Diagnosing and Treating Psychotic Disorders in Late Life

Although psychosis often emerges relatively early in life, it can also appear for the first time in older patients. These cases raise special challenges. The morbidity and mortality rates for psychosis in late life are significantly greater when compared with those for psychosis among younger individuals.¹ Furthermore, greater incidence of adverse effects is noted when antipsychotic medications are prescribed to older adults.² But once clinicians determine the root of the problem, they have an array of potentially effective treatment options.

Primary and Secondary Disorders

In identifying psychotic disorders in late life, a distinction must be made between primary psychotic disorders and secondary psychotic disorders.³ The term primary psychotic disorders describes conditions in which the psychotic symptoms are the main clinical presentation of the illness. Primary psychotic disorders include illnesses along the schizophrenia spectrum, major depressive disorder (MDD), and bipolar disorder with psychotic features.

The term secondary psychotic disorders refers to illnesses in which psychosis is the secondary or associated symptom, not the core clinical feature of the disorder. Examples of secondary psychotic disorders including delirium, neurocognitive disorders, psychosis due to drugs of abuse or prescribed medications, or psychosis due to medical or neurological disorders.⁴ Available evidence indicates that among older adults, approximately 60% of the cases are secondary disorders.^4,5

Diagnosis

A thorough history, including information from collateral sources, can help differentiate between primary and secondary causes.⁶ Acute or subacute onset of symptoms might suggest the occurrence of delirium or of substance- or medication-induced psychosis. Insidious onset of symptoms may suggest a primary psychotic disorder, such as a schizophrenia spectrum disorder.

Features suggestive of a secondary psychotic disorder include an atypical age of onset of symptoms, visual hallucinations presenting independently of auditory hallucinations, the occurrence of psychotic symptoms in an individual with no previous psychiatric history or no family history, the presence of abnormal findings on physical examinations, or evidence of the use of prescribed medications or abuse of illicit substances.⁷ The Figure describes a workup for psychotic disorders in late life.

Exploring Treatment Strategies

For secondary psychotic disorders, the initial treatment involves addressing possible causes, including the discontinuation of offending medications or drugs of abuse or the treatment of underlying medical or neurological causes.⁸ For psychotic symptoms that are unresponsive to these strategies, pharmacological treatment becomes essential.^5,8 Antipsychotic medications should be prescribed to older adults cautiously, as their long-term use may cause significant adverse effects.^9,10 Available guidelines recommend the short-term use of antipsychotics to treat the psychotic symptoms.² Before initiating treatment with antipsychotic medications, clinicians should always perform a risk-benefit analysis, keeping in mind the individual’s physical condition and comorbid medical disorders.^2,11 Starting medication at a lower dose (one-fourth to half the starting dose for adults) and gradually titrating to the optimal dose may reduce the incidence of adverse effects.¹²

Available evidence indicates that risperidone and olanzapine may be useful in the treatment of older adults with schizophrenia.¹³ One randomized controlled trial study that evaluated the use of amisulpride (not available in the United States) at 100 mg daily in patients who were diagnosed with very-late–onset schizophrenia found a significant improvement in the Brief Psychiatric Rating Scale compared with placebo.¹⁴ There is also some evidence for using paliperidone among older adults with schizophrenia.¹⁵ Expert consensus guidelines recommend using risperidone at 1.25 mg to 3.5 mg a day as the first-line agent for older adults with schizophrenia, followed by quetiapine at 100 mg to 300 mg a day, olanzapine at 7.5 mg to 15 mg a day, or aripiprazole at 15 mg to 30 mg a day.¹⁶ There is little support for using clozapine among older individuals with psychotic disorders, possibly due to its significant adverse effect profile.¹⁷

Among older adults who have MDD with psychotic features, the combination of olanzapine and sertraline was associated with higher remission rates during the treatment period when compared with treatment with olanzapine or placebo, with good tolerability noted for the medication combination.¹⁸ In a systematic review of meta-analyses that evaluated the use of antipsychotics among individuals with dementia, the investigators found that antipsychotics had modest efficacy in treating psychosis, aggression, and agitation.¹⁹ The use of these medications was often limited by their AE profile. The investigators noted that the use of antipsychotics should be reserved for severe symptoms that have failed to adequately respond to nonpharmacological management strategies.

