| Drug | Starting dose | Suggested dose range | Precautions* | Potential advantages |
| Selective serotonin reuptake inhibitors (SSRIs)¶ | ||||
| Escitalopram | 5 mg every morning or every evening | 5 to 20 mg daily | Mild discontinuation symptoms may occur absent tapering. | Applies to escitalopram and citalopram: Generally well tolerated. Non-sedating, low risk of sleep disturbance, comparatively few significant drug interactions. Good choice for initial treatment of depression in most older adults. |
| Citalopram | 10 mg every morning or every evening | 10 to 20 mgΔ daily | Dose-related risk of QT prolongation¶Δ. Mild discontinuation symptoms may occur absent tapering. | |
| Sertraline | 12.5 to 25 mg every morning | 25 to 200 mg daily | More frequent gastrointestinal symptoms including diarrhea. Variable oral bioavailability. Oral solution contains alcohol. Discontinuation symptoms may occur absent tapering. | Non-sedating, low risk of insomnia, lacks significant cardiovascular effects. Good choice for initial treatment of depression in most older adults. |
| Fluoxetine | 5 to 10 mg every morning | 5 to 60 mg daily | Activating. Significant drug interactions. Prolonged half-life and active metabolites require weeks to reach steady state, prolonging time needed to evaluate effect of dose adjustment and complicating wash-out and withdrawal. | Activating effect may be useful for treatment of depressed patients with low energy or hypersomnia. Tapering upon discontinuation is not needed due to long half-life. |
| Paroxetine | 10 mg every evening | 10 to 40 mg every evening | Weakly anticholinergic. May cause constipation, dry mouth, or drowsiness. Associated with more severe discontinuation symptoms in absence of tapering. | Useful for patients with insomnia. Moderate half-life with no active metabolites. |
| Fluvoxamine | 25 mg every evening | 25 to 200 mg every evening | Significant drug interactions. Short half-life associated with discontinuation symptoms in absence of tapering. | May be useful for patients with insomnia. |
| Serotonin-norepinephrine reuptake inhibitors (SNRIs)◊ | ||||
| Venlafaxine (extended release) | 37.5 mg once daily | 75 to 225 mg once daily | Applies to venlafaxine and desvenlafaxine: Activating. May cause dose-dependent increases in blood pressure (primarily diastolic) and heart rate. Monitor blood pressure regularly. Gastrointestinal symptoms (eg, nausea) may be more prominent with immediate-release venlafaxine. Associated with discontinuation symptoms absent tapering. Taper desvenlafaxine by increasing interval between doses. | Applies to venlafaxine and desvenlafaxine: Activating effect may be useful for treatment of melancholic depressed patients with low energy or hypersomnia. Useful for patients with comorbid painful conditions such as diabetic neuropathy. |
| Venlafaxine (immediate release) | 18.75 to 37.5 mg every morning or twice daily | 75 to 150 mg twice daily | ||
| Desvenlafaxine | 50 mg every morning CrCl <30 mL/min: 50 mg every other day | 50 mg every morning CrCl <30 mL/min: 50 mg every other day | ||
| Duloxetine | 10 to 20 mg daily | 20 to 60 mg once daily | Significant drug interactions. | Mildly sedating. Low risk of insomnia. Useful for patients with comorbid painful conditions such as diabetic neuropathy or chronic pain. |
| Atypical antidepressants◊ | ||||
| Mirtazapine | 7.5 mg every evening | 15 to 60 mg every evening | Prolonged half-life and active metabolites. Risk of accumulation with renal and/or hepatic insufficiency. Dose reductions necessary. Drowsiness, weight gain. Rare reports of agranulocytosis. | Sedating. Low risk of sexual dysfunction. Appetite stimulant and antinausea effects can be noted within days. Useful for patients with insomnia or who may benefit from weight gain. |
| Bupropion sustained release | 75 mg in morning initially then twice daily | 150 mg in morning and midafternoon (twice daily) | Avoid in seizure disorders and depressed patients with agitation. Dose-dependent increase in diastolic blood pressure. May worsen insomnia. | Stimulant effect may be useful for treatment of depressed patients with low energy and apathy. Low risk of cognitive toxicity. Dopaminergic action may be advantageous for depressed patients with Parkinson disease. |
| Vilazodone | 10 mg once daily with food for seven days or more | 20 to 40 mg once daily with food | Take with food to assure bioavailability. Diarrhea, nausea, vomiting, dizziness, insomnia. Significant drug interactions via CYP 3A4 require dose adjustment. | Low incidence of weight gain or sexual dysfunction. Role in therapy for treatment of depressed older adults or adults with comorbid illness is not yet defined. |
| Trazodone | 12.5 to 25 mg taken 30 to 60 minutes before bedtime for hypnotic effects | 25 to 100 mg taken 30 to 60 minutes before bedtime for hypnotic effects; antidepressant effects require higher doses | Sedation, orthostatic hypotension, nausea. Residual daytime sedation and cognitive impairment. Reports of hyponatremia. | Used in low doses as adjunct to SSRI for treatment of insomnia. |
| Tricyclic antidepressants (TCAs)§ | ||||
| Nortriptyline | 10 mg every evening | 10 to 100 mg every evening or in two divided doses | Applies to nortriptyline and desipramine: May be poorly tolerated by medically ill and older adults due to anticholinergic effects that include dry mouth, constipation, urinary retention, or altered vision (eg, avoid in prostatic disease or narrow angle glaucoma). May be fatal in overdose. Potentially cardiotoxic, can cause arrhythmia or orthostatic hypotension. Significant drug interactions. | Applies to nortriptyline: Established therapeutic serum concentration 50 to 150 ng/mL. Mildly sedating. Taken at bed time for depressed patients with insomnia. May be useful for melancholic, anxious, depressed patients who have not responded to first- and second-line antidepressants. |
| Desipramine | 10 mg every morning | 25 to 150 mg every morning or in two divided doses | Applies to desipramine: Established therapeutic serum concentration 125 to 300 ng/mL. Mild stimulant effects may be useful for depressed patients with low energy and hypersomnia who have not responded to first- and second-line antidepressants. | |
