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Antipsychotics – equivalent doses

Antipsychotic drugs vary greatly in potency (not the same as efficacy) and this is usually expressed as differences in ‘neuroleptic’ or ‘chlorpromazine’ ‘equivalents’. Some of the estimates relating to neuroleptic equivalents are based on early dopamine binding studies and some largely on clinical experience or even inspired guesswork. BNF maximum doses for antipsychotic drugs bear little rela-tionship to their ‘neuroleptic equivalents’. The following table gives some approximate equivalent doses for conventional drugs 1,2 . Values given should be seen as a rough guide when transferring from one conventional drug to another. An early review of progress is essential.

Table Equivalent doses

Drug Equivalent dose (consensus) Range of values in literature

Chlorpromazine 100 mg/day –

Fluphenazine 2 mg/day 2–5 mg/day

Trifluoperazine 5 mg/day 2.5–5 mg/day

Flupentixol 3 mg/day 2–3 mg/day

Zuclopenthixol 25 mg/day 25–60 mg/day

Haloperidol 3 mg/day 1.5–5 mg/day

Sulpiride 200 mg/day 200–270 mg/day

Pimozide 2 mg/day 2 mg/day

Loxapine 10 mg/day 10–25 mg/day

Fluphenazine depot 5 mg/week 1–12.5 mg/week

Pipotiazine depot 10 mg/week 10–12.5 mg/week

Flupentixol depot 10 mg/week 10–20 mg/week

Zuclopenthixol depot 100 mg/week 40–100 mg/week

Haloperidol depot 15 mg/week 5–25 mg/week

It is inappropriate to convert SGA doses into ‘equivalents’ since the dose–response relationship is usually well-defined for these drugs. Dosage guidelines are discussed under each individual drug. Those readers eager to find chlorpromazine equivalents for the newer drugs are directed to the only published paper listing such data 3 .

References 1. Foster P. Neuroleptic equivalence. Pharm J 1989; 243:431–432. 2. Atkins M et al. Chlorpromazine equivalents: a consensus of opinion for both clinical and research implications. Psychiatr Bull 1997; 21:224–226. 3. Woods SW. Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 2003; 64:663–667.

Taylor, David; Paton, Carol; Kapur, Shitij: The South London and Maudsley NHS Foundation Trust & Oxleas NHS Foundation Trust prescribing guidelines, Informa Healthcare 2009

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Antipsychotics – minimum effective doses

The table below suggests the minimum dose of antipsychotic likely to be effective in schizophrenia (first episode or relapse). At least some patients will respond to the dose suggested, although others may require higher doses. Given the variation in individual response, all doses should be considered approximate. Primary references are provided where available, but consensus opinion has also been used (as have standard texts such as the BNF and SPC). Only oral treatment with commonly used drugs is covered.

Table Minimum effective dose/day – antipsychotics

Drug First episode Relapse

FGAs

Chlorpromazine 200 mg* 300 mgHaloperidol 1–5 2 mg >4 mgSulpiride 6 400 mg* 800 mgTrifluoperazine 7 10 mg* 15 mg

SGAs

Amisulpride 8–10 400 mg* 800 mgAripiprazole 11,12 10 mg* 10 mgAsenapine 13 Not known 10 mg*Bifeprunox 13 Not known 20 mg*Iloperidone 14,15 4 mg* 8 mg*Olanzapine 5,16,17 5 mg 10 mgPaliperidone 18 3 mg* 3 mgQuetiapine 19–22 150 mg* 300 mgRisperidone 4,23–25 1–2 mg 3–4 mgSertindole 26 Not appropriate 12 mgZiprasidone 27–29 80 mg* 80 mgZotepine 30,31 75 mg* 150 mg

*Estimate – too few data available.

References 1. Oosthuizen P et al. Determining the optimal dose of haloperidol in first-episode psychosis. J Psychopharmacol 2001; 15:251–255. 2. McGorry PD. Recommended haloperidol and risperidone doses in first-episode psychosis. J Clin Psychiatry 1999; 60:794–795. 3. Waraich PS et al. Haloperidol dose for the acute phase of schizophrenia. Cochrane Database Syst Rev 2002; CD001951. 4. Schooler N et al. Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. Am J Psychiatry 2005; 162:947–953. 5. Keefe RS et al. Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis. Biol Psychiatry 2006; 59:97–105. 6. Soares BG et al. Sulpiride for schizophrenia. Cochrane Database Syst Rev 2000; CD001162. 7. Armenteros JL et al. Antipsychotics in early onset Schizophrenia: Systematic review and meta-analysis. Eur Child Adolesc Psychiatry 2006; 15:141–148. 8. Mota NE et al. Amisulpride for schizophrenia. Cochrane Database Syst Rev 2002; CD001357. 9. Puech A et al. Amisulpride, and atypical antipsychotic, in the treatment of acute episodes of schizophrenia: a dose-ranging study vs. haloperidol. The

Amisulpride Study Group. Acta Psychiatr Scand 1998; 98:65–72. 10. Moller HJ et al. Improvement of acute exacerbations of schizophrenia with amisulpride: a comparison with haloperidol. PROD-ASLP Study Group.