A meta-analysis that evaluated the prevention and treatment of delirium among surgical and medical patients found that antipsychotics had limited efficacy in treating delirium.²⁰ There is also significant controversy regarding the use of antipsychotics among older adults who present with severe psychosis due to dementia.¹⁹ The FDA has a boxed warning indicating an association between the use of antipsychotics among older adults with dementia and increased risk for mortality.²¹ Additionally, the use of antipsychotics in this patient population increases the risk for cerebrovascular adverse events, metabolic side effects, and pneumonia, when compared with age-matched controls who were not prescribed these drugs.^21,22

Antipsychotic medications should be discontinued as soon as clinically possible to avoid serious adverse effects among older adults.^19,21 However, there are limited data regarding discontinuation, especially among individuals with schizophrenia.²³ It would be prudent to attempt discontinuation of antipsychotics among older adults only when 1 or more of the following 3 conditions have been met: (1) the patient has not adequately responded to these medications; (2) the medications have resulted in intolerable adverse effects; or (3) the individual has demonstrated long-standing clinical remission. Decreasing the dose of medications to the lowest effective dosage should be attempted when discontinuation of these medications is not feasible due to persistent psychotic symptoms.

Bilateral electroconvulsive therapy has been found to be a safe and effective treatment for older patients with schizophrenia, in conjunction with antipsychotic medications, especially among those individuals who present with catatonia, aggression, or acute suicidal states, or when there is an acute onset of symptoms.²⁴

Available data indicate efficacy for cognitive behavioral social skills training (CBSST), functional adaptation skills training (FAST), supported employment, social skills training, and preventative health care programs among older individuals with psychotic disorders.^25-29 Additionally, better work outcomes and superior quality of life were noted for older individuals with schizophrenia who received supported employment when compared with conventional vocational rehabilitation programs.^30-31 The Table

describes further treatments for psychotic disorders arising in late life.

Concluding Thoughts

Most cases of psychotic disorders in late life likely occur due to underlying medical or neurological illnesses and/or due to the effects of medications or illicit drugs. The differentiation of primary and secondary causes can be accomplished via a thorough history, a comprehensive mental status examination, a focused physical examination, appropriate laboratory data or imaging studies, and a formal neuropsychological assessment for difficult-to-diagnose cases.

The use of antipsychotic medications among older adults is fraught with risks given these drugs’ significant adverse effect profile, including the increased risk of death among individuals with dementia. It is recommended that antipsychotic medications be used among older adults at the lowest effective doses and for the shortest time period.

The early identification and prompt removal or treatment of secondary causes of psychosis will reduce undue suffering among vulnerable older adults. Psychosocial treatments have been found to be effective in the treatment of primary psychotic disorders among older individuals. Future studies should focus on the risk factors, neurobiology, and treatment of psychotic disorders in late life, so that we better understand and treat these varied group of disorders.

Dr Tampi is professor and chairman, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, and Chief, Section for Geriatric Psychiatry, Department of Psychiatry and Psychology, Cleveland Clinic.

References

1. Talaslahti T, Alanen H-M, Hakko H, et al. 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(5):453-459.

2. Gareri P, Segura-García C, Manfredi VGL, et al. Use of atypical antipsychotics in the elderly: a clinical review. Clin Interv Aging. 2014;9:1363-1373.

3. Colijn MA, Nitta BH, Grossberg GT. Psychosis in later life: a review and update. Harv Rev Psychiatry. 2015;23(5):354-367.

4. Holroyd S, Laurie S. Correlates of psychotic symptoms among elderly outpatients. Int J Geriatr Psychiatry. 1999;14(5):379-384.

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

6. Freudenreich O, Schulz SC, Goff DC. Initial medical work-up of first-episode psychosis: a conceptual review. Early Interv Psychiatry. 2009;3(1):10-18.

7. Marsh L, Williams JR, Rocco M, et al. Psychiatric comorbidities in patients with Parkinson disease and psychosis. Neurology. 2004;63(2):293-300.

8. Targum SD. Treating psychotic symptoms in elderly patients. Prim Care Companion J Clin Psychiatry. 2001;3(4):156-163.

9. Nerius M, Johnell K, Garcia-Ptacek S, et al. The impact of antipsychotic drugs on long-term care, nursing home admission, and death in dementia patients. J Gerontol A Biol Sci Med Sci. 2018;73(10):
1396-1402.

10. Chahine LM, Acar D, Chemali Z. The elderly safety imperative and antipsychotic usage. Harv Rev Psychiatry. 2010;18(3):158-172.

