Clinical Considerations for Antipsychotic Use in Elderly Patients with Schizophrenia: A Case Series

Treating elderly persons with schizophrenia poses several challenges for clinicians. Antipsychotic side-effect profiles, medical conditions, physiologic effects of aging, and government regulations can complicate the clinical scenario. Important guidelines for use of antipsychotics in the elderly population include starting at low doses and increasing slowly, checking basic laboratory studies periodically and doing routine physical examinations, and weighing the risks versus benefits of discontinuing treatment with an antipsychotic medication. Schizophrenia is a chronic mental illness that in most all cases requires lifelong treatment. Discontinuation of antipsychotic medication can result in worsening psychosis and, ultimately, behaviors that place patients at high risk of self-harm. This article presents four cases of elderly persons with schizophrenia, each illustrating clinical points to consider in the treatment of this patient population. (Annals of Long-Term Care: Clinical Care and Aging 2009;17[9]:26-30)
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Introduction

The use of antipsychotic medications in the geriatric population can lead to many challenges for the prescribing physician. As patients with schizophrenia age, they may develop medical illnesses and cognitive changes that neuroleptic medications may adversely affect. Weight gain, metabolic syndrome, sedation, and movement disorders are just a few of the potential complications that need to be considered when treating psychosis in the elderly. In this article, we present several cases illustrating important clinical concepts to be considered in the treatment of geriatric schizophrenia.

Case 1

Ms. A is a 72-year-old woman with a long-standing history of paranoid schizophrenia successfully treated with risperidone 3 mg daily at bedtime. She also has a history of diabetes and coronary artery disease. Her diabetes had been under good control with diet and oral hypoglycemic agents. Ms. A had been residing at a nursing home (NH) for approximately 2 years and had been stable in terms of her psychotic symptoms. Following pharmacy medication review, it was recommended that her risperidone be tapered and discontinued. The medication was tapered gradually over a 3-month period. Approximately 2 weeks after discontinuing the medication, the patient was noted to become more agitated and withdrawn, and she began experiencing vivid auditory hallucinations. She became physically aggressive with a care provider in the facility and was emergently hospitalized on a psychiatric unit. Ms. A was hospitalized for 12 days. The risperidone was reinitiated first at a 1-mg dose and then titrated to her former dose of 3 mg at bedtime. Her symptoms gradually remitted, and she returned to her baseline behavior and mental status after approximately 10 days of hospitalization. She tolerated the risperidone well, and there was no evidence of parkinsonism, undue sedation, gait instability, or exacerbation of her diabetes status.

Case 1 – Discussion

In 1987, President Reagan signed the Omnibus Budget Reconciliation Act (OBRA ‘87), which contained national standards for NH resident care and resident rights. Included in OBRA ‘87 was a set of standards aimed at reducing physical and chemical restraints in NHs. Under OBRA ’87, all psychopharmacologic drugs must be prescribed for the treatment of a specific condition, and an independent review must occur annually.¹ As a result, psychopharmacologic medications are often tapered in medication reduction/elimination trials. Since implementation of OBRA ‘87, the use of physical restraints, antipsychotics, and sedative-hypnotics in NHs has decreased substantially.^2,3 Several studies have linked antipsychotics with increased risk of death in patients with dementia, prompting a Food and Drug Administration (FDA) black box warning for use of antipsychotics in patients with dementia.^4-6

It is unknown whether there is a similar risk in elderly patients with schizophrenia. While elimination or reduction to the lowest effective dose of psychopharmacologic agents offers potential benefits to many elderly NH residents, this case illustrates the necessity of maintaining persons with schizophrenia on their antipsychotic medications. Schizophrenia is a lifelong illness, and when antipsychotics are eliminated, the patient is at high risk for disease exacerbation. Currently, there is little research literature to guide a clinician in terms of drug selection or effective medication dosing in the treatment of elderly persons with schizophrenia.⁷ Without research guidelines, it is clinically reasonable to titrate antipsychotic medications to lower doses in these patients, particularly when other medical illnesses are present. Whenever dose reductions occur, clinicians, family members, and NH staff need to observe closely for exacerbation of psychotic symptoms. Dose reductions should be gradual, with patients spending several weeks at each incrementally lower dose to assure that psychotic symptoms do not worsen or recur. As Case 1 illustrates, reduction or elimination of antipsychotic medications can result in disease recurrence and the necessity for hospitalization.

