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Antipsychotic polypharmacy – confusion reigns

  • David Taylor (a1)

Polypharmacy is usually employed where single drugs are considered insufficiently effective. Some polypharmacy is rational and evidence based, some neither. Antipsychotic polypharmacy remains stubbornly widespread despite condemnation of the practice by numerous bodies. The practice could not be said to be evidence based. Its persistence probably stems from a well-meaning desire to improve response and from confusion about the mechanism of action of antipsychotics. In particular, the concept that more antipsychotic(s) must always be, or might be, ‘better’ is virtually groundless. Nonetheless, some specific antipsychotic polypharmacy regimens have shown particular benefits on adverse effect profiles. Targeted, evidence-based polypharmacy may be the way forward.

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This is an Open Access article, distributed under the terms of the Creative Commons Attribution (CC-BY) license (, which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
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David Taylor (
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See original paper, pp. 44–46, and review article, pp. 58–62, this issue.

Declaration of interest

D.T. has received consultancy fees, lecturing honoraria and/or research funding from AstraZeneca, Janssen-Cilag, Servier, Sanofi-Aventis, Lundbeck, Bristol-Myers Squibb, Novartis, Eli Lilly and Wyeth.

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Antipsychotic polypharmacy – confusion reigns

  • David Taylor (a1)
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BNF Limits vs Threshold Dosing

Geoffrey F Searle, Consultant Psychiatrist
23 March 2010

David Taylor is right that there is excessive poly-pharmacy in routine practice, however he does not examine or comment upon one of the root causes; "BNF limits". Many clinicians seem to believe they are behaving in the patient's interest by prescribing two compounds at close to the BNF maximum rather than one above this mark.As a clinician it is commonplace to come across patients who respond well to sub-BNF doses as well as those who are untouched by a drug at the BNF maximum dose. In the case of anti-psychotic drugs Agid et al. (2006) have once again demonstrated that response to these drugs is related to the measured blockade of striatal receptors. As I suggested in my paper 13 years ago (Searle 1998) this allows the clinician to quickly & accurately judge the sensitivity of an individual patient to anti-psychotic treatment by increasing the dose rapidly to the point at which extra-pyramidal side effects are just discernible - and then waiting for a response. Following this threshold dosage scheme has led me to occasionally use a much wider range of doses than the BNF limits "allow". For example I have prescribed risperidone in schizophrenia with good effect at as little as 0.5mg per day and as much as 32mg per day - a 64 fold dose range. Although those whopractice acute adult psychiatry often observe that severely psychotic patients may be dramatically medication resistant, unless they have used threshold dosing they do not know that the sensitivity of the patient to anti-psychotic medication increases as their mental state improves, allowing a reduction in dose with maintained efficacy.BNF limits are usually established in accessible and responsive out-patient populations with moderate symptoms. Practicing clinicians treat many patients who do not come from this population and may find themselveswith a difficult choice: Poly-pharmacy or prescription outside BNF limits.

Agid O, Mamo D, Ginovart N, Vitcu I, Wilson AA, Zipursky RB, et al. Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response.A double-blind PET study in schizophrenia. Neuropsychopharmacology 2006; 32: 1209 -15

G. F. Searle. Optimising neuroleptic treatment for psychotic illnessPsychiatric Bulletin, Sep 1998; 22: 548 - 551.
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