PSYCHOTIC DISORDERS IN ELDERLY PERSONS

1. PSYCHOTIC DISORDERS IN ELDERLY PERSONS Carl I. Cohen, M.D., SUNY Distinguished Service Professor, Professor & Director, Division of Geriatric Psychiatry,SUNY Downstate Medical Center Brooklyn, NY email: carl.cohen@downstate.edu

2. Two Preliminary Points In older adults, for all conditions: think “Comorbidity” Any new psychiatric conditions or change in symptoms: Must assume physical cause until proven otherwise

3. Presence of “hallucinations and/or delusions” Definition of Psychoses: Key Points:   1.Can be primary (due to psychiatric disorder) or secondary (due to medical/neurological disorder)

4. Key Points (continued) 2.There is no reliable pathognomonic signs to distinguish primary or secondary psychosis (need to rule out secondary causes)

5. A) Primary psychotic disorders: Schizophrenia and related disorders Schizophrenia Schizoaffective disorder Schizophreniform disorder Delusional disorder Brief psychotic disorder Affective psychoses Bipolar disorder with psychotic features Unipolar depression with psychotic features

6. B)    Secondary psychotic disorders: Psychotic symptoms associated with dementia Alzheimer’s Disease with psychoses Vascular dementia with psychoses Lewy Body Disease with psychoses Other dementing disorders with psychoses Psychotic symptoms during delirium Psychotic symptoms associated with medications and substance abuse Psychotic symptoms due to medical and surgical disorders

7. Lifetime Risk (1 in 4 lifetime risk) Up to 23% of the older adult population will experience psychotic symptoms at some time, with dementia being the main contributing cause (Khouzam & Emes, 2007).

8. Prevalence of Psychosis in Elderly Persons • Community: 0.2% to 4.7%; In NYC study (Cohen et al, 2004): 3% psychosis (7% Blacks vs 2% Whites), but if include paranoid ideation: 14 % of sample. • Age 85+(without dementia): 7.1% to 13.7%. May be prodromal for dementia Age 95+(without dementia): 7.4% • Nursing Homes: 10% to 62% • Geriatric Psychiatry In-Patient Units: 10% late onset psychosis--¾ are women, 40% due to AD or VaD

9. Etiologies of Psychoses in Older Adults(order of frequency) • Alzheimer’s disease and other dementias (40%) • Depressive disorder (33%) • Medical/toxic causes including substances (11%) • Delirium (7%) • Bipolar Affective Disorder (5%) • Delusional disorder (2%) • Schizophrenia spectrum disorders (1%) Manepalli et al, 2007 and Webster et al, 1998

10. Risk Factors for Psychoses in Older Adults • Sensory deficits • Social isolation • Cognitive decline • Medical comorbities • Polypharmacy • Age related changes in pharmacokinetics and pharmacodynamics • Comorbid psychiatric illnesses such as dementia and delirium • Age-related changes in cerebral structures such as frontotemporal cortices • Neurochemical changes associated with aging Psychoses may be multifactorial and occurs in the context of fraility, limited reserve capacity, increased vulnerability to stressors.

11. Delirium • Perceptual disturbances are common; however, hallucinations also are frequent: • Hallucinations: 40% to 67% • Delusions: 25% to 50% • Psychotic symptoms are more commonly seen with hyperactive rather than hypoactive delirium • Visual > > auditory> other hallucinations • Paranoid delusions are the most common delusions • Clinical evaluation should help identify; dementia and delirium are often related

12. Dementia

13. Alzheimer’s Disease • Prevalence of psychotic symptoms: 16% to 70%;Median: 37% for delusions; 4% to 76% (Median 23%) for hallucinations • Rates of psychoses: about 20% in early stages to 50% by third or fourth years of illness (Overall: 30% to 50%). • Most common in middle stages. • Hallucinations: visual> auditory> other. • Hallucinations most commonly people from past, e.g., deceased relatives, intruders, animals, objects. • Delusions: most common are false beliefs of theft, infidelity of one’s spouse, abandonment, house not one’s home, and persecution. Decreases in later stages.

14. Different from misidentification syndromes which may be more cognitively- related: Capgras Syndrome (imposters), Phantom Boarder Syndrome(guest in house); Mirror Sign (mistakes self in mirror for someone else, TV or Magazine Sign (believes people on TV or in magazine are real). 7. Some evidence that psychotic symptoms are associated with a more rapid decline. 8. Need to rule out underlying medical problems and visual difficulties

15. 9. Jeste & Finkel(2000) proposed classification of “Psychoses in AD” as presence of hallucinations and/or delusions of at least one month duration, even if intermittent, serious enough to disrupt life of patient or others, and patient meets criteria for AD, not explainable by delirium, drug effects, schizophrenia or other psychiatric disorders.

