Version May 2024
| Drug | Starting dose | Suggested dose range | Role | Precautions¶ |
| Psychostimulants | ||||
| Methylphenidate (immediate release) | 2.5 mg orally each morning and noon | 5 to 10 mg orally each morning and noon | Applies to methylphenidate, dextroamphetamine, and modafinil: Useful for treatment of depression in patients with life expectancy of weeks to months, or requiring prompt relief of symptoms including apathy, cognitive impairment, low energy, anorexiaΔ, and hypersomnia. Counteracts opioid associated sedation. Onset of action 24 to 48 hours. Titrate dose upward as needed after 1 to 2 days. | Applies to methylphenidate, dextroamphetamine, and modafinil: Insomnia, restlessness, agitation, palpitations, increased blood pressure, anorexiaΔ, tremor, dry mouth. Risk of cardiac decompensation in patients with heart disease. Give doses early in the day; some patients may need an additional half dose of methylphenidate in late afternoon. |
| Dextroamphetamine | 5 mg each morning | 5 to 15 mg orally each morning and noon | ||
| Modafinil | 100 mg each morning | 200 mg orally each morning | ||
| Selective serotonin reuptake inhibitors (SSRIs)◊ | ||||
| Citalopram | 10 mg per day | 20 to 40 mg per day§ | Applies to citalopram and escitalopram: Effective for anxiety, generally well-tolerated, non-sedating, low risk of sleep disturbance or sexual side effects. Comparatively few significant drug interactions. | Applies to citalopram: Dose related risk of QT prolongation. Mild discontinuation symptoms may occur absent tapering. |
| Escitalopram | 5 mg per day | 10 to 20 mg per day | Applies to escitalopram: Mild discontinuation symptoms may occur absent tapering. | |
| Sertraline | 25 mg per day | 50 to 100 mg per day | Non-sedating, low risk of insomnia, lacks significant cardiovascular effects. | More frequent gastrointestinal symptoms including diarrhea. Variable oral bioavailability. Oral solution contains alcohol. Discontinuation symptoms may occur absent tapering. |
| Fluoxetine | 10 mg per day | 20 to 40 mg per day | 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. | Prolonged half-life and active metabolites require weeks to reach steady-state, prolonging time needed to evaluate effect of dose adjustment and complicating washout and withdrawal. Less well tolerated than sertraline. |
| Paroxetine | 10 mg per day in evening | 20 to 40 mg per day | Sedating; possibly useful for depressed or anxious patients with insomnia. | Weakly anticholinergic. May cause constipation, dry mouth, or drowsiness. Associated with more severe discontinuation symptoms in absence of tapering. |
| Serotonin norepinephrine reuptake inhibitors (SNRIs) | ||||
| Venlafaxine (extended release) | 37.5 mg per day | 75 to 225 mg per day | 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. | Insomnia. May cause dose-dependent increases in blood pressure (primarily diastolic) and heart rate. Associated with more severe discontinuation symptoms in absence of tapering. |
| Duloxetine | 10 to 20 mg per day | 20 to 60 mg per day | Useful for patients with comorbid painful conditions such as diabetic neuropathy, chemotherapy-induced neuropathy, or chronic pain. Mildly sedating. Low risk of insomnia. | Significant drug interactions. |
| Atypical antidepressants | ||||
| Bupropion (sustained release) | 75 mg in morning initially then twice daily | 150 mg in morning and mid-afternoon (twice daily) | Activating 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. | Avoid in seizure disorders and depressed patients with agitation. Dose-dependent increase in diastolic blood pressure. Insomnia, constipation, dry mouth, dizziness. |
| Mirtazapine | 7.5 mg every evening | 15 to 60 mg every evening | Sedating; useful for patients with insomnia or who may benefit from weight gain. Appetite stimulant and antinausea effects can be noted within days. | Drowsiness, weight gain. Prolonged half-life and active metabolites. Risk of accumulation with renal and/or hepatic insufficiency. |
| Trazodone | 12.5 to 25 mg taken 30 to 60 minutes before bedtime for hypnotic effect | 25 to 100 mg taken 30 to 60 minutes before bedtime for hypnotic effect | Used in low doses as an adjunct to SSRI for treatment of insomnia. | Sedation, orthostatic hypotension, nausea. Residual daytime sedation and cognitive impairment. |
| Tricyclic antidepressants (TCAs) | ||||
| Desipramine | 10 mg every morning | 25 to 150 mg every morning or in two divided doses | Mild stimulant effects may be useful for depressed patients with low energy and hypersomnia who have not responded to first line antidepressants. Useful for patients with comorbid painful conditions such as diabetic neuropathy. Established therapeutic serum concentration 125 to 300 ng/mL. | Applies to desipramine and nortriptyline: Not well tolerated in palliative care patients due to anticholinergic effects including dry mouth, delirium, constipation, urinary retention, or altered vision. May be fatal in overdose. Can cause arrhythmia or orthostatic hypotension. Significant drug interactions. |
| Nortriptyline | 10 mg every evening | 10 to 100 mg every evening or in two divided doses | Mildly sedating. Taken at bedtime for depressed patients with insomnia. May be useful for melancholic, anxious, depressed patients who have not responded to first-line antidepressants. Useful for patients with comorbid painful conditions such as diabetic neuropathy. Established therapeutic serum concentration 50 to 150 ng/mL. | |
SSRIs: selective serotonin reuptake inhibitors.
* The onset of action for psychostimulants is generally faster than that for conventional antidepressants (<24 hours versus 4 to 8 weeks).
¶ For additional information on specific side effects, refer to table on side effects of antidepressant medications.
Δ Apathetic patients without appetite, who respond to stimulant medications, generally have an improvement in appetite.
◊ In general, SSRIs associated with few drug interactions; easy to titrate, minimal cardiac side effects.
§ Maximum recommended daily dose of citalopram is 20 mg for patients >60 years of age, with significant hepatic insufficiency, or taking interacting medications that can increase citalopram levels.
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