0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
APA Practice Guideline for Schizophrenia: Risperidone Equivalents
GARY REMINGTON, M.D., PH.D., F.R.C.P.C.; SHITIJ KAPUR, M.D., PH.D., F.R.C.P.C.; ROBERT ZIPURSKY, M.D., F.R.C.P.C.
Am J Psychiatry 1998;155:1301a-1302.
View Author and Article Information
Toronto, Ont.,Canada

Book Forum

To the Editor: Clinicians seek guidance regarding conversion factors that will allow them to compare novel neuroleptics to existing conventional agents in milligram equivalents. Recently published APA guidelines indicate that a 1–2-mg dose of risperidone equals a 2-mg dose of haloperidol R411559BCEDBBGD, suggesting that haloperidol may require doses twice as high as those of risperidone. However, several lines of investigation support equivalent dosing.

Positron emission tomography findings indicate that risperidone and haloperidol are approximately equivalent in terms of dopamine 2 (D2) occupancy. Specifically, mean D2 occupancies for risperidone and haloperidol at 2 mg are 66.3% and 66.7%, respectively (2, 3). While it might be argued that risperidone"s shared serotonin-dopamine antagonism prevents a comparison based simply on D2 occupancy, there is no evidence to date to suggest that risperidone is different from conventional neuroleptics such as haloperidol in terms of the need to achieve at least 60%–70% D2 occupancy for antipsychotic response R411559BCEDBGDE-R411559BCEBIIJC. This is in contrast to clozapine, which clearly demonstrates its therapeutic effect at levels of D2 occupancy below 60% R411559BCEBIIJC, R411559BCECHEJJ.

Comparative data between risperidone and haloperidol, when flexible dosing is employed, provide further support for dose equivalence. In a recent double-blind study of first-episode psychosis R411559BCEBGGAF, individuals were randomly assigned to 4 mg/day of either haloperidol or risperidone. Thereafter, doses of each could be titrated by 2 mg, on the basis of clinical response and side effects, to a maximum of 16 mg/day or a minimum of 2 mg/day. Results indicated that dosing changes over the 6-week trial were comparable for both compounds; at endpoint, the final doses for risperidone and haloperidol were 6.1 mg/day and 5.6 mg/day, respectively.

Comparative data between risperidone and haloperidol, when flexible dosing is employed, provide further support for dose equivalence. In a recent double-blind study of first-episode psychosis R411559BCEBGGAF, individuals were randomly assigned to 4 mg/day of either haloperidol or risperidone. Thereafter, doses of each could be titrated by 2 mg, on the basis of clinical response and side effects, to a maximum of 16 mg/day or a minimum of 2 mg/day. Results indicated that dosing changes over the 6-week trial were comparable for both compounds; at endpoint, the final doses for risperidone and haloperidol were 6.1 mg/day and 5.6 mg/day, respectively.

Evidence involving patients with chronic schizophrenia, although more indirect, also suggests equivalent dosing. Unfortunately, in controlled trials directly comparing risperidone to haloperidol, lower doses of risperidone (i.e., 1–16 mg/day) have been compared to haloperidol doses of 10–20 mg/day R411559BCEBBJGG-R411559BCEDGECG. This has made it virtually impossible to establish whether these two compounds may be equipotent. However, other reports involving neuroleptics in lower doses, including a meta-analysis of 22 randomized, controlled trials, have indicated that for a compound such as haloperidol, the optimal daily dose range is between 3 and 8 mg R411559BCEBICGI-R411559BCEBJCEH. This closely parallels the multiple fixed-dose studies with risperidone indicating that 4–8 mg/day appears to represent the optimal dose range for a similar patient population R411559BCEBBJGG-R411559BCEDGECG.

The recommendation that risperidone and haloperidol be considered equal in terms of dosing must be made with the caveat that these compounds are not necessarily clinically equivalent. Specific advantages have been linked to risperidone"s concomitant 5-hydroxytryptamine antagonism, such as diminished extrapyramidal side effects and improvement in negative symptoms (8–10). At the same time, though, the recommendation means that the results of studies comparing these agents must be revisited and that future investigations must employ comparable doses of each.