16. Vascular Dementia Cache County study found prevalence of hallucinations similar between AD and VaD, but delusions were higher in AD (23% vs 8%).

17. Lewy Body Dementia • About half have visual hallucinations (up to 80% in some studies), and it’s an early sign in 43%. • Auditory hallucinations (20%) and paranoid delusions(65%) are also common • Some texts say psychotic symptoms are more common than in AD.

18. Parkinson’s disease • Overall rates: 20 to 60% --- about ¼ have hallucinations in PD, but ¾ have hallucinations with Parkinson’s Disease with Dementia (PDD). Thus, psychosis is more common in later stages of PD. • Hallucinations much more common than delusions. • Extrinsic causes > Intrinsic causes, i.e., hallucinations in PD most commonly secondary to dopaminergic agents(extrinsic). Need to assess onset of symptoms. Medications produce vivid visual hallucinations.

19. Affective Psychoses

20. Unipolar Depression 1. Psychotic depression occurs in 20% to 45% of hospitalized elderly depressed patients; 15-25% of community depressed persons. • Delusions are more commonly mood-congruent, including delusions of guilt, delusions of deserved punishment for moral or personal inadequacies, delusions of nihilism, somatic delusions, delusions of poverty. • Auditory hallucinations are less common and not easily described, such as vague derogatory voices. • Catatonia in severe depressive episodes

21. Bipolar Illness • Psychotic symptoms occur in context of manic or depressive episodes. • Bipolar depression is similar to unipolar depression with respect to predominantly mood-congruent delusions. • Bipolar mania also presents with predominantly mood-congruent delusions such as grandiosity, erotomania, delusions about possessing special powers.

22. Are Schizophrenia, Schizoaffective Disorder (SAD), and Psychotic Mood Disorder Really One Disorder (or on a Continuum) Versus Separate Disorders ? Mood Disorder Bipolar –very psychotic (formerly Schizophrenia) Bipolar—moderate psychotic (formerly SAD) Classic Bipolar (non-psychotic) Psychotic Severity of Sx Mood Lake, Psychiatric Annals,Feb, 2010

23. Substance Induced Psychosis • Prevalence of substance use disorders in elderly persons: 2%-3% in women and 10% in men. • Psychotic symptoms may occur during alcohol (e.g., DTs), sedative, or barbiturate withdrawal, whereas stimulants (amphetamines, cocaine, OTC weight –reducing drugs) can cause symptoms with intoxication. • Opiates such as narcotic analgesics, heroin, codeine, and methadone may induce delirium, and consequently, psychoses • Prescribed medications that are most common causes of psychosis are antiparkinsonian drugs, anticholinergic drugs, antiarrhythmic agents, corticosteroids. • If tactile hallucinations occur, consider drug withdrawal states, toxic, or metabolic disturbances.

24. Medical Illness • Medical illnesses can cause psychosis with and without delirium. • DSM criteria require prominent hallucinations or delusions, with evidence from the history, physical examination, or laboratory findings that the disturbance is physiological consequence of the general medical condition. It should not be better accounted for by another mental disorder and does not occur exclusively during the course of a delirium. • Typical medical causes of psychosis are neurological, infectious, metabolic, and endocrine. • Elderly persons are more at-risk because of high rates of physical illness, polypharmacy, and susceptibility to disruption of brain function.

25. Adapted from Desai and Grossberg, 2003

26. Sorting Out Medical Causes of Psychoses from Non-MedicalCauses • Often characterized by paranoid delusions, persecutory thoughts, and ideas of reference • May resemble paranoid schizophrenia but delusions are usually more concrete, non-bizarre, and changeable • Paranoid schizophrenia is usually more abstract, bizarre, and unchanging Pies, 2008

27. Schizophrenia

28. Early-Onset Schizophrenia Schizophrenia typically develops in the second or third decade of life, but greater numbers of schizophrenia patients are surviving into old age. • Between 80-85% of persons aged 55 and over developed schizophrenia before age 45. Prevalence estimates for schizophrenia in adults aged between 45 and 60 are approximately 0.6% to 1%. • Over the next two decades there will be a doubling of the number of persons aged 55 and over with schizophrenia, from about 550,000 in 2005 to 1.1 million in 2025. By that time, about one-fourth of persons with schizophrenia will be in this older age bracket.

29. There is heterogeneity in outcome in schizophrenia into later life. Long-term studies observing the symptoms and functioning in early-onset schizophrenia suggest that the course of schizophrenia may not be as pessimistic as previously thought, and such findings challenge the notion implied in the term dementia praecox.

30. Based on long-term studies carried out in Europe ranging from 22 to 37 years, Ciompi found: *20 to 27% of patients attained complete symptomatic remission, *22 to 33% attained mild end states, *24% to 29% attained intermediate end-states, *14 to 18% attained severe end-states. Thus, roughly half of persons exhibited recovery or mild end-states, and half showed moderate or severe end states.

