• 来稿:陈琳   北京市虹天济神经科学研究院

  • Int J  Neuropsychopharmacol. 2008 Mar;11(2):269-87.

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  • A systematic review of existing data on  long-term lithium therapy: neuroprotective or  neurotoxic?

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  • Fountoulakis KN, Vieta E, Bouras C,  Notaridis G, Giannakopoulos P, Kaprinis G, Akiskal  H.

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  • Lithium is an efficacious agent for the treatment of  bipolar disorder, but it is unclear to what extent its long-term use may result  in neuroprotective or toxic consequences. Medline was searched with the  combination of the word 'Lithium' plus key words that referred to every possible  effect on the central nervous system. The papers were further classified into  those supporting a neuroprotective effect, those in favour of a neurotoxic  effect and those that were neutral. The papers were classified into research in  humans, animal and in-vitro research, case reports, and review/opinion articles.  Finally, the Natural Standard evidence-based validated grading rationale was  used to validate the data. The Medline search returned 970 papers up to February  2006. Inspection of the abstracts supplied 214 papers for further reviewing.  Eighty-nine papers supported the neuroprotective effect (6 human research, 58  animal/in vitro, 0 case reports, 25 review/opinion articles). A total of 116  papers supported the neurotoxic effect (17 human research, 23 animal/in vitro,  60 case reports, 16 review/opinion articles). Nine papers supported no  hypothesis (5 human research, 3 animal/in vitro, 0 case reports, 1  review/opinion articles). Overall, the grading suggests that the data concerning  the effect of lithium therapy is that of level C, that is 'unclear or  conflicting scientific evidence' since there is conflicting evidence from  uncontrolled non-randomized studies accompanied by conflicting evidence from  animal and basic science studies. Although more papers are in favour of the  toxic effect, the great difference in the type of papers that support either  hypothesis, along with publication bias and methodological issues make  conclusions difficult. Lithium remains the 'gold standard' for the prophylaxis  of bipolar illness, however, our review suggests that there is a rare  possibility of a neurotoxic effect in real-life clinical practice even in  closely monitored patients with 'therapeutic' lithium plasma levels. It is  desirable to keep lithium blood levels as low as feasible with  prophylaxis.


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锂盐远期疗法现有数据的系统评价:神经保护抑或神经毒害?