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Meta-Analysis
. 2016 Apr 14;4(4):CD004161.
doi: 10.1002/14651858.CD004161.pub2.

Risperidone (depot) for schizophrenia

Stephanie Sampson  1 , Prakash Hosalli, Vivek A Furtado, John M Davis
Affiliations
Meta-Analysis

Risperidone (depot) for schizophrenia

Stephanie Sampson et al. Cochrane Database Syst Rev. .

Abstract

Background: Risperidone is the first new generation antipsychotic drug made available in a long-acting injection formulation.

Objectives: To examine the effects of depot risperidone for treatment of schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.To critically appraise and summarise current evidence on the resource use, cost and cost-effectiveness of risperidone (depot) for schizophrenia.

Search methods: We searched the Cochrane Schizophrenia Group's Register (December 2002, 2012, and October 28, 2015). We also checked the references of all included studies, and contacted industry and authors of included studies.

Selection criteria: Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses.

Data collection and analysis: Two review authors independently selected trials, assessed trial quality and extracted data. For dichotomous data, we calculated the risk ratio (RR), with 95% confidence interval (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.

Main results: Twelve studies, with a total of 5723 participants were randomised to the following comparison treatments: Risperidone depot versus placebo Outcomes of relapse and improvement in mental state were neither measured or reported. In terms of other primary outcomes, more people receiving placebo left the study early by 12 weeks (1 RCT, n=400, RR 0.74 95% CI 0.63 to 0.88, very low quality evidence), experienced severe adverse events in short term (1 RCT, n=400, RR 0.59 95% CI 0.38 to 0.93, very low quality evidence). There was however, no difference in levels of weight gain between groups (1 RCT, n=400, RR 2.11 95% CI 0.48 to 9.18, very low quality evidence). Risperidone depot versus general oral antipsychotics The outcome of improvement in mental state was not presented due to high levels of attrition, nor were levels of severe adverse events explicitly reported. Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders (long-term:1 RCT, n=369, RR 1.34 95% CI 1.13 to 1.58, very-low quality evidence). Risperidone depot versus oral risperidoneData for relapse and severe adverse events were not reported. All outcomes of interest were rated as moderate quality evidence. Main results showed no differences between treatment groups with equivocal data for change in mental state, numbers leaving the study early, any extrapyramidal symptoms, weight increase and prolactin-related adverse events. Risperidone depot versus oral quetiapine Relapse rates and improvement in mental state were not reported. Fewer people receiving risperidone depot left the study early (long-term: 1 RCT, n=666, RR 0.84 95% CI 0.74 to 0.95, moderate quality evidence). Experience of serious adverse events was similar between groups (low quality evidence), but more people receiving depot risperidone experienced EPS (1 RCT, n=666, RR 1.83 95% CI 1.07 to 3.15, low quality evidence), had greater weight gain (1 RCT, n=666, RR 1.25 95% CI 0.25 to 2.25, low quality evidence) and more prolactin-related adverse events (1 RCT, n=666, RR 3.07 95% CI 1.13 to 8.36, very low quality evidence). Risperidone depot versus oral aripiprazoleRelapse rates, mental state using PANSS, leaving the study early, serious adverse events and weight increase were similar between groups. However more people receiving depot risperidone experienced prolactin-related adverse events compared to those receiving oral aripiprazole (2 RCTs, n=729, RR 9.91 95% CI 2.78 to 35.29, very low quality of evidence). Risperidone depot versus oral olanzapineRelapse rates were not reported in any of the included studies for this comparison. Improvement in mental state using PANSS and instances of severe adverse events were similar between groups. More people receiving depot risperidone left the study early than those receiving oral olanzapine (1 RCT, n=618, RR 1.32 95% CI 1.10 to 1.58, low quality evidence) with those receiving risperidone depot also experiencing more extrapyramidal symptoms (1 RCT, n=547, RR 1.67 95% CI 1.19 to 2.36, low quality evidence). However, more people receiving oral olanzapine experienced weight increase (1 RCT, n=547, RR 0.56 95% CI 0.42 to 0.75, low quality evidence). Risperidone depot versus atypical depot antipsychotics (specifically paliperidone palmitate)Relapse rates were not reported and rates of response using PANSS, weight increase, prolactin-related adverse events and glucose-related adverse events were similar between groups. Fewer people left the study early due to lack of efficacy from the risperidone depot group (long term: 1 RCT, n=749, RR 0.60 95% CI 0.45 to 0.81, low quality evidence), but more people receiving depot risperidone required use of EPS-medication (2 RCTs, n=1666, RR 1.46 95% CI 1.18 to 1.8, moderate quality evidence). Risperidone depot versus typical depot antipsychoticsOutcomes of relapse, severe adverse events or movement disorders were not reported. Outcomes relating to improvement in mental state demonstrated no difference between groups (low quality evidence). However, more people receiving depot risperidone compared to other typical depots left the study early (long-term:1 RCT, n=62, RR 3.05 95% CI 1.12 to 8.31, low quality evidence).