31. 1. Outcome from earlier life (depends on definitions): About half improve in psychopathology, one-third remain unchanged, and about 15% get worse. Textbook: (Jeste et al APPI Textbook of Geriatric Psychiatry,2004): 20% remission in positive and negative symptoms; 60% largely unchanged; 20% worsening of symptoms.2. “Social recovery” was observed in about half of subjects. 3. Looking at a more comprehensive definition of recovery, Auslander and Jeste found only 8% of older outpatients attained “sustained remission,” based on symptom remission, social functioning, and medication dosage. 4. Better prognosis: female, later development of illness, better premorbid functioning, married, acute-remitting course.

32. Community-dwelling persons with schizophrenia—who represent about 85% of the older population—have been generally found to have a non-progressive course.The non-progressive course has led some investigators to conceptualize schizophrenia as a static encephalopathy rather than a dementing disorder. Although approximately half of persons in the various symptom and social outcome categories achieve favorable outcomes, the correlations among outcome categories are modest (median value of .21 or about 4% shared variance).Because each of the outcome categories has been found to be associated with a variety of clinical and social variables, it is likely that effective treatments will require biological and psychosocial methods.

33. Table2: Symptom and Social Outcome in Schizophrenia Outcome Categories Trend with Age Comments Positive symptoms Improvement About half with mild or no symptoms Negative symptoms Possible improvement About half with mild or no symptoms Depressive symptoms Same or slightly worse About one-third no depression; one-third syndromal depression; one-third subsyndromal depression Cognitive symptoms Slight worsening About half show only minimal or no cognitive impairment on standard tests Adaptive Functioning Improvement About half with mild or no disability Quality of life Possible improvement Most in “moderate” range, and higher than persons with chronic pain. Global outcome Slight improvement, but not appreciable About one-tenth in full recovery Note: there is a subgroup of “poor outcome” persons (about 15 to 20%) who show marked impairment in all these categories.

34. Hallucinations in Older Adults with Early –Onset Schizophrenia • 36% (71/198) of NYC sample age 55+ had hallucinations (44/198 had 1 type; 19/198 had 2 types; 8/198 had 3+ types; 64/198 of sample had auditory hallucinations) • Form: Clear: • Frequency: • Type: Evaluation:34%; mundane:34%; information 32% • Evaluative: 87% 61% daily; 24% weekly Good : 44%; Bad 34% bad; Mixed 10%; not sure: 12%

35. Late-OnsetSchizophrenia A review of studies of late-onset schizophrenia found that approximately 23% of patients with schizophrenia were reported to have experienced the onset of the disorder after age 40, with 13% in the fifth decade of life, 7% in the sixth decade, and 3% in later decades. Roughly 15% onset over age 44, but a study in the UK found 29% with onset after age 44.

36. “Late paraphrenia” used by Martin Roth in 1950s(UK) to describe persons with no family history who developed a schizophrenia like illness (hallucinations and delusions) after age 65. Term has been used in various ways. In ICD 9 it referred to delusional disorder in later life; similar to DSM II. Not in DSM-IV-TR or ICD10.

37. DemarcationThe International Late-Onset Schizophrenia Group has proposed that schizophrenia with an onset between age 40 and 60 be termed “Late-Onset Schizophrenia” and be considered a subtype of schizophrenia. The authors believe that schizophrenia with onset in middle age is a neurodevelopmental disorder, and that differences with early-onset schizophrenia are more of degree than of kind.

38. No differences between early and late onset groups in: positive symptoms, family history, brain abnormalities, memory retention, or minor physical abnormalities.The late-onset group is more likely to:1. Be female versus no gender differences in early-onset, 2. Have the paranoid subtype of schizophrenia, 3. Have lower levels of negative symptoms,4. Have less impairment in learning, abstraction, and flexibility, 5. Better premorbid functioning with respect to work and marriage.

39. The International Late-Onset Group also proposed the term, “Very Late Onset Schizophrenia-Like Psychosis” for disorders that begins after age 60. This disorder has features that suggest a neurodegenerative component including more brain abnormalities and neuropsychological deficits.

40. This disorder is also distinguished from the other two types by: 1. many more females; 2. greater prevalence of persecutory and partition delusions; 3. higher rates of visual, tactile and olfactory hallucinations; 4. lower genetic load; 5. more sensory abnormalities;6. absence of negative symptoms or formal thought disorder.

