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Drug properties and doses of antidepressants in older adults and medically ill

Drug properties and doses of antidepressants in older adults and medically ill
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.

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 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

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.

Activating effect may be useful for treatment of patients with melancholic depression or 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.
Levomilnacipran 20 mg daily 40 to 120 mg once daily

May cause dose-dependent urinary hesitancy or erectile dysfunction.

May cause dose-dependent increases in heart rate and systolic and diastolic blood pressure. Monitor blood pressure regularly. Dose adjustment with chronic kidney dysfunction.		 Generally well tolerated.
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 patients with low energy and apathy. Low risk of cognitive toxicity. Dopaminergic action may be advantageous for patients with comorbid 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 older adults with depression or adults with comorbid illness and depression 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.
 For nortriptyline:
  • Established therapeutic serum concentration 50 to 150 ng/mL.
  • Mildly sedating. Taken at bedtime for patients with depression and insomnia.
  • May be useful for patients with melancholic or anxious depression who have not responded to first- or second-line antidepressants.
Desipramine 10 mg every morning 25 to 150 mg every morning or in two divided doses For desipramine:
  • Established therapeutic serum concentration 125 to 300 ng/mL.
  • Mild stimulant effects may be useful for patients with low energy and hypersomnia who have not responded to first- or second-line antidepressants.

CYP: cytochrome.

* Specific interactions of antidepressants with other medications may be determined using the drug interaction program included with UpToDate.

¶ For additional information, refer to UpToDate content on major depressive disorder in adults and SSRIs.

Δ Maximum recommended daily dose of citalopram is 20 mg for patients >60 years of age, with significant hepatic insufficiency, or taking other medications that can increase citalopram levels.

◊ For additional information, refer to UpToDate content on SNRIs and other antidepressants for treating adults with depression.

§ For additional information, refer to UpToDate content on tricyclic and tetracyclic antidepressants for treating adults with depression.
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