The Aging Patient with Chronic Schizophrenia
Schizophrenia is a disease marked by delusions, hallucinations, and disordered thinking. Currently, the overall worldwide prevalence of schizophrenia is 1%, with two-thirds of cases becoming chronic. As more people survive into their later years, the number of people over age 65 years with schizophrenia is likely to increase. Below we describe a case of an elderly single female, living in a supportive residence, with a history of many hospitalizations from chronic paranoid schizophrenia. Her case illustrates the factors influencing the prognosis of aging persons with schizophrenia, including cognitive dysfunction, medical comorbidities, and the adverse effects of antipsychotics. These factors, in part, may explain the heterogeneous course of this disease.
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Case Presentation
Ms. Z is a 66-year-old single, retired, overweight, Jewish female on Social Security Disability (SSD) and Medicare residing in a supportive psychiatric residence with Intensive Case Management (ICM) services. She presented to an inner-city hospital psychiatric emergency room (ER) in July 2008, complaining of not being in control and saying, “I feel like strangling someone.” She had a long history of schizophrenia and multiple prior hospitalizations.
On arrival to the ER, Ms. Z was feeling depressed secondary to poor relationships with people at her residence. She also reported feelings of guilt, hopelessness, and anxiety. She had thought of committing suicide by overdosing on clozapine, and she was concerned she would have to go to a state hospital. She was actively compliant with clozapine 550 mg at bedtime, with monthly blood draws; however, she had a history of intermittent noncompliance and paranoia about medication.
The patient was taking aspirin, esomepazole, simvastatin, docusate, clozapine, and calcium carbonate. Although her first psychiatric hospitalization occurred at age 20, she was not diagnosed with schizophrenia until age 30. She had a history of lengthy psychiatric hospitalizations at state facilities. Her last acute psychiatric hospitalizations were in January and April 2008. Her last psychiatric admission prior to that was in 2001, meaning that she had a period of 7 years of relative stability. She developed tardive dyskinesia (TD), consisting of abnormal and involuntary movements, in association with exposure to haloperidol approximately 15 years previously. At that time she was switched to clozapine, resulting in stabilization of psychiatric symptoms with residual TD. Ms. Z had been tried on several antidepressants including fluoxetine, paroxetine, and bupropion, with modest therapeutic effect. She had a history of overdosing on diazepam in the context of alcohol abuse in the late 1970’s. She smoked one pack of cigarettes a day.
The patient’s family psychiatric history includes a sister with major depressive disorder and a mother who had a possible history of schizophrenia. Ms. Z has an extensive medical history including gastro-esophageal reflux disease, hypercholesterolemia, coronary artery disease, osteoporosis, vitamin B12 deficiency, obesity, and a left mastectomy secondary to left localized breast cancer in 1997. The patient experienced great anxiety surrounding medical appointments, and therefore had difficulty with compliance.
Ms. Z was born in New York and has two sisters. She reports having had a poor relationship with her mother. After earning a bachelor’s degree in philosophy, she worked as a secretary for 15 years. She was never married and has no children. She has lived in supportive housing for ten years. She changed supportive residences several times, at one point requiring a five-month, acute inpatient psychiatric hospitalization because of paranoia about her housing.
The patient presented to the ER alert and fully oriented. She was oddly related and appeared disheveled, with poor eye contact. She had involuntary oral/buccal and head movements with manifest dysarthria secondary to TD. She described her mood as depressed, and her affect was anxious and constricted. Her thought process was disorganized, and she was easily distractible with evident thought-blocking. She had passive suicidal ideation with vague homicidal ideation. She reported paranoid thoughts about people laughing at her and talking about her. Her insight and judgment were poor.
Hospital Course
Ms. Z was admitted to an acute inpatient geropsychiatry unit because of her paranoia, isolative behavior, internal preoccupation, and passive suicidal ideation. She was restarted on regular dosing of clozapine. Venlafaxine extended-release 75 mg daily was added for depression. On the psychiatric unit, she had continued paranoia about the medication and believed that other patients were talking about her. At times she was withdrawn, anxious, and suspicious.
