This article was last revised in 2004. Much more is known about aripiprazole now, particularly its adverse effects and its uses have widened. I would still contend it is much less debilitating for many that take it than any of its predecessors but some people cannot tolerate it. Chris Barchard January 2017

by Chris Barchard

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.