วารสารสมาคมจิตแพทย์แห่งประเทศไทย
Journal of the Psychiatrist Association of Thailand
ISSN: 0125-6985
บรรณาธิการ มาโนช หล่อตระกูล
Editor: Manote Lotrakul, M.D.

นิพัทธิ์ กาญจนธนาเลิศ พ.บ. *

บทคัดย่อ

ริสเพอริโดนเป็นยารักษาโรคจิตที่จัดอยู่ในกลุ่มอนุพันธ์ benzisoxazole ซึ่งมีความสามารถในการจับกับ serotonin receptors ได้ดีกว่า dopamine D₂ receptors ในสมอง จึงมีผลทำให้มีประสิทธิภาพดีต่อ negative symptoms รวมทั้งพบอุบัติการของการเกิด extrapyramidal side effect ต่ำกว่ายารักษาโรคจิตกลุ่มดั้งเดิม การวิจัยแบบเปิดนี้ศึกษาการใช้ริสเพอริโดน 6 เดือน เพื่อประเมินประสิทธิภาพและความปลอดภัย โดยใช้เครื่องวัด PANSS พบว่า หลังจากสิ้นสุดการวิจัยผู้ป่วย 9 ราย มีค่าคะแนน PANSS เฉลี่ย ลดลงอย่างมีนัยสำคัญทางสถิติ โดยที่ฐานนิยมของขนาดริสเพอริโดนอยู่ที่ 4 มิลลิกรัมต่อวัน อาการข้างเคียงที่พบคือง่วงซึม tremors และ akathisia ซึ่งพบในช่วงแรกของการรักษา ผลการศึกษาเบื้องต้นพบว่าริสเพอริโดน มีประสิทธิภาพในการควบคุม positive และ negative symptoms โดยผู้ป่วยส่วนใหญ่ทนยาได้ด

ี วารสารสมาคมจิตแพทย์แห่งประเทศไทย 2541; 43(2): 130-5.

 คำสำคัญ ริสเพอริโดน โรคจิตเภท

*  ภาควิชาจิตเวชศาสตร์ คณะแพทยศาสตร์ โรงพยาบาลจุฬาลงกรณ์ กรุงเทพฯ 10330

 Nipatt Karnchanathanalers, M.D. *

 Abstract

Key words : risperidone, chronic schizophrenia

* Department of Psychiatry, Chulalongkorn University, Bangkok10300, Thailand.

 Risperidone represents a new class of antipsychotic agents, the benzisoxazole, pharmacologically characterized as serotonin-dopamine antagonists (SDAs). The therapeutic efficacy of risperidone for schizophrenia has been well established by several controlled trials conducted worldwide.¹ Recent evidence suggests that rispridone was effective for both negative and positive symptoms while producing fewer extrapyramidal side effects compared with haloperidol². The current study was designed to evaluate the efficacy and safety of risperidone after 6 months of treatment.

 MATERIALS AND METHOD

Subjects

Subjects were 10 chronic schizophrenic Thai patient aged 17 to 43 years (mean age 31.1 and the duration of illness ranged from 2 to 21 years (Mean = 5.8 years) diagnosed based on DSM IV criteria³, they were all paranoid type patients with total PANSS (Positive and Negative Syndrome Scale) of more than 60. All patients had been treated with conventional antipsychotics prior to entering the study and their severity evaluated by the Clinical Global Impression scale were moderate to severe.

Study design

• The study started with a wash-out period from previous antipsychotic drug (7 days for oral antipsychotic drug and at least one injection cycle for depot antipsychotics) then patients began risperidone titration at a dosage of 1 mg twice daily on day 1, 2 mg twice daily on day 2 and then 3 mg twice daily on day 3 through 7. After the first week the dose was adjusted upward or downward to optimize an individual patient's outcome. Concomitant psychotropic medications were not allowed during the study with exception of benzodiazepine use for agitation and insomnia and antiparkinson drug for treatment of emergent EPS.
• The PANSS and the Clinical Global Impression scale were used to evaluate the efficacy while the severity of extrapyramidal symptoms was assessed by clinician’s judgment from absent to severe (5-point scale). Routine physical and neurological examination, blood chemistry and hematology were evaluated at week 0 and at the end of the study whereas the vital signs, extrapyramidal symptoms and other adverse events were evaluated at week 0, month 1, month 3 and month 6.

 RESULTS

A total of 9 from 10 patients (90%) completed the study. One patient did not come for follow-up after he had been treated with risperidone for 2 months and discontinued the medication. His condition compared to the first visit were much improved after receiving risperidone. The modal dose for risperidone was 4 mg/day (range = 2-16 mg/day) while mean dose was 5.56 mg/day. All of them has a reduction significantly in total PANSS score from base line at the first month and extend this efficacy until the end of the study (Figure 1) by using non-parametric statistic, P-value < 0.05.

 Table 1. Total PANSS score at each visit

The reduction in total PANSS score was correlated with the clinical symptoms result which 8 of 9 patients showed very much improved while the rest was rated as much improved according to the Clinical Global Impression. The Clinical Global Impression scale and extrapyramidal symptoms were shown in Table 2.

 Figure 1. Reduction of mean total PANSS score at day 0, month 1, 3, and 6 respectively 

 Regarding the adverse effects, the common side effects were sedation, akathisia and tremors. These side effects occurred during the first month of the study and most patients can tolerate. Based on the observation that those patients who developed extrapyramidal symptoms were effectively treated by decreasing the dose of risperidone without losing of the antipsychotic effects or adding antiparkinson drug.

 DISCUSSION

The main findings of the study presented here showed the efficacy and tolerability of risperidone in treatment of chronic schizophrenia that were effective and safe. The mean risperidone dose of this study was 5.56 mg/day (modal dose = 4 mg/day) which was related to the general consensus of many clinical trials that 2-6 mg of risperidone is the optimal dose range for most patients. And this dose range produces the best antipsychotic effect with minimal extrapyramidal side effect.⁴ However, the side effects we found from this study which were akathisia and tremors may be due to wash-out period that we simultaneously stopped both previous antipsychotic and anticholinergic agents. This may therefore induce “rebound EPS” since plasma level of the antipsychotic are still relatively high when the anticholinergic agent has been fully excreted. To avoid this, it is recommended that anticholinergic medication be continued at full dose for 1-2 weeks after stopping the previous neuroleptic and introducing treatment with risperidone.

For benzodiazepine used to alleviate akathisia, it is recommended that it be continued for 1 or 2 weeks after introducing risperidone, and then gradually withdrawn over the course of 2 weeks, or, if necessary, longer should the former have been in long-term usage.⁵ For the dose titration, ideally the dose of risperidone should be increased as slowly as possible. However, in patients with marked positive symptoms (e.g. psychosis, agitation) this may be impractical and the dose may be increased to 4-6 mg/day over a period of 10-14 days. If extrapyramidal symptoms occur with this approach, the dose is probably too high and should be reduced in steps of 0.5 mg/day until the symptoms abate.⁶

In summary, risperidone was significantly effective in improving aspects of total PANSS score. However, long-term double-blind controlled studies in large scale are needed to conduct in Thai schizophrenic patients to definitely conclude the efficacy and safety of risperidone in the pharmacotherapy of schizophrenia.

 REFERENCES