The Strategy of Combining Antidepressants in the Treatment of Major Depression: Clinical Experience in Spanish Outpatients

Abstract

Introduction. The combination of antidepressants is a useful tool in the treatment of major depression, especially in cases where there is a partial response to antidepressant monotherapy. However, the use of this strategy is a matter of controversy, and its frequency of use in clinical practice is not clear. The aim of our study is to assess the use of antidepressants combination in Spain by reviewing three databases used between 1997 and 2001. Methods. Databases pertain to patients who are study subjects of major depression treatment. These databases are a result of studies performed in Spain and in which 550 psychiatrists participated. The total studied sample was comprised of N = 2, 842 patients, aged over 18, fitting DSM-IV criteria for Major Depressive Episode. The percentage of patients who received more than one antidepressant and the types of combinations used was described. Subsequently, a comparative study between the group which received a combination of antidepressants (N = 64) and the group which received antidepressant monotherapy (N = 775) was performed. Results. 27.1% of patients were on antidepressive monotherapy treatment, and 2.2% were on combination therapy. In the comparison of patients on combination therapy and monotherapy, there were significant differences only in episode duration (P = 0.001). The most frequent combinations are SSRIs and tricyclic antidepressants. The active principle most widely combined is fluoxetine. Conclusions. The prevalence of use of antidepressant combination therapy is 2.2% of the global sample and 8.3% of treated patients. Other than duration of the depressive episode, no clinical characteristics exclusive to patients who received combination rather than monotherapy were found. Our study found that the most frequent combination is SSRIs + TCAs, also being the most studied.

Treatment-resistant depression: therapeutic trends, challenges, and future directions

“…However, lithium is known to have a narrow therapeutic window and needs blood level monitoring to avoid the toxicity and fatalities associated with high lithium levels 77,78,80. With regard to newer generations of antidepressants, after failure of a first-line SSRI, neither a switch within a class nor a switch to a different class of antidepressant is unequivocally supported by the data, although switching from an SSRI to venlafaxine or mirtazapine may potentially offer greater benefits 75–77,141. In an open-label study, mirtazapine was effective in 38% of patients with depression resistant to standard antidepressants.…”

Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants

“…Other combinations, such as monoamine oxidase inhibitors (MAOI) + tricyclic antidepressants (TCA) or SSRIs + TCA, have less support but were also formerly widely used and accepted in clinical practice [19, 22]. More controversial, the combination of more than two antidepressants is less well studied and reported [13–15, 22]. This may be associated with the possibility of a greater side-effect burden (including serotoninergic syndrome and syndrome of inappropriate antidiuretic hormone secretion, SIADH) and with higher clinically significant medication interactions secondary to polypharmacy [14].…”

“…Regarding this latter strategy, although combining two antidepressants with complementary pharmacological actions is well accepted, the triple antidepressant combination is, on the contrary, less described and more controversial [13–16]. Here, we present a relapse of moderate-to-severe depressive symptoms in a patient with treatment-resistant depression that was efficaciously treated after adding trazodone to a dual antidepressant combination consisting of paroxetine and mirtazapine (in standard doses); we also discuss the pros and cons of combining three antidepressants as a strategy in the management of treatment-resistant depression.…”

Adjunctive pharmacotherapy and treatment patterns among initiators of SSRI therapy for major depressive disorder: A cohort study using a primary care database

“…A study of 12 European countries, including the UK, found the prevalence of adjunctive antidepressant therapy to be less than 7% [16]. Similarly, a study in Spain found the prevalence of adjunctive antidepressant therapy to be 8.3% among patients treated for MDD [17]; several other studies have reported a range of adjunctive therapy prevalence of between 2% to 25% [16,18,19]. Reflecting a different health care system, a study based on a US insurance claims database found that 38% of patients who initiated on SSRI monotherapy received adjunctive treatment in the year following the initial index prescription [20].…”