1

First Generation Antipsychotics.

Generic Name (& EPS
AntiTrade Name)
cholinergic
effects
Chlorpromazine
+
+++
(Thorazine)

Sedation

Orthostatic
hypotension

QTc
prol.

Prolactin
elevation

Route

Potency

Major interactions

+++

Weights
Gain/Diabetes
Mellitus
+++

+++

++

Tab
IM
IV

Low

-Decreases serum level of Li+.

-Concurrent use w/antidepressants may increase
serum level of both.
-Additive effects w/antiadrenergic, anticholinergic
and CNS depressants.
-Concurrent use w/antidepressants may increase
serum level of both.
-Additive effects w/antiadrenergic, anticholinergic
and CNS depressants.
-Carbamazepine and barbiturates decrease serum
level
-Quinidine increases serum level
-Same as chlorpromazine

Fluphenazine
(Prolix)

+++

ND

+++

Tab
Depot

High

Haloperidol
(Haldol)

+++

++

+++

High

ND

++

++

Tab
IM
Depot
Tab
IM
Tab
IM
Inhal
ent

Trifluoperazine
+++
+
+
+
++
(Stelazine)
Loxapine
++
+
++
+
++
(Loxapac) &
(Adasuve
(Inhalable form))
MOA: Antagonize D2 (Gi) receptor (increase [cAMP]) > 5-HT2

High
Medium

-Concurrent use w/antidepressants may increase

serum level of both.

A/E:
- Evolution of EPS: 4hrs acute dystonia (muscle spasms, stiffness, oculogyric crisis)
4days Akathisia/Restlessness (due to receptor sensitization/increase in the affinity of binding)
4weeks Pseudoparkinsonism
4month TD (due to receptor upregulation)
- NMS: rigidity, myoglobinuria, hyperthermia. (tx: dandroline, D2 agonist bromocriptine)
Pretreatment assessment:
- Baseline weight and height.
- Fasting blood sugar (or HbA1c) and fasting lipids
- Baseline ECG
- Absence or presence of abnormal motor movements should be documented using the Abnormal Involuntary Movement Scale (AIMS)
(AIMS records the occurrence of TD and follows the severity of patients TD over time.
Clozapine only:
- In addition to all of the above, WBC 3500/mm3 and ANC 2000/mm3 are acceptable for initiating clozapine.
- Individuals with a seizure disorder should have their seizures optimally controlled before clozapine is started.
- Follow-up electroencephalogram may be indicated after clozapine treatment is established.

TBZ

Haloperidol:
- Good choice for acute psychotic episodes as its rapidly absorbed and has high bioavailability post IM injection, w/plasma levels reaching max in 20min.
- Commonly used in drug-induced psychosis, Tourette syndrome, delirium.
- When given to lactating mothers its significantly found in their breast milk. Breast-feeding children can show EPS.
- Contraindicated in: Stoke, intoxication w/alcohol, cns depressants, CVS problems.
- Precaution in: Hyperthyroidism (intensifies action of haloperidol by modifying sensitivity of D2 receptors), compromised liver, hypo-K ptn (QTc prolongation)

Second Generation Antipsychotics.

Generic Name (& Trade
EPS AntiName)
cholinergic
effects
Clozapine
+++
(Clozaril)
Olanzapine
+
++
(Zyprexa)

Sedation

Orthostatic
hypotension

QTc
prolong

Prolactin
elevation

Route

Potency

Major interactions

+++

Weights
Gain/Diabetes
Mellitus
+++

+++

Tab

Low

++

+++

Tab
IM
Depot
Tab
Depot
Tab
IM
Depot
Tab

High

Possible interactions w/drugs

that induce or inhibit CYP1A2
Same as clozapine

Risperidone
(Risperdal)
Paliperidone
(Invega)

++

++

++

+++

++

++

++

+++

Iloperidone
(Fanapt)

+++

++

++

Aripiprazole
(Aripiprex)

Quetipine
(Seroquel)
Ziprasidone
+
(Geodon)
MOA: Antagonize 5-HT2 > D2

++

++

++

++

++

++

Tab
IM
Depot
Tab
Tab
IM

High

Possible interactions w/drugs

that induce or inhibit CYP2D6
ND

Possible interactions w/drugs

that induce or inhibit CYP2D6
& 3A4
Possible interactions w/drugs
that induce or inhibit CYP2D6
& 3A4
Possible interactions w/drugs
that induce or inhibit CYP3A4
Possible interactions w/drugs
that induce or inhibit CYP3A4

ND = No data

TBZ

Clozapine:
- Only used in treatment resistant schizophrenia (failure to respond to at least two different antipsychotics)
- Clozapine binds loosely and transiently to dopamine D2 receptor. This may explain its reduced potential for producing movement abnormalities relative to tightly
binding dopamine D2 antagonists such as haloperidol.
- Food has little effect on the bioavailability of clozapine
- Development of agranulocytosis is delayed, occurs 6-12 weeks after exposure to clozapine
- Clozapine is metabolised by liver, peripheral blood neutrophils and their bone marrow precursors to a chemically reactive intermediate (postulated to be a nitrenium
ion). This toxic metabolite has been shown to covalently bind to neutrophil cellular proteins and disrupt neutrophil function or, alternatively, it may act as a hapten and
initiate an immune reaction resulting in immune-mediated destruction of the neutrophil. Indirect evidence exists to support both mechanisms, although clear direct
evidence is still lacking.
- Suggested that administration along w/Vit-C (antioxidant) can reduce risk of agranulocytosis (Hsyuanyu Y., Dunford H.B. (1999). "Oxidation of Clozapine and
Ascorbate by Myeloperoxidase.")
A/E:
- Agranulocytosis (neutrophil number below 500 cells/ mm3). If agranulocytosis occurs, filgrastim (G-CSF) helps to return WBC and ANC counts to normal.
- Myocarditis (Need to monitor CRP & Troponin weekly for the first four weeks) (Post-mortem examination has revealed damaged myocytes and eosinophilic
infiltration suggesting a type-I IgE-mediated acute hypersensitivity reaction)
- GIT Hypomobility
- Hypersalivation full agonist at M4
- Disrupt metabolism & induces insulin resistance (Type 2 DM)
- (Rare) Deficiency of Selenium (Selenium is necessary for i) Glutathione peroxidase (protects from oxidative damage) and ii) the conversion of the thyroid hormone
T4 into its more active T3 form and as such a deficiency can cause symptoms of hypothyroidism, including extreme fatigue, mental slowing, etc.) (Vaddadi K., &
Soosai E. (2003) Low blood selenium concentrations in schizophrenic patients on clozapine)
Ziprazidone:
- Bioavailability increases when taken with the recommended 500 calorie meal.
- The oral drug is not affected by renal impairment, but a component of the intramuscular preparation is cleared through the kidney, leading to the manufacturers
recommendation that it be used with caution in that population.
Aripiprazole:
- Acts as a partial agonist at dopamine D2 receptors, activating the receptor but eliciting a reduced response compared to the natural neurotransmitter. The drug is also
a partial agonist at serotonin 5HT2a receptors
- Disadvantages include the use of aripiprazole in conjunction w/other antipsychotic, b/c the combination of a partial agonist w/an antagonist leads to unpredictable
levels of receptor activity.
Paliperidone:
- Bioavailability increases by about 50 percent when taken with a high calorie meal.
- The high level (60%) of urinary excretion makes it unique among antipsychotics in not requiring hepatic function for clearance
- Can be used to treat psychosis in patients with hepatic impairment