Posted by SLS on August 25, 2009, at 16:43:19
In reply to Re: Post SSRI Sexual Dysfunction » Phil, posted by SLS on August 25, 2009, at 13:27:19
This is off-topic regarding post-SSRI sexual dysfunction, but related to long-term drug induced changes in neural function.
Treatment resistance is often a function of the number of prior drug exposures. We already knew this, but now it has been formalized in studies.
- Scott
----------------------------------------------------1: Neuropsychobiology. 2009;59(4):227-33. Epub 2009 Jul 2.Click here to read Links
Tachyphylaxis after repeated antidepressant drug exposure in patients with recurrent major depressive disorder.
Amsterdam JD, Williams D, Michelson D, Adler LA, Dunner DL, Nierenberg AA, Reimherr FW, Schatzberg AF.Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-3309, USA. jamsterd@mail.med.upenn.edu
OBJECTIVE: The aim of this post hoc analysis was to examine whether tachyphylaxis occurs after repeated courses of antidepressant drug therapy. METHOD: 276 patients with major depressive disorder (MDD) were treated with sertraline (150-200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. Logistic regression was used to test the hypothesis that an increase in prior antidepressant drug exposure is associated with a reduced responsiveness to sertraline therapy. RESULTS: The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy. CONCLUSION: This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials. Copyright 2009 S. Karger AG, Basel.
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1: J Affect Disord. 2009 May;115(1-2):234-40. Epub 2008 Aug 9.Click here to read Links
Does tachyphylaxis occur after repeated antidepressant exposure in patients with Bipolar II major depressive episode?
Amsterdam JD, Shults J.
Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-3309, United States. jamsterd@mail.med.upenn.edu
OBJECTIVE: Tachyphylaxis often refers to the loss of antidepressant efficacy during long-term treatment. However, it may also refer to the gradual loss of efficacy after repeated antidepressant exposures over time. The aim of this study was to examine the phenomenon of tachyphylaxis in patients with Bipolar II major depression treated with either venlafaxine or lithium. We hypothesized that a greater number of prior antidepressant exposures would result in a reduced response to venlafaxine, but not lithium, therapy. METHODS: 83 patients were randomized to treatment with either venlafaxine (n=43) or lithium (n=40). The primary outcome was a >or= 50% reduction in baseline Hamilton Depression Rating score. A detailed history of prior drug therapy was obtained. Logistic regression was used to test the hypothesis that prior antidepressant exposure was associated with reduced response to venlafaxine therapy. RESULTS: The mean number of prior antidepressant and mood stabilizer exposures was significantly higher in venlafaxine non-responders versus responders (p=0.02). There was no significant association between response to lithium and the number of prior antidepressant and mood stabilizer exposures (p=0.38). The odds of responding to venlafaxine or lithium therapy decreased with an increasing number of prior antidepressant exposures (p=0.04). Response was not significantly affected by the number of prior mood stabilizer exposures (p=0.30). Adjustment for clinical and demographic covariates sharpened the estimated impact of prior antidepressant exposure on treatment outcome. LIMITATIONS: This study was a post hoc exploratory analysis. The study was not specifically powered to test the hypothesis of an association between number of prior antidepressant drug exposures and response to venlafaxine or lithium therapy. CONCLUSION: These observations support earlier findings suggesting the presence of tachyphylaxis occurring after repeated antidepressant drug exposures. Possible mechanisms of tachyphylaxis may include genetic predisposition for non-response, physiological adaptation after repeated antidepressant exposures, and inherent illness and pharmacokinetic heterogeneity
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: Am J Psychiatry. 1992 Dec;149(12):1727-9.Click here to read LinksComment in:
Am J Psychiatry. 1993 Nov;150(11):1756.
Am J Psychiatry. 1994 Oct;151(10):1522.Lithium-discontinuation-induced refractoriness: preliminary observations.
Post RM, Leverich GS, Altshuler L, Mikalauskas K.Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892.
The authors used a systematic life-chart methodology to observe four patients with bipolar disorder in whom long periods (6-15 years) of effective lithium prophylaxis were followed by relapses on lithium discontinuation. Once the drug was reinstituted, it was no longer effective. The incidence, predictors, and mechanisms underlying this phenomenon all require further systematic study. The current preliminary observations suggest an additional reason for caution when lithium discontinuation in the well-maintained patient is considered.
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poster:SLS
thread:913953
URL: http://www.dr-bob.org/babble/20090818/msgs/914048.html