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Atypical Antipsychotics.
Introduction.
Between the 1950s and and 1975, typical antipsyhcotics were the only drugs available for the treatment of psychosis. Clozapine (Clozaril) was introduced in Europe in 1975, and was the first of a new type of antipsychotic, now referred to as atypical or second generation antipsychotics. Whereas the typical drugs acted exclusively on dopamine receptors, these new drugs affect a variety of different neurotransmitter systems in the brain (varying from drug to drug), as well as dopamine. Because of this, they can effectively treat not only positive symptoms, but also negative and cognitive symptoms.
Studies show the atypicals as a group have a lower incidence of EPS side effects than the older drugs. Often you will hear it stated that they have "fewer side effects", but in fact they have different ones. A notable side effect of some of these new drugs is weight gain, but there are others too, such as diabetes and heart problems. Since most of these drugs are recent, there is not a lot of what you would call long term data about the side effects caused by decades of use.
The atypicals are still under patent and as result are surprisingly expensive. The final consideration is that since these drugs are new, not as many different preparations are available as with the older drugs, but no doubt this will change as time goes on.
Clozapine (Clozaril)
The first of the atypical antipsychotics, Clozapine was originally developed in 1961 and introduced in Europe in 1975. It was voluntarily taken off the market after 8 Finnish patients died due to infections picked up while they were affected by agranulocytosis (see below). More careful studies of the drug followed, where patients blood was monitored for signs of agranulocytosis. These studies showed without doubt that Clozapine is a very effective antipsychotic, and safe to use if the correct measures are taken. With these results and the implementation of stringent monitoring, Clozapine was licensed for use in the UK in 1990. Since it's reintroduction along with the blood monitoring procedures, only one person has died because of this in the UK.
Clozapine is often used for "treatment resistant patients" IE it can be effective where other drugs have failed to control a person's symptoms. However, due to the serious nature of the side effects it can cause, it is not considered a first choice, and a patient will usually try several of the other newer drugs, and possibly an older one, before Clozapine is even considered by their doctor.
Agranulocytosis is a condition where the number of white blood cells in the body is reduced. These cells are an essential part of our body's defences, and a reduction in their number can leave us open to other infections that would normally pose no threat. Some figures suggest Clozapine has a 3% of causing this condition. While this sounds worrying, the chances of it posing a threat to anyone taking Clozapine are minimal. Anyone taking the drug in the UK must be registered with the CPMS (Clozapine Patient Monitoring Service). This service will not allow the drug to be dispensed without a recent blood test being carried out, and it also ensures that the drug is stopped should any lowering of white blood cell levels be detected. Thus, it is next to impossible to encounter any problems using this drug in the UK these days.
Clozapine also has a high incedence of weight gain and can cause other side effects.
Overall, this is a very effective drug, but one with that presents some problems. It is not one you will be trying straight away, it requires regular blood tests and it can cause weight gain. However, it could well 'save the day' where other drugs have failed.
Clozapine information. Comment on Clozapine.
Risperidone (risperdal).
The second of the new drugs to appear, and available around the world since the eary 90s, Risperidone is now well established and tested. It is a result of the search for compounds that could replicate the effectiveness of Clozapine without the side effects.
It has a strong Dopamine blocking action, as well as affecting Serotonin receptors. Unlike most of the newer drugs, this is available in a depot form, called "Risperdal Consta", as well as in liquid and tablet forms.
Potential side effects include drowsiness, increase in appetite, insomnia, increased production of saliva and dizziness. Risperidone has a higher incidence of EPS side effects than any of the other newer drugs, especially at higher doses.
Risperidone information. Comment on Risperidone.
Amisulpride (Solian).
This drug, like all of the atypicals, treats all the symptoms of psychosis. It is not available in the USA but is quite common in Europe. It is a "dual dopamine blocker".
Amisulpride is available as a delicious-tasting liquid (I jest) and as pills.
Common side effects include anxiety, agitation and insomnia, but overall this drug is rather good in terms of side effects.
Amisulpride information. Comment on Amisulpride.
Olanzapine (Zyprexa).
Olanzapine was developed by Eli Lilly, and has been available in Europe and the USA since it's introduction in 1996. It is structurally similar to Clozapine and affects many different neurotransmitters.
This drug is available as tablets and fast acting injections for acute use.
There are several potential side effects, but perhaps the one worth drawing to your attention where Olazanpine is concerned is weight gain. Along with Clozapine, this can be a big weight-gainer.
A recent Times Online article describes how the makers of Olanzapine have agreed to pay out $1.2 billion dollars to 28,500 people who claim that their health was damaged by this drug. See here.
Olanzapine information. Comment on Olanzapine.
Ziprasidone (Geodon, Zeldox).
This is a relatively new antipsychotic available in both the USA and Europe. It affects the Dopamine and Serotonin systems of the brain, as well as others.
Ziprasidone is available as tablets and in a fast-acting intramuscular injection form.
Common side effects of this drug include drowsiness and feelings of sickness. Overall, this drug is quite good in terms of side effects.
Ziprasidone information. Comment on Ziprasidone.
Quetiapine (Seroquel).
Developed by Zeneca, this is another fairly recent addition to the ranks of antipsychotics. It was intially hoped to emulate some of the effectiveness of Clozapine without affecting white blood cells.
Quetiapine is available only as pills, but a slow-release version may soon arrive.
The most common side effect of this drug is that it is sedating. It can also cause a dry mouth and dizziness.
Quetiapine information. Comment on Quetiapine.
Aripiprazole (Abilify).
Aripirazole is one of the newest of the atypical antipsychotics, and was developed in Japan by Otsuka Pharmaceuticals. The action of Aripiprazole is so unique that it could arguably even be classed as a 'third generation antipsychotic'. Much as I am loathe to send you the corporate website of a pharmaceutical company, there is a decent animation of how Aripiprazole is thought to work on the Abilify website.
Aripiprazole comes as pills and a solution which probably tastes symptom-controlingly-scrumptious, though I have yet to have the pleasure.
This drug in particular is very good at not causing weight gain, but as usual, there are some side effects to look out for. One of these is restlessness, others are insomnia and nausea.
Aripiprazole information. Comment on Aripiprazole.
Paliperidone (Invega).
The latest of the atypical antipsychotics, Paliperidone is a metabolite of Risperidone (it is Risperidone with an extra OH group attached to it). Licensed in June 2007, it is believed to work in a similar way to Resperidone.
Perhaps expectedly, the drug has a lot of the characteristics of Risperidone, including the side effect profile. The major difference between this and other antipsychotics is that Paliperidone is available in a 'prolonged-release' tablet. This means that after the tablet is swallowed, it steadily releases the drug into the blood over a 24 hour period.
Paliperidone information. Comment on Paliperidone.
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