A Self-Controlled, Naturalistic Study of Selective Serotonin Reuptake Inhibitors versus Tricyclic Antidepressants

Abstract

Objective: To compare the effectiveness of serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) for anxiety and mood disorders in a naturalistic setting. Methods: 114 of 2,000 outpatients drawn from a private facility with a diagnosis of mood or anxiety disorder had two separate episodes during which they were treated once with a SSRI and once with a TCA. The drugs had to be in monotherapy and appropriate according to the recent guidelines. Key outcome measures included several rating scales, the results of which were combined into three measures of outcome: full response (no symptom), partial response (residual symptoms), poor response. Results: TCAs produced a better response in 63 cases and SSRIs in 18 cases (p < 0.00001). When the outcome was dichotomized, TCAs were still superior (stricter criterion of full response: p = 0.0002; lower threshold: p < 0.0001). Considering depressive and anxiety disorders separately, TCAs remained superior in terms of efficacy (for depression: p < 0.0001; for anxiety: p = 0.026). Moreover, the second episode of illness showed a better outcome than the first (p = 0.0008). Conclusions: In those cases where two different antidepressants were prescribed over two different episodes of illness, TCAs were significantly more effective than SSRIs, regardless of the type of disorder and order of prescription.

Increase in Antidepressant Medication in the US Adult Population between 1990 and 2003

“…SSRIs) which became available in the early to mid-1990s. However, there is no evidence that the newer antidepressants are more efficacious than the older tricyclics [44, 45], and they may even be less effective than older medications in real world settings [46], although the newer medications may be better tolerated than the older ones [44]. Financial reasons such as expiration of patents for older medications are likely a major reason for decreased pharmaceutical marketing efforts for these medications and their decline in popularity.…”

The Deceptive Manifestations of Treatment Resistance in Depression: A New Look at the Problem

“…Simpson and Kessel [6] provided an important specification: one trial should include the use of a high-dose (200–300 mg) tricyclic antidepressant such as imipramine for a minimum of 6 weeks. Such a specification was justified by the apparent superiority of tricyclics over other antidepressants in severe depression and their dose-response characteristics [7], despite the fact that a recent meta-analysis of trials comparing tricyclics to selective serotonin reuptake inhibitors failed to show any significant difference in efficacy for the average patient [8]. More recently, with the replacement of tricyclics by second generation antidepressants, switching and augmentation strategies have been advocated, despite their overall lack of efficacy [9, 10].…”

How to choose an antidepressant medication

“…Barbui and Hotopf and Faravelli et al. demonstrated superiority of TCAs over SSRIs, though a meta‐analysis of head‐to‐head MDD trials found no difference between TCAs vs. SSRIs while Anderson found comparable efficacy between the classes other than the superiority of the TCA amitriptyline over SSRIs in in‐patients (where melancholic depression may have been overrepresented). It has been argued that the superiority of TCAs reported in older studies may be an artefact of a decline in drug‐placebo differences over time due to increased response rates to placebo .…”