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FOCUS, VOL. 2, No. 1

CLINICAL SYNTHESIS | January 01, 2004

Quick Reference for Schizophrenia

FOCUS 2004;2:13-16.

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Table 1. Features Associated With Good and Poor Outcome in Schizophrenia

Feature	Good Outcome	Poor Outcome
Age	Older	Younger
Gender	Female	Male
Social class	High	Low
Marital history	Married	Never married
Family history of schizophrenia	Negative	Positive
Perinatal complications	Absent	Present
Transcultural factors	Developing nations	Industrialized nations
Premorbid functioning	Good	Poor
Onset	Acute	Insidious
Duration	Short	Chronic
Sensorium	Clouded	Clear
Symptoms/subtypes	Paranoid subtype	Deficit syndrome
Affective symptoms	Present	Absent
Neurological functioning	Normal	Soft signs present
Neurocognition	Normal	Abnormal
Structural brain abnormalities	None	Present
Reprinted with permission from Ho B, Black DW, Andreasen NC: Schizophrenia and other psychotic disorders, in The American Psychiatric Publishing Textbook of Clinical Psychiatry, 4th ed. Edited by Hales RE, Yudofsky SC. Arlington, Va, American Psychiatric Publishing, Inc, 2003, p 400.

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Table 2. Reasons to Hospitalize Patients With Schizophrenia

When the illness is new, to rule out alternative diagnoses and to stabilize the dose of antipsychotic medication

For special medical procedures such as electroconvulsive therapy

When aggressive or assaultive behavior presents a danger to the patient or others

When the patient becomes suicidal

When the patient is unable to properly care for himself or herself (e.g., refuses to eat or take fluids)

When medication side effects become disabling or potentially life threatening (e.g., severe pseudoparkinsonism, severe tardive dyskinesia, neuroleptic malignant syndrome)

Reprinted with permission from Ho B, Black DW, Andreasen NC: Schizophrenia and other psychotic disorders, in The American Psychiatric Publishing Textbook of Clinical Psychiatry, 4th ed. Edited by Hales RE, Yudofsky SC. Arlington, Va, American Psychiatric Publishing, Inc, 2003, p 418.

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Table 3. Atypical (Dopamine-Serotonin Antagonist) Antipsychotics: Overview

Efficacy

Schizophrenia (FDA approved for all)

Treatment-resistant schizophrenia (clozapine)

Mania (FDA approved for olanzapine)

Depression/anxiety/agitation (efficacy established but not FDA approved for these purposes)

Side effects

Weight gain

Sedation

Akathisia

Orthostatic hypotension

Dizziness

↑ Triglycerides

EPS, NMS (rare)

Agranulocytosis (clozapine) (rare)

Seizures (clozapine)

Safety in overdose

Seizures with clozapine in overdose. Respiratory depression in combination with other CNS depressants. QT interval changes. Lavage and vital sign support

Dosage and administration

Clozapine: 12.5—25 mg; then increase dosage 25—50 mg per week, as needed and tolerated, to 300—600 mg/day

Risperidone: 0.5—1 mg b.i.d. to 3 mg b.i.d. by end of first week, as tolerated

Olanzapine: 2.5—5 mg h.s.; increase by 5 mg every week to 20 mg h.s.

Quetiapine: 25 mg b.i.d.; increase total daily dose by 50 mg, as needed and tolerated, to 300—600 mg/day

Ziprasidone: 20 mg/day or b.i.d.; increase by 20—40 mg per week, to a maximum dosage of 80 mg b.i.d.

Aripiprazole: 15 mg/day; increase up to 30 mg/day after 1 week

Full benefits in 4 weeks to 6 months

Discontinuation

Mild cholinergic rebound, faster relapse

Taper as slowly as titrated up

Drug interactions

Fluvoxamine (1A2 inhibitors): ↑ atypical antipsychotic levels

EtOH: ↑ sedation and orthostasis

Antihypertensives: may ↑ orthostasis

Carbamazepine: ↓ serum levels of olanzapine; contraindicated with clozapine

CNS depressants: ↑ sedation

CNS = central nervous system; EPS = extrapyramidal symptoms; EtOH = ethanol; FDA = U.S. Food and Drug Administration; NMS = neuroleptic malignant syndrome

Reprinted with permission from Schatzberg AF, Cole J, DeBattista C: Antipsychotic drugs, in Manual of Clinical Psychopharmacology, 4th ed. Arlington, Va, American Psychiatric Publishing, Inc, 2003, pp 188—189.