Authors' conclusions: Depot risperidone may be more acceptable than placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia. The active drug, especially higher doses, may be associated with more movement disorders than placebo. People already stabilised on oral risperidone may continue to maintain benefit if treated with depot risperidone and avoid the need to take tablets, at least in the short term. In people who are happy to take oral medication the depot risperidone is approximately equal to oral risperidone. It is possible that the depot formulation, however, can bring a second-generation antipsychotic to people who do not reliably adhere to treatment. People with schizophrenia who have difficulty adhering to treatment, however, are unlikely to volunteer for a clinical trial. Such people may gain benefit from the depot risperidone with no increased risk of extrapyramidal side effects.

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Conflict of interest statement

Prakash Hosalli ‐ none known.

Steph Sampson ‐ none known.

Vivek Furtado ‐ none known.

John Davis ‐ none known.

Figures

1
1
Study flow diagram: 2010 and 2012, 2015 updated search
2
2
3
3
1.1
1.1. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 1 Mental state: 1. Change (exacerbation) in specific symptoms.
1.2
1.2. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 2 Leaving the study early: 1. Any reason (by time period).
1.3
1.3. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 3 Leaving the study early: 2. Any reason (by doses).
1.4
1.4. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 4 Leaving the study early: 3. Because of insufficient response (by doses).
1.5
1.5. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 5 Adverse events: 1. General: a. Death.
1.6
1.6. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 6 Adverse events: 1. General: b. Severe adverse event (by doses).
1.7
1.7. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 7 Adverse events: 1. General: c. Adverse event necessitating withdrawal from study (by doses).
1.8
1.8. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 8 Adverse events: 2. Specific: a. Cardiovascular.
1.9
1.9. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 9 Adverse events: 2. Specific: b. Gastrointestinal.
1.10
1.10. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 10 Adverse events: 2. Specific: c. Movement disorders: a. Extrapyramidal disorder ‐ spontaneously reported (by doses).
1.11
1.11. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 11 Adverse events: 2. Specific: d. Movement disorders: b. Hyperkinesia (by doses).
1.12
1.12. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 12 Adverse events: 2. Specific: e. Movement disorders: c. Hypertonia (by doses).
1.13
1.13. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 13 Adverse events: 2. Specific: f. Pain.
1.14
1.14. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 14 Adverse events: 2. Specific: g. Salivation.
1.15
1.15. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 15 Adverse events: 2. Specific: h. Sleep disturbances.
1.16
1.16. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 16 Adverse events: 2. Specific: i. Weight gain.
1.17
1.17. Analysis
Comparison 1 RISPERIDONE DEPOT vs PLACEBO, Outcome 17 Adverse events: 2. Specific: j. Others.
2.1
2.1. Analysis
Comparison 2 RISPERIDONE DEPOT vs GENERAL ORAL ANTIPSYCHOTICS, Outcome 1 Global state: 1. Relapse (any reason).
2.2
2.2. Analysis
Comparison 2 RISPERIDONE DEPOT vs GENERAL ORAL ANTIPSYCHOTICS, Outcome 2 Global state: 2. Needing use of benzodiazepine or sedative drugs.
2.3
2.3. Analysis
Comparison 2 RISPERIDONE DEPOT vs GENERAL ORAL ANTIPSYCHOTICS, Outcome 3 Service utilisation: 1. Hospitalisation.
2.5
2.5. Analysis
Comparison 2 RISPERIDONE DEPOT vs GENERAL ORAL ANTIPSYCHOTICS, Outcome 5 Not receiving allocated study medication.
2.6
2.6. Analysis
Comparison 2 RISPERIDONE DEPOT vs GENERAL ORAL ANTIPSYCHOTICS, Outcome 6 Leaving the study early: 1. Any reason.
2.7
2.7. Analysis
Comparison 2 RISPERIDONE DEPOT vs GENERAL ORAL ANTIPSYCHOTICS, Outcome 7 Leaving the study early: 2. Specific.
