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Patients with major depressive disorder (MDD) had a wide spectrum of symptomatic responses to antidepressants, a large meta-analysis indicated.

With data pooled from 87 randomized trials, response variability was 14% higher among those on an antidepressant compared with placebo (coefficients of variation ratio 1.14, 95% CI 1.11-1.17, P<0.001), reported Marta Maslej, PhD, of the Centre for Addiction and Mental Health in Toronto, and colleagues in .

"This suggests that there are systematic differences in the responses to antidepressants beyond the nonspecific outcomes seen in placebo response and provides empirical evidence to back the long-held belief that differences exist between individuals diagnosed with MDD that may allow for more personalized pharmacological treatment approaches," pointed out Gerard Sanacora, MD, PhD, of Yale University School of Medicine in New Haven, Connecticut, in an .

Maslej's group also found certain classes of antidepressants showed significantly less patient variability in response than others among the over 17,500 participants with MDD included.

Selective serotonin reuptake inhibitors (SSRIs) -- including citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), and vilazodone (Viibryd) -- showed significantly less response variability in patients than noradrenergic agents, including amitriptyline (Elavil) and reboxetine (Edronax) (coefficients of variation ratio 0.88, 95% CI 0.80-0.97, P=0.01).

Other types of antidepressants, such as agomelatine (Valdoxan, Melitor, Thymanax), mirtazapine (Remeron), and trazodone (Desyrel), also showed less variability in response versus noradrenergic agents (coefficients of variation ratio 0.87, 95% CI 0.79-0.97, P<0.001).

However, serotonin and norepinephrine reuptake inhibitors (SNRIs), such as desvenlafaxine (Khedezla, Pristiq) and venlafaxine (Effexor), as well as the norepinephrine dopamine reuptake inhibitor (NDRI) bupropion (Wellbutrin), both had similar profiles of response variability among patients as noradrenergic agents did.

Maslej and co-authors found in a sensitivity analysis that more recent trials tended to show less variability in patient responses to antidepressants compared with older literature. They found that the coefficient of variation response dropped by 0.005 (95% CI, 0.002-0.008, P=0.003) for each year a trial was more recently published.

As a whole, the 83 trials included in the meta-analysis ranged in publication year from 1979 to 2014. One possible explanation for this is how antidepressant trial methods have improved over time, the researchers suggested, explaining that more recent trials have larger sample sizes, use blinding, and are less biased than those published 40 years prior.

Another interesting finding was that baseline severity of a patient's depression had no significant effect on the variability in response to antidepressants. Sanacora called the finding surprising, but "comforting ... providing evidence supporting the existence of a clinically meaningful heterogeneity within the diagnosis of MDD and the possibility of better targeting the choice of antidepressant medications to individual patients."

However, Sanacora stressed that the meta-analysis doesn't answer practical questions for the prescribing healthcare provider, stating that "as clinicians, we should take little solace in the findings, because they bring little new information to enlighten clinical practice. The study was not designed to and is unable to provide any specifics on how to better diagnose depressive disorders or personalize antidepressant treatments."

"In the future, it would be interesting to parse out the specific associations of symptoms with known variability in response to the various classes of antidepressant drugs (ie, the specific symptoms of sleep and appetite that would likely be associated with different responses to the various treatments)," he said.

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