Improving Outcomes in Late-Life Schizophrenia

Psychiatric TimesVol 38, Issue 12

What treatment strategies are available to improve the quality of life for older adults who are aging with schizophrenia?

Older adults with schizophrenia include individuals with both early- and late-onset illness. A distinction based on age is not a separate diagnosis in the ICD or the DSM-5; however, the International Late-Onset Schizophrenia Group has proposed subdividing the diagnosis of schizophrenia into distinct age groups.1 A listing of the 3 distinct age groups is found in Table 1.

We focus here on treatment strategies to improve the quality of life for both older adults who are aging with schizophrenia, and those who are first diagnosed with schizophrenia after age 40 years.

Table 1. Subcategories From the International Late-Onset Schizophrenia Group

Table 1. Subcategories From the International Late-Onset Schizophrenia Group

Early-Onset Schizophrenia

Although patients diagnosed with early-onset schizophrenia (EOS) have an increased risk of premature mortality when compared with the general population, more individuals diagnosed with schizophrenia are living longer. This increased longevity is due to improvements in treatments for schizophrenia and for co-occurring medical conditions, such as hypertension, tobacco use, diabetes mellitus, and hyperlipidemia.2

In our clinical experience, adults with EOS will often develop adverse effects in association with medications that are no longer effective as they age. Staying receptive to changes in the needs of the older patient, as well as to the challenges presented for the family and caregivers, helps ensure the formulation of a treatment plan that is manageable and sustainable in the community.

Case Study 1

“Ms Kahn” is an African American woman, aged 63 years, who was diagnosed with schizophrenia during her adolescence. Her disease course is notable for prominent positive symptoms despite treatment with clozapine for more than 10 years. Her medical course is notable for chronic constipation complicated by paralytic ileus, severe tardive dyskinesia, and benign ethnic neutropenia. Her primary support is her sister, who is also her health care proxy.

Ms Kahn recently experienced an episode of paralytic ileus, which required a medical admission, followed by a psychiatric admission for a review of her medication regimen and a gastrointestinal consultation. An attempt was made to maintain Ms Kahn on clozapine because of her favorable response as compared with other atypical antipsychotics. Clozapine could be successfully maintained, however, only with a complex bowel regimen including osmotic diuretics, stool softeners, laxatives, gastric transit accelerators, and enemas. Subsequently, Ms Kahn’s sister reported the difficulty of maintaining this complex regimen, and family meetings were arranged with the patient and her multidisciplinary medical team that included her gastrointestinal specialist. Ultimately, clozapine was cross-tapered to aripiprazole, which she appears to tolerate.

This case illustrates the challenges of treating aging adults diagnosed with EOS. The importance of collaborative care among the treatment teams, the patient, their family, and caregivers cannot be overemphasized. The case also illustrates the need for regular interdisciplinary communication when working with older adults who are diagnosed with multiple medical comorbidities. Finally, it underscores the importance of parsimony in medication regimen for older patients, especially those with schizophrenia.1

New-Onset After Age 40 Years

Delusions and hallucinations in patients 40 years or older are usually associated with co-occurring medical illness, cognitive impairment, inappropriate medications, and sensory deficits.3,4 When such illnesses are not contributing to the origin of new-onset psychosis, a diagnosis of late-onset schizophrenia (LOS) or very late-onset schizophrenia (VLOS) should be considered. A summary of key risk factors for developing LOS and VLOS is found in Table 2.3

Table 2. Key Risk Factors for Developing LOS and VLOS

Table 2. Key Risk Factors for Developing LOS and VLOS


Epidemiology data for psychosis diagnosed after age 40 years are sparse, although some estimates state that 20% to 25% of patients with schizophrenia had an onset of the disorder after age 40 years.4 The prevalence estimate for schizophrenia is 0.6% to 1.0% in individuals aged between 45 and 64 years, and 0.1% and 0.5% in individuals 65 years and older.4

Case Study 2

“Ms Garcia,” a Hispanic woman aged 65 years, presented to the emergency department (ED) for sudden onset of strange thoughts and behaviors, accompanied by her husband. She had no personal or family history of psychiatric disorders, and was retired and the mother of 1 adult son. At home, she had been wandering aimlessly without eating or drinking for several days. Despite evidence to the contrary, Ms Garcia feared her son had been abducted.

