Tính hiệu quả và an toàn của liệu pháp dược lý cho bệnh Alzheimer và các triệu chứng hành vi và tâm lý của sa sút trí tuệ ở bệnh nhân cao tuổi có suy giảm chức năng vừa và nặng: một tổng quan hệ thống về các thử nghiệm kiểm soát
Tóm tắt
Nhiều bệnh nhân mắc bệnh Alzheimer (AD) đang gặp phải tình trạng yếu đuối về thể chất hoặc có những suy giảm chức năng đáng kể. Có nhiều bằng chứng cho thấy những bệnh nhân này có nguy cơ cao hơn về các sự kiện bất lợi do thuốc gây ra. Hơn nữa, tình trạng yếu đuối dường như dự đoán các kết quả lâm sàng kém hơn so với tuổi tác một cách đơn giản. Theo kiến thức của chúng tôi, chưa có bất kỳ nghiên cứu tổng quan hệ thống nào về các thử nghiệm lâm sàng liên quan đến liệu pháp thuốc cho AD hoặc các triệu chứng hành vi và tâm lý của sa sút trí tuệ (BPSD) tập trung đặc biệt vào chủ đề yếu đuối về thể chất. Mục tiêu của chúng tôi là đánh giá hiệu quả và an toàn của liệu pháp dược lý ở các bệnh nhân AD có tình trạng yếu đuối hoặc suy giảm chức năng đáng kể.
Chúng tôi đã thực hiện một tìm kiếm tài liệu hệ thống trong MEDLINE, Embase và Cochrane Central Register of Controlled Trials (CENTRAL) cho các thử nghiệm ngẫu nhiên có kiểm soát (RCTs) của liệu pháp thuốc cho AD và BPSD ở bệnh nhân có suy giảm chức năng đáng kể theo các mục tiêu báo cáo được ưu tiên cho các đánh giá hệ thống và phân tích tổng hợp (PRISMA) và tiêu chí nghiên cứu của Cochrane. Các quần thể bệnh nhân bị suy giảm chức năng đáng kể đã được xác định bằng cách sử dụng các khuyến nghị của Nhóm nghiên cứu Medication and Quality of Life in frail older persons (MedQoL). Việc sàng lọc, lựa chọn các nghiên cứu, trích xuất dữ liệu và đánh giá nguy cơ thiên lệch đã được thực hiện độc lập bởi hai người đánh giá. Các kết quả bao gồm tình trạng chức năng, chức năng nhận thức, thay đổi triệu chứng BPSD, ấn tượng toàn cầu về lâm sàng và chất lượng cuộc sống đã được phân tích. Để đánh giá tác hại, chúng tôi đã đánh giá các sự kiện bất lợi, tỷ lệ bỏ cuộc như một chỉ số của khả năng dung nạp điều trị và tử vong. Các kết quả đã được phân tích theo tiêu chuẩn Cochrane và phương pháp Đánh giá, Phát triển và Đánh giá Khuyến nghị (GRADE).
Trong số 45,045 kết quả tìm kiếm, 38,447 tóm tắt và 187 văn bản đầy đủ đã được sàng lọc, và cuối cùng có 10 RCTs được bao gồm trong tổng quan hệ thống. Các bài báo được chọn đã đánh giá liệu pháp dược lý với các chất ức chế acetylcholinesterase (AChEI), thuốc chống co giật, thuốc chống trầm cảm và thuốc chống loạn thần. Các nghiên cứu về AChEI cho thấy rằng bệnh nhân có suy giảm chức năng đáng kể có những cải thiện nhẹ nhưng có ý nghĩa trong nhận thức và rằng AChEI thường được dung nạp tốt. Các nghiên cứu về thuốc chống trầm cảm không cho thấy những cải thiện đáng kể về triệu chứng trầm cảm. Các thuốc chống loạn thần và thuốc chống co giật đã cho thấy hiệu ứng nhỏ đối với một số yếu tố BPSD nhưng cũng có tỷ lệ sự kiện bất lợi cao hơn. Tuy nhiên, do số lượng thử nghiệm rất nhỏ đã được xác định, chất lượng bằng chứng cho tất cả các kết quả là thấp đến rất thấp.
Nhìn chung, số lượng các nghiên cứu đủ tiêu chuẩn ít ỏi cho thấy rằng các bệnh nhân cao tuổi có suy giảm chức năng đáng kể không được xem xét đầy đủ trong hầu hết các thử nghiệm lâm sàng điều tra liệu pháp thuốc cho AD và BPSD.
Do thiếu bằng chứng, không thể đưa ra các khuyến nghị cụ thể cho liệu pháp dược lý cho AD và BPSD ở các bệnh nhân cao tuổi yếu đuối hoặc cao tuổi có suy giảm chức năng đáng kể. Do đó, các thử nghiệm lâm sàng tập trung vào những người cao tuổi yếu đuối là cần thiết một cách khẩn cấp. Một cách tiếp cận tiêu chuẩn hóa về tình trạng yếu đuối về thể chất trong các nghiên cứu lâm sàng trong tương lai là rất mong muốn.
Từ khóa
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