Review
Selective serotonin reuptake inhibitors and tricyclic antidepressants in the acute treatment of chronic depression and dysthymia: A systematic review and meta-analysis

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Abstract

Introduction

Chronic depression represents a substantial portion of depressive disorders and is associated with severe consequences. This review examined the efficacy and acceptability of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in the treatment of chronic depression. Additionally, the comparative effectiveness of the two types of antidepressants has been examined.

Methods

A systematic search was conducted in the following databases: CENTRAL, MEDLINE, EMBASE, ISI Web of Science, BIOSIS, PsycINFO, and CINAHL. Primary efficacy outcome was a response to treatment; primary acceptance outcome was dropping out of the study. Only randomized controlled trials were considered.

Results

We identified 20 studies with 22 relevant comparisons. 19 studies focused on samples with a majority of dysthymic patients. Both SSRIs and TCAs are efficacious in terms of response rates when compared to placebo (Benefit Ratio [BR]=1.49; p<0.001 for SSRIs and BR=1.74; p<0.001 for TCAs) and no statistically significant differences between the active drugs and placebo in terms of dropout rates could be found. No differences in effectiveness were found between SSRIs and TCAs in terms of response rates (BR=1.01; p=0.91), yet, SSRIs showed statistically better acceptability in terms of dropout rates than TCAs (Odds Ratio [OR]=0.41; p=0.02).

Limitations

The methodological quality of the primary studies was evaluated as unclear in many cases and more evidence is needed to assess the efficacy of SSRIs and TCAs in patients suffering from chronic forms of depression other than dysthymia.

Conclusions

This systematic review provides evidence for the efficacy of both SSRIs and TCAs in the treatment of chronic depression and showed a better acceptability of SSRIs.

Introduction

Approximately 20% of all patients who experience a major depressive episode develop a chronic course (Gilmer et al., 2005) and approximately 47% of patients who are treated in mental health care facility suffer from some form of chronic depression (Torpey and Klein, 2008). Four subtypes of chronic depression are usually distinguished: (1) dysthymia, (2) chronic major depression, (3) recurrent major depression with incomplete remission between episodes, and (4) double depression (Klein, 2010). Dysthymic disorder is defined as a mild condition that is chronic and persistent for at least 2 years. A major depressive episode, chronic type, refers to a more severe condition that meets all criteria for major depression continuously for a minimum of 2 years. Patients who have recovered to the point where they no longer meet all criteria for a major depressive episode but continue to experience significant symptoms for a total duration of illness greater than 2 years are referred to as having recurrent major depression with incomplete remission during episodes. The superimposition of a major depressive episode on antecedent dysthymia is referred to as double depression (Klein, 2010).

Chronic depression is associated with increased functional impairment (Satyanarayana et al., 2009), increased health care utilization, and higher rates of hospitalization compared with non-chronic forms of depression (Berndt et al., 2000, Gilmer et al., 2005).

Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are two groups of antidepressants often used as pharmacological interventions in the treatment of chronic depression. An increasing number of studies have assessed the efficacy and effectiveness of these two groups of antidepressants in the last several decades.

These studies have been partly summarized in current guidelines and systematic reviews. Meta-analytic findings regarding the treatment of dysthymic patients showed that both types of antidepressants are effective but highlighted the differential acceptability of the two drug groups (Lima et al., 2005). Accordingly, the practice guideline for the treatment of patients with major depressive disorder of the American Psychiatric Association (American Psychiatric Association, 2010) comes to the conclusion, that both types of antidepressants are effective in the treatment of dysthymia and may also be used for other forms of chronic depression. The national clinical practice guideline for the treatment and management of depression in adults of the National Institute for Health and Clinical Excellence (National Institute for Health and Clinical Excellence (NICE), 2009) further highlights that SSRIs are better tolerated than TCAs by patients suffering from subthreshold depressive symptoms (including dysthymia). In contrast to these findings, the superiority of antidepressants to placebo was questioned for mild to moderately depressed patients in a controversially discussed meta-analysis (Kirsch et al., 2008). Thus, it remains unclear how chronicity and severity of depression influence the effectiveness of antidepressants. A systematic review considering the whole spectrum (i.e., all subtypes) of chronic depressions is still missing.

The objectives of this systematic review are first to examine the efficacy and acceptability of SSRIs and TCAs in the treatment of chronic depression, and second, to assess the comparative effectiveness of the two types of antidepressants.

Section snippets

Methods

The methods and results are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (Moher et al., 2009). Methods were specified a priori in a freely accessible review protocol, which included a detailed description of the methods, which are summarized briefly here (Kriston et al., 2010).

Study selection

After the removal of 1710 duplicates 2417 potentially relevant publications were identified through the electronic database search (Fig. 1). The number of publications was reduced to 275 after screening the title and abstract. Through the additional search strategies another 83 possibly relevant studies were identified. Of these 358 studies, seven studies were not available in full text. The full text of the available studies was screened and 20 primary studies, reported in 51 publications,

Summary

Similar results were obtained in terms of efficacy for both SSRIs and TCAs. Both classes of drugs showed statistically significant higher rates of response and remission than their placebo control treatments. The low NNTs assessed for both SSRIs and TCAs further highlight the clinical relevance of our findings, more precisely between four and seven patients have to be treated to cause one additional clinical improvement. No differences in terms of efficacy could be detected in studies directly

Conclusions

This systematic review provides evidence for the efficacy of SSRIs and TCAs in the treatment of chronic depression. As both groups of drugs lead to promising results, clinicians may make treatment decisions about the best option based upon the patients' personal needs and drug tolerance. As TCAs are more likely to produce dropouts and adverse events than SSRIs, SSRIs seem to be the first choice for the treatment of chronic depression. These findings may serve as supplementary information for

Role of funding source

This study was funded by a grant from the German Ministry of Education and Research (project 01KG0923).

Conflict of interest

All other authors declare that they have no conflicts of interest.

Acknowledgments

None.

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