Low rate of membrane lithium transport during treatment correlates with outcome of maintenance pharmacotherapy in bipolar disorder.

Lithium is transported across cell membranes by an exchange diffusion process (Na(+)-Li+ countertransport) that is inhibited during lithium treatment. We hypothesized that low rates of lithium efflux (a potential manifestation of strong transport inhibition) would be associated with better clinical outcome of maintenance pharmacotherapy. We measured the erythrocyte (RBC) apparent rate constant for lithium efflux (kexch) in 22 patients with bipolar disorder who had been euthymic on lithium for 1 month. Subsequently, clinical mood ratings and in vivo RBC: plasma lithium ratios (LiR) were determined monthly. Outcome was categorized according to whether subjects completed 1 year of successful maintenance treatment (n = 10), experienced a recurrent affective episode (n = 8), or dropped out (n = 4). The kexch at the outset of the study was significantly lower (potentially because of greater transport inhibition) in 1-year completers than in patients with recurrences or those who dropped out (median kexch = 0.09, 0.24, and 0.27 h-1, respectively; P < .03). Moreover, 77% of patients with a kexch of 0.11 h-1 or lower were successfully maintained on lithium for 1 year, whereas only 23% of those with a kexch greater than or equal to 0.12 h-1 had a successful treatment outcome. LiR measured during the course of maintenance treatment was significantly higher (suggesting greater transport inhibition) in 1-year completers than in noncompleters (recurrences and dropouts). Measurement of kexch at an early point in treatment may provide a means for prospectively identifying those bipolar patients at greater risk for failure of maintenance lithium therapy.