Assessment of Efficacy

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Overall, based on clinical experience and the available scientific data, SSRIs and TCAs may be considered useful for the treatment of depression in PD, and the agent that provides the best overall clinical benefit-to-risk profile should be selected (168). Amoxapine and lithium should be avoided, given the propensity of these agents to worsen motor symptoms and the availability of safer agents (169,170). Additionally, the nonselective MAO inhibitors (e.g., isocarboxazid, phenelzine, and tranylcypromine) should be avoided in levodopa-treated patients due to the risk of hypertensive crisis. Several antidepressants, such as bupropion, fluoxetine, fluvoxamine, nefa-zodone, and paroxetine, are potent in vivo inhibitors of various cytochrome P450 (CYP450) drug-metabolizing isoenzymes (171,172). These antidepressants may increase the risk for drug interactions.

The first step in treating a patient who fails to respond to treatment is to increase the dosage of the antidepressant. If a patient fails to respond to a maximal, tolerated therapeutic dosage, then the antidepressant should be discontinued and replaced by another from a different pharmacologic class. For example, if a patient fails to respond to an SSRI, a switch to a dual action antidepressant (e.g., duloxetine, venlafaxine) should be made. When anxiety is present with depression, there may initially be a slowed response to antidepressant therapy (13,173). Since depression is a potentially recurrent disorder, once depressive symptoms have improved or recovery has been achieved, it is recommended that maintaining treatment at the effective dose should continue for at least six months to reduce the risk for relapse. Persisting symptoms of concurrent anxiety have been found to increase the risk for relapse of depression (174).

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