Table 4. Typical Antipsychotics: Metabolism and Enzyme Inhibition

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Note: Data presented relate to parent drug and metabolites combined. FMO3 = flavin monooxygenase

a Bold type indicates major pathway

b Bold type indicates potent inhibition

Modified and reprinted with permission from Cozza KL, Armstrong SC, Oesterheld JR: Psychiatry, in Concise Guide to Drug Interaction, 2nd ed. Arlington, Va, American Psychiatric Publishing, Inc, 2003, p 368.

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Table 5. Atypical Antipsychotics: Metabolism and Enzyme Inhibition

Drug	Major Metabolism Site(s)	Enzyme(s) Inhibited
Aripiprazole	2D6, 3A4	None known
Clozapine	1A2, 3A4, 2D6, 2C19, UGT1A4, UGT1A3	2D6^a
Olanzapine	1A2, 2D6, UGT1A4, ?other UGTs, ?FMO3	None known
Quetiapine	3A4, sulfation	None known
Risperidone	2D6, 3A4	2D6^b
Ziprasidone	Aldehyde oxidase, 3A4, 1A2	None known
Note: Data presented relate to parent drug and metabolites combined. FMO3 = flavin monooxygenase; UGT = uridine 5’-diphosphate glucuronosyltransferase
a Mild
b Moderate
Modified and reprinted with permission from Cozza KL, Armstrong SC, Oesterheld JR: Psychiatry, in Concise Guide to Drug Interaction, 2nd ed. Arlington, Va, American Psychiatric Publishing, Inc, 2003, p 361.

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Table 6. Summary of Sex Differences in Schizophrenia

Women experience more mood symptoms

Men experience more deficit symptoms

Women present as more socially appropriate

Delusional themes differ between the two sexes

Men engage in more substance abuse

Women have more comorbid problems (allergies, endocrine disturbances, eating disorders, posttraumatic stress disorders, psychophysiological disorders)

Reprinted with permission from Seeman MV: Gender differences in schizophrenia across the life span, in Schizophrenia Into Later Life: Treatment, Research, and Policy. Edited by Cohen CI. Arlington, Va, American Psychiatric Publishing, Inc, 2003, p 143.

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Table 7. Differentiating Chronic Schizophrenia from Alzheimer’s Disease With Psychotic Symptoms

Symptoms	Alzheimer’s Disease	Schizophrenia
Delusions
Someone stealing	+++	++
Thought control	+/−	++/+++
Hallucinations
Auditory	+/++	++/+++
Visual	++/+++	+
Cognitive impairment
Short-term memory loss	+++	+
Word-finding difficulties	++/+++	−/+
Disorientation	++	−/+
Mini-Mental State Examination	Gradual decline	More or lesss constant
Family history	Alzheimer’s disease	Major mental disorder
Course	Progressive decline	Variable
Typical social situation	Married, widowed, divorced, not socially isolated	Single, socially isolated
+/− = may or may not be present; + = may be present; ++ = often present; +++ = present in most
Reprinted with permission from Desai AK, Grossberg GT: Differential diagnosis of psychotic disorders in the elderly, in Schizophrenia Into Later Life: Treatment, Research, and Policy. Edited by Cohen CI. Arlington, Va, American Psychiatric Publishing, Inc, 2003, p 61.

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Table 8. Selected Side Effects of Commonly Used Antipsychotic Medications

	Extrapyramidal Side Effects/Tardive Dyskinesia	Prolactin Elevation	Weight Gain	Glucose Abnormalities	Lipid Abnormalities	QTc Prolongation	Sedation	Hypotension	Anticholinergic Side Effects
Thioridazine	+	++	+	+?	+?	+++	++	++	++
Perphenazine	++	++	+	+?	+?	0	+	+	0
Haloperidol	+++	+++	0	0	0	0	++	0	0
Clozapine^a	0^b	0	+++	+++	+++	0	+++	+++	+++
Risperidone	+	+++	++	++	++	+	+	+	0
Olanzapine	0^b	0	+++	+++	+++	0	+	+	++
Quetiapine^c	0^b	0	++	++	++	0	++	++	0
Ziprasidone	0^b	+	0	0	0	++	0	0	0
Aripriprazole^d	0^b	0	0	0	0	0	+	0	0
0 = no risk or rarely causes side effects at therapeutic dose; + = mild or occasionally causes side effects at therapeutic dose; ++ = sometimes causes side effects at therapeutic dose; +++ = frequently causes side effects at therapeutic dose
a Also causes agranulocytosis, seizures, and myocarditis
b Possible exception of akathisia
c Also carries warning about potential development of cataracts
d Also causes nausea and headache
Reprinted with permission from American Psychiatric Association: Practice Guideline for the Treatment of Patients With Schizophrenia, Second Edition. Arlington, Va, American Psychiatric Publishing, Inc, 2004, in press.