She showed persistent depressive symptoms, such as remaining in bed for most of the day and acting withdrawn. She refused to attend group sessions on the unit. She had vague physical concerns but could not provide specific complaints due to her poor verbal communication. The patient had trouble managing her frustrations and maintaining a steady stream of thought.
It was determined that her basic functioning was intact as she demonstrated adequate instrumental activities of daily living on the unit. Her concentration seemed impaired at times as she tended to perseverate on one complaint (“I don’t like the clozapine because it is not helpful”), and she remained vague in her thinking. She was oriented to her surroundings and the time, and she had good recall for recent events. She could not be specific about her remote history, although this may have been related to her suspiciousness of doctors. Her comprehension of words was sophisticated and at a college level, but she often struggled to find just the right word to use, and many of her statements were childlike in nature.
Ms. Z reported low self-esteem, and she required constant reassurance. With good medication compliance on the inpatient unit her mood improved, and she was discharged to her residence with ICM and outpatient psychiatric follow-up.
Outpatient Course
Ms. Z’s outpatient course has been marked by continuing negotiations over the dose of her clozapine. She has had fixed ideas that this medication causes “anxiety,” “depression,” or “agitation.” Ms. Z always wants to lower the medication because, she says, “I know it’s not good for me.” She responds better to support and encouragement than to efforts at psycho-education.
In the outpatient setting, the patient expresses hopelessness at times, fear that her doctor is angry with her at other times, and a need for validation nearly all of the time. When not given reassurance, she begins to express suspicion about her doctor’s thoughts and intentions (eg, whether the doctor thinks she is capable of independent living). Her affect is childlike and fluctuates between fearfulness, irritability, and blunting.
Earlier in her life, Ms. Z’s prognosis was mixed, characterized by positive prognostic factors, including high psychosocial functioning and completion of a college education. She also had negative prognostic factors such as the presence of an insidious onset. Over time, other negative prognostic factors, including prominent negative symptoms, have become more prominent.
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Discussion
General Background
Chronic schizophrenia is traditionally thought of as a psychiatric illness with a deteriorating course that develops before age 45. Late-onset schizophrenia refers to patients who do not meet diagnostic criteria for the illness until after age 45.1 In general, late-life schizophrenia refers to schizophrenia in any individual age 50 years or older irrespective of age of onset.2 This article will focus on the 85% of people with schizophrenia who develop the disorder before age 45 and who age with it.
The prevalence of schizophrenia in people age 45-64 years is approximately 0.6%; for those age 65 and over it ranges from 0.1% to 0.5%. This current generation of persons aging with chronic mental illness will have spent considerably less time in mental institutions than in earlier generations, and thus will need to negotiate health and social service systems that may be unprepared to deal with them. Recent data indicate that costs for community care of persons with schizophrenia are significantly higher for those age 65 and over than those age 30-64.3
Currently, at least 85% of older people with schizophrenia live in the community; the remainder reside in nursing homes or as psychiatric inpatients. According to a review by Lamberti and Tariot,4 several studies have shown that the prevalence of schizophrenia in nursing homes ranges from 1.5% to 12% of residents. Downsizing of public psychiatric hospitals has left some inpatients who are unable to survive in the community with inadequate support.5
MEDLINE and PsychInfo literature searches revealed that only 1% of articles on schizophrenia have focused on aging individuals, showing that there is a paucity of data focusing on the aging person with schizophrenia.5
Mortality and Medical Comorbidities
In general, persons with schizophrenia have a higher rate of mortality than the general population. This appears to be based on sedentary lifestyle, increased smoking, and a higher degree of medical comorbidity. The extent and consequences of medical comorbidity among older persons with schizophrenia have been unappreciated. Nearly half of comorbid medical conditions are missed by medical providers.6,7 Illnesses highly prevalent among persons with schizophrenia include coronary artery disease, myocardial infarction, and diabetes.8 Jeste and coworkers9 found that older persons with schizophrenia did not have more physical illnesses than their aging peers, but their illnesses may be more severe. They concluded that persons with schizophrenia receive inadequate healthcare. Both structural barriers in the healthcare system and physicians’ attitudes may create impediments to care. Mortality rates among persons with schizophrenia have been estimated to be two to four times the rates in the general population. However, it is not clear whether excess mortality persists with advancing age.
