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

1 st used in 1845: “psychosis” (soul/mind) + “osis”
(abnormal state of)

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

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 (“toxic psychoses”)
•
Psychotic symptoms associated with medications and substance abuse
•
Psychotic symptoms due to medical and surgical disorders

Freudenreich, 2010

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

1. Alzheimer’s disease and other dementias (40%)
2. Depressive disorder (33%)
3. Medical/toxic causes including substances (11%)
4. Delirium (7%)
5. Bipolar Affective Disorder (5%)
6. Delusional disorder (2%)
7. Schizophrenia spectrum disorders (1%)
Manepalli et al, 2007 and Webster et al, 1998

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

Delirium
1. 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

Alzheimer’s Disease
• Prevalence of psychotic symptoms: 16% to 70%;
Median: 37% for delusions; 4% to 76% ( M edian 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.

•
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

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.

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

• About half have visual hallucinations (up to 80% in some studies), and it’s an early sign in 43%.
1.Auditory hallucinations (20%) and paranoid delusions(65%) are also common
2.Some texts say psychotic symptoms are more common than in AD.
3. Recent studies have reported 29% to 50% rate of misidentification syndromes such as Capgras syndrome or Phantom Boarder Syndrome (about twice rate of AD patients)

• 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.
• PD without cognitive decline:
(a) No medication: psychotic sx may occur but rare.
(b) On medication: minor psychotic sx, with or without insight may occur (10-20%) such as:
• visual illusions (distorted perceptions)
• benign visual hallucinations/sense presence
(someone is nearby when there is no one)
• passage hallucinations (fleeting imagery in peripheral vision)

•
PD and Dementia : often experience psychotic symptoms in the absence of medications; dopaminergic therapies may trigger or exacerbate symptoms
(75% prevalence of psychosis in this category)
•
REMEMBER:
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.

1. Psychotic depression occurs in 20% to 45% of hospitalized elderly depressed patients; 15-25% of community depressed persons.
•
Delusions are more commonly moodcongruent, 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

• 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.

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. Most common causes of psychosis are the
“anti’s ”:anti-inflammatories (inc steroids), antiparkinsonian drugs, anticholinergic drugs, antiarrhythmic agents, antivirals, antibiotics, antimalarials.
• If tactile hallucinations occur, consider drug withdrawal states, toxic, or metabolic disturbances.

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.

Table 1. Common Medical Causes of Psychosis in
Older Persons
M etabolic
I nfections
Vitamin B
12 or folate deficiency, electrolyte abnormalities
Meningitis, encephalitis(e.g., herpes), syphilis, HIV/AIDS
N eurological
E ndocrine
Parkinson’s disease, epilepsy, subdural hematoma, stroke,
Huntington’s disease (rare), tumor(rare)
Thyroid disease, adrenal disease, hyper- or hypoglycemia
Adapted from Desai and Grossberg, 2003

•
Medical causes are 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

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%.
• 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 onefourth of persons with schizophrenia will be in this older age bracket.

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.

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.

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.

Community-dwelling older persons with schizophrenia (about 85% this population) have been generally found to have a nonprogressive course. The non-progressive course suggests schizophrenia is a static encephalopathy rather than a dementing disorder.

Public Policy Issues
Remission is Not Typically
Stable (“quiescent”) in Later
Life (so called “end –stage”)
On 4 ½ year follow-up:
One-quarter of older persons with schizophrenia remain in remission;
One-third never attain remission;
Two-fifths fluctuate between states.
(Cohen et al, AAGP annual meeting, 2012)
Suggests need for more intense interventions in later life

Based on hospital data
Based on community crosssectional data

2 . Increasingly, there is a more nuanced approach to outcome. There are outcome measures based on symptoms (e.g., positive symptoms, negative symptoms, cognition, depression) and global parameters (e.g. remission, community integration, quality of life, social adaptive functioning) that are only weakly associated with each other (4% shared variance).
Thus,
Each outcome category may require separate interventions rather than a single intervention that impacts on all outcome measures.

Late-Onset Schizophrenia
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.

“
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.

Demarcation
The 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.

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.

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.

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.

Schizoaffective Disorder (DSM-5)
Must have uninterrupted period of illness in which symptoms meet Criterion A for schizophrenia and a major mood episode (depression or mania). During this episode there must have been delusions or hallucinations for at least 2 weeks in the absence of major mood sx.
Symptoms of major mood disorder must be present for majority(“substantial” in DSM
IV-TR) of the active & residual phase of illness.
Critique: A shifting (unstable) and irrational dx: a. Differs between episodes; b. How can having both depression and schizophrenia turn into a 3 rd disorder?

Schizoaffective Disorder
• 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.

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.

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.

