Cochrane Briefs

Risperidone vs. Placebo for Schizophrenia


Am Fam Physician. 2010 May 1;81(9):1096.

Clinical Scenario

A 39-year-old man with schizophrenia has been taking chlorpromazine for years and has developed a tremor. He asks if risperidone (Risperdal) would be more effective.

Evidence-Based Answer

Compared with placebo, risperidone improves symptoms based on some disease-specific symptom scores for schizophrenia. However, it does not appear to improve symptoms on a more important Clinical Global Impression scale. (Strength of Recommendation = A, based on consistent, good-quality patient-oriented evidence)

Practice Pointers

Risperidone is a second-generation antipsychotic that has been widely adopted as first-line treatment for schizophrenia. Compared with first-generation antipsychotics, such as haloperidol (formerly Haldol) and chlorpromazine, second-generation antipsychotic medications have a decreased risk of extrapyramidal adverse effects and tardive dyskinesia. However, they cause weight gain and metabolic symptoms.1 As acknowledged in the American Psychiatric Association's practice guideline, first-generation agents also may be appropriate as first-line medications.2

Despite its broad use in clinical practice, the clinical effectiveness of risperidone for schizophrenia and schizophrenia-like psychoses is still unclear. In a recent Cochrane review, the authors searched for randomized controlled trials comparing risperidone with placebo in adults. They found three trials with 397 participants that used the Clinical Global Impression score as a measure of effectiveness. Using this score, risperidone was no more effective than placebo.

They also found seven trials with 856 participants that used a “Brief Psychiatric Rating Scale/Positive and Negative Symptom” score. These trials showed that more participants in the risperidone arm had at least a 20 percent reduction in their score (number needed to treat = 7). However, the authors questioned the clinical significance of this measure of improvement; the Clinical Global Impression is a more clinically relevant scale. Furthermore, the authors noted a potential bias because seven of the 10 studies were sponsored by manufacturers of the drug and did not report important details about methods. When a trial not funded by the drug industry was excluded, the results were more favorable for risperidone.

There are not adequate data to compare risperidone with other second-generation antipsychotics.3 When selecting a treatment, adverse effect profiles and effectiveness should be considered. Data supporting haloperidol are also weak, but there is robust evidence that chlorpromazine improves symptoms and function.4

Author disclosure: Nothing to disclose.


Rattehalli RD, Jayaram MB, Smith M. Risperidone versus placebo for schizophrenia. Cochrane Database Syst Rev. 2010;(1):CD006918.


show all references

1. Hunter RH, Joy CB, Kennedy E, Gilbody SM, Song F. Risperidone versus typical antipsychotic medication for schizophrenia. Cochrane Database Syst Rev. 2003;(2):CD000440....

2. Dixon L, Perkins D, Calmes C. Guideline watch (September 2009): practice guideline for the treatment of patients with schizophrenia. American Psychiatric Association; 2009. Watch. Accessed March 2, 2010.

3. Gilbody SM, Bagnall AM, Duggan L, Tuunainen A. Risperidone versus other atypical antipsychotic medication for schizophrenia. Cochrane Database Syst Rev. 2000;(3):CD002306.

4. Adams CE, Awad G, Rathbone J, Thornley B. Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev. 2007;(2): CD000284.



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