Drug | Initial daily oral dose* | Daily oral dose range* | Primary metabolism¶ | Effect on metabolism of other drugs¶ | Selected characteristics relevant to treatment of adults with GAD |
SSRI antidepressants Applies to all SSRIs: Onset of effect may be delayed 2 to 4 weeks or more. Adverse effects among the SSRIs include: Nausea, diarrhea, insomnia/agitation, somnolence, impaired sexual function, and hyponatremia. Adverse effects of individual agents are presented in a separate table in UpToDate. |
Citalopram | 10 mg | 10 to 40 mg | CYP3A4, 2C19 | None | - Lower risk of insomnia/agitation
- Few drug interactions
- Can prolong QT interval with increasing blood levels
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Escitalopram | 5 to 10 mg | 10 to 20 mg | CYP3A4, 2C19 | None | - Lower risk of insomnia/agitation
- Few drug interactions
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Sertraline | 25 to 50 mg | 50 to 200 mg | Limited (minor CYP2C9, 2D6, and 3A4) | None | - Greater risk of insomnia/agitation
- More frequent diarrhea and other gastrointestinal complaints
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Paroxetine | 10 to 20 mg | 20 to 50 mg | CYP2D6 | Inhibits 2D6 | - Mildly sedating
- Weakly anticholinergic
- Lower risk of insomnia/agitation
- Withdrawal symptoms if not tapered
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Fluoxetine | 10 to 20 mg | 20 to 60 mg | CYP2D6, 2C9, and several minor | Inhibits CYP2D6, 2C19 | - Greater risk of insomnia/agitation
- No withdrawal symptoms if not tapered
- Takes weeks to reach steady blood levels due to long half-life
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Fluvoxamine | 50 mg | 50 to 300 mg | CYP1A2, 2D6 | Inhibits CYP1A2, 2C19 | - Lower risk of insomnia/agitation
- Withdrawal symptoms if not tapered
- Significant drug interactions
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SNRI antidepressants Onset of effect and adverse effects of the SNRIs are similar to the SSRIs (refer to above). Adverse effects of individual agents are presented in a separate table in UpToDate. |
Duloxetine | 30 mg | 60 to 120 mg | CYP1A2, 2D6 | Inhibits CYP2D6 | - Greater risk of insomnia/agitation
- Useful for treatment of comorbid painful conditions
- Withdrawal symptoms if not tapered
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Venlafaxine (extended-release) | 75 mg | 75 to 225 mg | CYP2D6, 3A4 | None | - Greater risk of insomnia/agitation
- Increased blood pressure (primarily diastolic) and heart rate with increasing doses
- Useful for treatment of comorbid painful conditions
- Few drug interactions
- Withdrawal symptoms if not tapered
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Other |
Buspirone | 10 mg in divided doses | 10 to 60 mg in divided doses | CYP3A4 | None | - A nonbenzodiazepine anxiolytic
- Augmentation choice for partial response to antidepressant
- Slow onset and modest efficacy
- Lacks tolerance, dependence, and withdrawal
- Ineffective for comorbid major depression
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Gabapentin | 300 mg | 300 to 2400 mg in divided doses | Dependent on renal function for clearance | None | - A GABA analog calcium-channel modulator antiseizure medication
- Onset within days of starting treatment
- Sedation and dizziness
- Tolerance, dependence, and withdrawal possible
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Pregabalin | 50 mg in divided doses | 50 to 300 mg in divided doses | Dependent on renal function for clearance | None | - A GABA analog calcium-channel modulator antiseizure medication
- Onset within days of starting treatment
- Approved for treatment of anxiety in some countries (not United States)
- Sedation and dizziness
- Tolerance, dependence, and withdrawal possible
- Schedule V controlled substance in United States
- Many patients require >150 mg/day, up to 300 mg/day
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Mirtazapine | 15 mg | 15 to 60 mg | CYP1A2, 2D6, 3A4 | None | - An atypical antidepressant
- Alternate or augmentation choice for anxiety with insomnia
- Sedating; notably increases appetite
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Quetiapine | 25 to 50 mg | 50 to 300 mg | CYP3A4 | None | - An SGA
- Potential augmentation choice for partial response to antidepressant or alternate as monotherapy
- Sedation, extrapyramidal effects, weight gain, and metabolic side effects (refer to separate table on SGA adverse effects)
- Rarely tardive dyskinesia
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Hydroxyzine | 50 mg at bedtime | 25 to 50 mg three to four times per day as needed | None | None | - A sedating antihistamine with anxiolytic properties
- Augmentation option for treatment of insomnia
- Anticholinergic side-effects with increasing doses
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Imipramine | 75 mg in divided doses | 75 to 200 mg in divided doses | CYP2C19, 2D6 | None | - A tricyclic antidepressant
- Anticholinergic side effects
- Cardiotoxic in overdose
- May be poorly tolerated relative to SSRI and SNRI antidepressants
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