41. Table3. Comparison of early-onset schizophrenia , late-onset schizophrenia , and very late onset schizophrenia Early-Onset Late-Onset Very Late Onset Age of onset <40 40 to 60 >60 Female preponderance - + ++ Negative symptoms ++ + - Visual, tactile and olfactory hallucinations + + ++ Persecutory/Partition delusions + ++ +++ Minor physical abnormalities + + - Neuropsych deficits Learning Retention ++ -   + - ++(?) ++(?) Progressive cognitive deterioration - - ++ Brain structure abnormalities(e.g. tumors, infarcts) - - ++ Family history of schizophrenia + + - Early childhood maladjustment + + - Daily antipsychotic dose Higher Lower Lower Risk of TD + + ++ • =absent, • + =mildly present, • ++ =strongly present, • +++ = very strongly present • Adapted from Jeste et al, 2004

42. Schizoaffective Disorder Must have uninterrupted period of illness in which symptomsmeet Criterion A for schizophrenia and a major depressive episode, a manic episode, or mixed episode.During this episode there must have beendelusions or hallucinations for at least 2 weeks in theabsence of prominent mood symptoms. A shifting (unstable) and irrational diagnosis: a. Differs between episodes; b. How can having both depression and schizophrenia turn into a 3rd disorder?

43. Schizoaffective Disorder (cont.) • Research suggests that schizoaffective disorder may be subcategory of schizophrenia or psychotic depression because they share epidemiology, clinical, and neuropsychological features. • High prevalence of depressive symptoms in schizophrenia--11% to 75% depending on the level of severity-- make diagnosis more problematic.

44. Delusional Disorder 1.Delusional disorder is differentiated from schizophrenia by a lack of prominent auditory or visual hallucinations (and if present, related to delusional theme), and an absence of deterioration in areas of functioning outside the delusional scope. -Distinguished from dementia by absence of cognitive impairment. -Distinguished from mood disorder by delusions preceding any mood disturbances. 2.The delusions are non-bizarre and involve situations that may occur in real life, such as theft, suffering from a disease, spousal infidelity, or being followed.

45. 3.  Delusional disorder difficult to differentiate from the paranoid schizophrenia, but the latter has more bizarre delusions and auditory hallucinations. Poor psychosocial functioning in delusional disorder is directly related to the delusional beliefs. 4.  Prevalence:0.03%5.  Risk factors: Persons with schizotypal or paranoid personality disorders; mixed findings regarding association with hearing loss.6.  MRI findings had no significant differences from normals. 7. The course of delusional disorder may vary but tends to be chronic, especially in those with the persecutory type of delusional disorder.

46. Treatment

47. Early-Onset Schizophrenia • Lack of control studies, e.g., CATIE trial from ages 18 to 65. • Recent federal warnings about increased mortality risk in elderly dementia patients adds to the concern regarding use of antipsychotic medications. • An expert review panel recommended risperidone (1.25–3.5 mg/day) as the first line of treatment. Quetiapine (100–300 mg/day), olanzapine (7.5–15 mg/day), and aripiprazole (15–30 mg/day) were viewed as good second-line treatments. Expert reviews have recommended starting antipsychotic medication at 25% of the recommended adult dose and maintenance doses at 25-50% of the adult dose.

48. There has been only two large-scale randomized, double-blind controlled trial comparing atypical antipsychotics—risperidone(1mg to 3mg/day, median dose 2mg/day) and olanzapine(5mg to 20mg/day, median dose 10mg/day)-- in adults older than 60. Positive symptoms, negative symptoms, disorganized thoughts, and symptoms of anxiety/depression improved significantly from baseline in both groups. There were no significant differences in side effects except for more clinically significant weight gain in the olanzapine group.

49. Table 4. Studies supporting use of specific atypical antipsychotics in older persons with schizophrenia Total, n Design Clozapine Chengappa et al. 1995[70] 12 Retrospective Chart Review Factor and Brown, 1992[36] Open Label Risperidone Jeste et al. 1999[71] 53 Open Label Madhusoodanan et al. 1999[72] 100 Open Label Feldman et al. 2003[73] 39 Double Blinded Randomised Jeste et al. 2004[74] 175 Double Blinded Randomised Olanzapine Madhusoodanan et al 2000[75] 10 Open Label Sajatovic et al. 1998[76] 27 Open Label Feldman et al. 2003[73] 39 Double Blinded Randomised Jeste et al. 2004[74] 175 Double Blinded Randomised Quetiapine Arvantis and Rak, 1997 152 Open Label Madhusoodanan et al. 2000[77] 7 Open Label Ziprasidone Barak et al. 2006[78] 21 Open Label Aripiprazole Madhusoodanan et al. 2004[79] 10 Retrospective Chart Review Adapted from Vahia et al, 2007.

50. Risk of developing tardive dyskinesia with conventional antipsychotic medications: 29% (after 1year –nearly 6x that of younger persons), 50% (2 years), 63% (3 years). Rates substantially lower with atypical antipsychotic medications (5% after one year).Other side effects: EPS and anticholinergic effects are higher in elderly persons.