DRUG THERAPY OF

SCHIZOPHRENIA
Applied Therapeutics II
 DRUG THERAPY OF SCHIZOPHRENIA

• ETIOLOGY
• The pathology of schizophrenia is poorly
understood
• Classically it has been thought that the main
pathology was linked to over-activity of the
dopaminergic neurotransmitter. As such
traditional therapies have consisted of
dopamine receptor antagonists for example
chlorpromazine
 DRUG THERAPY OF SCHIZOPHRENIA

• ETIOLOGY
• The lack of immediate response to dopamine
receptor antagonists indicates that there are
other processes involved
• In addition to targeting the dopaminergic
system, currently utilised drug therapy also
acts on serotonergic, and noradrenaline
system, GABAergic
 DRUG THERAPY OF SCHIZOPHRENIA
EPIDEMIOLOGY
• Schizophrenia is thought to affect 20 million
people worldwide, with half of these being in
the developed world
• It is estimated to affect 1% of the UK
population
• The age of onset is commonly during a
patient’s early 20s
 DRUG THERAPY OF SCHIZOPHRENIA

• EPIDEMIOLOGY
• Up to 20% of patients suffer only a single acute
episode
• The cause of death in appropriately 10% of
those with schizophrenia is suicide
• Drug use such as amphetamine is responsible
for some cases, however other risk factors
have yet to be well defined
 DRUG THERAPY OF SCHIZOPHRENIA
• SIGNS AND SYMPTOMS
• Positive symptoms: hallucinations, delusions,
thought dysfunction. These symptoms are due to
excess dopamine in the mesolimbic pathway
• Negative symptoms can include affective blunting,
avolition, anhedonia and memory impairment.
These symptoms are due to deficiency of dopamine
in mesocortical pathway and frontal
cortex( regulated by serotonin)
 DRUG THERAPY OF SCHIZOPHRENIA

• SIGNS AND SYMPTOMS

• Patients may have some or all of the symptoms
during an acute episodes, while some being
more prominent than others;foe example in
some patients thought disorders may
dominate whereas in others it may be
delusions
• Negative symptoms are often much more
difficult to treat than positive symptoms
 DRUG THERAPY OF SCHIZOPHRENIA

• INVESTIGATIONS
• Making a diagnosis of schizophrenia is difficult
as there are few objective measurement
possible
• The criteria laid out in the American Psychiatric
Association’s Diagnostic and Statistical Manual
of Mental Disorders are usually used to reach a
diagnosis
 Management
The aims of treatment are to:

• Manage initial psychotic symptoms

• Improve quality of life
• Attempt to prevent relapse
• Avoid or minimize adverse effects
• Treatment is often long-term
 Management
• Drugs used for the management of schizophrenia
can be broadly split into two categories: typical and
atypical antipsychotics
• Both classes have significant action on dopamine D2
receptors
• Current treatment strategies recommend that the
newer atypical antipsychotic drugs should be use as
the initial treatment as they have less association
with the development of extrapyramidal effects
 Management
• Extrapyramidal and endocrine symptoms can
be a problem in many patients especially when
reaching higher doses
• Inhibition of dopamine transmission can cause
hyperprolactinaemia
• The difference in the effects of individual drugs
mainly reflect their relative actions on alpha-
adrenoceptors and muscarinic and histaminic
and serotonin receptors
 Management
• Atypical antipsychotic drugs
• Atypical antipsychotic drugs include
olanzapine, risperidone, quetiapine
• They have different side- effect profiles,
cautions, formulation and dosing schedules
and careful consideration must be given to
which is appropriate agent for each patient
• They are associated with weight gain and
metabolic disorders such as diabetes
 Management
• CLOZAPINE
• Is an atypical antipsychotic drug that is not
recommended as first-line therapy. It is often
effective in those who have an inadequate
response to other antipsychotic drugs and is
specially active against negative symptoms. It
should only be used in those with treatment-
resistant schizophrenia cond’
 Management
• CLOZAPINE
who have tried at least two antipsychotic drugs,
One of which was typical, at recommended
doses for 6-8 weeks. This is because there is a
drug-specific risk of agranulocytosis. Patients
initiated on clozapine require specific intense
monitoring
 Management
Typical Antipsychotic Drugs
• chlorpromacine, levomepromazine,
prochlorperazine, trifluperazine, haloperidol
and sulpiride
• The typical antipsychotic drugs are associated
with side-effects such as extrapyramidal
effects, hypotension and muscarinic effects
 COMMON ADVERSE EFFECTS
• Common adverse effects and the drugs are
most associated with include:
• Weight gain with atypical drugs
• Sexual dysfunction with sulpiride
• Endocrine effects such as galactorrhoea and
amenorrhoea with sulpiride and
phenothizines
• Drowsiness with chlorpromazine
 COMMON ADVERSE EFFECTS
• Extrapyramidal effects with haloperidol and
the phenothizines
• Antimuscarinic effects with clozapine and
phenothiazines
• Cardiac arrhythmias with sertindole,
phenothizines, clozapine
• Blood dyscrasias with clozapine
• Hypotension with quetiapine, haloperidole,
phenothiazines
 THOUGHT QUESTIONS
• 1. What are the mechanisms of action of
neuroleptics(typical and atypical antipsychotics)
and how do they affect the positive and negative
symptoms of schizophrenia?

• 2. How are neuroleptics and atypical antipsychotics

classified and how do they differ in potency, dosing
range and adverse effects?
 THOUGHT QUESTIONS

3. What are extrapyramidal symptoms(EPS) and

what are the predisposing risk factors? What is
the recommended treatment of choice
4.Neuroleptics and typical drugs have many side-
effects, some related to their principal
mechanism of action( dopamine receptor
antagonism) and some unrelated to this. What
are they?