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Schizophrenia
affecting about 7 per thousand of the adult population
mostly in the age group 15-35 years
the incidence is low (3-10,000), the prevalence is high due to
chronicity
about 24 million people wordwide
More than 50% of persons with schizophrenia are not
receiving appropriate care
90% of people with untreated schizophrenia are in developing
countries

Prescription for an antipsychotic


Physician Specialty
Psychiatry
General family practice
Internal medicine
Pediatrics
Neurology
Other specialties

Estimated %
70.31%
11.46%
9.99%
0.68%
1.50%
6.10%

Outpatient Use of Major Antipsychotic Drugs in Ambulatory Care Settings in the United
States, 1997-2000
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,

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Tintinalli's Emergency Medicine

Indications

Antipsychotic drugs
First generation

Second generation

Low-potency

Chlorpromazine (Taroctyl )
Thioridazine (Ridazin )

Midpotency

Trifluoperazine
Perphenazine (Perphenan )
Loxapine
Molindone

Highpotency

Haloperidol (Haldol )
Fluphenazine (Fludecate )
Thiothixene

Clozapine (Leponex, Lozapine )


Risperidone (Risperdal )
Olanzapine (Zyprexa )
Quetiapine (Seroquel )
Ziprasidone (Geodon )
Aripiprazole (Abilify )
Paliperidone (Xeplion )
Iloperidone
Asenapine
Lurasidone

aripiprazole

Antipsychotic Medications
10 and older for bipolar disorder, manic or mixed episodes;
13 to 17 for schizophrenia and bipolar;

chlorpromazine
clozapine
fluphenazine (generic only)
haloperidol
iloperidone
loxapine
molindone
olanzapine

paliperidone
perphenazine (generic only)
pimozide (for Tourette's syndrome)
quetiapine

risperidone

thioridazine (generic only)


thiothixene
trifluoperazine
ziprasidone

18 and older
18 and older
18 and older
3 and older
18 and older
18 and older
18 and older
18 and older; ages 13-17 as second line treatment
for manic or mixed episodes of bipolar disorder and
schizophrenia
18 and older
18 and older
12 and older
13 and older for schizophrenia;
18 and older for bipolar disorder;
10-17 for treatment of manic and mixed episodes of
bipolar disorder
13 and older for schizophrenia;
10 and older for bipolar mania and mixed episodes;
5 to 16 for irritability associated with autism
2 and older
18 and older
18 and older
18 and older NIMH


.1



CNS-PNS-
5 D1-D5


D2CNS-
( (clozapine
D4 , D2- ,
-


.2
, 5-HT2A

.3 , ,



cytochrome P-450 enzyme system-
PO 1-6
- (
sulpiride -) remoxipride-
extrapyramidal D2

Tintinalli's Emergency Medicine


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100% ,





chlorpromazine
promethazine
pimozide Tourettes disorder-
risperidone

12


First generation
Extrapyramidal side effects
Metabolic disorders

Second generation
Metabolic disorders
Extrapyramidal side effects

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Clinical pharmacology & Therapeutics | VOLUME 90 NUMBER 1 | July 2011


.1 80%
.2 -
akathisia ,acute dystonia -
neuroleptic malignant ,parkinsonism -
syndrome
tardive dyskinesia

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Motor side effects of typical


antipsychotics

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ORAL DOSAGE (mg/day)

ACUTE PSYCHOSIS
Dosage Forms

1ST Episode

Chronic

MAINTENANCE
1ST Episode

Chronic

METABOLIC SIDE EFFECTS


Weight Gain

Lipids

Glucose

Typical Antipsychotic Agents

Chlorpromazine
O, S, IM

200-600

800400

150-600

250-750

+++

+++

++

Perphenazine
O, S, IM

12-50

24-48

12-48

24-60

/+

Trifluoperazine
O, S, IM

5-30

10-40

2.5-20

10-30

/+

Fluphenazine
O, S, IM

2.5-15

5-20

2.5-10

5-15

/+

/+

Fluphenazine
decanoate
Depot IM

Not for acute use

5-75 mg/2 wks

Molindone
O, S

15-50

30-60

15-50

30-60

Loxapine
O, S, IM

15-50

30-60

15-50

30-60

Haloperidol

102.5

205

102.5

155

/+

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Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e

