Quando utilizar terapia combinada no tratamento da depressão

Pessoal, o que eu percebi foi que a terapia combinada no tratamento da depressão só deve ser realizada quando a monoterapia não é eficaz e somente após várias tentativas de aumento de dose da medicação e até mesmo associação desta com a psicoterapia.


Combined therapy — A systematic review of 12 randomized trials comparing antidepressant treatment alone with antidepressant treatment combined with psychotherapy found a higher response rate for patients in the combination group (OR 1.86, 95% CI 1.38-2.52); the severity or chronicity of depression was not noted in this review.
Combined treatment is both more costly and time consuming. An earlier meta-analysis comparing psychotherapy alone with antidepressant plus psychotherapy found no significant difference in response rates for mild depression, but significantly increased response to combination therapy for more severe and recurrent depression. Most data favor combination therapy for patients with severe, chronic (more than two years) or recurrent symptoms
(UpToDate)
As estratégias utilizadas quando um paciente não responde ao tratamento com medicamento antidepressivo consiste em: a) aumento de dose(A); b) potencialização(A); c) associação de antidepressivos(B); d) troca de antidepressivo(D); e) Eletroconvulsoterapia (D); f) associação com psicoterapia(A).
Sociedade Brasileira de Psiquiatria (Projeto Diretrizes)



Choice of antidepressant — Most systematic reviews have concluded that clinical and quality of life outcomes, as well as overall treatment costs, provide no clear guidance on the choice among specific antidepressants. As an example, a meta-analysis of 93 randomized trials (>20,000 patients with unipolar major depression) found treatment effects among second-generation antidepressants were comparable. However, results from these systematic reviews are limited to acute treatment (6 to 12 weeks), and thus do not address long-term outcomes and cumulative side effects.
The choice of antidepressant is likely to be less important than treating patients with medications that they can tolerate, and with doses sufficient to achieve symptom remission.
SSRIs are often first line in primary care because they cause fewer side effects than other drugs and are less dangerous with overdose. The 2008 clinical practice guidelines from the American College of Physicians (ACP) make a strong recommendation to initiate one of 12 second-generation antidepressants (bupropion, citalopram, duloxetine, escitalopram,fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, or venlafaxine), based on their similar efficacy and side effect profiles. We do not recommend use of nefazodone, however, due to its hepatotoxicity.
Multiple meta-analyses have evaluated comparisons of antidepressant medications. Findings include:
 The guidelines for the ACP were based on a meta-analysis of 203 randomized trials comparing efficacy and effectiveness of 12 second generation antidepressants. Most trials compared drugs with placebo and 70 percent were supported by pharmaceutical companies. Drugs were similar in regard to acute and maintenance phase response rates, impact on quality of life indices, and treatment response for associated symptoms (anxiety, insomnia, pain). Small effect size differences were not considered to be clinically relevant.
 Another meta-analysis included 117 randomized trials in which two or more of the following 12 second-generation antidepressants, used as monotherapy, were evaluated:bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine. In the absence of head-to-head drug trials, multiple treatment (network) meta-analysis was used to compare two dichotomous outcomes (response, defined as >50 percent improvement in symptom score; and patient drop out during treatment). Escitalopram and sertraline showed the best combined profile of acceptability and efficacy. Methodological concerns with indirect comparisons (including heterogeneity in patient populations and comparability of drug doses), pharmaceutical sponsorship of most trials, and inadequate reporting of randomization techniques or allocation concealment may limit the validity of these findings. In addition, it is unclear whether the differences between drugs were clinically meaningful or would be sustained beyond the eight week-average study period.
 Two meta-analyses evaluated randomized trials of sertraline and escitalopram versus other antidepressive agents. The studies found both sertraline and escitalopram more effective than the comparator drugs, although it is uncertain if differences were clinically significant.
 In a meta-analysis of 28 randomized, controlled trials involving 5940 primary care patients with major depression, dysthymia, or mixed anxiety depression, newer antidepressants (including selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, reversible inhibitors of monoamine oxidase, and dopamine antagonists) resulted in higher rates of response than placebo (RR 1.6, 95% CI 1.2-2.1), but rates were similar to those for tricyclic agents.
 A systematic review of 55 randomized, controlled trials of MAO inhibitors versus tricyclic antidepressants found that MAO inhibitors were less effective for severe depressive disorders but possibly more effective in atypical depressive disorders.
 A systematic review of 46 randomized controlled trials and 24 observational studies of head-to-head comparisons between second-generation antidepressants (SSRIs, bupropion,duloxetine, mirtazapine, and venlafaxine) concluded that there were no significant differences in efficacy or tolerability among these drugs. By contrast, a meta-analysis of 12 randomized trials (2626 patients with major depression) found that response occurred in significantly more patients who received mirtazapine than an SSRI (OR 1.2).
There is limited evidence that tricyclics may be preferred for more severely depressed patients. A meta-analysis of 25 randomized controlled trials for treatment of hospitalized, depressed patients found tricyclics were significantly more efficacious compared to SSRIs, but the clinical difference was small. The role of tricyclic antidepressants in treating major depression is discussed separately.
Patients who have been successfully treated with a well-tolerated drug in the past should resume that agent if depression recurs. A positive response to a particular antidepressant by a first degree relative may be another factor to consider. Some meta-analyses suggest small differences in clinical efficacy that are unlikely to have clinical relevance. Since efficacy differences are not a clinically important issue, other factors to be considered in drug selection include physician familiarity, cost, formulary preference, and side effects (tabela)