Very late-onset schizophrenia-like psychosis: positive findings but questions remain unanswered
Authors: Carl I Cohen
Journal: The Lancet Psychiatry (2018)

Robert Howard and colleagues1Howard R Cort E Bradley R et al.Antipsychotic treatment of very late-onset schizophrenia-like psychosis: a randomised controlled double-blind trial.Lancet Psychiatry. 2018; (published online June 4.)http://dx.doi.org/10.1016/S2215-0366(18)30141-XSummary Full Text Full Text PDF Scopus (21) Google Scholar should be commended for doing the first randomised controlled trial of an antipsychotic agent in patients diagnosed with very late-onset schizophrenia-like psychosis. Individuals with this diagnosis are notoriously difficult to engage in treatment. One study2Sin Fai Lam CC Reeves SJ Stewart R Howard R Service and treatment engagement of people with very late-onset schizophrenia-like psychosis.B J Psych Bulletin. 2016; 40: 185-186Google Scholar found that, on hospital discharge, 54% of participants did not engage in care or were lost to follow-up. In the study by Howard and colleagues, only 12 (40%) of 30 patients assigned to amisulpride throughout the study (group A) remained on treatment at 24 or 36 weeks. Although participants in the amisulpride group had significantly improved BPRS scores at 12 weeks, seven (37%) of 19 dropped out over the next 12 to 24 weeks. The proportion of dropouts is frustrating since the findings showed that many patients who chose to stay in care responded robustly to the medication. It would be helpful to explore patients' perceptions of care and whether there are differences between patients who drop out and those who remain in the study. Howard and colleagues found that people taking amisulpride did not perceive any notable improvement in their quality of life and 11 (18%) of all 61 medicated patients stopped treatment because of side-effects versus three (10%) of 31 people given placebo. Thus, with respect to stopping care because of side-effects, I calculated that the number needed to harm would be 12. The number of side-effects per person was more than double in the groups that received amisulpride (as shown in the Article's appendix), and the NNH for serious adverse events during stage 1 of the study was 8, which is worrisome. People who are reluctant to take medications might see the risk of adverse events as too high. Anosognosia occurs in over half of people with schizophrenia and it has been linked to neuropathological processes.3Chakraborty K Basu D Insight in schizophrenia—a comprehensive update.German J Psychiatry. 2010; 13: 17-30Google Scholar It might be even more common in very late-onset schizophrenia-like psychosis, which would suggest a greater likelihood of underlying brain transformations in the latter group. A clinical paradox is that some patients still accept treatment even if they do not believe that there is anything wrong with them. A future investigation might examine strategies that clinicians use to successfully engage patients. Like many clinicians who work with this population, often my goal is to try to change denial into rationalisation (ie, collaborate with the patient to find a compelling reason to stay in treatment). Sometimes rating scales are unable to capture the benefits that patients accrue from treatment. Many patients continue to have some psychotic symptoms but are less concerned by them. Therapeutic strategies (eg, CBT and supportive therapy) that help patients to cope and not engage in antisocial acts can be useful, even if symptoms remain. Given the increased risks of side-effects, mortality, and medical conditions associated with the use of antipsychotics in older adults, 4Sahlberg M Holm E Gislason GH Køber L Torp-Pedersen C Andersson C Association of selected antipsychotic agents with major adverse cardiovascular events and noncardiovascular mortality in elderly persons.J Am Heart Assoc. 2015; 4: e001666Crossref PubMed Scopus (33) Google Scholar non-pharmacological alternatives are attractive and should be included in future research. Finally, a closer look at the phenotype is warranted. Very late-onset schizophrenia-like psychosis is not included in the DSM-5 or ICD-10; indeed, the latter omitted the ICD-9 diagnosis of late paraphrenia. The term very late-onset schizophrenia-like psychosis was coined by an international consensus group that met in 1998.5Howard R Rabins PV Seeman MV Jeste DV the International Late-Onset Schizophrenia GroupLate-onset schizophrenia and very late-onset schizophrenia-like psychosis: an international consensus.Am J Psychiatry. 