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Antipsychotics = Neuroleptics

Indications:
schizophrenia and other psychotic disorders, mood disorders with or
without psychosis, violent behaviour, autism, Tourette's, somatoform
disorders, dementia, OCD
onset of action:
immediate calming effect and decrease in agitation; thought disorder
responds in 2-4 weeks.
Mechanism of action according to pathophysiology of
Schizophrenia :
Brain Area
Limbic System

Frontal Cortex

Basal Ganglia

Tuberoinfundibul
ar Tract

Pathophysiology
in Schizophrenia
ExcessDA
+ve symptoms
(hallucinations,
dulusions)
Decreased DA
-ve symptoms
( flat affect,
anhedoniam
avolition ),
cognitive
impairment
Unchanged

Typical
Antipsychotic
D2 blockade
Treats +ve
symptoms

Atypical Antipsychotic

D2 blockade
May worsen ve
symptoms and
cognitive
impairment

Unchanged

D2 blockade
Hyperprolactinemia

Robust 5-HT block


increases
DA transmission
Theoritical improvement
in negative/cognitive
symptoms only
observed with clozapine
Robust 5-HT block
increases
DA transmission
Decreased EPS
incidence
5-HT block increases DA
Less hyperprolactinemia

D2 blockade
Relative Ach
excess causes EPS
symptoms

Weak 5-HT block, D2/1


blockade maintained
Treats +ve symptoms

Rational use of Antipsychotics :


-

No reason to combine antipsychotics


Choosing an antipsychotic :
All antipsychotics are equally effective
Atypical antipsychotics are as effective as typical antipsychotics
but have better side effect profiles
Choose a drug patient has responded to in the past
Route : PO, short-acting or long-acting depot, IM injections,
sublingual
Duration : minimum 6 months, usually for life

Common Antipsychotic Agents :Typicals


-

Pimozide
Haloperidol
Fluphenazine enanthate
Zuclopenthixol HCl
Zuclopenthixol acetate
Zuclopenthixol decanoate
Trifluoperazine
Perphenazine
Loxapine HCl
Thioridazine
Chlorpromazine

Atypicals
-

Risperidone
Risperdal Consta
Olanzapine
Ziprasidone
Clozapine
Quetiapine
Aripiprazole

Atypical Antipsychotics:

fewer EPS than typicals (except risperidone above 8 mg/d)


risperidone, olanzapine, quetiapine are the "first line atypical
antipsychotics"
no significant difference in efficacy; speed of response and stability
of remission between first line atypicals
disadvantage: expensive, metabolic side effects

Commonly used Atypical Antipsychotics :

Canadian Guidelines for the Treatment of Acute Psychosis in the


Emergency Setting
haloperidol5 mg IM 2 mg 1M lorazepam
olanzapine 2.5-10 mg (PO, 1M, quick dissolve)
risperidone 2 mg (M-tab, liquid)
Side Effects of Antipsychotics :
Side effects of typical Antipsychotics:
low potency: anticholinergic, antiadrenergic, anti histaminic side effects
high potency: risk of movement disorder side effects (extrapyramidal
side effects) and
neuroleptic malignant syndrome (allergic reaction)
Side effects of Atypical Antipsychotics:

Atypical antipsychotics have better side effect profiles


They have metabolic side effects

Extrapyramidal Symptoms (EPS)


incidence related to increased dose and potency
acute (early-onset; reversible) vs. tardive (late-onset; often irreversible)
Neuroleptic Malignant Syndrome (NMS)
psychiatric emergency
due to massive dopamine blockade; increased incidence with high
potency and depot
Neuroleptics
Features: FARM
- Fever
- Autonomic changes (e.g. increased HR/BP, sweating)
- Rigidity of muscles
- Mental atatus changes ( e.g. confusion)
Metabolic Syndrome
A collection of clinical and laboratory abnormalities including abdominal
obesity, insulin resistance, HTN, low levels of high-density lipoprotein
cholesterol, and high levels of triglycerides.
Note :
-

Antiparkinsonian agents are not always prescribe with neuroleptics


Antiparkinsonian agents are only given if at high risk for acute EPS
or if acute EPS develops
and do not give these for tardive syndromes because they worsen the
condition