials of new atypical antipsychotics. The results indicated a significantly smaller number of females participating in the latest PCTs (p< 0.0003). Moreover, our findings suggest that the characteristics of patients in the current controlled trials are rather uniform; thus, the generalizability of new study findings for certain groups of patients with schizophrenia (e.g., with early or late onset or brief duration of illness) may be compromised.

High doses of antipsychotic medications are sometimes prescribed in clinical practice, although the efficacy and safety of such treatment have not been established. The purpose of this study was to determine whether high-dose, long-term antipsychotic treatment prescribed on the basis of clinical judgment can be justified. Patients who were receiving high doses of haloperidol were screened, and those patients whose plasma levels were at least 15 ng/mL were randomly assigned to an experimental group (N = 11) or to a control group (N = 12). The experimental group underwent a dose reduction to achieve the target plasma level of 10 ng/mL. The reduction was gradual over a period of 12 weeks. The control group treatment was maintained at the original level. Both groups were then followed up for another 16 weeks, during which the plasma levels of haloperidol were kept constant. The study used double-blind procedures. Both groups showed an average slight symptom reduction. There was no significant difference in the severity of symptoms between the two groups at any time point. The dose reduction had no apparent adverse effects. Thus, the results of this study did not provide justification for high-dose, long-term antipsychotic treatment. However, these results must be interpreted with caution because the sample studied here was small and biased.