According to the many trials and guidelines the use of antipsychotic polypharmacy is not recommended, however more than 1/3 of patients are treated with antipsychotic polypharmacy (APP). Risperidone was often used in many trials and many of them are negative (N Engl J Med. 2006 Feb 2;354(5):472-82.). In last years paliperidone is available, however there is a big lack of studies with APP, where paliperidone is included, although is often used in clincal practice. It is interestingly why these studies have not been conducted yet; if it is because of negative trials with risperidone and 'afraid' or another reasons have been existed.
It is certainly worth having data on all combinations to guide us.
One reason I sometimes choose other second generation antipsychotics over risperidone (R) and paliperidone (P) is because both cause clinically significant increases in serum prolactin. And as regards hyperprolactinemia, P is worse than R, probably because higher doses of P are required to pass the blood brain barrier...but the pituitary is not 'protected' by the blood brain barrier and is therefore exposed to high levels of P
Dear Lewis,
I totally agree with you about the guidelines. I think it is the most important to try combination which is proven in RCT. On the other side, prescribing without respect to RCT on this field could be inappropriate prescribing of APP. Sometimes aripiprazole is added because of hyperprolactinemia, which is also not appropriate in long term treatment, because combinations with aripiprazole can lead to psychosis and consequently dose of first antipsychotic should be adjusted (higher dose). Finally it can lead to EPS and cycle is repeated.
Regards
I believe that oral risperidone is superior to paliperdone , in effectiveness, when used as monotherapy. This is my experience. I use risperidone more often. Paliperidone usually doesn't work ,if risperidone does not work.
I also agree with Dr. Opler about the problem of prolactin increase with paliperidone.
I have many concerns about so wide prescribing of paliperidone in some countries, cost-effectiveness could be a good question.
I think risperidone is still good treatment option and very cheap. According to the relative small differences there is also possibility of inappropriate prescribing in combination therapy with paliperidone. I am little afraid of those trials, which should be conducted, because as far long we do not have ANY evidence we are still in dark room and can make things very different, on the other side, when we will have studies like those published in NEJM about combination of clozapine with risperidone or clozapine alone, prescribing percentage will be lower.
There are also some question about QT prolongation and prolactine levels. Some of them answered the new network metaanalysis published in Lancet.
Dear Matej,
your side note about aripiprazole is very interesting for me. How did you exactly mean that a long-term use of aripiprazole can lead to psychosis?
By the way, your original question about a lack of trials with paliperidone vs other atypical antipsychotics is attractive and fully unaswered.
Thank you!
Dear MIchal,
thanks to be interested in this question. Question about paliperidone is still unanswered, however we cannot except that industry will have an interest to do it. Otherwise we do not have trials and we can say.. OK, we do not have trials, opposite to risperidone.
Question about aripiprazole is very interesting. We have several case reports that its use can lead to psychosis, especially via acting of dopamine increase (D2, D1), because aripiprazole is a partial agonist. Exttremely unlogical combination is to combine D2 blocker and aripiprazole, because aripiprazole convert in to the antagonist almost. We know that time to act on receptor completely is very long for aripirazole, because Wan Der Waals bonds are very week. In this point of view many combinations with aripiprazole are senseless and not supported by evidence-based medicine (e.g. except that with clozapine). In this view, aripiprazole need long time to act and in this point of view it means that these adverse events are often seen after many days.
Regards, Matej
I realize, that combinations of aripiprazole with other antipsychotics are neurobiologically problematic, but except of combination with clozapine I am often using a combination with olanzapine. Your answer about aripiprazole leading to relaps of psychosis I originally understood as a consequence of insufficient antipsychotic dose or antipsychotic effect of aripiprazole, when using it alone. It is true, that I have a lot of patients who have remission of psychosis only on aripiprazole alone.
Thank you!
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