2.8
2.8. Analysis
Comparison 2 RISPERIDONE DEPOT vs GENERAL ORAL ANTIPSYCHOTICS, Outcome 8 Adverse events: 1. General: a. Death.
2.9
2.9. Analysis
Comparison 2 RISPERIDONE DEPOT vs GENERAL ORAL ANTIPSYCHOTICS, Outcome 9 Adverse events: 2. Specific.
2.10
2.10. Analysis
Comparison 2 RISPERIDONE DEPOT vs GENERAL ORAL ANTIPSYCHOTICS, Outcome 10 Adverse events: Nervous system disorders (inc. EPS).
3.1
3.1. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 1 Global state: 1. Moderate to severely ill at end of study period (CGI rating).
3.2
3.2. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 2 Global state: 2. Mean change from baseline (CGI‐S, high score = worse).
3.3
3.3. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 3 Global state: 3. Mean (SD) GAF score change to endpoint.
3.4
3.4. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 4 Global state: 4. Needing use of benzodiazepine or sedative drugs.
3.5
3.5. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 5 Mental state: 1. Average change/endpoint scores (PANSS, high score = worse).
3.6
3.6. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 6 Leaving the study early: 1. Any reason.
3.7
3.7. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 7 Leaving the study early: 2. Specific.
3.8
3.8. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 8 Quality of life: Mean (SD) SF‐36 score change/endpoint (high score = better).
3.9
3.9. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 9 Adverse events: 1. General.
3.10
3.10. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 10 Adverse events: 1. General: UKU average change score (high = worse).
3.11
3.11. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 11 Adverse events: 2. Specific.
3.12
3.12. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 12 Adverse events: 2. Specific: Mean (SD) weight increase in kg.
3.13
3.13. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 13 Adverse events: 3. Movement disorder.
3.14
3.14. Analysis
Comparison 3 RISPERIDONE DEPOT vs ORAL RISPERIDONE, Outcome 14 Adverse events: Mean (SD) change in movement disorder rating scales.
4.1
4.1. Analysis
Comparison 4 RISPERIDONE DEPOT vs ORAL QUETIAPINE, Outcome 1 Leaving the study early: 1. Any reason.
4.2
4.2. Analysis
Comparison 4 RISPERIDONE DEPOT vs ORAL QUETIAPINE, Outcome 2 Leaving the study early: 2. Specific.
4.3
4.3. Analysis
Comparison 4 RISPERIDONE DEPOT vs ORAL QUETIAPINE, Outcome 3 Adverse events: 1. General.
4.4
4.4. Analysis
Comparison 4 RISPERIDONE DEPOT vs ORAL QUETIAPINE, Outcome 4 Adverse events: 2. Specifc.
4.5
4.5. Analysis
Comparison 4 RISPERIDONE DEPOT vs ORAL QUETIAPINE, Outcome 5 Adverse events: 2. Specific: Mean (SD) weight increase in kg.
4.6
4.6. Analysis
Comparison 4 RISPERIDONE DEPOT vs ORAL QUETIAPINE, Outcome 6 Adverse events: 3. Movement disorder.
5.1
5.1. Analysis
Comparison 5 RISPERIDONE DEPOT vs ORAL ARIPIPRAZOLE, Outcome 1 Global state: 1. Relapse (any reason).
5.2
5.2. Analysis
Comparison 5 RISPERIDONE DEPOT vs ORAL ARIPIPRAZOLE, Outcome 2 Global state: 3. Mean time in remission (days).
5.3
5.3. Analysis
Comparison 5 RISPERIDONE DEPOT vs ORAL ARIPIPRAZOLE, Outcome 3 Mental state: 1. Average change scores (PANSS, high score = worse).
5.4
5.4. Analysis
Comparison 5 RISPERIDONE DEPOT vs ORAL ARIPIPRAZOLE, Outcome 4 Leaving the study early: 1. Any reason.
5.5
5.5. Analysis
Comparison 5 RISPERIDONE DEPOT vs ORAL ARIPIPRAZOLE, Outcome 5 Leaving the study early: 2. Specific.
5.6
5.6. Analysis
Comparison 5 RISPERIDONE DEPOT vs ORAL ARIPIPRAZOLE, Outcome 6 Adverse events: 1. General.
5.7
5.7. Analysis
Comparison 5 RISPERIDONE DEPOT vs ORAL ARIPIPRAZOLE, Outcome 7 Adverse events: 2. Specific.
5.8
5.8. Analysis
Comparison 5 RISPERIDONE DEPOT vs ORAL ARIPIPRAZOLE, Outcome 8 Adverse events: 2. Specific 12. Mean (SD) weight increase in kg.
5.9
5.9. Analysis
Comparison 5 RISPERIDONE DEPOT vs ORAL ARIPIPRAZOLE, Outcome 9 Adverse events: 3. Movement disorder.
6.1
6.1. Analysis
Comparison 6 RISPERIDONE DEPOT vs ORAL OLANZAPINE, Outcome 1 Mental state: 1. Average change scores (PANNS, high score = worse).