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Table 1. Features Associated With Good and Poor Outcome in Schizophrenia

Feature	Good Outcome	Poor Outcome
Age	Older	Younger
Gender	Female	Male
Social class	High	Low
Marital history	Married	Never married
Family history of schizophrenia	Negative	Positive
Perinatal complications	Absent	Present
Transcultural factors	Developing nations	Industrialized nations
Premorbid functioning	Good	Poor
Onset	Acute	Insidious
Duration	Short	Chronic
Sensorium	Clouded	Clear
Symptoms/subtypes	Paranoid subtype	Deficit syndrome
Affective symptoms	Present	Absent
Neurological functioning	Normal	Soft signs present
Neurocognition	Normal	Abnormal
Structural brain abnormalities	None	Present
Reprinted with permission from Ho B, Black DW, Andreasen NC: Schizophrenia and other psychotic disorders, in The American Psychiatric Publishing Textbook of Clinical Psychiatry, 4th ed. Edited by Hales RE, Yudofsky SC. Arlington, Va, American Psychiatric Publishing, Inc, 2003, p 400.

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Table 2. Reasons to Hospitalize Patients With Schizophrenia

When the illness is new, to rule out alternative diagnoses and to stabilize the dose of antipsychotic medication

For special medical procedures such as electroconvulsive therapy

When aggressive or assaultive behavior presents a danger to the patient or others

When the patient becomes suicidal

When the patient is unable to properly care for himself or herself (e.g., refuses to eat or take fluids)

When medication side effects become disabling or potentially life threatening (e.g., severe pseudoparkinsonism, severe tardive dyskinesia, neuroleptic malignant syndrome)

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Table 3. Atypical (Dopamine-Serotonin Antagonist) Antipsychotics: Overview

Efficacy

Schizophrenia (FDA approved for all)

Treatment-resistant schizophrenia (clozapine)

Mania (FDA approved for olanzapine)

Depression/anxiety/agitation (efficacy established but not FDA approved for these purposes)

Side effects

Weight gain

Sedation

Akathisia

Orthostatic hypotension

Dizziness

↑ Triglycerides

EPS, NMS (rare)

Agranulocytosis (clozapine) (rare)

Seizures (clozapine)

Safety in overdose

Seizures with clozapine in overdose. Respiratory depression in combination with other CNS depressants. QT interval changes. Lavage and vital sign support

Dosage and administration

Clozapine: 12.5—25 mg; then increase dosage 25—50 mg per week, as needed and tolerated, to 300—600 mg/day

Risperidone: 0.5—1 mg b.i.d. to 3 mg b.i.d. by end of first week, as tolerated

Olanzapine: 2.5—5 mg h.s.; increase by 5 mg every week to 20 mg h.s.

Quetiapine: 25 mg b.i.d.; increase total daily dose by 50 mg, as needed and tolerated, to 300—600 mg/day

Ziprasidone: 20 mg/day or b.i.d.; increase by 20—40 mg per week, to a maximum dosage of 80 mg b.i.d.

Aripiprazole: 15 mg/day; increase up to 30 mg/day after 1 week

Full benefits in 4 weeks to 6 months

Discontinuation

Mild cholinergic rebound, faster relapse

Taper as slowly as titrated up

Drug interactions

Fluvoxamine (1A2 inhibitors): ↑ atypical antipsychotic levels

EtOH: ↑ sedation and orthostasis

Antihypertensives: may ↑ orthostasis

Carbamazepine: ↓ serum levels of olanzapine; contraindicated with clozapine

CNS depressants: ↑ sedation

CNS = central nervous system; EPS = extrapyramidal symptoms; EtOH = ethanol; FDA = U.S. Food and Drug Administration; NMS = neuroleptic malignant syndrome

