Managing suicidality in schizophrenia

The primary objective of this review article is to provide a coherent, systematic synthesis of the literature on the management of suicidality in schizophrenia that is relevant to the front-line clinician. Literature searches were conducted on MEDLINE (1996 to 2007) and PubMed (1993 to 2007), using the key words "schizophrenia" and "suicide," as well as references from the resulting articles. I used my own clinical experience to create fictional case examples to illustrate the applicability of the literature discussed in this paper. Suicidality in schizophrenia is high, and early detection relies on the appreciation and evaluation of the clinical manifestations of depression, despair, and hopelessness, as well as on the nature and severity of the psychotic experience itself, particularly in recent-onset patients with higher cognitive function and educational background. Clinical management includes ensuring immediate safety, the use of psychosocial techniques to address depression and psychosocial stressors, targeted pharmacotherapy for depression and psychosis, and adequate discharge planning. Clozapine is the only antipsychotic with good evidence for efficacy in decreasing suicidal behaviour in schizophrenia. The optimal management of suicidality in schizophrenia involves the incorporation of traditional bedside clinical skills, selection of psychosocial modalities based on individual needs, and selective pharmacotherapy directed primarily at psychotic and depressive symptoms.peer-reviewe

Low dose vs standard dose of antipsychotics for relapse prevention in schizophrenia : meta-analysis

Background: It remains unknown as to whether the antipsychotic dose needed for the acute-phase treatment of schizophrenia is also necessary for relapse prevention. Aim: To compare the efficacy between standard dose [(World Health Organization daily defined dose (DDD)] vs low dose (≥50% to <1 DDD) or very low dose (<50% DDD) for relapse prevention in schizophrenia. Data source: Double-blind, randomized, controlled trials with a follow-up duration of ≥24 weeks, including ≥2 dosage groups of the same antipsychotic drug for relapse prevention in schizophrenia, were searched using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE (last search: August 2009). Data extraction: Data on overall treatment failure, hospitalization, relapse, and dropouts due to side effects were extracted and combined in a meta-analysis. Data synthesis: Thirteen studies with 1395 subjects were included in this meta-analysis. Compared with the standard-dose treatment, the low-dose therapy did not show any statistically significant difference in overall treatment failure or hospitalization, while the standard dose showed a trend-level (P = .05) superiority in risk of relapse. The very low–dose group was inferior to the standard-dose group in all efficacy parameters. No significant difference was found in the rate of dropouts due to side effects between either standard dose vs low dose or very low dose. Conclusions: Although antipsychotic treatment with ≥50% to <1 DDD may be as effective as standard-dose therapy, there are insufficient clinical trial data to draw firm conclusions on standard- vs low-dose maintenance antipsychotic therapy for schizophrenia.peer-reviewe

Differentiating the Cognitive Profile of Schizophrenia from That of Alzheimer Disease and Depression in Late Life

To compare the cognitive profile of older patients with schizophrenia to those with other neuropsychiatric disorders assessed in a hospital-based memory clinic.Demographic, clinical, and cognitive data of all patients referred to the memory clinic at the Centre for Addiction and Mental Health between April 1, 2006 and August 15, 2008 were reviewed. We then identified four groups of older patients with: (1) late-life schizophrenia (LLS) and no dementia or depression (DEP); (2) Alzheimer's disease (AD); (3) DEP and no dementia or LLS; (4) normal cognition (NC) and no DEP or LLS.The four groups did not differ in demographic data except that patients with AD were about 12 years older than those with LLS. However, they differed on cognitive tests even after controlling for age. Patients with LLS were impaired on most cognitive tests in comparison with patients with NC but not on recalling newly learned verbal information at a short delay. They experienced equivalent performance on learning new verbal information in comparison with patients with AD, but better performance on all other tests of memory, including the ability to recall newly learned verbal information. Finally, they were more impaired than patients with DEP in overall memory.Patients with LLS have a different cognitive profile than patients with AD or DEP. Particularly, memory impairment in LLS seems to be more pronounced in learning than recall. These findings suggest that cognitive and psychosocial interventions designed to compensate for learning deficits may be beneficial in LLS

Neurobiology of delusions in Alzheimer’s disease

Alzheimer’s disease (AD) is associated with cognitive and functional impairment as well as neuropsychiatric sequelae, including psychotic symptoms such as delusions and hallucinations. Strong evidence supports the need to study delusions separate from hallucinations. Integrating the epidemiology, clinical correlates, and neuropathological and genetic literature for delusions in AD allows us to speculate on etiology and mechanisms. Plaque and tangle deposition in individuals with susceptible alleles of serotonergic, muscarinic, nicotinic, or Apoε4 genes appears to result in disruption of cortical circuitry, culminating in delusions. While delusions in AD correspond to a phenotype distinct from AD without delusions, subtypes of delusions may also define further distinct clinical entities. Persecutory delusions may occur earlier in the illness and have a more significant genetic component than misidentification delusions, which are associated with increased cognitive impairment and advanced dementia. Clearly distinguishing between these two syndromes is essential to making progress in the area of delusions in AD.peer-reviewe

Is desire for social relationships mediated by the serotonergic system in the prefrontal cortex? An [18F] setoperone PET study

Social behavior and desire for social relationships have been independently linked to the serotonergic system, the prefrontal cortex, especially the orbitofrontal cortex (OFC), and the anterior cingulate cortex (ACC). The goal of this study was to explore the role of serotonin 5HT2A receptors in these brain regions in forming and maintaining close interpersonal relationships. Twenty-four healthy subjects completed the Temperament and Character Inventory (TCI) prior to undergoing [18F]setoperone brain positron emission tomography (PET) to measure serotonin 5HT2A receptor availability within the OFC (BA 11 and 47) and ACC (BA 32). We explored the relationship between desire for social relationships, as measured by the TCI reward dependence (RD) scale, and 5HT2A receptor non-displaceable binding potential (BPnd) in these regions. Scores of RD were negatively correlated with 5HT2A BPnd in the ACC (BA 32, r = –.528, p = .012) and OFC (BA 11, r = –.489, p = .021; BA 47, r = –.501, p = .017). These correlations were corroborated by a voxel-wise analysis. These results suggest that the serotonergic system may have a regulatory effect on the OFC and ACC for establishing and maintaining social relationships.peer-reviewe