Several etiologies can underlie the development of late-onset psychosis, defined by first psychotic episode after age 40 years. Late-onset psychosis is distressing to patients and caregivers, often difficult to diagnose and treat effectively, and associated with increased morbidity and mortality.

The literature was reviewed with searches in Pubmed, MEDLINE, and the Cochrane library. Search terms included “psychosis,” “delusions,” hallucinations,” “late onset,” “secondary psychoses,” “schizophrenia,” bipolar disorder,” “psychotic depression,” “delirium,” “dementia,” “Alzheimer’s,” “Lewy body,” “Parkinson’s, “vascular dementia,” and “frontotemporal dementia.” This overview covers the epidemiology, clinical features, neurobiology, and therapeutics of late-onset psychoses.

Late-onset schizophrenia, delusional disorder, and psychotic depression have unique clinical characteristics. The presentation of late-onset psychosis requires investigation for underlying etiologies of “secondary” psychosis, which include neurodegenerative, metabolic, infectious, inflammatory, nutritional, endocrine, and medication toxicity. In delirium, psychosis is common but controlled evidence is lacking to support psychotropic medication use. Delusions and hallucinations are common in Alzheimer’s disease, and hallucinations are common in Parkinson’s disease and Lewy body dementia. Psychosis in dementia is associated with increased agitation and a poor prognosis. Although commonly used, no medications are currently approved for treating psychosis in dementia patients in the USA and nonpharmacological interventions need consideration.

The plethora of possible causes of late-onset psychosis requires accurate diagnosis, estimation of prognosis, and cautious clinical management because older adults have greater susceptibility to the adverse effects of psychotropic medications, particularly antipsychotics. Research is warranted on developing and testing efficacious and safe treatments for late-onset psychotic disorders.

To review the evidence for the use of paliperidone palmitate for people with schizophrenia and schizophrenia-like illnesses. We searched the Cochrane Schizophrenia Group Specialised Register and contacted the manufacturer of paliperidone palmitate, the US Food and Drug Administration, and the authors of papers that reported study results.

Based on the evidence from five short-term, placebo-controlled studies, paliperidone palmitate is efficacious as an antipsychotic. Its adverse effects are similar to those of the closely related compounds paliperidone and risperidone. Extrapyramidal side-effects, weight gain and tachycardia are more common with paliperidone palmitate than placebo. Paliperidone palmitate was associated with substantial increases in serum prolactin but not with increased sexual side-effects in these studies. In two studies paliperidone palmitate was similar to depot risperidone.

Paliperidone palmitate is an effective antipsychotic whose optimal dose appears to be between 39 and 234 mg every 4 weeks. We have no data assessing its long-term effectiveness or comparing it with any long-acting injected antipsychotic other than depot risperidone.

There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs.

To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and perphenazine in people with schizophrenia.

Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. Mixed model analyses of change in rating scales from baseline were also conducted.

There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and perphenazine.

The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and perphenazine or between second-generation antipsychotics in people with schizophrenia.

Violence is an uncommon but significant problem associated with schizophrenia

To compare antipsychotic medications in reducing violence among patients with schizophrenia over 6 months, identify prospective predictors of violence and examine the impact of medication adherence on reduced violence

Participants (n=1445) were randomly assigned to double-blinded treatment with one of five antipsychotic medications. Analyses are presented for the intention-to-treat sample and for patients completing 6 months on assigned medication

Violence declined from 16% to 9% in the retained sample and from 19% to 14% in the intention-to-treat sample. No difference by medication group was found, except that perphenazine showed greater violence reduction than quetiapine in the retained sample. Medication adherence reduced violence, but not in patients with a history of childhood antisocial conduct. Prospective predictors of violence included childhood conduct problems, substance use, victimisation, economic deprivation and living situation. Negative psychotic symptoms predicted lower violence

Newer antipsychotics did not reduce violence more than perphenazine. Effective antipsychotics are needed, but may not reduce violence unrelated to acute psychopathology

Although people with schizophrenia display impaired abilities for consent, it is not known how much impairment constitutes incapacity.

To assess a method for determining the categorical capacity status of potential participants in schizophrenia research.

Expert-judgement validation of capacity thresholds on the sub-scales of the MacArthur Competence Assessment Tool – Clinical Research (MacCAT–CR) was evaluated using receiver operating characteristic (ROC) analysis in 91 people with severe mental illness and 40 controls.

The ROC areas under the curve for the understanding, appreciation and reasoning sub-scales of the MacCAT–CR were 0.94 (95% CI 0.88–0.99), 0.85 (95% CI 0.76–0.94) and 0.80 (95% CI 0.70–0.90). These findings yielded negative and positive predictive values of incapacity that can guide the practice of investigators and research ethics committees.

By performing such validation studies for a few categories of research with varying risks and benefits, it might be possible to create evidence-based capacity determination guidelines for most schizophrenia research.