Treating Depression in Primary Care: Are Biomarkers the Key?

Charles P. Vega, MD


November 06, 2014

In This Article

Which Drug When?

We need to identify and treat depression more effectively. But what is the best antidepressant? There really is no answer to that question.

Antidepressants are far more similar than different with regard to efficacy of treatment. Previous systemic reviews have found that citalopram and escitalopram have some significant improvements in depression scores compared with other antidepressants, but this difference is limited to the acute phase of treatment and is of questionable clinical relevance.[10,11] Similarly, venlafaxine has been demonstrated to be superior to SSRIs in terms of treatment response and remission in depression, and dropout rates from clinical trials are similar in comparing venlafaxine and SSRIs.[12]

However, in clinical practice, the individual response to antidepressant therapy may be quite variable, and no antidepressant medication clearly separates itself in terms of overall efficacy. One approach to choosing an antidepressant includes selecting therapy on the basis of a cluster of symptoms.

A recent review recommended SSRIs, such as citalopram, escitalopram, or sertraline, for patients with depression with features of anxiety, whereas such medications as venlafaxine should be avoided in these patients.[13] Depression with fatigue may respond better to a norepinephrine/dopamine reuptake inhibitor, such as bupropion, or such medications as venlafaxine or fluoxetine. Depression with insomnia might be best treated with mirtazapine or nefazodone. Finally, patients with depression with pain may respond best to tricyclic antidepressants or duloxetine.

A new symptom cluster to consider in depression is cognitive function. Cognition is often impaired among depressed patients and is associated with a poor response to medical treatment.[14] In two clinical trials, the relatively new antidepressant vortioxetine has been associated with improvements in not only depression scores, but also cognition scores.[15,16] Post hoc analysis suggested that most of the cognitive benefit associated with vortioxetine was independent of its antidepressive effect.

However, other well-considered reviews have raised serious questions about the effectiveness of using symptom clusters to choose an antidepressant, particularly with regard to anxiety and pain.[17]

Another important factor to consider in treatment choice is tolerability. The most common side effects among second-generation antidepressants include gastrointestinal effects, along with dizziness and sleep disturbance.[17] Sexual dysfunction may affect more than one half of patients receiving antidepressants. Bupropion and vortioxetine[18] are associated with lower rates of sexual dysfunction, whereas paroxetine is associated with higher rates.

Other adverse events to keep in mind when considering specific antidepressants vs comparator drugs include higher risk for weight gain with mirtazapine and paroxetine, higher incidence of diarrhea with sertraline, and increased risk for nausea and vomiting with venlafaxine.[17]

A Step in the Right Direction?

The lack of appropriate biomarkers has always hindered the identification and treatment of depression. Physicians prefer to order tests, interpret the results, and allow objective evidence to guide therapeutic choices. Depression is not so clear-cut. It takes some extra effort, but the benefit of a diligent approach in the diagnosis and management of depression can be outstanding.

Clinicians should familiarize themselves with multiple antidepressants to tailor treatment for individual patients. Treatment should be continued for at least 6 months after initiation, so assessing the side effect profile of antidepressant therapy is a good idea. There appears to be some value in using symptom clusters to predict the response to treatment, but it is far from perfect.

On the basis of the results of the current study, should CRP levels be routinely examined among depressed patients and tricyclic antidepressants prescribed to patients with evidence of inflammation? No and no. The promising results of this study need to be replicated in other trials. The decision to (re)apply tricyclic antidepressants more broadly in the treatment of depression is not to be taken lightly. Higher rates of adverse events with this drug class will result in more treatment discontinuation and nonadherence.

Nonetheless, as the healthcare community continues to wait for a groundbreaking change in depression management, innovative research regarding biomarkers may help to provide truly personalized care for depression.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: