Are all Antipsychotics Equal, or are some more Equal
Than Others?
By Dr. Flowers, Medical Director of the Anne Sippi
Clinic Treatment Facilities and a Diplomat of the American Board of Psychiatry
and Neurology
Schizophrenia became a medically treatable illness since
the introduction of chlorpromazine (Thorazine) in 1952. With anti psychotic
medications came the ability to provide significant relief from the acute
symptoms of schizophrenia while conferring substantial relapse prevention. In
fact, few medical therapies are more thoroughly demonstrated in all of medicine
than the effectiveness of anti psychotic medication. In 1964, one of the largest
double blind, placebo-controlled studies of anti psychotic medications was
completed by the National Institute of Mental Health. In this study, more than
300 patients diagnosed with schizophrenia were randomly assigned to one of three
standard anti psychotic medications or to a placebo. Seventy-five percent of the
patients taking active medication were considered to have either moderate to
marked improvement. In fact, countless subsequent studies have shown similar
outcomes. Together, they demonstrate that patients improve with medication, and
this improvement is not a chance occurrence!
Despite this remarkably
effective treatment, significant clinical difficulties remain. First, depending
on operational criteria and patient characteristics, some 30% to 50% of patients
with the signs and symptoms of schizophrenia do not respond to a trial of
standard anti psychotic medication. Second, anti psychotic medications are not
without troublesome side effects both neurologic (tardive dyskinesia) and
metabolic (weight gain). In addition, standard anti psychotic medications have
minimal or at best only partial effects on the negative symptoms, cognitive
symptoms and mood symptoms of schizophrenia. Finally, with the current
availability of over a dozen different medications, including both older
conventional and newer atypicals, the issue of which medication to use is
raised. Even more important: are all medications equal with regard to
effectiveness or efficacy?
In most clinical practice situations, if a
given patient in the midst of an acute episode of schizophrenia is treated with
a standard anti psychotic medication and fails to demonstrate response, one of
three alternatives is chosen. First, continue the current medication at the same
dose for a longer period of time. Second, increase the dosage of the current
medication.
Third, switch to a different standard anti psychotic
medication.
Unfortunately, researchers have shown that chronic patients
who have failed to respond to an adequate anti psychotic dosage given for an
adequate duration are unlikely to respond to higher doses, longer trials or
trials of other standard anti psychotic treatments. This situation changes
considerably with the addition of clozapine (Clozaril). Most research indicates
that response rates with clozapine in treatment resistant patients ranges from
30% to 60% for treatment periods of 6 weeks to 1 year. Given this clearly
superior effectiveness, trying one standard anti psychotic after another,
raising the dosage, or waiting longer, are likely to cost the patient an
increased length of psychosis and an ultimately reduced chance for remission or
a favorable outcome.
A more reasonable approach to the pharmacotherapy of
schizophrenia would be as follows: acute psychotic episodes should be treated
with a single standard anti psychotic agent at an adequate dosage for an
adequate duration.
For treatment failures, when compliance is not an issue
and side effects do not limit treatment, a trial or a clozapine-like medication
is indicated. For treatment failures related to questionable compliance a depot
anti psychotic medication is indicated.
The treatment algorithm for
schizophrenia continues to gradually develop as more research is completed with
the newer medications. However, to us, a basic questions remains: Do older
standard anti psychotic medications continue to have a place in the modern
therapy of psychosis?