A Retrospective Review of the Use of Clozapine in Restoration of Competency to Stand Trial.

Most defendants found incompetent to stand trial have psychotic illnesses. Clozapine has been shown to be superior to other antipsychotic medications in treatment-resistant schizophrenia. It is vastly underutilized, however, including in forensic settings. To our knowledge, there have been no studies exploring the risks and benefits of clozapine for incompetent to stand trial defendants with severe mental illness. We sought to explore the characteristics of patients who were prescribed clozapine in a retrospective sample of defendants deemed incompetent to stand trial with diagnoses of psychotic and bipolar disorders. We found that 25 of 240 defendants (10%) were prescribed clozapine, with 15 (60%) eventually being discharged on it. Of those 15, 8 defendants were successfully restored to competency to stand trial. The restoration rate in the clozapine group was much lower than in the non-clozapine group (32% versus 87%). Our results emphasize the need for prospective comparative studies assessing the efficacy and tolerability of clozapine and other antipsychotic medications related to restoration of competency to stand trial.

Long-Acting Injectable versus Oral Antipsychotics for Restoration of Competency to Stand Trial.

Treatment with antipsychotics is a mainstay of trial competency restoration, particularly given that most defendants deemed incompetent to stand trial have psychotic illnesses. We explored the association between competency restoration and antipsychotic type in a retrospective sample of defendants diagnosed with psychotic disorders and deemed incompetent to stand trial. Using regression models, we calculated the odds ratio of being competent to stand trial, adjusting for relevant confounders. We found that the use of long-acting injectable antipsychotics was not significantly associated with increased odds of restoration of trial competency. Our results highlight the need for larger, longitudinal studies to further explore the efficacy and tolerability of long-acting injectable drugs compared with oral antipsychotics. Future research will help develop treatment guidelines within the setting of trial competency restoration.

Serotonin signaling is associated with lower amyloid-ß levels and plaques in transgenic mice and humans.

Aggregation of amyloid-ß (Aß) as toxic oligomers and amyloid plaques within the brain appears to be the pathogenic event that initiates Alzheimer's disease (AD) lesions. One therapeutic strategy has been to reduce Aß levels to limit its accumulation. Activation of certain neurotransmitter receptors can regulate Aß metabolism. We assessed the ability of serotonin signaling to alter brain Aß levels and plaques in a mouse model of AD and in humans. In mice, brain interstitial fluid (ISF) Aß levels were decreased by 25% following administration of several selective serotonin reuptake inhibitor (SSRI) antidepressant drugs. Similarly, direct infusion of serotonin into the hippocampus reduced ISF Aß levels. Serotonin-dependent reductions in Aß were reversed if mice were pretreated with inhibitors of the extracellular regulated kinase (ERK) signaling cascade. Chronic treatment with an SSRI, citalopram, caused a 50% reduction in brain plaque load in mice. To test whether serotonin signaling could impact Aß plaques in humans, we retrospectively compared brain amyloid load in cognitively normal elderly participants who were exposed to antidepressant drugs within the past 5 y to participants who were not. Antidepressant-treated participants had significantly less amyloid load as quantified by positron emission tomography (PET) imaging with Pittsburgh Compound B (PIB). Cumulative time of antidepressant use within the 5-y period preceding the scan correlated with less plaque load. These data suggest that serotonin signaling was associated with less Aß accumulation in cognitively normal individuals.

Is patient travel distance associated with survival on phase II clinical trials in oncology?

BACKGROUND: Prior research has suggested that patients who travel out of their neighborhood for elective care from specialized medical centers may have better outcomes than local patients with the same illnesses who are treated at the same centers. We hypothesized that this phenomenon, often called "referral bias" or "distance bias," may also be evident in curative-intent cancer trials at specialized cancer centers. METHODS: We evaluated associations between overall survival and progression-free survival and the distance from the patient residence to the treating institution for 110 patients treated on one of four phase II curative-intent chemoradiotherapy protocols for locoregionally advanced squamous cell cancer of the head and neck conducted at the University of Chicago over 7 years. RESULTS: Using Cox regression that adjusted for standard patient-level disease and demographic factors and neighborhood-level economic factors, we found a positive association between the distance patients traveled from their residence to the treatment center and survival. Patients who lived more than 15 miles from the treating institution had only one-third the hazard of death of those living closer (hazard ratio [HR] = 0.32, 95% confidence interval [CI] = 0.12 to 0.84). Moreover, with every 10 miles that a patient traveled for care, the hazard of death decreased by 3.2% (HR = 0.97, 95% CI = 0.94 to 0.99). Similar results were obtained for progression-free survival. CONCLUSION: Results of phase II curative-intent clinical trials in oncology that are conducted at specialized cancer centers may be confounded by patient travel distance, which captures prognostic significance beyond cancer stage, performance status, and wealth. More work is needed to determine what unmeasured factors travel distance is mediating.

Psychological effects of musky compounds: comparison of androstadienone with androstenol and muscone.

Previously, we have shown that delta4,16-androstadien-3-one modulates psychological state, reducing negative mood and increasing positive mood (Jacob and McClintock, 2000; Jacob et al., 2001a). In order to determine whether similar musky compounds also produce these effects, we compared the effects of androstadienone to those of androstenol and muscone, measuring the psychological states of 37 participants. Androstenol and muscone were chosen because they too have a musky odor at high concentrations, while androstenol is a steroid like androstadienone and muscone is not. In a controlled laboratory setting, we conducted a double-blind, within-subject, repeated-measures experiment counterbalanced for order of presentation. Under each participant's nose, a nanomolar amount of each compound was presented, masked by clove oil to minimize perceptible olfactory differences. Participants completed a baseline psychological battery and twice again at 25-min intervals after exposure. Androstadienone's effects on psychological state were unique in comparison with those of androstenol and with muscone. Exposure through passive inhalation, rather than dermal contact, was sufficient for these effects. Although this is additional evidence that androstadienone may be a pheromone, it is yet to be determined whether humans exude concentrations into the air adequate for social communication or process this chemical information within natural social contexts.