Case 2

Mrs. B is a 65-year-old female with a past medical history significant for asthma, migraine headaches, and schizophrenia who presented to the Emergency Department with worsening disorganized thoughts and delusions of reference after recent self-discontinuation of her antipsychotic medications. She was subsequently hospitalized in an effort to restart her medications and gain better control of her psychosis. The patient was initiated on olanzapine 5 mg, with the dose titrated up to 15 mg at bedtime over the course of 2 weeks, with subsequent control of her psychotic symptoms. After discharge from the hospital, fasting blood glucose (FBG) levels and a lipid panel were obtained 3 months after initiating treatment with olanzapine. Results of blood glucose were found to be elevated at 127 mg/dL, and a review of the lipid panel revealed increased total cholesterol (TC) at 280 mg/dL and low-density lipoprotein (LDL) of 195 mg/dL. In addition, Mrs. B reported a 10-15–pound weight gain. She was cross-tapered from olanzapine to risperidone over the course of 2 weeks. She tolerated risperidone 2 mg twice a day without relapse of her psychosis. Repeat blood work after cross-tapering revealed FBG of 118 mg/dL and TC level of 267 mg/dL, with LDL of 169 mg/dL, and she had lost 10 pounds of weight. No baseline labs were available for comparison prior to initiating treatment with olanzapine.

Case 2 – Discussion

Patients receiving atypical antipsychotics are at increased risk for diabetes, hyperglycemia, and lipid dysregulation. Although the prevalence of diabetes has been shown to be increased in patients with schizophrenia before the introduction of second-generation antipsychotics, there is substantial evidence to suggest that some or all second-generation antipsychotics can cause weight gain, dyslipidemia, and diabetes.⁸ The National Institute of Mental Health–sponsored Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) is the largest sample available that reports the rate of metabolic syndrome in patients with schizophrenia. This study found that the adjusted odds ratios of metabolic syndrome status for CATIE subjects relative to matched individuals in the National Health And Nutrition Examination Survey III (NHANES III) were twice as high for men in the CATIE sample and three times as high for women.

These findings propose that both primary care providers and psychiatrists pay closer attention to the risk-benefit analysis when it comes to second-generation antipsychotics and metabolic syndrome.⁹ The American Diabetes Association/American Psychiatric Association (ADA/APA) Consensus Development Conference suggests that a baseline assessment of personal and family history of risk factors for cardiovascular disease, weight and height, waist circumference, blood pressure, FBG level, and fasting lipid profile be obtained before initiating treatment with a second-generation antipsychotic, and at periodic intervals during treatment. In addition, these guidelines suggest switching to a second-generation antipsychotic with less weight gain liability if a patient gains more than 5% of his or her initial weight or develops worsening dyslipidemia or hyperglycemia.^10,11

Of the second-generation antipsychotics, clozapine and olanzapine have been shown to carry the greatest risk for the development of diabetes and dyslipidemia. Studies have also shown that atypical antipsychotics such as risperidone and quetiapine have lower risks, and newer agents such as ziprasidone and aripiprazole are associated with minimal metabolic risks.¹² Elderly patients often have comorbid medical conditions that metabolic syndrome may complicate or exacerbate. Careful consideration of the patient’s medical history and risks that metabolic syndrome may pose are important when initiating treatment with an antipsychotic medication.

