Early Improvement Under Mirtazapine and Paroxetine Predicts Later Stable Response and Remission With High Sensitivity in Patients With Major Depression
J Clin Psychiatry 2003;64(4):413-420
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Objective: Current clinical knowledge holds that
antidepressants have a delayed onset of efficacy. However, the
delayed onset hypothesis has been questioned recently by survival
analytical approaches. We aimed to test whether early improvement
under antidepressant treatment is a clinically useful predictor
of later stable response and remission.
Method: We analyzed data from a randomized
double-blind controlled trial with mirtazapine and paroxetine in
patients with major depression (DSM-IV). Improvement was defined
as a 17-item Hamilton Rating Scale for Depression (HAM-D-17)
score reduction of >= 20%. Stable response was defined as
>= 50% HAM-D-17 score reduction at week 4 and week 6, and
stable remission as a HAM-D-17 score of <= 7 at week 4 and
week 6. Sensitivity, specificity, positive predictive value
(PPV), and negative predictive value (NPV) were calculated.
Results: Improvement occurred in a majority of
the analyzed patients within 2 weeks (mirtazapine: 72.7% of 109
patients; paroxetine: 64.9% of 103 patients). Early improvement
was a highly sensitive predictor of later stable response or
stable remission for both drugs. NPV approached maximum values as
early as week 2 for mirtazapine and week 3 for paroxetine. After
2 weeks of treatment with mirtazapine and 3 weeks with
paroxetine, almost none of the patients who had not yet improved
became a stable responder or stable remitter in the later course.
Conclusion: Our results strongly suggest that
early improvement predicts later stable response with high
sensitivity. These empirically derived data question the delayed
onset hypothesis for both antidepressants tested and provide
important clinical clues for an individually tailored