As a clinical pharmacist, you should individualize the choice of antidepressant combos. So the question is, does it make sense to combine antidepressants?
Yes, sometimes. Fewer than half of patients with depression achieve remission with one first-line medication (SSRI, SNRI, etc). Adding a different medication class may work faster than switching, and help treat other symptoms or conditions. But there’s no “BEST” next step and data are limited.
Consider SWITCHING antidepressants if patients don’t respond after 4 to 6 weeks at an optimized dose, or it’s not tolerated. With a partial response, individualize options to AUGMENT, based on side effects and interactions. Often add bupropion (Abstain SR, Wellbutrin SR) to an SSRI or SNRI, especially if patients have fatigue or low sexual desire. But lean away from bupropion in patients with agitation, since it’s activating. Or add mirtazapine (Remeron, Mirtimash) to an SSRI or SNRI, especially in patients with insomnia or poor appetite. But avoid mirtazapine if weight gain is a concern.
Lean away from an SSRI plus SNRI. Data are scant, benefit seems less likely due to similar mechanisms and this combo may be riskier. Continue to consider adding low-dose trazodone (Trittico) for insomnia, or a low-dose tricyclic for insomnia, headaches, or neuropathic pain. But low doses aren’t likely to improve depression.
When patients come to you on an antidepressant combo, or you get refill requests for a combo, confirm it’s intended instead of a switch. Counsel to report symptoms of serotonin syndrome (sweating, tremor, etc) if patients take more than one serotonergic drug. Most cases occur within a day or so of adding a medication or a dose increase.
REFERENCES
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Henssler J, Alexander D, Schwarzer G, Bschor T, Baethge C. Combining Antidepressants vs Antidepressant Monotherapy for Treatment of Patients With Acute Depression: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2022 Apr 1;79(4):300-312. Available at: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2789300
Ruberto VL, Jha MK, Murrough JW. Pharmacological Treatments for Patients with Treatment-Resistant Depression. Pharmaceuticals (Basel). 2020 Jun 4;13(6):116. Available at: https://www.mdpi.com/1424-8247/13/6/116
Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, Hasnain M, Jollant F, Levitt AJ, MacQueen GM, McInerney SJ, McIntosh D, Milev RV, Müller DJ, Parikh SV, Pearson NL, Ravindran AV, Uher R; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016 Sep;61(9):540-60. Available at: https://journals.sagepub.com/doi/10.1177/0706743716659417
McCarron RM, Shapiro B, Rawles J, Luo J. Depression. Ann Intern Med. 2021 May;174(5):ITC65-ITC80. Available at: https://pubmed.ncbi.nlm.nih.gov/33971098
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