How to initiate lithium therapy: a systematic review of dose estimation and level prediction methods

Background: Throughout the past decades, several methods have been developed to achieve therapeutic lithium blood levels as quick and safe as possible. The present study will systematically review the methods developed and studied for lithium dose estimation or level prediction at the initiation of therapy.

Methods: A systematic computerized Medline search was performed for papers published in English, French or Dutch between 1966 and April 2012 describing or studying methods for dosing lithium or predicting the lithium level on a certain dosage. References of relevant articles were screened for additional papers.

Results: Of 273 unique references retrieved, 65 met the inclusion criteria. Apart from the empirical titration method, 38 predictive methods for initiating lithium were identified. These methods can be classified into two categories: the a priori predictive methods, and the test-dose predictive methods requiring the administration of a test dose of lithium prior to starting treatment.

Limitations: The methodological strength was not taken into account for a study to be included in the review.

Conclusions: The most important distinction between the empirical titration method and the predictive methods appears to be the shorter time the latter need to achieve the targeted lithium level. The vast majority of predictive methods, however, show inconsistent or poor results or have not been replicated since their initial description. The empirical titration method, although not extensively studied, appears to be a time-honored method that can be recommended for use in daily clinical practice.