2000; 157: 172-178Crossref PubMed Scopus (437) Google Scholar The group suggested that there were differences between late-onset schizophrenia beginning at age 40 years and very late-onset schizophrenia-like psychosis that began after the age of 60 years. Basing a diagnosis on age without a persuasive rationale for that specific age cutoff is rare in medical nosology. Ideally, the syndrome should have been identified, and then tested for an association with an increased probability of occurrence after age 60 years. Stability of diagnosis is important for validation. Given that the risk for dementia in patients with very late-onset schizophrenia-like psychosis can be three times that of their age-matched peers,6Kørner A Lopez AG Lauritzen L Andersen PK Kessing LV Late and very-late first-contact schizophrenia and the risk of dementia—a nationwide register based study.Int J Geriatr Psychiatry. 2009; 24: 61-67Crossref PubMed Scopus (50) Google Scholar, 7Lagodka A Robert P Is late-onset schizophrenia related to neurodegenerative processes? A review of literature.Encephale. 2009; 35: 386-393Crossref PubMed Scopus (17) Google Scholar and one study found that nearly half of patients had developed dementia on 5-year follow-up,8Brodaty H Sachdev P Koschera A Monk D Cullen B Long-term outcome of late-onset schizophrenia: 5-year follow-up study.Br J Psychiatry. 2003; 183: 213-219Crossref PubMed Scopus (86) Google Scholar the symptoms thought to be those of late-onset schizophrenia could, instead, be prodromes of dementia. It is still under debate whether this propensity to develop dementia is a true characteristic of this subtype or suggests an initial misdiagnosis. Moreover, the prevalence of mild cognitive impairment is estimated to be 17% among the general elderly population.9Petersen RC Lopez O Armstrong MJ et al.Practice guideline update summary: mild cognitive impairment report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.Neurology. 2018; 90: 126-135Crossref PubMed Scopus (817) Google Scholar It is not known if people with very late-onset schizophrenia-like psychosis are at increased risk of mild cognitive impairment, which carries a high risk of progression into a dementia. In the study by Howard and colleagues,1Howard R Cort E Bradley R et al.Antipsychotic treatment of very late-onset schizophrenia-like psychosis: a randomised controlled double-blind trial.Lancet Psychiatry. 2018; (published online June 4.)http://dx.doi.org/10.1016/S2215-0366(18)30141-XSummary Full Text Full Text PDF Scopus (21) Google Scholar about half of participants might have had mild cognitive impairment (ie, Mini Mental State Examination score 25–27). Another consideration is that psychotic symptoms in many individuals with early-onset schizophrenia continue to fluctuate in later life and people can move in and out of remission;10Cohen CI Freeman K Ghoneim D Vengassery A Ghezelaiagh B Reinhardt MM Advances in the Conceptualization and Study of Schizophrenia in Later Life.Psychiatr Clin North Am. 2018; 41: 39-53Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar it is not known to what extent these fluctuations occur among those with very late-onset schizophrenia-like psychosis. Clearly, longitudinal data are needed. Medical conditions might also confound the diagnosis of very late-onset schizophrenia-like psychosis. Mortality rates are higher in this group of patients than in older adults with early-onset schizophrenia,11Talaslahti T Alanen HM Hakko H Isohanni M Hakkinen U Leinonen E Patients with very late-onset schizophrenia-like psychosis have higher mortality rates than elderly patients with earlier onset schizophrenia.Int J Geriatr Psychiatry. 2015; 30: 453-459Crossref PubMed Scopus (26) Google Scholar and the effect of physical comorbidities on symptoms in very late-onset schizophrenia-like psychosis should be elaborated. A final concern is that the precise age of onset of the disorder is difficult to determine and a diagnosis of very late-onset schizophrenia-like psychosis might be based on age at clinical contact rather than onset age. Because of these concerns, the findings reported by Howard and colleagues should be viewed as encouraging but provisional. I declare no competing interests. Antipsychotic treatment of very late-onset schizophrenia-like psychosis (ATLAS): a randomised, controlled, double-blind trialLow-dose amisulpride is effective and well tolerated as a treatment for very late-onset schizophrenia-like psychosis, with benefits maintained by prolonging treatment. Full-Text PDF Open Access