Comparative efficacy of lithium and aducanumab for cognitive decline in patients with mild cognitive impairment or Alzheimer's disease: A systematic review and network meta-analysis.

Background: In 2021, the US Food and Drug Administration granted an accelerated approval to aducanumab for patients with mild cognitive impairment (MCI) and mild dementia caused by Alzheimer's disease (AD); however, the cost of aducanumab is high, at approximately $28,000 for one year per person. On the other hand, lithium is much cheaper at $40 a year, and has been reported to be effective for the cognitive decline observed in both patients with MCI and AD. In contrast to acetylcholinesterase inhibitors and N-methyl D-aspartate receptor antagonists, aducanumab and lithium may be disease-modifying drugs. Therefore, we focused on aducanumab and lithium and compared the effects of these drugs on the cognitive decline in MCI and AD patients using a network meta-analysis.
Methods: PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov were searched for randomized controlled trials testing lithium or aducanumab for the treatment of cognitive decline in patients with MCI or AD, up to January 31, 2022. A frequentist fixed-effect network meta-analysis was performed to estimate direct and indirect effects. The primary outcome was change scores in cognitive decline measured by Mini-Mental State Examination. This study has been registered with PROSPERO (number CRD42022304807).
Results: Network meta-analysis demonstrated that lithium was significantly more effective than aducanumab in the primary outcome.
Conclusion: Although there were various limitations in this study, lithium may be a more cost-effective treatment than aducanumab for MCI and AD.
Competing Interests: Conflicts of interest Takeshi Inoue has received personal compensation from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Daiichi Sankyo; grants from Shionogi, Astellas, Tsumura, and Eisai; and grants and personal compensation from Otsuka Pharmaceutical, Dainippon Sumitomo Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Novartis Pharma, and Meiji Seika Pharma; and is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma. The other authors declare that they have no actual or potential conflicts of interest associated with this study.
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