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Case Report

Clozapine in the Geriatric Patient With Neuropsychiatric Comorbidities

Megha J. Gupta, BS,a and Kim G. Johnson, MDb,*

Published: October 20, 2022

Prim Care Companion CNS Disord 2022;24(5):21cr03203

To cite: Gupta MJ, Johnson KG. Clozapine in the geriatric patient with neuropsychiatric comorbidities. Prim Care Companion CNS Disord. 2022;24(5):21cr03203.
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© 2022 Physicians Postgraduate Press, Inc.

aDuke University School of Medicine, Durham, North Carolina
bDepartment of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina
*Corresponding author: Kim G. Johnson, MD, 823 Broad St, Durham, NC 27705 (



Little is known about the development of cognitive changes or psychiatric symptoms in patients with intellectual disabilities as they age. Psychiatric symptoms with functional decline could be confused with or contribute to cognitive decline in patients experiencing neurodegeneration. The combination of intellectual disability with cognitive decline increases risk for behavioral manifestations including abnormal perceptions and agitation. There are little to no guidelines for treating these behavioral symptoms.1–3

Antipsychotics can be used in the geriatric population for primary psychosis and psychosis and agitation related to dementia. Data support the use of clozapine in this population, particularly for debilitating behavioral disturbances refractory to treatment with first-line antipsychotics, but with strong recommendations for low-dose initiation and slow titration.4–6

This case will explore the initiation of clozapine for a geriatric patient with intellectual disability who developed treatment-refractory behavioral disturbances and delusions.

Case Report

Ms A is a 68-year-old woman with diagnoses of Asperger syndrome (AS), social anxiety, and obsessive-compulsive disorder (OCD), which was successfully managed intermittently with quetiapine for many years.

She functioned and lived independently for most of her adult life. Then, at age 66 years, she experienced a subacute decline in her ability to care for herself secondary to an increase in obsessive thoughts, paranoia, and delusions requiring hospitalization. On neuropsychological testing, she displayed lack of frontal lobe function with utilization behavior, perseveration, and OCD-like qualities. She was presumed to have a frontotemporal lobar dementia (FTLD)–like process and was placed in a locked memory care facility. She continued to have prominent bizarre delusions triggered by anxiety. Her in-office cognitive testing and magnetic resonance imaging (MRI) of the brain were normal. Repeat formal neuropsychological testing indicated a frontal subcortical process with functional deficits thought most likely to be secondary to psychiatric causes. She was treated with risperidone and then switched to olanzapine. She developed a prominent hand tremor and oral tardive dyskinesia. Due to ongoing distressing bizarre delusions and movement symptoms, clozapine was started at low doses and titrated to 75 mg twice daily. After a period of 1 month of starting clozapine, the delusions, severe anxiety, tremor, and tardive dyskinesia resolved, and her functioning increased. The patient was able to move out of memory care into an assisted living facility.


This patient, over the age of 65 with multiple behavioral disturbances and paranoid delusions refractory to treatment with risperidone and olanzapine, did meet criteria for treatment with clozapine.5 In particular, autism spectrum disorder (ASD) did not preclude use of clozapine.7

Complicating factors in this patient’s treatment course include significant psychiatric comorbidities, comprising a historical diagnosis of AS and a possible FTLD diagnosis. Prior research with patients with ASD and AS has shown a relationship between earlier onset of cognitive impairments and dementia, especially FTLD, with anatomic differences on MRI and sustained impairments of executive function into later adulthood.3,8–14

Anxiety, such as this patient had, can serve as a prognostic indicator for future cognitive decline in dementia.1,14,15 Patients with ASD and AS also have a higher incidence of comorbid psychiatric diagnoses with complex presentations.16,17 Effective treatment of comorbidities in addition to multimodal treatment for dementia may augment management of patients already at a higher risk of early onset cognitive impairment due to AS and ASD.12,14,18

In conclusion, this case demonstrates how clozapine allowed a treatment-refractory geriatric patient otherwise limited by severe anxiety, OCD, possible FTLD, and AS to manage her symptoms, thereby giving her the ability to live independently once more.

Published online: October 20, 2022.
Relevant financial relationships: None.
Funding/support: None.
Patient consent: Consent was obtained from the patient’s power of attorney and guardian, who is her sister. All information has been de-identified to protect anonymity.

Volume: 24

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