Table 4. Typical Antipsychotics: Metabolism and Enzyme Inhibition

View Large | Download Slide(.ppt)
Add to My POL

Note: Data presented relate to parent drug and metabolites combined. FMO3 = flavin monooxygenase

a Bold type indicates major pathway

b Bold type indicates potent inhibition

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Table 5. Atypical Antipsychotics: Metabolism and Enzyme Inhibition

Drug	Major Metabolism Site(s)	Enzyme(s) Inhibited
Aripiprazole	2D6, 3A4	None known
Clozapine	1A2, 3A4, 2D6, 2C19, UGT1A4, UGT1A3	2D6^a
Olanzapine	1A2, 2D6, UGT1A4, ?other UGTs, ?FMO3	None known
Quetiapine	3A4, sulfation	None known
Risperidone	2D6, 3A4	2D6^b
Ziprasidone	Aldehyde oxidase, 3A4, 1A2	None known
Note: Data presented relate to parent drug and metabolites combined. FMO3 = flavin monooxygenase; UGT = uridine 5’-diphosphate glucuronosyltransferase
a Mild
b Moderate
Modified and reprinted with permission from Cozza KL, Armstrong SC, Oesterheld JR: Psychiatry, in Concise Guide to Drug Interaction, 2nd ed. Arlington, Va, American Psychiatric Publishing, Inc, 2003, p 361.

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Table 6. Summary of Sex Differences in Schizophrenia

Women experience more mood symptoms

Men experience more deficit symptoms

Women present as more socially appropriate

Delusional themes differ between the two sexes

Men engage in more substance abuse

Women have more comorbid problems (allergies, endocrine disturbances, eating disorders, posttraumatic stress disorders, psychophysiological disorders)

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Table 7. Differentiating Chronic Schizophrenia from Alzheimer’s Disease With Psychotic Symptoms

Symptoms	Alzheimer’s Disease	Schizophrenia
Delusions
Someone stealing	+++	++
Thought control	+/−	++/+++
Hallucinations
Auditory	+/++	++/+++
Visual	++/+++	+
Cognitive impairment
Short-term memory loss	+++	+
Word-finding difficulties	++/+++	−/+
Disorientation	++	−/+
Mini-Mental State Examination	Gradual decline	More or lesss constant
Family history	Alzheimer’s disease	Major mental disorder
Course	Progressive decline	Variable
Typical social situation	Married, widowed, divorced, not socially isolated	Single, socially isolated
+/− = may or may not be present; + = may be present; ++ = often present; +++ = present in most
Reprinted with permission from Desai AK, Grossberg GT: Differential diagnosis of psychotic disorders in the elderly, in Schizophrenia Into Later Life: Treatment, Research, and Policy. Edited by Cohen CI. Arlington, Va, American Psychiatric Publishing, Inc, 2003, p 61.

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Table 8. Selected Side Effects of Commonly Used Antipsychotic Medications

	Extrapyramidal Side Effects/Tardive Dyskinesia	Prolactin Elevation	Weight Gain	Glucose Abnormalities	Lipid Abnormalities	QTc Prolongation	Sedation	Hypotension	Anticholinergic Side Effects
Thioridazine	+	++	+	+?	+?	+++	++	++	++
Perphenazine	++	++	+	+?	+?	0	+	+	0
Haloperidol	+++	+++	0	0	0	0	++	0	0
Clozapine^a	0^b	0	+++	+++	+++	0	+++	+++	+++
Risperidone	+	+++	++	++	++	+	+	+	0
Olanzapine	0^b	0	+++	+++	+++	0	+	+	++
Quetiapine^c	0^b	0	++	++	++	0	++	++	0
Ziprasidone	0^b	+	0	0	0	++	0	0	0
Aripriprazole^d	0^b	0	0	0	0	0	+	0	0
0 = no risk or rarely causes side effects at therapeutic dose; + = mild or occasionally causes side effects at therapeutic dose; ++ = sometimes causes side effects at therapeutic dose; +++ = frequently causes side effects at therapeutic dose
a Also causes agranulocytosis, seizures, and myocarditis
b Possible exception of akathisia
c Also carries warning about potential development of cataracts
d Also causes nausea and headache
Reprinted with permission from American Psychiatric Association: Practice Guideline for the Treatment of Patients With Schizophrenia, Second Edition. Arlington, Va, American Psychiatric Publishing, Inc, 2004, in press.

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Quick Reference for Schizophrenia. FOCUS: The Journal of Lifelong Learning in Psychiatry. 2004 Jan;2(1):13-16.

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