Antipsychotics have been classified into

2 groups: Typical and Atypical

Typical antipsychotics are those which
typically produce EPS at clinically
effective doses.
Atypical antipsychotics are those which
are less likely to produce EPS at clinically
effective doses.

Also called neuroleptics due to their
inhibitory effect on locomotion activity.
Their major mode of action is to block
dopamine D2 receptors in the limbic
system
They vary in affinity for the D2 receptor,
from low affinity drugs which require high
doses for clinical efficacy, to high affinity
drugs which are effective at lower doses

For typical neuroleptics, the adverse effects
that are most routinely concerning are
extrapyramidal adverse effects (EPS).
High potency drugs (eg haloperidol,
fluphenazine) are more likely to produce EPS
than low potency agents (eg chlorpromazine,
thioridazine).
The latter may have lower potential for EPS
than other typical neuroleptics because of its
relatively higher affinity for muscarinic
receptors.

There are a wide range of EPS produced
by typical neuroleptics, including the
following:
Dystonic reactions (when first administered)
Akathisia (during the first 2-3 weeks)
Parkinsonism (during the first several weeks with
variable persistence)
Neuroleptic malignant syndrome (at any time
point )
Tardive dyskinesia

Characterized by intermittent spasmodic or
sustained involuntary contractions of muscles
in the face, neck, trunk, pelvis, and extremities
They are rarely life threatening, yet are very
uncomfortable and often produce significant
anxiety and distress for patients
Can be treated with parenteral anticholinergic
agents or diphenhydramine, an antihistamine
with some anticholinergic properties.

This may be the most common of the EPS
effects, occurring in up to 70% of patients
treated long term with haloperidol.
It refers to a subjective uncomfortable
experience of motor restlessness which is
relieved my movement. Patients will complain
of discomfort, and manifest increases in
psychomotor behavior.
These symptoms can be so distressing as to
increase the risk of agitation or even suicidal
behavior.

Women are believed to be at higher risk
Management:
Reduction in dosage or switching to an
atypical antipsychotic drug, or drug less likely
to cause akathisia
If not feasible, symptoms may respond to
anticholinergics usually within 3-7 days.
Other options: low doses of benzodiazepines
or beta-blockers

A neurological syndrome characterized by
tremor, hypokinesia, rigidity, and postural
instability.
Resembles idiopathic parkinsonism
Severe neuroleptic induced parkinsonism
may resemble depression or negative
symptoms of schizophrenia
However associated motor signs and time
course of symptoms in relation to starting
antipsychotic treatment distinguishes it

Onset and severity of antipsychotic
induced parkinsonism is related to
medication dosage, like akathisia
Hence lowering dosage or switching to
medication that is less likely to cause the
effect may provide significant relief
If not feasible, anticholinergics may provide
relief, usually within 3-7 days
Involuntary movements of the tongue,
lips, face, trunk, and extremities
Emerges at various rates depending on
age, sex and diagnosis.
It is related to dose, and will be less likely
with lower doses of typical neuroleptics
It is ordinarily reversible, although
irreversible/severe forms can occur.

Management:
There are no definitive treatments for
tardive dyskinesia
Best way to minimize the occurrence is to
use an atypical antipsychotic instead of
typical agent
These drugs are associated with a much
lower risk of tardive dyskinesia
Periodic screening with a structured
assessment tool (eg AIMS)

A rare life-threatening side-effect related to an
apparent compromise of the neuromuscular and
sympathetic nervous system
Usually occurs at the initiation of treatment with a
high-potency agent
It is characterized by:
Muscle rigidity
Breakdown of muscle fibers, leading to large increases in
plasma creatine kinase
Fever
Autonomic instability
Changing levels of consciousness
Sometimes death

Management:
Immediate discontinuation of medication is
essential.
Applying external hypothermia
Supporting blood pressure
Administering a direct-acting dopamine
agonist (eg. Bromocriptine, Pergolide) which
blocks release of intracellular stored calcium
ions
After successful treatment, an atypical
antipsychotic should be used

Typical neuroleptic drugs produce a wide
variety of other side-effects including:
Weight gain
Seizures (especially pimozide)
Sedation
Hypotension
Elevated liver enzymes
Retinitis pigmentosa (thioridazine)


Orthostatic hypotension
Prolongation of QT interval (low potency
phenothiazines, pimozide)
Anticholinergic effects (mesoridazine,
chlorpromazine, thioridazine)
All typical neuroleptics produce marked
increases in serum prolactin levels. The
prolactin elevations may affect sexual
function in both males and females.