Psychopharmacology 1997; 132:396–401. 11. Taylor D. Aripiprazole: a review of its pharmacology and clinical utility. Int J Clin Pract 2003; 57:49–54. 12. Cutler AJ et al. The efficacy and safety of lower doses of aripiprazole for the treatment of patients with acute exacerbation of schizophrenia. CNS Spectr

2006; 11:691–702. 13. Bishara D et al. Upcoming agents for the treatment of schizophrenia. Mechanism of action, efficacy and tolerability. Drugs 2008; 68:2269–2296. 14. Kane JM et al. Long-term efficacy and safety of iloperidone: results from 3 clinical trials for the treatment of schizophrenia. J Clin Psychopharmacol

2008; 28:S29–S35. 15. Potkin SG et al. Efficacy of iloperidone in the treatment of schizophrenia: initial phase 3 studies. J Clin Psychopharmacol 2008; 28:S4–11. 16. Sanger TM et al. Olanzapine versus haloperidol treatment in first-episode psychosis. Am J Psychiatry 1999; 156:79–87.

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17. Kasper S. Risperidone and olanzapine: optimal dosing for efficacy and tolerability in patients with schizophrenia. Int Clin Psychopharmacol 1998; 13:253–262.

18. Meltzer HY et al. Efficacy and tolerability of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 6-week, placebo-controlled studies. J Clin Psychiatry 2008; 69:817–829.

19. Small JG et al. Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group. Arch Gen Psychiatry 1997; 54:549–557.

20. Peuskens J et al. A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia. Acta Psychiatr Scand 1997; 96:265–273. 21. Arvanitis LA et al. Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol

and placebo. Biol Psychiatry 1997; 42:233–246. 22. Kopala LC et al. Treatment of a first episode of psychotic illness with quetiapine: an analysis of 2 year outcomes. Schizophr Res 2006; 81:29–39. 23. Lane HY et al. Risperidone in acutely exacerbated schizophrenia: dosing strategies and plasma levels. J Clin Psychiatry 2000; 61:209–214. 24. Williams R. Optimal dosing with risperidone: updated recommendations. J Clin Psychiatry 2001; 62:282–289. 25. Ezewuzie N et al. Establishing a dose–response relationship for oral risperidone in relapsed schizophrenia. J Psychopharmacol 2006; 20:86–90. 26. Lindstrom E et al. Sertindole: efficacy and safety in schizophrenia. Expert Opin Pharmacother 2006; 7:1825–1834. 27. Bagnall A et al. Ziprasidone for schizophrenia and severe mental illness. Cochrane Database Syst Rev 2000; CD001945. 28. Taylor D. Ziprasidone – an atypical antipsychotic. Pharm J 2001; 266:396–401. 29. Joyce AT et al. Effect of initial ziprasidone dose on length of therapy in schizophrenia. Schizophr Res 2006; 83:285–292. 30. Petit M et al. A comparison of an atypical and typical antipsychotic, zotepine versus haloperidol in patients with acute exacerbation of schizophrenia: a

parallel-group double-blind trial. Psychopharmacol Bull 1996; 32:81–87. 31. Palmgren K et al. The safety and efficacy of zotepine in the treatment of schizophrenia: results of a one-year naturalistic clinical trial. Int J Psychiatry

Clin Pract 2000; 4:299–306.

Further reading Davis JM et al. Dose response and dose equivalence of antipsychotics. J Clin Psychopharmacol 2004; 24:192–208.

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Antipsychotics – licensed maximum doses

The table below lists the UK licensed maximum doses of antipsychotics.

Drug Maximum dose

FGAs – oral Chlorpromazine 1000 mg/dayFlupentixol 18 mg/dayHaloperidol 30 mg/day (See BNF)Levomepromazine 1000 mg/dayPericyazine 300 mg/dayPerphenazine 24 mg/dayPimozide 20 mg/daySulpiride 2400 mg/dayTrifluoperazine None (suggest 30 mg/day)Zuclopenthixol 150 mg/day

SGAs – oral Amisulpride 1200 mg/dayAripiprazole 30 mg/dayClozapine 900 mg/dayOlanzapine 20 mg/dayPaliperidone 12 mg/dayQuetiapine 750/800 mg/day (see BNF)Risperidone 16 mg/day (see BNF)Sertindole 24 mg/dayZiprasidone* 160 mg/dayZotepine 300 mg/day

Depots Flupentixol depot 400 mg/weekFluphenazine depot 50 mg/weekHaloperidol depot 300 mg every 4 weeks (see BNF)Pipotiazine depot 50 mg/weekRisperidone** 25 mg/weekZuclopenthixol depot 600 mg/week

Note : Doses above these maxima should only be used in extreme circumstances: there is no evidence for improved efficacy.*Not available in the UK at time of publication, European labelling used.**May only be given two weekly.

Taylor, David; Paton, Carol; Kapur, Shitij: The South London and Maudsley NHS Foundation Trust & Oxleas NHS Foundation Trust prescribing guidelines, Informa Healthcare 2009