Case 3

Mrs. C is a 72-year-old female with a history of hypertension, type 2 diabetes mellitus, and schizoaffective disorder, bipolar type treated with ziprasidone 60 mg twice daily, clonazepam 0.5 mg twice daily, and divalproex sodium 400 mg in the morning and 500 mg at bedtime. Her psychotic symptoms had been well controlled on this regimen for 4 years. After receiving a report from the NH that she had developed worsening tremor (especially evident in her left hand) and gait disturbances with multiple falls, she was evaluated by her psychiatrist. On examination, Mrs. C was alert, oriented, and cooperative, with no evidence of active psychosis. Neurological examination revealed resting tremor of the left hand and shuffling slowed gait. The decision was made to taper and discontinue treatment with ziprasidone over the course of 1 week. Approximately 2 months after this medication was discontinued, the staff reported that Mrs. C had developed worsening paranoia, began locking herself in her room, and stopped eating because she believed her food was poisoned.

She became noncompliant with all of her medications. Staff noted that her gait and tremor were improved. On re-evaluation by her psychiatrist, she was noncooperative with the interview and locked herself in the bathroom, requiring assistance from security to remove her; she was then hospitalized. Careful review of Mrs. C’s records revealed that over the course of approximately 15 years she had been psychiatrically hospitalized multiple times and had been treated with multiple antipsychotic medications, including olanzapine and quetiapine, both of which had been discontinued secondary to poor response and the development of parkinsonism. The treatment team reinitiated ziprasidone, and improvements were noted in her psychotic symptoms. She was discharged from the hospital back to the NH on ziprasidone 60 mg twice daily, which had been slowly titrated over 2 weeks from a starting dose of 20 mg twice daily. Her psychotic symptoms had improved significantly. In the NH, after weighing the risks and benefits of maintaining Mrs. C on ziprasidone, this medication was reduced to a dose of 20 mg twice daily. In addition, clonazepam was decreased to 0.5 mg at bedtime. Several months after these medication changes were made, a mild improvement in her shuffling gait and tremor was noted. The patient continued to have mild paranoia, but the NH staff was able to manage these behaviors without further incidents, and no reports of falls have been received.

Case 3 – Discussion

Antipsychotic-induced parkinsonism arises as a result of dopamine blockade in the nigrostriatal dopamine pathway, which is part of the extrapyramidal nervous system.¹³ Blockade of dopamine neurotransmission in this pathway by medication creates an imbalance between the inhibitory actions of dopamine and the excitatory actions of acetylcholine in the striatum.¹⁴ There are several movement disorders associated with antipsychotic use. These include dystonia, parkinsonism, and myoclonic jerks, collectively referred to as extrapyramidal symptoms (EPS). In addition, late-occurring and a potentially irreversible involuntary movement disorder such as tardive dyskinesia (TD) can also occur with these medications. The risk of EPS and TD is greater with first-generation antipsychotics than with second-generation antipsychotics.

There are three treatment strategies that may be used for the treatment of antipsychotic-induced parkinsonism: dose reduction, switching to another antipsychotic agent, or the use of anticholinergic agents.¹⁵ In the geriatric population, however, use of anticholinergic agents may not be tolerated due to side effects that include blurred vision, urinary retention, and, particularly, cognitive impairment. Other more serious side effects that may be seen in the elderly individual when using these agents include anticholinergic-induced delirium and intestinal stasis. Case 3 illustrates the importance of weighing the risks versus benefits of antipsychotic use. Mrs. C was at increased risk for falls, medical complication due to medication noncompliance, and erratic behaviors when her antipsychotic medication was discontinued. Reinitiating this medication at a lower dose was successful in diminishing her psychosis and decreasing symptoms related to parkinsonism. In addition, decreasing the dose of benzodiazepine may also have proved to be beneficial in decreasing the incidence of falls.

