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SUBSTITUTION

Substitution refers to the practice of stopping one active antidepressant before introducing a second, active antidepressant. Indeed, substitution is the most commonly used strategy for patients who prove to be intolerant to the first medication prescribed.

Regardless of the antidepressant being substituted, the following conditions and/or situations necessitate caution when changing from one antidepressant to another:

1. Age: Older patients over the age of 65 are more susceptible to drug interactions and toxicities; as such, the recommended "washout" period (during which one drug is stopped and the second one initiated) should be observed (See Table).
2. Previous side effects: Substitution should also be approached with caution in patients who have developed significant side effects to other antidepressant medications.
3. Concurrent medications: Again, introduce the new antidepressant therapy with caution in patients who are taking concurrent non-antidepressant medications.
4. Medically ill patients: Caution must also be used when introducing antidepressant therapy in patients who are medically ill.

In each of these situations, the best approach is to either elongate the washout period, or start the second antidepressant slowly, at a very low dose, titrating the second drug up to therapeutic levels gradually to avoid precipitating any adverse effects or interactions.

These cautions aside, it may be necessary to shorten the process of substitution in any patient in whom the risk of suicide is heightened. Thus, especially in the severely depressed individual, it is reasonable to take more risks in terms of potential side effects or drug interactions in order to avoid increased suicidal risk from long washout periods free of any antidepressant.

Alternatively, practitioners should consider combination therapy if patients are likely to revert to baseline symptoms during the washout period, with subsequent escalation in suicide risk.

First Drug Second Drug Washout Responses

TCA TCA No washout period; Dose equivalent amounts may be substituted. Anticipated response rate: 20 – 30%

TCA MAOI No washout period; however, TCA dose may be lowered if caution is needed. Exception clomipramine (Anafranil) can lead to lethal reaction if followed by an MAOI. Anticipated response rate: 50 – 60%; higher with anxious atypical depression

TCA SSRI No washout period; with exception of clomipramine (Anafranil) which requires a two week washout period. SSRIs increase TCA blood levels; to compensate, lower TCA doses over 3-7 days prior to adding in an SSRI Anticipated response rate: 50 – 60%

MAOI TCA Two week washout period. Anticipated response rate 50 – 60 %

MAOI MAOI Two week washout period. Anticipated response 50 – 60%

RIMA TCA Minimum 48 hour washout period. Anticipated response rate: unknown

RIMA MAOI Minimum 48 hour washout period. Anticipated response rate: unknown

RIMA SSRI 48 hour washout period, caution with paroxetine (Eli Lilly Medical recommends a 2 week washout period prior to switching from a RIMA to a SSRI such as fluoxetine. Anticipated response rate: unknown

SSRI SSRI No washout period required. Anticipated response rate: unknown

SSRI TCA No washout period required. Introduce TCA at lower dose because of drug interactions. Anticipated response rate 50-60%

SSRI MAOI 2-5 week washout period, depending upon the half-life of SSRI. The longer the half-life, the longer the washout period. (Fluoxetine) requires a 5 week washout; other SSRIs are closer to 2 weeks. Anticipated response rate: Unknown

SSRI RIMA No washout period required. More caution required when using paroxetine. (Eli Lilly Medical recommends a 5 week washout period prior to switching from an SSRI such as fluoxetine to a RIMA.) Anticipated response rate: Unknown

continue : combining antidepressants

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Reviewed: 02/2006