6 “Ds” of Psychiatric Diagnoses in Older
Adults that Co-Occur with Psychoses
Think of these possibilities and consider course:
•
Delirium: days to weeks
•
Drugs: days to months
•
Disease: days to months
•
Depression: weeks to months
•
Dementia: months to years
•
Delusional disorder and schizophrenia: months to decades

Freudenreich, 2010
Growing
Importance

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. Starting dosages for late-onset persons at 25% of the recommended adult dose and maintenance doses at 25-50% of the adult dose. Often, effective doses for early-onset can be 50-75% of younger patients.

There has been only one 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.

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.

Various neurocognitive and social cognitive abilities are targeted such as :
•Neurocognition(e.g., working memory: storage & manipulation of information for learning; cognitive flexibility: ability to shift sets )
•Social Cognition & Perception
•Verbal Communication
•Social Skills
•Interpersonal Problem Solving Skills

Examples with Middle-Age and Older Adults
• Integrated Psychological Therapy (IPT; Mueller et al, 2013): cognitive remediation therapy(CRT)and social skills therapy (SST)
• Functional Adaptation Skills Training (FAST;
Patterson et al, 2003):SST
• Helping Older People Experience Success(HOPES;
Pratt et al, 2008): SST
• Cognitive Behavioral Social Skills Training
(CBSST; Granholm et al, 2005): SST & CBT
• CRT: McGirk & Mueser, 2008; Wykes et al, 2005)

New community treatment strategies for older adults with mental illness can be divided into:
(1) Collaborative programs : between psychiatrists and PCPs
(2) Case management strategies : social and cognitive skills in tandem with physical health enhancing strategies & promoting interdisciplinary communication .
(3) Some combination of (1) and (2).

Late-Onset Schizophrenia a.
Based on limited data, late-onset schizophrenia patients appear to have good symptomatic improvement with antipsychotic treatment compared to early-onset illness individuals.
b. Substantially reduced doses of antipsychotics are necessary in late-onset schizophrenia patients.
Maintenance therapy is frequently required, because many of these patients relapse if they discontinue the medication.

c. Cochrane 2013: A lack of published data specifically examining antipsychotics in late-onset schizophrenia (LOS), and investigations have often mixed early- and late-onset patients. Only one randomized trial using risperidone and olanzapine, and both were well-tolerated, but study had no other usable data. d. Open studies of typical antipsychotics in LOS indicated that 48%–61% of patients demonstrated full remission of psychotic symptoms.
e. Cognitive behavioral therapy and social skills training also have shown promise.

Delusional Disorders a.
Commonly, persons deny their illness .
Consequently, non-adherence to antipsychotics is a common problem in the treatment b. Antipsychotic agents often are effective, especially in agitated delusional patients.
of patients with delusional disorder.
c. For refractory cases, modified electro-convulsive therapy has been reported as successful.
d. Cognitive-behavior therapy has been demonstrated as an effective treatment approach.

•
Critical to adjust anti-parkinsonian medication
• Quetiapine 12.5mg to 150mg has been effective for psychotic symptoms
• Clozapine; 6.25mg to 50mg has been effective.
• Pimavanserin(?)--a serotonin (HT2) inverse agonist– recently successfully completed
Phase 3 trials.

CATIE study, in which time to discontinuation did not differentiate antipsychotic medications from placebo, and black box warnings regarding higher mortality rates, suggests that medications must be used judiciously. In CATIE study, the median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine and risperidone, but the time to the discontinuation of treatment due to adverse events or intolerability favored placebo.
Mean doses used in CATIE trial: risperidone(1mg), olanzepine (5.5mg) , and quetiapine (56.5mg).

Recommended doses:
Risperidone:0.75mg to 1.5mg
Olanzepine: 2.5mg to 7.5mg
Quetiapine : 25mg to 200mg
Psychosocial modalities:
Sensory enhancement, structured activities, social contact, behavior therapy.

1. Delusional disorder
2. Schizophrenia
3. Depression
4. Alzheimer’s disease

1. Schizophrenia
2. Alzheimer’s disease
3. Delusional disorder
4. Depressive disorder

1. Auditory
2. Tactile
3. Visual
4. Olfactory

1. Auditory hallucinations are the most common type of hallucination
2. Psychoses are most common in the early stages of the disorder
3. Delusions concerning theft are common
4. Misidentification syndromes are a type of delusion

1. Extrinsic causes of hallucinations are greater than intrinsic causes
2. Rates of hallucinations are about 10%
3. The preferred treatment for hallucinations is risperidone
4. Rates of hallucinations are similar among those persons with and without dementia

1. Auditory hallucinations are common
2. Permeable wall delusion often occurs
3. Delusions are mood-congruent
4. Psychosis occurs in about 10% of hospitalized cases

1. Approximately a quarter of early onset cases show recovery or mild end states
2. Men develop the disorder more commonly after age 45
3. Persecutory delusions are more common in late onset disorders
4. Prevalence of auditory hallucinations is similar to delusional disorder