Effects of Protriptyline on Diurnal and Nocturnal Oxygenation in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Objective: To determine the effects of a nonsedating tricyclic antidepressant (protriptyline) on pulmonary function (lung volume, expiratory flow), arterial blood gases, sleep architecture, and sleep-induced breathing abnormalities in patients with chronic obstructive pulmonary disease.

Design: A before-and-after trial in which patients, blinded to treatment, were given a placebo for 2 weeks, followed by 2 and 10 weeks of protriptyline treatment.

Setting: Referral-based pulmonology clinic in a public institution.

Patients: Sixteen outpatients were enrolled in the trial. Complete results for 11 patients and partial results for 3 patients are presented.

Interventions: Patients were evaluated at baseline, after receiving placebo for 2 weeks, and after 2 and 10 weeks of protriptyline therapy (20 mg/d, taken at bedtime).

Measurements and Main Results: At baseline, for the whole group, forced expiratory volume in 1 second (FEV₁) was 1.0 ±0.08 L (mean ±SE); the partial pressure of O₂ in arterial blood (PaO₂) was 59 ±1.2 mm Hg; and the partial pressure of CO₂ in arterial blood (Paco₂) was 48.9 ±1.2 mm Hg. These variables remained stable after placebo. Pulmonary function test results were unchanged with protriptyline therapy. Arterial blood gas levels improved with such therapy: PaO₂ levels increased by 5.1 ±1.4 mm Hg after 2 weeks and 6.7 ±2.4 mm Hg after 10 weeks (P < 0.01); PaCO₂ levels decreased by 4.2 ±0.9 mm Hg after 2 weeks and 2.2 ±1.1 mm Hg after 10 weeks (P < 0.01). Total sleep times were similar at these visits. The only change in sleep architecture was a significant decrease in rapid eye movement (REM) sleep. The lowest value for the saturation of hemoglobin with O2 in arterial blood (SaO₂) seen during sleep was 72.0% ±2.0% at baseline. After 2 and 10 weeks of protriptyline therapy, SaO₂ values increased by 7.1% ±1.6% and 5.0% ±2.1%, respectively (P < 0.01). With protriptyline therapy, the cumulative SaO₂ curve, derived from data obtained during sleep, shifted down and to the right.

Conclusions: Protriptyline improves diurnal and nocturnal hypoxemia in patients with chronic obstructive pulmonary disease. These changes are not related to changes in pulmonary mechanics.