Progress in Pharmacotherapy of Borderline Disorders: A Double-blind Study of Amitriptyline, Haloperidol, and Placebo

Abstract

In symptomatic patients with borderline disorder, we conducted a double-blind, placebo-controlled trial of haloperidol and amitriptyline hydrochloride to test the differential efficacy of medication against the affective and schizotypal symptoms that characterize the disorder. Sixty-one patients, diagnosed by the Diagnostic Interview for Borderline of Gunderson et al, completed randomized trials of haloperidol (n = 21), amitriptyline (n = 20), and placebo (n = 20). Medications were given in dose ranges of 4 to 16 mg for haloperidol (mean, 7.24 mg) and 100 to 175 mg for amitriptyline hydrochloride (mean, 147.62 mg) for five-week periods, with weekly self-rated and observer-rated measures of mood, schizotypal symptoms, and global functioning. Haloperidol was superior to both amitriptyline and placebo on a composite measure of overall symptom severity, with no difference between amitriptyline and placebo. Haloperidol produced significant improvement on a broad spectrum of symptom patterns, including depression, anxiety, hostility, paranoid ideation, and psychoticism. In contrast, amitriptyline was minimally effective, with small gains limited to some areas of depressive content. The magnitude of change tended to be modest and was more apparent in self-rated than observer-rated measures.