Course of the Disease
Schizophrenia has traditionally been thought of as a progressive illness associated with functional and cognitive decline. Davidson et al10 showed that 60% of institutionalized patients showed signs of dementia. However, community-dwelling patients are different than their institutional counterparts. Prior research shows that 20% of patients with schizophrenia decline, but 20-30% show improvement or even remission, and about 60% remain unchanged.11 Thus, outcomes may be highly heterogeneous. Initial deterioration usually occurs shortly after the disease is diagnosed and can be limited to the first 5-10 years. This may be followed by stability or even improvement in symptoms. “Schizophrenia burnout,” the idea that, with age, positive symptoms remit and negative symptoms persist, is not necessarily characteristic. Some research shows diminished positive symptoms without complete resolution; other studies show continuing positive as well as negative symptoms.12 Factors associated with a poorer prognosis include: chronicity, insidious onset, premorbid psychosocial functioning, and prominent negative symptoms. Poorer community functioning is associated with limited social support, persistent negative symptoms, cognitive impairment, and abnormal movements.13
Levels of depression may be high among older persons with schizophrenia, with more than two-fifths showing signs of clinical depression. This depression has been linked to positive symptoms, poor physical health, low income, and diminished network support.5
Level of Functioning
The level of functioning of elderly persons with schizophrenia varies. Palmer et al14 found that 30% of elderly individuals maintained some employment after the onset of psychosis; 43% were current drivers; and 73% were living independently. In general, however, they had lower education, poorer neuropsychological testing, and more negative symptoms as compared to their age-matched healthy counterparts.
One study found that the majority of older people with schizophrenia were satisfied with their lives, but that level of satisfaction was lower than that of their age-matched healthy peers.15 Cohler and Beeler16 pointed out that for older persons with schizophrenia, the most appropriate goal may not be recovery or rehabilitation per se, but making life more meaningful and satisfying to the individuals and those close to them. Older persons with schizophrenia often have intact insight into their difficulty in taking initiative, giving emotional support, and dealing with conflict.17
Cognitive Decline
Cross-sectional reports suggest that persons with late-life schizophrenia are most consistently impaired in executive function, visuospatial ability, psychomotor speed, and verbal fluency. Impairment has less consistently been observed in attention and memory, and working memory. Longitudinal studies suggest that persons with late-life schizophrenia begin to decline cognitively around age 65 years, starting with a loss of visuospatial abilities. Over six years, the average drop in Mini-Mental State Examination score (reflecting decline in global cognition) has been estimated to be about 1 point per year. In contrast, the decline is 2-3 points per year in patients with Alzheimer’s dementia.18 However, most studies have been conducted in institutionalized patients; these patients appear to have more cognitive impairment than community patients. Other limitations to prior studies include small sample size, short follow-up, and lack of comprehensive neuropsychological assessment.
Thus, the available literature suggests that the course and nature of cognitive decline is variable.19 For instance, Eyler Zorilla et al19 compared community-dwelling patients age 40-85 years with early-onset schizophrenia with normal comparison subjects. In this cross-sectional study, measures of cognitive functioning were lower in the group with schizophrenia but remained stable with age. Therefore, it seems that while the majority of patients with schizophrenia do not experience an inevitable decline in cognitive functioning, there is a group, more likely to be institutionalized, who do show a progressive decline.19
Treatment
The primary treatment for schizophrenia includes antipsychotic medication. (The Table outlines main considerations in the management of the elderly person with schizophrenia.) Elderly patients typically require lower doses of medication due to such age-related pharmacokinetic changes as increased adipose tissue, decreased total body water, and decreased muscle mass. Pharmacodynamic changes include reduced dopamine neurotransmission in the nigrostriatal tract.20 As a result of both pharmacokinetic and pharmacodynamic changes, elderly persons receiving antipsychotic medication are more susceptible to extrapyramidal symptoms (EPS), toxicity, and sedation.1
The older so-called “typical antipsychotics” generally do not improve negative symptoms and can cause movement disorders. Typical antipsychotics that are low-potency, such as chlorpromazine, are more likely to cause sedation and anticholingeric or anti-adrenergic effects. This in turn can increase the risk of falls. The high-potency typical antipsychotics, such as haloperidol, are more likely to cause EPS.
