Drugs vs Psychotherapy for MDD: Patient’s Choice?


A new finding that may help optimize the treatment of major depressive disorder.


Since primary care physicians have taken the lead in the diagnosis and initial treatment of MDD, pharmacotherapy has generally become the first line of defense. Recently, however, a meta-analysis demonstrated that the benefit/risk ratio of pharmacotherapy may be equivalent to that of cognitive behavioral therapy (CBT).1 The researchers note that this finding will help optimize the treatment of MDD, which should be based on patient preference.

Only about half of persons with major depression seek help each year. Of those who do and receive a prescription for pharmacotherapy, 20% do not fill their prescription, and many of those who do fill their prescriptions discontinue treatment prematurely.2 Reasons for nonadherence typically include adverse events or concerns about taking antidepressant drugs. The alternative to pharmacotherapy is at least 8 weeks of psychotherapy.

Amick and colleagues1 compared second-generation antidepressants (eg, citalopram, escitalopram, fluvoxamine, paroxetine, sertraline, trazodone, venlafaxine) with CBT. They performed a systematic review that included a qualitative assessment and random- and fixed-effects–model meta-analyses. The primary outcome measure was comparison of benefits and harms.

A comprehensive literature search spanning 25 years turned up 11 randomized, controlled trials that compared a second-generation antidepressant with CBT. Ten of these trials compared antidepressant monotherapy with CBT alone, and 3 compared antidepressant monotherapy with combination antidepressant therapy and CBT.

Benefits were measured in relation to response and remission, including time to response or remission, relapse, quality of life, functioning, suicidal ideation or behaviors, and hospital admission. Harms were measured in relation to overall and serious adverse events; specific adverse events, including hyponatremia, seizures, suicidal ideation or behaviors, hepatotoxicity, weight gain, gastrointestinal symptoms, and sexual adverse effects; and discontinuations due to adverse events.

Equivalent benefits/harms found

No statistically significant differences between second-generation antidepressants and CBT were found for treatment response (pooled rate, 44% vs 46%; risk ratio [RR], 0.91; 95% confidence interval [CI], 0.77 - 1.07), remission (pooled rate, 41% vs 48%; RR, 0.9; 95% CI, 0.73 - 1.32), or change in Hamilton Rating Scale for Depression scores at 8 weeks (weighted mean difference, −0.38; 95% CI, −2.87 - 2.10). No significant differences in overall study discontinuation rates were found either, including discontinuation due to lack of efficacy.

Although more patients who received pharmacotherapy withdrew from the trials because of adverse events, compared with those who received CBT, the difference was not statistically significant (RR, 3.29; 95% CI, 0.42 - 25.72). The findings held true for pharmacotherapy versus CBT alone and for pharmacotherapy versus CBT plus pharmacotherapy.

The strength of evidence in the individual trial outcomes reviewed was low to moderate; thus, Amick and colleagues advise that the findings should be interpreted with caution. Nevertheless, the evidence appears to suggest that the difference in treatment effects between second-generation antidepressants and CBT may be minimal.


The most efficient option for the treatment of first-episode MDD, therefore, may simply be to follow the patient’s preference. Studies show that patients who are allowed to follow their treatment preferences fare better than those whose preferences are misaligned with the treatment prescribed.3,4


1. Amick HR, Gartlehner G, Gaynes BN, et al. Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis. BMJ. 2015;351:h6019.
2. Xing S, Dipaula BA, Lee HY, et al. Failure to fill electronically prescribed antidepressant medications: a retrospective study. Prim Care Companion CNS Disord. 2011;13:pii: PCC.10m00998.
3. Raue PJ, Schulberg HC, Heo M, et al. Patients’ depression treatment preferences and initiation, adherence, and outcome: a randomized primary care study. Psychiatr Serv. 2009;60:337-343.
4. Mergl R, Henkel V, Allgaier AK, et al. Are treatment preferences relevant in response to serotonergic antidepressants and cognitive-behavioral therapy in depressed primary care patients? Results from a randomized controlled trial including a patients’ choice arm. Psychother Psychosom. 2011;80:39-47.

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