Patients with depression treated with a combination of antidepressants appear to experience greater improvement than those treated with just one medication, according to a meta-analysis in JAMA Psychiatry.
Especially effective are the combination of “reuptake inhibitors” and α2-autoreceptor antagonists. Reuptake inhibitors include selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine or sertraline; serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine or duloxetine; or tricyclic antidepressants, such as desipramine or nortriptyline. The medications mianserin and mirtazapine are two examples of α2-autoreceptor antagonists.
Jonathan Henssler, M.D., of Cologne Medical School, Germany, and colleagues analyzed 39 randomized, controlled trials comparing combinations of antidepressant medication with treatment with just one medication. The studies, which included 6,751 patients, were published between 1977 and 2020. The primary outcome was the difference in treatment efficacy (symptom improvement) between combination therapy and monotherapy. Most studies measured depression symptoms using the Montgomery-Asberg Depression Rating Scale or the Hamilton Depression Scale. Secondary outcomes included remission from depression (symptoms below clinical threshold), response to treatment (50% or better symptom improvement) and tolerability (number of patients who dropped out of studies).
The researchers found that combination treatment was significantly superior to monotherapy in treatment efficacy, response to treatment, and depression remission. There was no difference between combination or monotherapy in terms of patient tolerability.
Henssler and colleagues also analyzed specific drug combinations and found that combining a reuptake inhibitor with an α2-autoreceptor antagonist was superior to other combinations of medications, both for patients new to medication and those who did not respond to another medication. In contrast, combinations involving bupropion were not superior to monotherapy as a first-line treatment but were slightly more effective when given to patients who did not respond to another medication.
“Physicians should be aware that combinations of reuptake inhibitors … with α2-autoreceptor antagonists are a potent treatment option, associated with superior outcomes relative to monotherapy,” the researchers concluded. “Clinicians can inform patients that on average this advantage does not come at the cost of lower tolerability… .”
For more information, see the Psychiatric News special report “Management of Major Depression: Yesterday, Today and Tomorrow.”
(Image: iStock/katleho Seisa)
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