Electrocardiogram changes and plasma desipramine levels during treatment of depression

Twenty-six symptomatic subjects who met research diagnostic criteria for major affective disorder and were free of cardiovascular disease were treated for 3 wk with a fixed dosage schedule of desipramine (DMI) to a maximum of 200 mg/day. An electrocardiogram (ECG) and DMI plasma level determinations were obtained before treatment and weekly thereafter. DMI levels during the trial ranged from 13.4 to 882.2 ng/ml. DMI treatment was associated with increase in heart rate (p less than 0.001), prolongation of the PR (p less than 0.001), QRS (p less than 0.001), and QTc intervals (p less than 0.001), and increase in T wave amplitude (p less than 0.001). Significant (p less than 0.001) but relatively weak correlations were noted between DMI plasma levels and heart rate (r = 0.405), QRS interval (r = 0.346), QTc interval (r = 0.534), and T wave amplitude (r = -0.386). PR interval prolongation was independent of DMI levels (r = 0.171). DMI treatment induced no clinically significant ECG alterations or cardiovascular adverse effects. The relevance of DMI plasma level and the possible roles of other contributing factors in the production of these ECG changes are discussed.