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Antipsychotics for Schizophrenia – Changing Minds, Minding Change
useful clinical knowledge. Perhaps the most significant contribution of With the realisation that antipsychotics comprise a very diverse group
the recent pragmatic studies mentioned above was the illumination of drugs comes the opportunity to identify potential niches in clinical
of the real-life strengths and weaknesses of antipsychotics. CATIE practice for each of them. A clear example is clozapine, whose niche
reported the following important points: in treatment-resistant schizophrenia has long been established. It
would be logical to assume that by using multiple dimensions to
• Olanzapine was shown to have a modest edge compared with describe and classify antipsychotics one could identify their specific
other antipsychotics in terms of longer time to discontinuation, but clinical uses. However, this approach comes with a risk that sounds
this edge was hampered by significant side effects. familiar: there is a risk of replicating the same monocategorical
• Similarly, therapy with olanzapine was associated with better initial, dichotomy that we have been using so far in the case of atypicality,
but short-lived effect on positive and negative symptoms and lower
hospitalisation rates compared with other antipsychotics, but was
also associated with significantly more weight gain. The latter was
In addition to showing a convergence of
the reason for most patients discontinuing the drug.
• Olanzapine was also associated with increases in serum glycated older and newer agents on measures of
), triglycerides and cholesterol. In patients
real-life effectiveness, recent studies also
treated with ziprazidone, some of these levels actually improved.
• Perphenazine, an FGA of middle potency, was discontinued most showed that the newer agents have
often by patients due to induced EPS. However, the incidence of
more numerous and more serious
EPS induced by perphenazine did not differ from that of the SGAs.
• Quetiapine induced more anticholinergic side effects and was the adverse effects than originally thought.
most sedating, together with olanzapine.
• Risperidone was linked to higher prolactin levels.
• Importantly, no difference between the compared antipsychotics only applied to several domains. In other words, instead of having
was found in suicide rates, QTc prolongation and cataract formation. just conventional and atypical antipsychotics, we may end up
with multiple, equally absolute dichotomies such as sedating and
CUtLASS 1 corroborated some of the above points, most importantly non-sedating, or even expensive and cheap. Considering
that SGAs are not better than FGAs in terms of quality of life and antipsychotics collectively as groups, assuming that there are
effectiveness on symptoms, and that EPS were similar with SGAs boundaries between these groups and disregarding the fact that the
and FGAs. They also concluded that patients did not have a most important qualities of drugs cut through classification boundaries
preference for either group. CUtLASS 2 added confidence to the may lead to category-specific and not drug-specific therapeutic
established view that clozapine is currently our best answer for decisions. This is important because a drug-specific approach leads to
treatment-resistant schizophrenia. a patient-specific decision, which may not be achieved if we consider
all drugs belonging to a category as being more or less the same. In
Changing Minds, Minding Change addition to hindering clinical decision-making, it is also worth
One of the most fundamental consequences of these findings is that considering that such groupings may be exploited in marketing in the
they question the validity of the classification of antipsychotics, by way that atypicality has been in the past.
confirming that antipsychotics substantially differ among themselves
in terms of their strengths and weaknesses. Antipsychotics were In our view, the benefits of having the order and structure of a
originally categorised according to their tendency to induce EPS. The classification do not outweigh the risk of thought-framing and its
findings of the studies summarised above suggest that EPS are not consequences in education, research and clinical practice, not to
a categorical discriminator, but can be regarded, at best, as a mention the stigma and resentment that can be experienced by
dimensional concept that may define a continuous spectrum of patients who are treated with an antipsychotic that is classified as, for
atypicality. The same pattern is observed for other antipsychotic instance, ‘sedating’ or ‘weight-inducing’. Instead, perhaps it is wise to
characteristics such as weight gain and various measures of avoid a classification altogether (in other words, just sail the
effectiveness. Each of these characteristics has the potential to Bosporus), and thus support the choice of antipsychotic purely on the
formulate an arbitrary classification. It is important to be mindful of basis of personalised clinical judgement. We believe that this
the monodimensionality of such classifications and their thought- approach will promote a more person-centred, evidence-based and
sensitive clinical practice. ■
1. Graves R, The Greek Myths, Aylesbury, England: Penguin, 12. Keefe RS, et al., Schizophr Bull, 1999;25:201–22. 22. McEvoy JP, et al., Am J Psychiatry, 2006;163:600–610.
1960;242. 13. Bekelman JE, et al., JAMA, 2003;289:454–65. 23. Stroup TS, et al., Am J Psychiatry, 2006;163:611–22.
2. David Cunningham Owens, Advances Psyc Treatment, 14. Lexchin J, et al., Br Med J, 2003;326:1167–70. 24. Jones PB, et al., Arch Gen Psychiatry, 2006;63:1079–87.
2008:14;17–28. 15. Valenti AM, et al., Schizophr Bull, 2003;29/2(195–9): 25. Lewis SW, et al., Schizophr Bull, 2006;32:715–23.
3. Kane JM, et al., J Clin Psychiatry, 2003;64(Suppl. 12):1–100. 0586–7614. 26. Kahn RS, et al., Lancet, 2008;371(9618):1085–97.
4. Tandon R, Fleischhacker WW, Schizophr Res, 2005;79: 16. Taylor D, Mir S, Kerwin R, Psychiatric Bul, 2000;24/3(106–8): 27. Smith M, et al., Br J Psych, 2008;192/6(406–11):
145–55. 1472–3. 0007–1250.
5. Moller HJ, Eur Psychiatry, 2005;20(5–6):379–85. 17. Conley RR, Kelly DL, Isr J Psychiatry Relat Sci, 2005;42(1): 28. Rege S, Aust N Z J Psych, 2008;42:1440–1614.
6. Carr V, Aust Prescr, 2004;27:149–51. 51–60. 29. Melkersson K, Dahl M-L, Drugs, 2004;64:12–6667.
7. Harvey PD, Keefe RS, Am J Psychiatry, 2001;158:176–84. 18. Daumit GL, et al., Arch Gen Psych, 200;121–8. 30. Grunder G, et al., Nature Rev Drug Discovery, 2009;8:
8. Leucht S, et al., Lancet, 2003;36:1581–9. 19. Marder SR, et al., Am J Psychiatry, 2003;160(8):1405–12. 1474–84.
9. Bagnall A, et al., Health Technol Assess, 2003;7(13):1–502. 20. Lieberman JA, et al., Am J Psychiatry, 2003;160(8): 31. Bonham C, Abbott C, J Psychiatric Prac, 2008;14:1538–45.
10. Geddes J, et al., BMJ, 2000;321(7273):1371–6. 1396–1404. 32. Leucht S, et al., Lancet, 2009;3:31–41.
11. Tollefson GD, et al., Arch Gen Psychiatry, 1998;55:250–58. 21. Lieberman JA, et al., N Engl J Med, 2005;353:1209–23. 33. Stip E, J Psychiatry Neurosci, 2000;25(2):137–53.
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