Hemodialysis hypotension (HH) is a very common disorder and has a multifactorial etiology. Autonomic dysfunction occurs in up to 50% of patients with end-stage renal disease (ESRD) and plays a key role in HH in some patients. Sertraline hydrochloride, a central nervous system serotonin reuptake inhibitor, has been shown to be an effective treatment of hypotension caused by autonomic dysfunction in disorders such as neurocardiogenic syncope and idiopathic orthostatic hypotension. This study sought to determine whether sertraline was effective in ameliorating HH. A retrospective chart analysis was performed that included nine consecutive patients (aged greater than or equal to 54 years, time on hemodialysis greater than or equal to 2.2 years) placed on sertraline (50 to 100 mg/d) for depression who also had HH (defined as prehemodialysis systolic blood pressure [SBP] less than or equal to 100 mm Hg, greater than or equal to 40 mm Hg decrease in SEP during hemodialysis, SEP <90 mm Hg, any diastolic blood pressure <40 mm Hg, or a decrease in blood pressure-causing symptoms) before treatment with sertraline. The data from a 6-week pre-sertraline period were compared with the data from a B-week sertraline period (defined as 6 weeks after drug begun). Blood pressure medications were unchanged during the trial period of sertraline, However, nadir mean arterial pressure recorded during a given dialysis session in the pre-sertraline period (55 +/- 4 mm Hg) was significantly lower than that recorded in the sertraline period (68 +/- 5 mm Hg; P < 0.05). In addition, the number of hypotensive episodes (same definition as HH) per dialysis session during the sertraline period was significantly lower than that during the pre-sertraline period (mean, 0.6 +/- 0.2 episodes per session v1.4 +/- 0.3 episodes per session; P < 0.005). The number of therapeutic interventions required for hypotension during the sertraline period was also significantly less than that during the pre sertraline period (mean, 1.7 +/- 0.8 interventions v11.0 +/- 3.0 interventions; P < 0.005). The urea reduction ratio (62.7% +/- 4.7% v63.1% +/- 9.3%; P = NS) and hematocrit (28.9% +/- 0.8% v29.5% +/- 1.0%; P = NS) did not change significantly. It is concluded that the short-term (6 weeks) use of sertraline hydrochloride reduces HH in some patients with ESRD, A possible mechanism for this effect is sertraline-induced attenuation of the paradoxical sympathetic withdrawal that may underlie HH in some patients with ESRD. (C) 1998 by the National Kidney Foundation, Inc.