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Low dose typical antipsychotics — a brief evaluation

Department of Psychiatry, University of Stellenbosch, PO Box 19063, Tygerberg 7505, Cape Town, South Africa

Sir: We were disturbed by David Taylor's article in the December 2000 issue of the Psychiatric Bulletin (vol. 24, pp. 465-468). The paper comes across as a somewhat selective interpretation of current knowledge on this highly controversial and very topical issue. This paper clearly supports a particular point of view, giving selective weight to some studies and downplaying the importance of those that do not fit with the author's hypothesis. Some important recent studies on the issue have been completely omitted (e.g. Kapur et al, 2000) and the findings of the study by McEvoy et al (1991) are presented in such a way that the principal message of the paper is obscured. It is also regrettable that the author chooses not to consider the opinions of those leaders in the field with a different point of view (Kulkarni & Power, 1999) and seems to disregard the side-effects of the second-generation antipsychotics altogether.

We believe that, at this time, there is insufficient evidence to come to the kind of conclusions that the author has come to and that the paper is more of a statement of personal opinion than of scientific fact. There has never been a real dose-finding study with haloperidol (or most of the traditional antipsychotics) and no proper evaluation of low-dose traditional antipsychotics v. second-generation antipsychotics. Until properly designed studies are done, it would probably be wise not to come to premature conclusions. The harsh reality is that, for most patients in the world, medications like haloperidol are the only option. Finding the optimal dose of the so-called typical antipsychotics is something that should be pursued with vigour. This issue is far from resolved and a more balanced evaluation of the current state of knowledge would be welcome.

References

KAPUR, S., ZIPURSKY, R., JONES, C., et al(2000) Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. American Journal of Psychiatry, 157, 514-520.[Abstract/Free Full Text]

KULKARNI, J. & POWER, P. (1999) Initial treatment of first-episode psychosis. In The Recognition and Management of Early Psychosis (eds P. D. McGorry & H. J. Jackson), pp. 184-205. Cambridge: Cambridge University Press.

McEVOY, J. P., HOGARTHY, G. E. & STEINGARD, S. (1991) Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. Archives of General Psychiatry, 48, 739-745.[Abstract]

Author's reply

In regard to the study by McEvoy et al (1991), it is difficult to see how the findings were misrepresented. Of 106 subjects given haloperidol 2 mg daily, 49 (46%) showed "an increase in cogwheel rigidity from baseline" at this dose and 15 of these required a dose decrease because of "excessive rigidity". Of 48 patients continued on the "neuroleptic threshold" dose, four were removed "due to severe EPSEs". The study did suggest that increasing to dosage above the neuroleptic threshold "did not lead to greater improvement in measures of psychosis but... regularly lead to significant increases in distressing extrapyramidal side effects". However, no justification is given for the numbers of subjects recruited, so equivalence in efficacy certainly cannot be assumed. Overall, this study demonstrated that extrapyramidal symptoms (albeit largely mild ones) were induced at very low doses of haloperidol; doses that were effective but that were by no means proven to be optimally so. Moreover, extrapyramidal side-effects and efficacy seemed again to be inexorably linked.

As your correspondents point out, this issue is far from resolved. However, the burden of proof surely now lies with those who support the continued wide-spread use of typical antipsychotics. If data relating to atypical drugs are to be scrutinised and criticised from every angle, then the sparse data supporting the existence of a ‘therapeutic window’ for typical antipsychotics are inevitably liable to potent censure. In this respect, it is noteworthy that Oosthuizen and colleagues present no cogent data to counter the conclusions of the original article but resort instead to vague and unsubstantiated accusations of bias.

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Oosthuizen, P. P. Articles by Turner, J. Search for Related Content PubMed Articles by Oosthuizen, P. P. Articles by Turner, J.