American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. Am J Psychiatry 1997; 154(April suppl)
 
Kapur S, Remington G, Zipursky RB, Wilson AA, Houle S: The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study. Life Sci  1995; 57:103–107
[PubMed]
[CrossRef]
 
Kapur S, Remington G, Jones C, Wilson A, Da Silva J, Houle S, Zipursky R: High levels of dopamine D2 receptor occupancy with low-dose haloperidol treatment: a PET study. Am J Psychiatry  1996; 153:948–950
[PubMed]
 
Nordström A-L, Farde L, Wiesel F-A, Forslund K, Pauli S, Halldin C, Uppfeldt G: Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients. Biol Psychiatry  1993; 33:227–235
[PubMed]
[CrossRef]
 
Farde L, Nordström A-L, Wiesel F-A, Pauli S, Halldin C, Sedvall G: Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry  1992; 49:538–544
[PubMed]
 
Nordström A-L, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G: D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry  1995; 152:1444–1449
[PubMed]
 
Emsley RA, McCreadie R, Livingston M, De Smedt G, Lemmons P: Risperidone in the treatment of first-episode patients with schizophreniform disorder (abstract). Eur Neuropsycho­pharmacol  1995; 5:350
 
Chouinard G, Jones B, Remington G, Bloom D, Addington D, MacEwan GW, Labelle A, Beauclair L, Arnott W: A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol  1993; 13:25–40
[PubMed]
 
Marder SR, Meibach RC: Risperidone in the treatment of schizophrenia. Am J Psychiatry  1994; 151:825–835
[PubMed]
 
Peuskens J, Risperidone Study Group: Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Br J Psychiatry  1995; 166:712–726
[PubMed]
[CrossRef]
 
McEvoy JP, Hogarty GE, Steingard S: Optimal dosing of neuroleptic in acute schizophrenia. Arch Gen Psychiatry  1991; 48:739–745
[PubMed]
 
Bolini P, Pampallona S, Orza MJ, Adams ME, Chalmers TC: Antipsychotic drugs: is more worse? A meta-analysis of the published randomized control trials. Psychol Med  1994; 24:307–316
[PubMed]
[CrossRef]
 
Stone CK, Garver DL, Griffith J, Hirschowitz J, Bennett J: Further evidence of a dose-response threshold for haloperidol in psychosis. Am J Psychiatry  1995; 152:1210–1212
[PubMed]
 
+

References

American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. Am J Psychiatry 1997; 154(April suppl)
 
Kapur S, Remington G, Zipursky RB, Wilson AA, Houle S: The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study. Life Sci  1995; 57:103–107
[PubMed]
[CrossRef]
 
Kapur S, Remington G, Jones C, Wilson A, Da Silva J, Houle S, Zipursky R: High levels of dopamine D2 receptor occupancy with low-dose haloperidol treatment: a PET study. Am J Psychiatry  1996; 153:948–950
[PubMed]
 
Nordström A-L, Farde L, Wiesel F-A, Forslund K, Pauli S, Halldin C, Uppfeldt G: Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients. Biol Psychiatry  1993; 33:227–235
[PubMed]
[CrossRef]
 
Farde L, Nordström A-L, Wiesel F-A, Pauli S, Halldin C, Sedvall G: Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry  1992; 49:538–544
[PubMed]
 
Nordström A-L, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G: D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry  1995; 152:1444–1449
[PubMed]
 
Emsley RA, McCreadie R, Livingston M, De Smedt G, Lemmons P: Risperidone in the treatment of first-episode patients with schizophreniform disorder (abstract). Eur Neuropsycho­pharmacol  1995; 5:350
 
Chouinard G, Jones B, Remington G, Bloom D, Addington D, MacEwan GW, Labelle A, Beauclair L, Arnott W: A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol  1993; 13:25–40
[PubMed]
 
Marder SR, Meibach RC: Risperidone in the treatment of schizophrenia. Am J Psychiatry  1994; 151:825–835
[PubMed]
 
Peuskens J, Risperidone Study Group: Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Br J Psychiatry  1995; 166:712–726
[PubMed]
[CrossRef]
 
McEvoy JP, Hogarty GE, Steingard S: Optimal dosing of neuroleptic in acute schizophrenia. Arch Gen Psychiatry  1991; 48:739–745
[PubMed]
 
Bolini P, Pampallona S, Orza MJ, Adams ME, Chalmers TC: Antipsychotic drugs: is more worse? A meta-analysis of the published randomized control trials. Psychol Med  1994; 24:307–316
[PubMed]
[CrossRef]
 
Stone CK, Garver DL, Griffith J, Hirschowitz J, Bennett J: Further evidence of a dose-response threshold for haloperidol in psychosis. Am J Psychiatry  1995; 152:1210–1212
[PubMed]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Related Content
Books
APA Practice Guidelines > Chapter 7.  >
APA Practice Guidelines > Chapter 4.  >
APA Practice Guidelines > Chapter 4.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 32.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 26.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles