Combined Treatment With Venlafaxine and Tricyclic Antidepressants in Depressed Patients Who Had Partial Response to Clomipramine or Imipramine: Initial Findings

Background: We report, after 3 years of work, a case series showing our initial results (efficacy, tolerability, and safety) with the addition of venlafaxine immediate release (IR) to either clomipramine or imipramine in depressed patients who had shown only partial response to maximal doses of one of those tricyclic antidepressants (TCAs) and no further improvement after addition of usual augmentation drugs.

Method: Eleven patients were treated, 10 of them having a recurrent depressive disorder (DSM-IV) and all of them having current major depression (DSM-IV) that in 9 patients was moderate or severe despite intense TCA treatment as well as usual augmentations. Under open and outpatient conditions, we maintained TCA doses, discontinued previous augmentations, and then added venlafaxine IR to a maximum dosage, if necessary, of 150 mg every 12 hours. There was no control group. Response was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D), DSM-IV criteria, the Clinical Global Impressions-Severity of Illness scale, and persistence of improvements after 6 months. We measured clinical tolerance (using the UKU Side Effect Rating Scale), blood pressure and heart rate, electrocardiogram (ECG), and blood TCA levels after adding venlafaxine IR.

Results: A sustained improvement (> 50% decrease in HAM-D score plus decrease in DSM-IV severity level) appeared in 9 patients, and sustained full remission (DSM-IV criteria plus HAM-D score < 5) in 7. Panic-agoraphobic symptoms improved in the 2 patients suffering from them. There were no dropouts, and tolerability was good. No significant changes in blood pressure and heart rate, ECG, or blood tricyclic levels were found.

Conclusion: Addition of venlafaxine to clomipramine or imipramine could be an effective and safe augmentation strategy in depressive patients with partial response to maximum-dose monotherapy. A consistent replication of these initial findings is strongly needed.