Predicting response to atypical antipsychotics based on early response in the treatment of schizophrenia☆

Kinon, Bruce J.; Chen, Lei; Ascher-Svanum, Haya; Stauffer, Virginia L.; Kollack-Walker, Sara; Sniadecki, Jennifer; Kane, John M.

doi:10.1016/j.schres.2008.02.021

Cited by 145 publications

(177 citation statements)

References 25 publications

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“…Presently, other predictors, such as early response, are likely to be of greater value in predicting response to antipsychotic medications. 2,3,[27][28][29] In conclusion, we found two SNPs (COMT rs165599 and GRM3 rs724226) to have significant associations with 12 weeks of risperidone treatment response in both African-American and white patients. The differences in the prevalence of responder alleles may be clinically useful in predicting ethnic-specific risperidone response rates.…”

Section: Discussionmentioning

confidence: 56%

“…1 The ability to predict response to a given medication is desirable for many reasons. 2,3 First among them is the desire to stabilize the patient as quickly as possible. In addition, treating patients with ineffective medicines places them at an undue risk and may cause them to lose confidence in medication as a means of controlling their symptoms, especially if the medications cause undesirable adverse events.…”

Section: Introductionmentioning

confidence: 99%

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Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

et al. 2009

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Clinical trial data were evaluated for the association between 22 singlenucleotide polymorphisms (SNPs) and response in acutely ill patients diagnosed with schizophrenia, schizoaffective disorder or schizophreniform disorder, who were treated with oral risperidone. All patients in the exploratory (78 African Americans) and validation (65 whites) data sets received risperidone 2-6 mg per day over 2-12 weeks. Two SNPs were found to have significant associations with response to risperidone over 2-12 weeks in both African-American and white patients and had a consistent direction of effect in both cohorts. Metabotropic glutamate receptor (GRM3) SNP, rs724226, was associated with a change in the positive and negative syndrome scale (PANSS) total response. Catechol-O-methyltransferase (COMT) SNP, rs165599, was moderately associated with a change in the PANSS Negative score. The greater prevalence of poor-responder GRM3 and COMT alleles in white versus African-American patients might have a clinical significance in evaluating the ethnic-specific response to risperidone.

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Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

et al. 2009

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“…These studies also show that a majority of patients (nearly 70%) do not reach this 'early response' criterion with either a typical or atypical antipsychotic drug Kinon et al, 1993;Kinon et al, 2008). The clinical dilemma in these patients who do not show early response is whether one should 'switch' or 'stay'.…”

Section: Introductionmentioning

confidence: 97%

“…Although for nearly four decades the field of schizophrenia has viewed antipsychotic drug response as delayed, recent research has showed that the onset of response can occur rapidly within the first week or two (Agid et al, 2003;Leucht et al, 2005a). Compared with patients who lack at least minimal symptom improvement following 2 weeks of treatment ('early non-responders'), early responders were previously found to have greater improvement in symptoms and functioning, a higher symptom remission rate (AscherSvanum et al, 2008;Kinon et al, 2008) and lower health care costs . Thus, it is important when possible to identify patients as early responders or early non-responders, and consider alternative treatment options for patients who are less likely to respond.…”

Section: Introductionmentioning

confidence: 99%

“…To date, all of the studies on early response/non-response have been retrospective in nature, and have shown that early non-response is a robust predictor of subsequent nonresponse with continued treatment of the same medication Correll et al, 2003;Kinon et al, 2008;Leucht et al, 2007;Leucht et al, 2008). These studies also show that a majority of patients (nearly 70%) do not reach this 'early response' criterion with either a typical or atypical antipsychotic drug Kinon et al, 1993;Kinon et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

Kinon

Chen

Ascher-Svanum

et al. 2009

Neuropsychopharmacol

167

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Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether 'switching' early non-responders to another antipsychotic is a better strategy than 'staying'. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as X20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2-6 mg/day or switch to olanzapine 10-20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; po001). Early response/nonresponse was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p ¼ 0.020) and in depressive symptoms (end point; p ¼ 0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatmentemergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a 'switching' strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients.

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Approaches to Treatment‐Resistant Patients

2010

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Predicting response to atypical antipsychotics based on early response in the treatment of schizophrenia☆

Cited by 145 publications

References 25 publications

Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia

Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

Approaches to Treatment‐Resistant Patients

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