In the ED, she was suspicious, irritable, and disheveled. Ms Garcia was admitted to the medical unit where an exhaustive workup, including blood tests, heavy metals panel, lumbar puncture, and brain imaging, did not suggest a contributing etiology. She was transferred to psychiatric care, where she was diagnosed with VLOS. Her symptoms responded well to a gradual titration of olanzapine 10 mg at bedtime. During her hospitalization, she responded favorably to group interventions focused on recreational activities, peer supports, social skills training, and cognitive-enhancing interventions.

Engagement with Ms Garcia’s family began in the ED and continued throughout her admission. Early contacts obtained collateral history and information on the patient’s level of daily functioning. As her admission progressed, family meetings provided psychoeducation about her diagnosis and treatment planning to encourage the engagement of her family as collaborators in her care. Particular attention was given to the family’s language preferences, cultural values, and spiritual beliefs, and how these might influence their understanding of her diagnosis and treatment plan. Ms Garcia was referred to a community adult recreational center where she enjoys participating with peers and staff in social activities and treatment groups. Working with the family and case manager, her treatment team continues to monitor her symptoms, providing regular cognitive and functional assessments of other possible etiologies for her psychosis, such as dementia.

This case illustrates the importance of a comprehensive history and medical workup for older adults to rule out secondary causes of psychosis prior to a diagnosis of VLOS.4 Determining the correct diagnosis is imperative to facilitate early intervention and treatment. This case also illustrates good clinical practice of obtaining collateral information while engaging with the patient and the family in a manner that is culturally sensitive. Finally, the case underscores the value of combining pharmacology with psychosocial interventions to sustain recovery while engaging the patient in postdischarge treatment by offering regular assessments. This case also underscores the importance of a comprehensive approach when developing treatment plans for older adults diagnosed with VLOS.4

Clinical Evaluation

Privacy and communication are essential for a thorough clinical evaluation. Privacy is important because adults are concerned about discussing personal matters in the presence of their adult children and nonfamilial caregivers. Language barriers are bridged with translation services.

Adults with Disabilities

For older adults with disabilities, mobile apps are useful.5 Properly fitted eyeglasses and hearing aids in good working condition are essential. Patients who are deaf or hearing impaired necessitate specialized interpreter services.6

Clinical Presentation

There are significant differences in the clinical presentations of EOS when compared with LOS and VLOS, which have fewer negative symptoms. Patients diagnosed with LOS and VLOS tend to have a more successful history of employment and of intimate relations when compared with those with EOS.

Hallucinations and Delusions

The persecutory delusions of LOS are notable for accusatory voices and persecutory third-person commentaries. These symptoms are unlike the partition delusions and persecutory beliefs common in VLOS. Table 3 lists some distinguishing features of the hallucinations and delusions that are common in other disorders.

Table 3. Hallucinations and Delusions

Table 3. Hallucinations and Delusions

Cognitive Features

Teasing out the cognitive symptoms associated with LOS and VLOS that are superimposed on an aging brain can be difficult. Older adults with schizophrenia have twice the likelihood of developing dementia when compared with healthy peers.7 For clinical presentations that are complex, a comprehensive neuropsychological battery of testing with brain imaging can be helpful to clarify the diagnosis.

Pharmacology Treatment

Initial interventions with older patients should begin with a review of all medications, including prescribed treatments, herbal remedies, and over-the-counter supplements. This review is important to identify possible drug-to-drug interactions and medications that are on the Beers Criteria for Potentially Inappropriate Use in Older Adults.8 Care should be taken to avoid the risks and hazards of polypharmacy.

Antipsychotics have long been established as the standard treatment in schizophrenia. That means the big challenge for the clinician is include balancing the risks and benefits of treatment. Part of the difficulties of making this assessment, however, is a relative lack of research and evidence for the use of antipsychotics in older adults diagnosed with LOS.9 Metabolic and physiological changes associated with aging predispose the patient to be more sensitive to adverse effects, such as anticholinergic symptoms, increased fall risk, arrythmias, and QTc prolongation. In addition, concerns for increased risk of cerebrovascular events and mortality in elderly dementia patients with psychosis led to US Food and Drug Administration (FDA) black-box warnings on all antipsychotics. Expert consensus guidelines on the use of antipsychotic agents in older patients encourage the use of atypical antipsychotics at minimally effective dosage and using a slow titration.9

Early extrapyramidal symptoms (EPS) and advancing age are known risk factors for tardive dyskinesia (TD), a condition associated with higher mortality in psychiatric patients.10 Monitoring for EPS and TD is imperative. The Abnormal Involuntary Movement Scale should be used to monitor symptoms and to rate their severity.

