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 tr eatment. We hypothesized that low rates of lithium efflux (a potential manifestation of strong transport inhibition) would be associated wit h better clinical outcome of maintenance pharmacotherapy. We measured the erythrocyte (RBC) apparent rate constant for lithium efflux (k(exc h)) in 22 patients with bipolar disorder who had been euthymic on lith ium for 1 month. Subsequently, clinical mood ratings and in vivo RBC: plasma lithium ratios (LiR) were determined monthly. Outcome was categ orized according to whether subjects completed 1 year of successful ma intenance treatment (n = 10), experienced a recurrent affective episod e (n = 8), or dropped out (n = 4). The k(exch) at the outset of the st udy was significantly lower (potentially because of greater transport inhibition) in 1-year completers than in patients with recurrences or those who dropped out (median k(exch), = 0.09, 0.24, and 0.27 h(-1), r espectively; p < .03). Moreover, 77% of patients with a k(exch) of 0.1 1 h(-1) or lower were successfully maintained on lithium for 1 year, w hereas only 23% of those with a k(exch) greater than or equal to 0.12 h(-1) had a successful treatment outcome. LiR measured during the cour se of maintenance treatment was significantly higher (suggesting great er transport inhibition) in 1-year completers than in noncompleters (r ecurrences and dropouts). Measurement of k(exch) at an early point in treatment may provide a means for prospectively identifying those bipo lar patients at, greater risk for failure of maintenance lithium thera py. (C) 1997 American College of Neuropsychopharmacology.