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ARIPIPRAZOLE - DOES THIS HERALD THE FUTURE IN ANTIPSYCHOTICS?
Aripiprazole is different
and it's now licensed in the UK. It has a different type of
action to any previous antipsychotic drug and many of the side-effects
experienced commonly with other drugs in this class tend to be
very much less if not absent. There is little weight gain
associated with it. Most people changing to it from other
antipsychotics lose weight because many of these drugs are
associated with significant weight gain. There is no significant
increase in prolactin, a substance in the body associated with
the reproductive system. Increases in this are associated with
decreased sexual drive and impotence in men and the secretion of
breast milk in women. There are few EPS symptoms, the range of
movement disorders such as tremors, symptoms similar to
Parkinson's Disease, stiffness and muscle spasms, which have been
associated with antipsychotics in varying degrees. It is not
usually sedating. There are no significant changes in the QTc
interval, part of the heart rhythm affected by many other
antipsychotic drugs. Other antipsychotic drugs vary considerably
in the degree to which they cause particular side-effects and not
everyone taking them is affected. Individual response is a very
important factor.
Most of the things that were reported as adverse events during
studies of aripiprazole were occurring at not much less frequency
in those taking placebos (inactive pills given to some patients
for comparison with those taking the real ones). There were such
things as vomiting, nausea, headaches, insomnia and somnolence
reported. Though these things might sound unpleasant, a lot of
the time they were probably not the result of the drug and the
rates for people staying on this drug have been favourable.
So what is it that makes aripiprazole different apart from
apparently having less side-effects than previous drugs?
Basically rather than suppressing the dopamine system in the
brain it tends to stabilise it. Dopamine is a so-called
neurotransmitter; a substance in the brain that is involved in
sending electrical signals between brain cells (neurons). It also
affects the 5HT (another neurotransmitter) system. Basically,
whereas other antipsychotics, including the newer so-called
atypicals, more or less block activity at the points they occupy,
aripiprazole allows a more or less normal flow of signals at most
of the important points it occupies. This even means that
activity is increased where there is too little. Not all synapses
(connection points where the drug displaces dopamine or 5HT) are
occupied by antipsychotic drugs otherwise drugs that more or less
block activity would shut down those areas of the brain where
they were acting almost completely.
The so-called "dopamine theory" of schizophrenia has
been around for many years and is based on observations that
there is rather a lot of dopamine activity in some areas in the
brains of people with this label. The theory has been broadened
out a lot recently to include other neurotransmitters such as 5HT.
It is now known that in some other parts of the brain in those
labelled schizophrenic there is in fact rather little dopamine
activity. No drug before has ever tackled this. Although it
remains a mystery what actually drives all this unusual brain
activity drugs that block dopamine have long been shown to reduce
at least some of the manifestations of schizophrenia. The early
drugs blocked dopamine pretty widely throughout the brain,
including areas that had nothing to do with schizophrenia. These
drugs only tended to change the so-called positive symptoms,
delusions, hallucinations and strange ideas. The unnecessary
areas blocked resulted in EPS side-effects. The atypicals aimed
to address this problem by being more selective about where they
blocked dopamine. They also blocked activity at some 5HT sites.
This resulted in a lot of people experiencing a lot less of the
troubling EPS symptoms. These drugs tended to have less effect on
prolactin levels as well with the result that a lot of men found
their sexual potency return to normal. They also improved the so-called
negative symptoms of schizophrenia like apathy and feeling flat,
which most of the older drugs did little to help. However these
drugs still had problems with other side-effects like weight gain
and changes in heart rhythm, the heart either beating faster or
slower than normal for instance, although such effects depended
on the particular drug in question as well as the individual
taking it.
Although it is impossible to tell if long-term side-effects will
emerge with aripiprazole, to date it is displaying a unique
combination of effectiveness against positive and negative
symptoms with few side-effects that has made its use grow rapidly
in the USA, where it has been licensed since 2002. Like all drugs
it probably will not suit everyone. As with the atypicals, there
may be a delay before NICE make a directive such that doctors
have to make it an option for patients. There was a postcode
lottery about your likelihood of getting atypicals for some years.
But I reckon aripiprazole and other new drugs like it are likely
to start taking over in the UK soon in the same way the atypicals
have in recent years.