11. Steinberg M, Lyketsos CG. Atypical antipsychotic use in patients with dementia: managing safety concerns. Am J Psychiatry. 2012;169(9):900-906.

12. Lehman AF, Lieberman JA, Dixon LB, et al; American Psychiatric Association; Steering Committee on Practice Guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 Suppl):1-56.

13. Marriott RG, Neil W, Waddingham S. Antipsychotic medication for elderly people with schizophrenia. Cochrane Database Syst Rev. 2006;2006(1):
CD005580.

14. Howard R, Cort E, Bradley R, et al; ATLAS Trialists Group. Antipsychotic treatment of very late-onset schizophrenia-like psychosis (ATLAS): a randomised, controlled, double-blind trial. Lancet Psychiatry. 2018;5(7):553-563. Published correction appears in Lancet Psychiatry. 2018;5(7):e16.

15. Tzimos A, Samokhvalov V, Kramer M, et al. Safety and tolerability of oral paliperidone extended-release tablets in elderly patients with schizophrenia: a double-blind, placebo-controlled study with six-month open-label extension. Am J Geriatr Psychiatry. 2008;16(1):31-43.

16. 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.

17. Shanker Reddy Mukku S, Sivakumar PT, Varghese M. Clozapine use in geriatric patients – challenges. Asian J Psychiatr. 2018;33:63-67.

18. Meyers BS, Flint AJ, Rothschild AJ, et al; STOP-PD Group. A double-blind randomized controlled trial of olanzapine plus sertraline vs olanzapine plus placebo for psychotic depression: the study of pharmacotherapy of psychotic depression (STOP-PD). Arch Gen Psychiatry. 2009;66(8):838-847. Published correction appears in Arch Gen Psychiatry. 2011;68(6):626.

19. Tampi RR, Tampi DJ, Balachandran S, Srinivasan S. Antipsychotic use in dementia: a systematic review of benefits and risks from meta-analyses. Ther Adv Chronic Dis. 2016;7(5):229-245.

20. Neufeld KJ, Yue J, Robinson TN, et al. Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2016;64(4):705-714.

21. Mittal V, Kurup L, Williamson D, et al. Risk of cerebrovascular adverse events and death in elderly patients with dementia when treated with antipsychotic medications: a literature review of evidence. Am J Alzheimers Dis Other Demen. 2011;26(1):10-28.

22. Rochon PA, Normand S-L, Gomes T, et al. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Intern Med. 2008;168(10):1090-1096.

23. Takeuchi H, Suzuki T, Remington G, et al. Effects of risperidone and olanzapine dose reduction on cognitive function in stable patients with schizophrenia: an open-label, randomized, controlled, pilot study. Schizophr Bull. 2013;39(5):993-998.

24. Meyer JP, Swetter SK, Kellner CH. Electroconvulsive therapy in geriatric psychiatry: a selective review. Psychiatr Clin North Am. 2018;41(1):79-93.

25. Granholm E, McQuaid JR, McClure FS, et al. A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia. Am J Psychiatry. 2005;162(3):520-529.

26. Granholm E, McQuaid JR, McClure FS, et al. Randomized controlled trial of cognitive behavioral social skills training for older people with schizophrenia: 12-month follow-up. J Clin Psychiatry. 2007;68(5):730-737.

27. Patterson TL, Mausbach BT, McKibbin C, et al. Functional adaptation skills training (FAST): a randomized trial of a psychosocial intervention for middle-aged and older patients with chronic psychotic disorders. Schizophr Res. 2006;86(1-3):291-299.

28. Bartels SJ, Pratt SI, Mueser KT, et al. Long-term outcomes of a randomized trial of integrated skills training and preventive healthcare for older adults with serious mental illness. Am J Geriatr Psychiatry. 2014;22(11):1251-1261.

29. Mueser KT, Pratt SI, Bartels SJ, et al. Randomized trial of social rehabilitation and integrated health care for older people with severe mental illness. J Consult Clin Psychol. 2010;78(4):561-573.

30. Twamley EW, Narvaez JM, Becker DR, Bartels SJ, Jeste DV. Supported employment for middle-aged and older people with schizophrenia. Am J Psychiatr Rehabil. 2008;11(1):76-89.

31. Twamley EW, Padin DS, Bayne KS, et al. Work rehabilitation for middle-aged and older people with schizophrenia: a comparison of three approaches. J Nerv Ment Dis. 2005;193(9):596-601. ❒