From the Guidelines
First-line non-SSRI/SNRI antidepressant options for major depressive disorder include bupropion (Wellbutrin) and mirtazapine (Remeron), with selection based on symptom profile, side effect concerns, and comorbidities. These medications are particularly useful for patients who cannot tolerate or don't respond to SSRIs/SNRIs.
- Bupropion works by inhibiting dopamine and norepinephrine reuptake, typically started at 150 mg daily and titrated up to 300-450 mg daily in divided doses 1.
- Mirtazapine acts as an alpha-2 antagonist and serotonin modulator, usually started at 15 mg at bedtime and increased to 30-45 mg if needed 1. Second-line non-SSRI/SNRI options include:
- Tricyclic antidepressants such as nortriptyline (starting at 25 mg and titrating to 75-150 mg daily)
- Monoamine oxidase inhibitors (MAOIs) like phenelzine (starting at 15 mg three times daily, increasing to 60-90 mg daily)
- Agomelatine (a melatonergic antidepressant)
- Trazodone (often used at 50-150 mg for depression with insomnia) These medications have specific requirements and considerations, such as ECG monitoring for tricyclics and strict dietary restrictions for MAOIs, to minimize risks and ensure safe use 1. The choice of medication should be based on the individual patient's needs, including symptom profile, side effect concerns, and comorbidities, as well as the potential benefits and risks associated with each option 1.
From the FDA Drug Label
Antidepressants including but not limited to: Other MAOIs (e.g., (SSRIs) in and norepinephrine reuptake inhibitors (SNRIs) Tricyclic antidepressants Amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine
The first-line and second-line non-SSRI/SNRI antidepressant options for treating major depressive disorder include:
- Monoamine Oxidase Inhibitors (MAOIs): such as tranylcypromine
- Tricyclic antidepressants:
- Other antidepressants: such as amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine 2 2 2
From the Research
Non-SSRI/SNRI Antidepressant Options
The following non-SSRI/SNRI antidepressants are available for the treatment of major depressive disorder:
- Bupropion: a dopamine-norepinephrine reuptake inhibitor with no appreciable activity on serotonin concentrations in the central nervous system 3, 4
- Mirtazapine: enhances norepinephrine and serotonin neurotransmission by blocking the alpha-2 presynaptic adrenoceptors 3
- Trazodone: a 5-HT2A and 5-HT2C receptor antagonist and selective serotonin reuptake inhibitor 3
- Vortioxetine: a novel antidepressant that combines direct serotonin transporter inhibition and 5-HT1A receptor modulation 3
- Vilazodone: a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist 3
First-Line and Second-Line Treatment Options
These non-SSRI/SNRI antidepressants can be considered as first-line or second-line treatment options for major depressive disorder, depending on the patient's response and tolerability to the medication. For example, bupropion has been shown to be as efficacious as and have a similar tolerability profile to some SSRIs, but with less somnolence and sexual dysfunction 4. Switching to a different antidepressant, such as venlafaxine, may also be considered if there is an inadequate response to a first SSRI 5.
Augmentation and Adjunctive Strategies
In cases where there is an inadequate response to antidepressant therapy, augmentation and adjunctive strategies involving atypical antipsychotics, as well as off-label options including buspirone, stimulants, thyroid hormone, and lithium, may be considered 6. The efficacy of antidepressants for dysthymic disorder has also been demonstrated, with a larger margin of efficacy compared to major depressive disorder 7.