6.2
6.2. Analysis
Comparison 6 RISPERIDONE DEPOT vs ORAL OLANZAPINE, Outcome 2 Leaving the study early: 1. Any reason.
6.3
6.3. Analysis
Comparison 6 RISPERIDONE DEPOT vs ORAL OLANZAPINE, Outcome 3 Leaving the study early: 2. Specific.
6.4
6.4. Analysis
Comparison 6 RISPERIDONE DEPOT vs ORAL OLANZAPINE, Outcome 4 Adverse events: 1. General.
6.5
6.5. Analysis
Comparison 6 RISPERIDONE DEPOT vs ORAL OLANZAPINE, Outcome 5 Adverse events: 2. Specific.
6.6
6.6. Analysis
Comparison 6 RISPERIDONE DEPOT vs ORAL OLANZAPINE, Outcome 6 Adverse events: 3. Movement disorder.
7.1
7.1. Analysis
Comparison 7 RISPERIDONE DEPOT vs ALL ORAL ANTIPSYCHOTICS (PRIMARY OUTCOMES), Outcome 1 Global state: 1. Relapse (any reason).
7.2
7.2. Analysis
Comparison 7 RISPERIDONE DEPOT vs ALL ORAL ANTIPSYCHOTICS (PRIMARY OUTCOMES), Outcome 2 Mental state: 1. Average change scores (PANSS, high score = worse) 1. total.
7.3
7.3. Analysis
Comparison 7 RISPERIDONE DEPOT vs ALL ORAL ANTIPSYCHOTICS (PRIMARY OUTCOMES), Outcome 3 Leaving the study early: 1. Any reason.
7.4
7.4. Analysis
Comparison 7 RISPERIDONE DEPOT vs ALL ORAL ANTIPSYCHOTICS (PRIMARY OUTCOMES), Outcome 4 Adverse events: 1. Death.
7.5
7.5. Analysis
Comparison 7 RISPERIDONE DEPOT vs ALL ORAL ANTIPSYCHOTICS (PRIMARY OUTCOMES), Outcome 5 Adverse events: 1. General: a. any.
7.6
7.6. Analysis
Comparison 7 RISPERIDONE DEPOT vs ALL ORAL ANTIPSYCHOTICS (PRIMARY OUTCOMES), Outcome 6 Adverse events: 1. General: b. serious.
7.7
7.7. Analysis
Comparison 7 RISPERIDONE DEPOT vs ALL ORAL ANTIPSYCHOTICS (PRIMARY OUTCOMES), Outcome 7 Adverse events: 2. Movement disorder: a. any extra pyramidal symptoms.
8.1
8.1. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 1 Global State: 1. CGI‐S mean change from baseline (high score = worse).
8.2
8.2. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 2 Global state: 2. Schedule for Deficit Syndrome (SDS) scale (mean change from baseline, high score = worse).
8.3
8.3. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 3 Mental state: 1. PANSS scores (high score = worse) ‐ medium term.
8.4
8.4. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 4 Mental state: 2. Improved by 30% in total PANSS score (ITT data).
8.5
8.5. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 5 General functioning: Personal and Social Performance (PSP) scale (high score = better).
8.6
8.6. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 6 Leaving the study early: 1. Any reason.
8.7
8.7. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 7 Adverse events: 1. General.
8.8
8.8. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 8 Adverse events: 2. Specific.
8.9
8.9. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 9 Adverse events: 3. Prolactin related.
8.10
8.10. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 10 Adverse events: 4. Movement disorder.
8.11
8.11. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 11 Adverse events: 5. Body weight (mean increase).
8.12
8.12. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 12 Adverse events: 6. Mean prolactin level increase (ng/mL).
8.13
8.13. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 13 Adverse events: 7. Glucose related.
8.14
8.14. Analysis
Comparison 8 RISPERIDONE DEPOT vs ATYPICAL DEPOT ANTIPSYCHOTICS (PALIPERIDONE PALMITATE), Outcome 14 Adverse events: 8. Injection site pain (mean (sd) Visual Analogue Scale score (0‐100mm)).
9.1
9.1. Analysis
Comparison 9 RISPERIDONE DEPOT vs TYPICAL DEPOT ANTIPSYCHOTICS, Outcome 1 Mental state: 1. Total endpoint scores (PANNS, high score = worse).
9.2
9.2. Analysis
Comparison 9 RISPERIDONE DEPOT vs TYPICAL DEPOT ANTIPSYCHOTICS, Outcome 2 Leaving the study early.
9.3
9.3. Analysis
Comparison 9 RISPERIDONE DEPOT vs TYPICAL DEPOT ANTIPSYCHOTICS, Outcome 3 Hospitalisation by 6 months.
9.5
9.5. Analysis
Comparison 9 RISPERIDONE DEPOT vs TYPICAL DEPOT ANTIPSYCHOTICS, Outcome 5 Adverse events: 2. Sexual experiencesm, total endpoint (ASEX, high score = worse).
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Update of

References

References to studies included in this review

Bai 2006 {published data only}
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Kane 2002* {published data only}
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Keks 2007 {published data only (unpublished sought but not used)}
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Li 2011 {published data only}
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MacFadden 2010 {published data only}
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Pandina 2011 {published data only}
    1. Pandina G, Lane R, Gassmann‐Mayer C, Hough D, Remmerie B, Simpson G. A randomised double blind study of flexible doses of paliperidone palmitate and risperidone long acting therapy in patients with schizophrenia. Proceedings of the 27th International College of Neuropsychopharmacology Congress; 2010 June 6‐10; Hong Kong. 2010.
    1. Pandina G, Lane R, Gopal S, Gassman‐Mayer C, Hough D, Remmerie B, et al. A randomized double blind study of flexible doses of paliperidone palmitate and risperidone long acting therapy in patients with schizophrenia. Biological Psychiatry 2010;67(9):77‐8.
    1. Pandina G, Lane R, Gopal S, Gassmann‐Mayer C, Hough D, Remmerie B, et al. A double‐blind study of paliperidone palmitate and risperidone long‐acting injectable in adults with schizophrenia. Progress in Neuro‐Psychopharmacology & Biological Psychiatry 2011;35:218‐26. - PubMed
Quinn 2012* {published data only}
    1. Quinn A, Camacho F, Mitchell D, Chue P, Malla A. Open‐label randomized exploratory investigation of Risperdal* Consta* and oral antipsychotics treatment of early psychosis. Autumn Conference of the International Society for CNS Clinical Trials and Methodology, October 1‐3. Marina Del Rey, California, 2012.
Rosenheck 2011 {published data only}
    1. Barnett PG, Scott JY, Krystal JH, Rosenheck RA. Cost and cost‐effectiveness in a randomized trial of long‐acting risperidone for schizophrenia. Journal of Clinical Psychiatry 2012;73:696‐702. - PubMed
    1. Rosenheck RA, Krystal JH, Lew R, Barnett PG, Fiore L, Valley D, et al. Long‐ acting risperidone and oral antipsychotics in unstable schizophrenia. New England Journal of Medicine March 3, 2011;364(9):842‐51. - PubMed

