發展治療思覺失調症負性症狀的藥物

Developing Drugs for Negative Symptoms of Schizophrenia

思覺失調症的負性症狀，因為影響病人的功能甚鉅，是臨床上發展藥物治療的重要標的。這個症狀群仍缺乏有效的治療，是目前重大的未能滿足的治療需求。早期的負性症狀的臨床試驗，因為同時包括首發的及次發的負性症狀為治療標的，以及缺乏標準的試驗流程，而備受批評。本篇綜說第一部份將會回顧負性症狀臨床試驗相關的方法學，包括負性症狀的定義及量測，以及臨床試驗設計原則的共識。缺損症狀及持續性負性症狀，而非廣義的負性症狀，更適合做為臨床試驗的治療標的。目前有五種常用的由訪談者評估的負性症狀量表做為評估工具，皆有不錯的心理計量品質。目前專家已達成臨床試驗設計原則的共識。第二部份將回顧不同種類藥物對負性症狀的治療效果，結果顯示某些第二代抗精神病藥物，抗憂鬱劑，精神刺激劑，麩胺酸路徑相關分子，血清素受體拮抗劑，已及某些抗發炎藥物，比起安慰劑，對負性症狀有顯著但輕微的治療效果。上述藥物雖然在負性症狀的進步上達到顯著，在臨床上卻尚未達到顯著進步的程度。目前仍有一些有潛力的新分子仍在發展中。

Negative symptoms in schizophrenia represent a clinically important target for drug development due to their profound effect on an individual’s ability to function normally. The lack of effective medications for this domain of psychopathology is a major unmet medical need in schizophrenia. Earlier clinical trials for negative symptoms have been criticized mixing primary and secondary negative symptoms as treatment target and lack of standard protocols for clinical trial design. In the fi rst part, The author is reviewing the methodological issues on defi ning and measuring negative symptoms and on developing the consensus for clinical trial design for negative symptoms. Defi cit symptoms and persistent negative symptoms, instead of broadly defi ned negative symptoms, have been advocated as the treatment target of clinical trial. There were fi ve commonly used interviewbased negative symptom scales with satisfactory psychometric profi les. The consensus has been achieved for the design of clinical trials for negative symptoms. In the second part, the treatment effi cacy of different class of drugs on negative symptoms is reviewed. Some second-generation antipsychotics, antidepressants, psychostimulants, glutamate pathway molecules, serotonin receptor antagonists, and anti-infl ammatory agents have modest effects on improving negative symptoms than placebo. Although some statistically signifi cant effects on negative symptoms are evident, none has reached the threshold for clinically signifi cant. Several new molecules with potentials in treating negative symptoms are still in development.