Comparison of immediate and sustained release formulations of lithium salts

Abstract

Lithium salts are widely used clinically, mainly for treatment of bipolar disorder, in which it is highly effective. Various preparations have been developed and tested, including older immediate-release (IR) forms of lithium carbonate and other salts and formulations with slow-release (SR) properties, developed in hopes of increasing the tolerability of lithium treatment, adherence to its use, and possibly its efficacy. Systematic reviews of head-to-head comparisons of pharmacological and clinical properties of such preparations are lacking. Accordingly, we systematically reviewed clinical studies of both IR and SR formulations of lithium salts, seeking to compare their pharmacokinetic properties, adverse effects, clinical tolerability, and clinical effectiveness. Very few such comparative studies were identified and they are highly heterogeneous in design and findings. In 11 included reports, SR formulations appeared to be better tolerated and possibly to be associated with greater adherence to treatment. Studies of comparative clinical efficacy are lacking. Despite decades of use of various lithium salts, systematic comparisons of the pharmacological and clinical properties of IR vs. SR preparations remain rare and to be deepened, though with suggestive superiority of SR salts.

Keywords:

• Adverse effects
• lithium
• rapid-release
• slow-release

Acknowledgments

Supported by a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Psychiatry Research Fund (to RJB).

Disclosure statement

Dr. Pompili took part in educational initiatives and clinical trials of lithium supported by Angelini Pharma and, in the past 2 years, received honoraria for lectures, advisory board membership, or engaged in clinical trial activities with Lundbeck, Janssen, Recordati, Pfizer, and MSD Corporations – none of which is related to this study. No other author or immediate family member has financial relationships with commercial organizations that might appear to represent potential conflicts of interest with the material presented.