References to studies excluded from this review

Agid 2010 {published data only}
    1. Agid O, Foussias G, Remington G. Long acting injectable antipsychotics in the treatment of schizophrenia: Their role in relapse prevention. Expert Opinion on Pharmacotherapy 2010;11(14):2301‐17. - PubMed
Bouchard 2000 {published data only}
    1. Bouchard RH, Merette C, Pourcher E, Demers MF, Villeneuve J, Roy Gagnon MH, et al. The Quebec Schizophrenia Study Group. Longitudinal comparative study of risperidone and conventional neuroleptics for treating patients with schizophrenia. Journal of Clinical Psychopharmacology 2000;20(3):295‐304. [MEDLINE: ] - PubMed
Canas 2010 {published data only}
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DeMartinis 2012a {published data only}
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Eerdekens 2002 a {published data only}
    1. Chue P, Devos E, Duchesne I, Leal A, Mehnert A. Hospitalization rates in patients during long‐term treatment with long‐acting risperidone injection. Poster presented at the XXIII CINP Congress, Montreal, Canada. June 23‐ 27, 2002.
    1. Eerdekens M, Fleischhacker WW, Xie Y, Gefvert O. Long‐term safety of long‐acting risperidone microspheres. Schizophrenia Research (Abstracts of the 11th Biennial Winter Workshop on Schizophrenia) 2002;3(Suppl 1):174.
    1. Fleischhacker WW, Eerdekens M, Xie Y, Beauclair L, Sauret H, Chrzanowski W, et al. Long‐term saftey and efficacy of risperdal consta(TM) a long‐acting injection formulation of risperidone. ACNP, Hawaii, USA, December 2001 (Promotional slides on file from Janssen‐Cliag UK Ltd) 2002.
Eerdekens 2002 b {published data only}
    1. Eerdekens M. Treatment delivery: a hope for the future. Nordic Journal of Psychiatry (Abstracts of The Scandinavian College of Neuro‐Psychopharmacology Annual Conference; 2002 10‐13 Apr; Juan‐Les‐Pins, France) 2002;56(2):1.
Gallhofer 1995 {published data only}
    1. Gallhofer B. Cognitive dysfunction in schizophrenia: comparison of treatment with a novel atypical antipsychotic agent versus conventional neuroleptic drugs. 8th Congress of the European College of Neuropsychopharmacology; 1995 Sep 30 ‐ Oct 4; Venice, Italy. 1995. - PubMed
Geffen 2012 {published data only}
    1. Geffen Y, Keefe R, Rabinowitz J, Anand R, Davidson M. Bl‐1020, a new ‐aminobutyric acid‐enhanced antipsychotic: Results of 6‐week, randomized, double‐blind, controlled, efficacy and safety study. Journal of Clinical Psychiatry 2012;73(9):e1168‐e74. - PubMed
Gefvert 2001 {published data only}
    1. Gefvert O, Nyberg S, Persson P, Helklin L, Bjorner A. Pharmacokinetics, D2 receptor occupancy, and clinical effects of a long‐acting injectable formulation of risperidone in patients with schizophrenia. Annual Meeting of the American Psychiatric Association; 2001 May 5‐10; LA, USA. Marathon Multimedia, 2001.
Kogeorgos 1995 {published data only}
    1. Kogeorgos J, Kanellos P, Michalakeas A, Ioannidis J. Sulpiride and risperidone vs. "classical neuroleptics" in schizophrenia: a follow‐up study. 8th Congress of the European College of Neuropsychopharmacology; 1995 Sep 30 ‐ Oct 4; Venice, Italy. 1995.
Koola 2009 {published data only}
    1. Koola MM, Bustillo J, Lauriello J. Insight and its to baseline characteristics of schizophrenia patients randomized to long acting injectable risperidone or oral atypical antipsychotics: results from the proactive study. Proceedings of the 12th International Congress on Schizophrenia Research; 2009 Mar 28‐ Apr 1; San Diego, CA. Oxford Univ Press, 2009.
Lindenmayer 1995 {published data only}
    1. Lindenmayer J, Grochowski S, Hyman RB. Five factor model of schizophrenia ‐ replication across samples. Schizophrenia Research 1995;14(3):229‐34. [MEDLINE: ] - PubMed
Litman 2014 {published data only}
    1. Litman R, Smith M, Doherty J, Cross A, Raines S, Zukin S. AZD8529, a positive allosteric modulator at the MGGLUR2 receptor, does not improve symptoms in schizophrenia: A proof of principle study. European Neuropsychopharmacology 2014;24:S508‐9. - PubMed
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Littrell 1999 {published data only}
    1. Littrell KH. Patients switched from depot antipsychotics to oral risperidone or olanzapine: an open‐label randomized trial. 152nd Annual Meeting of the American Psychiatric Association; 1999 May 15‐20; Washington, USA. 1999. [MEDLINE: ]
Liu 2014f {published data only}
    1. 刘芳, 张炳奎, 谢丽琴, 郑英君, 欧建军, 吴仁容, et al. 米诺环素辅助治疗早期精神分裂症阴性症状的双盲、随机、对照研究. 长治医学院学报 2014; Vol. 27, issue 1:30‐2.
Lloyd 2010 {published data only}
    1. Lloyd K, Latif MA, Simpson S, Shrestha KL. Switching stable patients with schizophrenia from depot and oral antipsychotics to long acting injectable risperidone: Efficacy, quality of life and functional outcome. Human Psychopharmacology 2010;25(3):243‐52. - PubMed