Few studies focus on the elderly population and antipsychotic medications. Most available studies include younger patients and use extrapolated data. Jeste and colleagues21 found that in 439 psychiatric patients over age 65, 28% met criteria for TD by 12 months; 50.1% at the end of 24 months; and 63.1% at the end of 36 months. Thus, aging is clearly a major risk factor for TD. Atypical antipsychotics may be a better alternative, as they have a lower risk of inducing TD. However, atypicals do have a risk of metabolic side effects, including diabetes, weight gain, and elevated cholesterol.22
Regarding the use of the atypical antipsychotic cloza-pine, it should be noted that clozapine requires regular blood monitoring because of the risk of agranulocytosis. The justification for using this agent, in this patient, is that clozapine may be most effective in patients who failed to respond to treatment with other agents. Additionally, clozapine can suppress abnormal movements in TD, and may be an excellent choice for the long-term management of patients who already have TD.
On April 12, 2005, the U.S. Food and Drug Administration issued a public health advisory to notify healthcare providers, patients, and caregivers of a newly identified concern associated with the off-label use of atypical antipsychotic medications for the treatment of dementia-related behavioral disorders in elderly individuals. They found antipsychotic medications to be associated with a 1.6 to 1.7-fold increase in mortality rate when patients treated with antipsychotic medications were compared to those treated with placebo during acute trials. Although no placebo-controlled trials of some atypicals such as ziprasidone or clozapine were conducted, it is reasonable to view the increased mortality as a class effect. The older, typical antipsychotic medications may also be associated with an increased risk of mortality when given in the context of dementia. In this regard, evidence published in the Centers for Medicare & Medicaid Services database has shown that atypical antipsychotic medications, unlike older antipsychotics, do not appear to be associated with an increased risk of ventricular arrhythmias or cardiac arrest. Clinicians should be cautious when prescribing any antipsychotic medications for older adults.
However, the benefits outweigh the risks in treating elderly persons with schizophrenia as the new warnings apply to dementia-related behavioral disorders, not schizophrenia. There are no published studies that established cardiac risk with atypical antipsychotics in elderly persons with schizophrenia.23
Conclusion
Ms. Z’s case helps to illustrate basic principles that apply to the treatment of mental disorders in the elderly population. She was maintained in the residence with the help of outpatient psychiatry and ICM, but she still experienced exacerbations of her schizophrenia requiring acute hospitalizations. Ms. Z seems to fall into the 60% of elderly persons with schizophrenia whose disease remains static. Unfortunately, she has multiple poor prognostic factors, including limited social support, persistent negative symptoms, cognitive impairment, and abnormal movements.
Ms. Z had TD while taking a typical antipsychotic and then was successfully switched to an atypical antipsychotic. She has had refractory and difficult-to-manage depressive symptoms secondary to her schizophrenia. She has also had multiple medical comorbidities that need to be closely monitored and may greatly increase her risk of mortality. Finally, Ms. Z will need further screening for cognitive decline, as that could further affect her functioning that has already been compromised by the negative and positive symptoms of schizophrenia.
Schizophrenia in elderly persons presents a unique set of treatment considerations. In the coming decade, this will be a growing population requiring special consideration.
The authors report no relevant financial relationships.
From Beth Israel Medical Center, Department of Psychiatry, New York, NY.