Case 4

Ms. D is a 65-year-old woman with a long-standing history of schizoaffective disorder, bipolar type, with several hospitalizations throughout her adult life, and only marginal control of her positive symptoms of schizophrenia. At her baseline, she would have delusions and hallucinations, even while taking medications, and she would at times become very agitated when the psychotic symptoms would worsen. She had been living recently in an adult foster care setting and had been maintained on haloperidol 10 mg twice daily, divalproex ER 500 mg in the morning and 1000 mg in the evening, and venlafaxine XR 150 mg twice daily. Ms. D had been diagnosed with breast cancer 8 years previously and had undergone bilateral simple mastectomies, but did not receive radiation or chemotherapy. Her medical history also includes a history of pelvic endometriosis and ovarian cysts. Ms. D began experiencing an exacerbation of psychotic symptoms, also complaining of back pain. She became more restless and was more difficult for adult foster care members to manage in terms of irritability and agitation. After wandering from the facility in a somewhat confused state, the patient was brought to the Emergency Department and was hospitalized on a Medical Psychiatry unit. Ms. D underwent medical evaluation that included computed tomography and magnetic resonance imaging scans of the head. These evaluations showed a large lytic mass in the midline frontal bone with cortical disruption of the right frontal lobe. A nuclear medicine bone scan showed tracer uptake in the midline frontal skull and in the posterior parieto-occipital skull and several lesions in the thoracic vertebral bodies. Electrolytes, complete blood count, liver function tests, and serum calcium were all within normal limits. Biopsy was consistent with metastatic breast cancer. The patient experienced worsening decompensation of her psychotic disorder with the news of her breast cancer diagnosis. Over the next several months the patient required hospitalization for exacerbation of her psychosis on three occasions. She also had a heightening of back pain, and the family decided to pursue only palliative care with radiation therapy to the lytic lesions in her thoracic spine. The patient died 6 months later.

Case 4 – Discussion

As with all patients, persons with psychotic disorders will develop medical illnesses. When psychotic or affective symptoms worsen in these patients, it is incumbent upon evaluating physicians to be aware of their medical histories and to pursue possible medical origins of symptom exacerbation. Often, this is difficult when severe mental illness is present. As in Case 4, obtaining a thorough and detailed medical history may be difficult, and corroborative information from family members, caregivers, and other people involved in the patient’s life may be helpful in delineating whether or not a medical process is present and could possibly be contributing to the patient’s behavioral changes. Medical management of patients with psychotic disorders can be challenging. Often, such patients will not have the insight or capacity to effectively deal with difficult diagnoses and treatments. Compliance with medical care can be problematic whenever paranoia adversely affects the patient’s insight into the nature of his or her illness. Effective treatment strategies will often entail incorporating family members, caregivers, and social services into an overall care plan. Often, psychotic patients will not be able to provide informed consent, thus complicating the treatment process. Generally, patients with psychotic disorders should be told the truth about their medical conditions and the treatments, but care needs to be taken to ensure that guardians, caregivers, family members, and social service supports are present and able to help the patients make appropriate decisions regarding their care, and to offer support and management of difficult behavioral syndromes should they arise.

Conclusion

Treating psychotic disorders in elderly persons can be particularly challenging. Important guidelines to keep in mind when using antipsychotic medications in this population include: start at low doses and increase slowly; this patient population may already have comorbid conditions that could make them especially sensitive to antipsychotic medications. In addition, the elderly are more likely than other patient populations to be taking several medications that may interact with an antipsychotic. Another guideline is to check basic laboratory studies periodically, and do routine physical examination. Studies have shown that patients with schizophrenia are less likely to receive appropriate medical care for medical illness. This may be secondary to the patient’s inability to clearly describe a medical problem, reluctance to discuss medical problems, or assumption that physical complaints are secondary to delusions. Finally, weigh the risks versus benefits of discontinuing treatment with an antipsychotic medication. Schizophrenia is a chronic mental illness that in most all cases requires lifelong treatment. Discontinuation of antipsychotic medication can result in worsening psychosis and, ultimately, behaviors that place patients at high risk of self-harm. If side effects occur, consideration should be given to decreasing the dose of medication or switching to another agent before considering discontinuations.

The authors report no relevant financial relationships.