Atypical antipsychotic overdose: signs and symptoms


Alpha-1:
Dizziness, orthostatic hypotension, reflex tachycardia,
miosis, nasal congestion
Histamine-1:
CNS depression, appetite stimulation, hypotension
Muscarinic-1:
Central agitation, hallucinations, memory dysfunction, dry
skin and mucous membranes, hypertension, constipation,
mydriasis, blurry vision, tachycardia, urinary retention

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Risk factors for type II diabetes


Age 40 years
First-degree relative with type 2 diabetes
Member of high-risk population (e.g. people of Aboriginal, Hispanic, South Asian, Asian or
African descent)
History of IGT or IFG*
Presence of complications associated with diabetes
Vascular disease (coronary, cerebrovascular or peripheral)*
History of gestational diabetes mellitus
History of delivery of a macrosomic infant
Hypertension*
Dyslipidemia*
Overweight*
Abdominal obesity*
Polycystic ovary syndrome*
Acanthosis nigricans*
Schizophrenia (The incidence of type 2 diabetes is at least 3 times higher in people with
schizophrenia than in the general population)
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Canadian Diabetes Association
Other

Cause of overweight or obese in patients with psychotic


disorders
Non-medical
excessive food intake
poor diet composition
low physical activity
Medical
SGAs

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ACUTE PSYCHOSIS
Dosage Forms 1ST Episode

Chronic

MAINTENANCE
1ST Episode

Chronic

METABOLIC SIDE EFFECTS


Weight Gain

Lipids

Glucose

Atypical Antipsychotic Agents


Aripiprazole
O, S, ODT, IM
Asenapine
ODT
Clozapine
O, ODT
Iloperidone
O
Olanzapine
O, ODT, IM
Paliperidone
O
Paliperidone
palmitate
Depot IM

2010

3015

2010

3015

/+

10

2010

10

2010

/+

600200

900400

600200

900300

++++

+++

+++

168

/+

/+

1224b
207.5

3010

157.5

3015

++++

+++

+++

96

126

93

156

/+

/+

/+

/+

See notec on dosing

Quetiapine
XR O
Risperidone
O, S, ODT
Sertindole
O

600200

900400

600200

900300

/+

42

63

62

83

/+

/+

164

2012

2012

3212

/+

Ziprasidone
O,
25IM

160120

200120

16080

200120

/+

Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e

NCEP:ATPIII 2001

IDF Criteria for Central Adiposity

Three or more of the following:

Waist circumference

Central obesity:
Waist circumference >102 cm
(M), >88 cm (F)
Hypertriglyceridemia:
Triglycerides 150 mg/dL or
specific medication
Low HDL cholesterol:
<40 mg/dL and <50 mg/dL,
respectively, or specific
medication
Hypertension:
Blood pressure 130 mm
systolic or 85 mm diastolic or
specific medication
Fasting plasma glucose
100 mg/dL or previously
diagnosed Type 2 diabetes

Harrison's Principles of
Internal Medicine, 18e
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Men

Women

Ethnicity

94 cm

80 cm

Europid, Sub-Saharan African,


Eastern and Middle Eastern

90 cm

80 cm

South Asian, Chinese, and


ethnic South and Central
American

85 cm

90 cm

Japanese

Two or more of the following:

Fasting triglycerides >150 mg/dL or specific medication


HDL cholesterol <40 mg/dL and <50 mg/dL for men and women, respectively, or
specific medication
Blood pressure >130 mm systolic or >85 mm diastolic or previous diagnosis or specific
medication
Fasting plasma glucose 100 mg/dL or previously diagnosed Type 2 diabetes

From: Antipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis

American Journal of Psychiatry 1999; 156:1686-1696

Figure Legend:
95% Confidence IntervaIs for Weight Change After 10 Weeks on Standard Drug Doses, Estimated From a Random -Effects Model

Copyright American Psychiatric Association.


All rights reserved.

Side effects

Weight gain/
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sedation

Inactivity/obesity

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Clinical pharmacology & Therapeutics | VOLUME 90 NUMBER 1 | July 2011

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Prim Care Companion J Clin Psychiatry 2004;6[suppl 2]:813

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Monitoring protocol for patients on SGAs*

DIABETES CARE, VOLUME 27, NUMBER 2, FEBRUARY 2004


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