Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder: A Randomized Controlled Trial.

OBJECTIVE: Several single-center studies have found raloxifene, an estrogen agonist, to be effective in ameliorating symptoms of schizophrenia in stable patients as augmentation of antipsychotics. This multicenter study assessed whether raloxifene plus antipsychotic treatment, in comparison to placebo plus antipsychotics, improves symptoms or cognition in severely ill decompensated schizophrenia patients. METHODS: In this 16-week, double-blind, randomized, placebo-controlled study, 200 severely ill, decompensated postmenopausal women who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were recruited from January 2011 to December 2012 and were randomized to receive either raloxifene 120 mg/d plus antipsychotics or placebo plus antipsychotics. The primary outcome measure was Positive and Negative Syndrome Scale (PANSS) total score at the end of the trial. RESULTS: The placebo plus antipsychotics group experienced statistically significant improvement in PANSS total score (P < .001) compared to the raloxifene plus antipsychotics group, using mixed models for repeated measures, with results favoring placebo by 4.5 points (95% CI, 2.3-6.7). These results were clearly outside the 95% confidence interval. This negative effect was more pronounced in patients who had more frequent relapses and in those with baseline PANSS scores of 100 or higher. There were no differences between groups in Clinical Global Impression Scale-Severity scores or Composite Brief Assessment of Cognition in Schizophrenia scores at 16 weeks (P > .3). Baseline follicle-stimulating hormone and estradiol levels did not alter the drug-placebo differences. CONCLUSIONS: Individuals in the active treatment arm showed worse outcome than those in the placebo arm, most likely as a result of chance variation, but the results unequivocally show no benefit of antipsychotics plus raloxifene versus antipsychotics plus placebo in this large randomized, double-blind, placebo-controlled trial in postmenopausal women. These data do not support the use of raloxifene in severely decompensated schizophrenia patients until reliable research identifies what subgroup of patients or domain of outcome is benefited. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01280305.

The SWITCH study: rationale and design of the trial.

Many patients do not respond to the first antipsychotic drug prescribed, but require multiple trials with different drugs before response is achieved. Current treatment guidelines vary substantially in their recommendations as to how long clinicians should wait before an antipsychotic treatment attempt should be considered as failed and the compound switched. It has, however, recently been shown that poor early response to an antipsychotic is associated with continuous poor later response in the course of the same treatment attempt. This finding suggests that patients who do experience poor early response might benefit from a switch in antipsychotic medication as early as 2 weeks after treatment initiation. In the SWITCH trial, 350 patients suffering from an acute episode of schizophrenia are randomly assigned to double-blind treatment with either olanzapine or amisulpride. The primary endpoint is symptomatic remission at week 8. Patients not experiencing at least minor response after 2 weeks are randomized again to either staying on the initially assigned drug or being switched to the alternative compound for another 6 weeks. In case early switching proves superior to maintaining treatment, time wasted for unsuccessful treatment attempts could be minimized, patients' outcomes improved, duration of hospital stays reduced, and thus overall treatment expenses saved. The current report will present the methods of the trial, focusing on various specific features which could be adopted by future studies.

When does subliminal affective image priming influence the ability of schizophrenic patients to perceive face emotions?

BACKGROUND: Deficits in face emotion perception are among the most pervasive aspects of schizophrenia impairments which strongly affects interpersonal communication and social skills. MATERIAL AND METHODS: Schizophrenic patients (PSZ) and healthy control subjects (HCS) performed 2 psychophysical tasks. One, the SAFFIMAP test, was designed to determine the impact of subliminally presented affective or neutral images on the accuracy of face-expression (angry or neutral) perception. In the second test, FEP, subjects saw pictures of face-expression and were asked to rate them as angry, happy, or neutral. The following clinical scales were used to determine the acute symptoms in PSZ: Positive and Negative Syndrome (PANSS), Young Mania Rating (YMRS), Hamilton Depression (HAM-D), and Hamilton Anxiety (HAM-A). RESULTS: On the SAFFIMAP test, different from the HCS group, the PSZ group tended to categorize the neutral expression of test faces as angry and their response to the test-face expression was not influenced by the affective content of the primes. In PSZ, the PANSS-positive score was significantly correlated with correct perception of angry faces for aggressive or pleasant primes. YMRS scores were strongly correlated with PSZ's tendency to recognize angry face expressions when the prime was a pleasant or a neutral image. The HAM-D score was positively correlated with categorizing the test-faces as neutral, regardless of the affective content of the prime or of the test-face expression (angry or neutral). CONCLUSIONS: Despite its exploratory nature, this study provides the first evidence that conscious perception and categorization of facial emotions (neutral or angry) in PSZ is directly affected by their positive or negative symptoms of the disease as defined by their individual scores on the clinical diagnostic scales.

A randomized controlled trial of allopurinol vs. placebo added on to antipsychotics in patients with schizophrenia or schizoaffective disorder.

Adenosine agonists produce behavioral effects similar to dopamine antagonists, hence increasing adenosine levels might improve symptoms of schizophrenia. This hypothesis is supported by three single-site studies indicating that allopurinol, which increases adenosine levels, improved symptoms in patients with schizophrenia. We performed a multi-center, 8-week RCT of allopurinol vs. placebo added to anti-psychotic medications in 248 patients with schizophrenia or schizoaffective disorder. Both groups showed improvement in the PANSS (effect size 1.13) and in clinical and cognitive measures. No difference was observed between groups in primary (t=0.01, p=0.992) or secondary outcome measures. These findings do not support allopurinol as a treatment for schizophrenia.