Past Issues

Psychiatric education and clinical practice
show that fi rst-generation antipsychotics (FGAs)
should be carefully monitored for the drug induced-
movement disorders including acute dystonia,
parkinsonian symptoms, tardive dyskinesia,
neuroleptic malignant syndrome (NMS), and
akathisia. Previous reports show that ambient
temperature, high speed in dose escalation of
FGAs, and dehydration can put patients into higher
rsik of developing NMS. Second-generation
antipsychotics (SGAs) also have side effects of
metabolic syndrome, rhabdomyolysis, but not
NMS itself. According to DSM-IV-TR, research
diagnostic criteria of NMS (333.92) are: (A) The
development of severe muscle rigidity and elevated
temperature associated with use of neuroleptic
medication. (B) Two (or more) of the following:
diaphoresis, dyphagia, tremor, incontinence,
changes in level of consciousness ranging from
confusion to coma, mutism, tachycardia, elevated
or labile blood pressure, leukocytosis,and laboratory
evidence of muscle injury (e.g., elevated creatinine
phosphokinase, CPK). (C) The symptoms
in Criteria A and B are not due to another substance
(e.g., phencyclidine) or a neurological or
other general medical condition (e.g., viral encephalitis).
(D) The symptoms in Criteria A and B
are not better accounted for by a mental disorder
(e.g., mood disorder with catatonic features) [1].
Previous central pathophysiologic hypotheses
of NMS include that potent dopaminergic blockade
effects by neuroleptics causing the hypothalamic
and nigrastriatal dopamine hypofunctioning
presenting with severe drug-induced extrapyramidal
symptoms (EPS), autonomic instability, themodysregulation
and changes of consciousness.
This mechanism also supported by the treatment
response using central dopaminergic agonist such
as bromocriptine. Peripheral pathophysiologic hypothesis
of NMS shows it may be related to familial
genetic neuromuscular disorder malignant hyperthermia
causing high fever after the use of
anesthetic agents. Both conditions can be relieved
by peripheral muscular relaxant dantrolene. These
different pathophysiologic mechanisms are not
yet well-confi rmed. But worldwide psychiatric
treatment suggestions always advise to avoid using
rapid neuroleptization to decrease the risk potential
of developing NMS.
SGAs are well-known to have more different
central receptor blockades than FGAs. The different
mechanisms of receptor actions could also
show that SGAs have less risk of provoking NMS
than FGAs. Clinically we also experience that patients
received SGAs, e.g. zotepine and clozapine,
could induce elevated CPK blood level but not
NMS itself. Different central dopaminergic blockades
may play a role in the cause of NMS and serotoninergic
receptors also may involve in antagonizing
such effect. SGAs also should be carefully
monitored for the side effect of elevated level
CPK too. Psychiatric clinical practice guideline
should be modifi ed not to stop giving SGA when
the abnormal laboratory data show elevated CPK
level without hyperthermia, autonomic dysfunctions,
severe EPS and changes of the consciousness.
The reasons for having less frequently reported
cases of SGA-induced NMS may be due to
using small ranges of the treatment SGA doses,
having less available formulations of the injectable
SGAs and owing multiple different central
receptor blockade effects. But SGAs have increased
risk of metabolic syndrome rather than
movement disorders.
In conclusions, newer SGAs might have better
benefi t for patients’ improvement of psychotic
symptoms, mood symptoms, cognitive function,
and social motivations. Patients’ SGA-induced
metabolicside effects can be carefully monitored
by checking body mass index regularly, encouraging
daily exercise, and having strict diet control.
Drug induced-side effects can be easily observed
in the use of FGAs but not SGAs. Psychiatrists
should also keep in mind checking patients’ CPK
level routinely and identifying NMS symptoms at
the critical point of its development.