Macfadden 2008 {published data only}
    1. MacFadden W, Bossie CA, Turkoz I, Haskins JT. Risperidone long acting therapy in stable patients with recently diagnosed schizophrenia. International Clinical Psychopharmacology 2010;25(2):75‐82. - PubMed
    1. Macfadden W, Bossie C, Turkoz I, Diekamp B, Ibach B, Haskins JT. Effect of long acting injectable risperidone on clinical outcomes in recently diagnosed stable schizophrenia patients. Proceedings of the XXVI Collegium Internationale Neuro Psychopharmacologicum congress; 2008 Jul 13‐17; Munich, Germany. 2008.
    1. Macfadden W, Bossie C, Turkoz I, Dorson P, Haskins T. Effect of long acting injectable risperidone on clinical outcomes in stable schizophrenia patients with early illness. Proceedings of the 161st Annual Meeting of the American Psychiatric Association; 2008 May 3‐8; Washington DC, USA 2008.
McClure 2009a {published data only}
    1. McClure MM, Koenigsberg HW, Reynolds D, Goodman M, New A, Trestman R, et al. The effects of risperidone on the cognitive performance of individuals with schizotypal personality disorder. Journal of Clinical Psychopharmacology 2009;29(4):396‐8. - PMC - PubMed
Pikalov 2012a {published data only}
    1. Pikalov A, Cucchiaro J, Ogasa M, Silva R, Hsu J, Xu J, et al. Effect of lurasidone on weight and metabolic parameters: A comprehensive database analysis. Schizophrenia Research 2012;136:S278.
Procyshyn 2010 {published data only}
    1. Procyshyn RM, Barr AM, Flynn S, Schenk C, Ganesan S, Honer WG. Long acting injectable risperidone in treatment refractory patients: A 14 week open label pilot study. Schizophrenia Research 2010;123(2‐3):273‐5. - PubMed
Ritchie 1999 {published data only}
    1. Ritchie C, Ames D, Chiu E, O'Connor D, Hall K, Hassett A. Schizophrenia cohort study of olanzapine v risperidone in the elderly (score): analysis of conversion period. International Psychogeriatrics (Abstracts of the 9th Congress of the International Psychogeriatric Association, "Challenges for the New Millennium: Professional, Cultural and Regional Diversity"; 1999 Aug 15‐20; Vancouver, Canada) 1999;11(Suppl 1):157‐8.
Robinson 2000 {published data only}
    1. Robinson G, Wheeler A, Byrd J, Visser S. Longer‐term effects of switching from typical to atypical antipsychotics in patients with stable schizophrenia. Journal of the European College of Neuropsychopharmacology 2000;10(Suppl 3):S291.
Schmechtig 2010 {published data only}
    1. Schmechtig A, Dourish C, Craig K, Dawson GR, Williams S, Deakin W, et al. Effects of risperidone, amisulpride and nicotine on eye movement control and their modulation by high schizotypy. Pharmacopsychiatry 2011;21:A99. [MEDLINE: ] - PubMed
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Simpson 2006 {published data only}
    1. Simpson GM, Mahmoud RA, Lasser RA, Kujawa M, Bossie CA, Turkoz I, et al. A 1‐year double‐blind study of 2 doses of long‐acting risperidone in stable patients with schizophrenia or schizoaffective disorder. Journal of Clinical Psychiatry 2006;67:1194‐203. - PubMed
Vaughan 2000 {published data only}
    1. Vaughan K, McConaghy N, Wolf C, Myhr C, Black T. Community Treatment Orders: Relationship to clinical care, medication compliance, behavioural disturbance and readmission. Australian and New Zealand Journal of Psychiatry 2000;5:801‐8. - PubMed
Verma 2010 {published data only}
    1. Verma S, Subramaniam M, Abdin E, Sim K, Su A, Lee N, et al. Saftey and efficacy of long acting injectable risperidone in patients with schizophrenia spectrum disorders: A 6 month open label trial in Asian patients. Human Psychopharmacology 2010;25(3):230‐5. - PubMed
Weiden 2007 {published data only}
    1. Weiden PJ, Goldfinger SM, Hindi A, Sunakawa A, Schooler NR. Acceptance of a recommendation of a long acting antipsychotic route in first episode schizophrenia: initial findings of a prospective randomized study. Proccedings of the 160th Annual Meeting of the American Psychiatric Association; 2007 May 19‐24; San Diego, CA. 2007.
    1. Weiden PJ, Schooler NR, Weedon JC, Elmouchtari A, Sunakawa, Goldfinger SM. A randomized controlled trial of long acting injectable risperidone vs continuation on oral atypical antipsychotics for first episode schizophrenia patients: initial adherence outcome. Journal of Clinical Psychiatry 2009;70(10):1397‐406. - PubMed
    1. Weiden PJ, Schooler NR, Weedon JC, Elmouchtari A, Sunakawa‐McMillan A. Maintenance treatment with long‐acting injectable risperidone in first‐episode schizophrenia: A randomized effectiveness study. Journal of Clinical Psychiatry 2012;73(9):1224‐33. - PubMed
Wiffen 2010 {published data only}
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References to studies awaiting assessment

