USMLE STEP 3 MCQ 26:A newly diagnosed patient with depression


A newly diagnosed patient with depression is treated with serotonin selective reuptake inhibitors. A four week drug trial is performed but the patient shows only a partial response. The physician suspects that this is because the patient is a known 'rapid metabolizer' .
An appropriate next step should now include


a) giving a second larger loading dose and increasing the maintenance dose
b) giving a second larger loading dose only
c) increasing the maintenance dose only
d) stopping the medication
e) decreasing the maintenance dose


Correct Answer: C



If the depressive episode has had a partial response but not a full remission after a 4-week trial, then a dose increase with all of the antidepressants except TCAs is a reasonable approach. This recommendation even holds true for the serotonin selective reuptake inhibitors despite their flat dose-response curve because the patient may be a rapid metabolizer and hence may develop plasma drug levels too low for an optimal response. The patient should receive a 4-week trial of this higher dose, assuming that his/her condition is improved sufficiently to warrant this disciplined approach and that s/he is agreeable to it. An increased maintenance dose would be the most rational drug regimen for fast metabolizers. A loading dose is often given because a drug is heavily bound to plasma proteins; this quickly saturates plasma proteins so that therapeutic levels of free drug will be available rapidly. The amount of plasma protein binding is not affected by the rate of drug metabolism, so increasing the loading dose is unnecessary. The maintenance dose is given to maintain adequate levels of free drug in the plasma. Drug clearance is accelerated in rapid metabolizers, and free drug levels decline quickly. Increasing the maintenance dose can help prevent this decline.

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