Potential reasons to select a non-SSRI antidepressant

Clinical characteristic	Potential antidepressant choice
Severe insomnia or other need for a sedating agent	Mirtazapine
Severe hypersomnia/lack of energy or other need for less sedating agent	Bupropion^*¶ Reboxetine Vilazodone
Depression-related weight loss or other need for agent that can cause weight gain	Mirtazapine^Δ
Desire for agent that is weight neutral or causes weight loss	Bupropion^*¶
Desire for agent that concurrently aids in smoking cessation	Bupropion^¶
Desire to treat concomitant chronic neuropathic pain	SNRI (eg, duloxetine, milnacipran) Tricyclic antidepressants^◊
Prior remission with agent from a different class	Previously used antidepressant
Prior or expected inability to tolerate SSRI-related sexual dysfunction	Bupropion^¶ Mirtazapine Vortioxetine Vilazodone
Severe depression	SNRI (or SSRI)^§ Tricyclic antidepressants or mirtazapine

For initial treatment of most individuals with mild to moderate depression, we suggest an SSRI, typically escitalopram or sertraline. SSRIs optimize efficacy and safety for most patients. However, efficacy for mild to moderate depression is similar within and across classes of antidepressants, and other antidepressants may be an attractive choice in certain circumstances. Common reasons for choosing a non-SSRI medication include undesirable medication side effects (eg, risk of erectile dysfunction with SSRIs), patient comorbidities that non-SSRIs can address (eg, neuropathic pain), patient symptoms that a specific antidepressant might treat (eg, using mirtazapine in a patient with weight loss), and history of prior antidepressant use.

SNRI: serotonin-norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor.

* Some SSRIs can be used in this clinical situation; fluoxetine is the least sedating.

¶ Bupropion is contraindicated in individuals with seizure disorder or increased risk of seizure, including anorexia nervosa and bulimia.

Δ Paroxetine is an SSRI that can be used in this clinical situation.

◊ Tricyclic antidepressants are effective for chronic neuropathic pain, but adverse effects and safety concerns limit their use in initial management.

§ Both SNRIs and SSRIs are reasonable first-line options for treating severe major depression.

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Potential reasons to select a non-SSRI antidepressant