Nasrallah 2002 {published data only}
    1. Nasrallah H, Duchesne I, Mehnert A, Janagap C. Long‐acting risperidone improves quality of life. Proceedings of the 12th World Congress of Psychiatry; 2002 Aug 24‐29; Yokohama, Japan. 2002.
    1. Nasrallah H, Duchesne I, Mehnert A, Janagap C. Long‐acting risperidone injection improves quality of life. International Journal of Neuropsychopharmacology 2002;5(Suppl 1):S189.
    1. Nasrallah H, Duchesne I, Mehnert A, Janagap C. Long‐acting, injectable risperidone ‐ the first long‐acting, atypical antipsychotic ‐ improves quality of life. European Neuropsychopharmacology 2002;12(Suppl 3):S282.
    1. Nasrallah HA, Duchesne I, Mehnert A, Janagap C, Eerdekens M. Correction. Journal of Clinical Psychological Medicine [临床精神医学杂志] 2004;65(8):1150.
    1. Nasrallah HA, Duchesne I, Mehnert A, Janagap C, Eerdekens M. Health‐related quality of life in patients with schizophrenia during treatment with long‐acting, injectable risperidone. Journal of Clinical Psychiatry 2004;65(4):531‐6. [MEDLINE: ] - PubMed
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Turner 2000 {published data only}
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References to other published versions of this review

Hosalli 2003
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