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• Depression
• Not only psychiatrics prescribe antidepressant
drugs… oncologist, pediatric
• SSRI=specific=less side effects=reduction in sexual
ability
• Always describe drug according to the side effect not
the efficacy
• SNRI= main side effect is hypertension
• After 8 weeks of Tx of 100 pt= only 50 will respond
to the Tx=only 20 of those have remission+ only 20 of
those have reduction in symptoms
• Most serious problem in depressant pt is suicide
Schizophrenia
• Pathogenesis is unknown.
• Onset of schizophrenia is in the late teens early ‘20s.
• Genetic predisposition -- Familial incidence.
• Multiple genes are involved.
• Afflicts 1% of the population worldwide.
• A thought disorder
Schizophrenia
Mainly In males esp. in second decade. smoking is a risk
factor.
Increase dopamine In CNS.
‫القدرة على التكلم وعمل عالقات اجتماعية بتقل‬...‫القدرة االدراكية تقل‬
Positive Symptoms.
Hallucinations, delusions, paranoia, ideas of reference.
Negative Symptoms. (some say bcz of decrease dopamine
in some parts in the brain or increase serotonin!!!)
Apathy, social withdrawal, anhedonia, emotional blunting, cognitive deficits, lack
of motivation to interact with the environment.
These symptoms are progressive and non-responsive to medication.
Pt may cure in his own…with cognitive Tx
Placebo is very effective as antipsychotic and anti
depressant (35%).
Schizophrenia
•
Drugs currently used in the prevention of psychosis.
** These drugs are not a cure **
•
Schizophrenics must be treated with medications
indefinitely, in as much as the disease in lifelong and it is
preferable to prevent the psychotic episodes than to treat
them.
SCHIZOPHRENIA IS FOR LIFE
There is no remission
Dopamine Theory of Schizophrenia
Many lines of evidence point to the aberrant
increased activity of the dopaminergic
system as being critical in the
symptomatology of schizophrenia.
There is a greater occupancy of D2 receptors
by dopamine => greater dopaminergic
stimulation
Effect of drug appears after 9 weeks
All antipsychotic drugs should be taken
before sleep bcz of sedative effect
Classification of Antipsychotic drugs
• Main categories are:
– Typical antipsychotics :dopamine antagonists( induce
extrapyrimidal side effect (Tardive dyskinesia:
irreversible) and Parkinson)
Phenothiazines (chlorpromazine, perphenazine,
fluphenazine, thioridazine et al)
Thioxanthenes (flupenthixol, clopenthixol)
Butyrophenones (haloperidol, droperidol)
– Atypical antipsychotics: serotonin antagonists
– (e.g. clozapine, risperidone>>> ‫أكثر انتشارا في األردن‬
)‫غالي الثمن‬, sulpiride, olanzapine)
Classification of Antipsychotic drugs
• Distinction between ‘typical’ and ‘atypical’
groups is not clearly defined, but rests on:
– Incidence of extrapyramidal side-effects (less in
‘atypical’ group)
– Efficacy in treatment-resistant group of
patients
– Efficacy against negative symptoms.
First Generation Antipsychotic Drugs
Compound
Seda- Hypotion
tension
Motor
(EP)
Effects
Phenothiazines
Chlorpromazine:‫حفظ‬
Fluphenazine
Haloperidol: most effective
‫حفظ‬
+++
++
++
+
+
++++
+
+
++++
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Second Generation Antipsychotic Drugs
Compound
Sedation
Risperidone:maximum
dose:6mg ‫مهم جدا‬
Hypotension
Motor
effects
++
+++
+/++
++
++
-
Dose
dependent
Risperdal
Clozapine ‫مهم‬
Clozaril
Aripiprazole
Abilify
0/+
0/+
0/+
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Pharmacological effects of antipsychotic drugs: blockade of
DA action
Area
What
What
dopamine antipsychotic
does
drug does
Drug profile
Basal ganglia
Control of
movement
Less with 2nd gen. None
with clozapine or quetiapine.
Limbic and
frontal cortex
Affective
behavior;
cognition
Temp.
regulation;
 prolactin
Hypothalamus
& endocrine
Chemoreceptor Nausea,
trigger zone
emesis
Extrapyramidal
(motor) side
effects: DA
deficiency
Site of
antipsychotic
action
prolactin
Reduce nausea,
emesis
Most equally efficacious,
ex. Clozapine &
olanzapine
1st Generation and
risperidone
1st Generation and
risperidone
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Tolerance and dependence to
antipsychotic drugs
• Not addicting
• Relapse in psychosis if discontinued
abruptly
• Tolerance develops to sedative effects
• No tolerance to prolactin secretion
• No tolerance to antipsychotic effect
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Withdrawal-like syndrome
1. Symptoms: nausea, vomiting, insomnia, and headache
2. Symptoms may persist for up to 2 weeks.
3. Symptoms can be minimized with a tapered reduction
of drug dosage.
Clozapine and
olanzapine
• VERY low EPS
• Blocks D1, D2, D4, adrenergic, 5HT2, muscarinic,
and histamine H1 receptors
• May show greater efficacy
against negative symptoms than
other antipsychotic drugs
• Agranulocytosis is a potentially
fatal side effect for clozapine
Both drugs have high efficacy, but cause significant weight gain
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and diabetes
Aripiprazole
• Partial agonist at D2 receptor
• Intrinsic activity depends on synaptic levels
of DA
• Affinity for muscarinic, α1-adrenergic,
serotonin and histamine receptors
• Good oral absorption, 3-5 hr to peak plasma
concentration, long elimination half life
• Few extrapyramidal side effects
• Efficacy is less than others
• Little hypotension
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Tardive dyskinesia
comprises mainly involuntary movements of
face and tongue, but also of trunk and
limbs, appearing after months or years of
antipsychotic treatment due to accumulation
of the drug. Irreversible side effect
You should follow your pt over years of the
Tx
Risperidone
Endocrine effect


One of the most prescribed drugs in Jordan.
In women, these disturbances include:
 galactorrhea
 loss of libido
 delayed ovulation and menstruation or amenorrhea.
 In men, these disturbances include:
 gynecomastia
 impotence.
 Ultra-rapid metabolizes (13% of the Jordanians)
need higher dose
• Patients on antipsychotic drugs have low cognitive and complex motor
•
abilities.
In psychiatry, we start the drug on high dose to relieve the primary symptom,
then reduce the dose.