From the Guidelines
The most effective antidepressant combinations typically involve pairing an SSRI or SNRI with another medication that has a different mechanism of action, such as SSRI + bupropion or SSRI + mirtazapine, to target multiple neurotransmitter systems and provide broader symptom relief. When selecting antidepressant combinations, it's essential to consider the individual's symptoms, medical history, and potential side effects. Some common combinations include:
- SSRI (e.g., sertraline 50-200mg daily) + bupropion (150-300mg daily)
- SSRI + mirtazapine (15-45mg at bedtime)
- SNRI (e.g., venlafaxine 75-225mg daily) + mirtazapine These combinations are often used after monotherapy with at least 2-3 different antidepressants has failed to provide adequate relief, as approximately 38% of patients do not achieve a treatment response during 6 to 12 weeks of treatment with second-generation antidepressants 1. It's crucial to start and adjust medications gradually to minimize side effects, and always consult a psychiatrist before combining antidepressants, as there can be risks of drug interactions or serotonin syndrome 1. Regular follow-ups are necessary to monitor effectiveness and any adverse effects. The choice of combination should be tailored to the individual's symptoms, medical history, and potential side effects, considering factors such as anxiety, insomnia, and pain, as evidence suggests that second-generation antidepressants do not differ significantly in efficacy, effectiveness, or quality of life for treating acute-phase MDD 1.
From the Research
Effective Combinations of Antidepressant Medications
The most effective combinations of antidepressant medications include:
- Augmenting SSRI/SNRIs with mirtazapine/mianserin, as recommended by 2
- Combining a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) with a dissimilar antidepressant, such as bupropion or mirtazapine, as discussed in 3
- Combining venlafaxine with selective serotonin reuptake inhibitors (SSRIs), as shown in 4 to be effective in patients with partial response to venlafaxine
- Combining olanzapine and fluoxetine, as approved for treatment-resistant depression, although its use may be limited by metabolic side-effects, as noted in 5
- Augmenting with certain second generation antipsychotics, such as quetiapine or aripiprazole, as identified in 5 as effective for treatment-resistant depression
Considerations for Combination Therapy
When considering combination therapy, clinicians should be cautious regarding pharmacokinetic and pharmacodynamic interactions, including the serotonin syndrome, as warned in 6 Clinicians should also be mindful of the potential for increased risk of pharmacokinetic drug-drug interactions and adverse effects, as noted in 2 Additionally, it is essential to consider the individual patient's needs and use a shared decision-making approach to guide treatment selection, as recommended in 5
Available Options for Treatment-Resistant Depression
Other effective strategies for treatment-resistant depression include: