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  • The effectiveness of antidepressant medications is generally comparable between and within classes of medications, including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). Therefore, choose a medication largely based on the following:

    • Patient preference

    • Nature of prior response to medication

    • Safety, tolerability, and anticipated side effects

    • Co-occurring psychiatric or general medical conditions

    • Pharmacological properties of the medication (e.g., half-life, actions on cytochrome P450 enzymes, other drug interactions; consult the full guideline or a current drug database)

    • Cost

  • For most patients, a SSRI, a SNRI, mirtazapine, or bupropion is optimal.

  • In general, the use of MAOIs should be restricted to patients who do not respond to other treatments.

  • Table 2 provides the starting and usual doses of medications that have been shown to be effective for treating major depressive disorder.

  • If side effects occur, lowering the dose or changing to a different antidepressant should be considered. If these approaches are not effective, other strategies can be considered, as shown in Table 3.

  • When the medication is being changed to or from an MAOI, a washout period is essential (Table 4) to prevent a potentially lethal interaction: the serotonin syndrome.

  • The initial dose should be raised incrementally as tolerated until a therapeutic dose is reached or the patient achieves remission. Titration generally can be accomplished over initial weeks, but more time may be needed depending on development of side effects, the patient's age, and the presence of co-occurring medical and psychiatric conditions.

  • Improvement may be observed as early as the first 1–2 weeks and continue for up to 12 weeks. Remind patients who achieve some improvement during initial weeks that full benefit at a given dose may not be achieved until 4–8 weeks.

  • Some antidepressants can be lethal in overdose (e.g., ingestion of a 10-day supply of a tricyclic agent administered at a dose of 200 mg/day). Early on in treatment, it is prudent to dispense only small quantities of such medications and to keep in mind the possibility of hoarding. In patients who are suicidal, it may be preferable to employ an agent that is safer in overdose, such as an SSRI.

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Table 2. Dosing of Medications Shown to Be Effective in Treating Major Depressive Disordera

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Table 2. Dosing of Medications Shown to Be Effective in Treating Major Depressive Disordera
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Table 3. Potential Treatments for Side Effects of Antidepressant Medications

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Table Reference Number
Table 3. Potential Treatments for Side Effects of Antidepressant Medications
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Table 4. Required Washout Times between Antidepressant Trials

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Table Reference Number
Table 4. Required Washout Times between Antidepressant Trials
Table Reference Number
Table 2. Dosing of Medications Shown to Be Effective in Treating Major Depressive Disordera
Table Reference Number
Table 3. Potential Treatments for Side Effects of Antidepressant Medications
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Table 4. Required Washout Times between Antidepressant Trials

References

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