Once EPS is diagnosed, a reasonable first step is to lower the antipsychotic dosage while considering a switch to an antipsychotic with less risk of EPS. Caution should be used with the addition of agents that may increase anticholinergic load.

Once TD is diagnosed, continued treatment with antipsychotics should be reviewed, including whether to discontinue treatment, decrease the dosage, or switch to an antipsychotic with less dopamine blockade. FDA-approved medications for the treatment of TD, such as the selective vesicular monoamine transporter 2 inhibitors valbenazine and deutetrabenazine, should be considered, especially for patients for whom continued use of antipsychotics is indicated. Given that the cumulative duration of antipsychotic treatment increases the risk of TD, antipsychotic dosage adjustments should be routinely considered in the older adult.

Psychosocial Interventions

In the older adult, the treatment plan should reflect an array of supports, ideally in an integrated care setting. Integrative care models have been shown to be effective for community-dwelling adults with severe mental illness, and efforts are being made to disseminate this collaborative approach on a global scale.11

Examples of other effective psychosocial interventions include family therapy, peer support, occupational therapy, cognitive behavioral therapy, cognitive remediation, and social skills training. Community resources, social programs, and support for caregivers are also known to promote and sustain recovery and to minimize the loneliness, isolation, and stigma associated with aging and a severe mental disorder.

Concluding Thoughts

Improving outcomes in late-life schizophrenia begins with a thorough medical evaluation to rule out secondary sources of psychosis. Ideally, treatment is patient-centered, culturally sensitive, and includes the judicious use of antipsychotics and psychosocial interventions.

More research is needed to understand the development of schizophrenia in late life. Initiatives to minimize the disease burden and improve the quality of life for older adults with schizophrenia and their families /caregivers are important. These interventions benefit society as a whole and should be a legislative priority.

Dr Diaz is an assistant clinical professor of psychiatry at Columbia University Irving Medical Center. Dr Clarke is an assistant clinical professor of psychiatry at Columbia University Irving Medical Center. Dr Holderness is an associate clinical professor of psychiatry at Columbia University Irving Medical Center. Drs Diaz, Clarke, and Holderness do not have any financial conflicts of interest to disclose.


1. Howard R, Rabins PV, Seeman MV, Jeste DV. Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: an international consensus. The International Late-Onset Schizophrenia Group. Am J Psychiatry. 2000;157(2):172-178.

2. World Health Organization. Global Health Risks: Mortality and Burden of Disease Attributable to Selected Major Risks. World Health Organization; 2009.

3. Tampi RR, Young J, Hoq R, et al. Psychotic disorders in late life: a narrative review. Ther Adv Psychopharmacol. 2019;9:2045125319882798.

4. Cohen CI, Meesters PD, Zhao J. New perspectives on schizophrenia in later life: implications for treatment, policy, and research. Lancet Psychiatry. 2015;2(4):340-350.

5. Accessibility apps. Accessed September 28, 2021.

6. Barnett S, McKee M, Smith SR, Pearson TA. Deaf sign language users, health inequities, and public health: opportunity for social justice. Prev Chronic Dis. 2011;8(2):A45.

7. Cai L, Huang J. Schizophrenia, and risk of dementia: a meta-analysis study. Neuropsychiatr Dis Treat. 2018;14:2047-2055.

8. 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694.

9. Alexopoulos GS, Streim J, Carpenter D, Docherty JP; Expert Consensus Panel for Using Antipsychotic Drugs in Older Patients. Using antipsychotic agents in older patients. J Clin Psychiatry. 2004;65 Suppl 2:5-99;discussion 100-102;quiz 103-104.

10. Woerner MG, Alvir JM, Saltz BL, et al. Prospective study of tardive dyskinesia in the elderly: rates and risk factors. Am J Psychiatry. 1998;155(11):1521-1528.

11. Bartels SJ, DiMilia PR, Fortuna KL, Naslund JA. Integrated care for older adults with serious mental illness and medical comorbidity: evidence-based models and future research directions. Clin Geriatr Med. 2020;36(2):341-352. ❒

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