957__969__

Psychiatr. Pol. 2018; 52(6): 957–969

 

Jay D. Amsterdam, Lorenzo Lorenzo-Luaces
 

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Summary
Objective. This study examined the presence of increased pharmacodynamic tolerance with reduced effectiveness following repeated antidepressant trials over the course of the affective
illness in subjects with treatment-responsive bipolar II depression.
Methods. Data were derived from the open-label phase of a prospective, randomized, placebo-controlled trial of long-term fluoxetine versus lithium monotherapy in 148 subjects >=18 years old with treatment-responsive bipolar II depression, who were initially administered open-label fluoxetine monotherapy for 12 weeks. Response was defined as >=50% reduction in baseline Hamilton Rating Scale for Depression (HRSD) score, and remission was defined as a final HRSD score =<8.
Results. Subjects reported a mean (SD) total of 1.61 (1.85) (range: 0–9) prior adequate, antidepressant trials over the course of their affective illness, before study enrollment. There was a 25% reduction in the likelihood of fluoxetine response (p < 0.01) and a 22% lower likelihood of remission (p = 0.02), respectively, with each increase in the number of prior antidepressant treatment trials over the illness course. There was no clinically meaningful correlation between fluoxetine response or remission and any other baseline clinical or demographic variable. Thus, only the number of prior antidepressant trials meaningfully impacted the likelihood of fluoxetine response or remission.
Limitations. This was an exploratory study of post hoc, analyses, and the trial was not specifically powered to test the development of increased pharmacodynamic tolerance. Disease heterogeneity or inter-individual differences in antidepressant responsiveness may have influenced fluoxetine effectiveness.
Conclusion. These results confirm prior observations of an increased pharmacodynamic tolerance after repeated antidepressant administration, resulting in a step-wise loss of antidepressant effectiveness over the course of the illness.


ISSN 0033-2674 (PRINT)

ISSN 2391-5854 (ONLINE)


Psychiatria Polska
is an Open Access journal:
Creative Commons: CC-BY
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Zadanie finansowane
w ramach umowy
nr 739/P-DUN/2018
ze środków MNiSW
przeznaczonych
na działalność
upowszechniającą naukę



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