Abstract:
RATIONALE:The noradrenergic and dopaminergic systems are targets for antidepressants and are stimulated by serotonergic antidepressant drugs. The COMT enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (rs4680) influences the enzyme activity. Clinical studies on the effect of rs4680 on antidepressant response gave contrasting results. OBJECTIVES:We studied the effect of rs4680 on response to paroxetine antidepressant monotherapy at doses administered upon clinical need. MATERIALS AND METHODS:Fifty-five consecutively referred outpatients affected by a major depressive episode without psychotic features in course of major depressive disorder were administered paroxetine at a mean daily dose of 31.64 mg for 1 month. Changes in severity of depression were assessed with weekly Hamilton depression ratings and analyzed with repeated measures analysis of variance in the context of general linear model, taking into account potential confounding variables (age, sex, number of previous illness episodes, duration of current episode and paroxetine daily dose). RESULTS:rs4680 significantly interacted with time in affecting antidepressant response to paroxetine, with outcome being inversely proportional to the enzyme activity: better effects in Met/Met homozygotes, worse effects in Val/Val homozygotes and intermediate effects in heterozygotes. The effect became significant at the third week of treatment. Paroxetine daily dose was proportional to baseline severity, but did not influence outcome. CONCLUSIONS:This is the first study that reports a positive effect of rs4680 on response to selective serotonin reuptake inhibitors monotherapy in a Caucasian sample. Our findings support the hypothesis that factors affecting catecholaminergic neurotransmission might contribute to shape the individual response to antidepressants.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Benedetti F,Colombo C,Pirovano A,Marino E,Smeraldi Edoi
10.1007/s00213-008-1381-7subject
Has Abstractpub_date
2009-03-01 00:00:00pages
155-60issue
1eissn
0033-3158issn
1432-2072journal_volume
203pub_type
杂志文章abstract::In a phase II study the antidepressive effect of citalopram, a selective and potent serotonin reuptake inhibitor, was examined in 20 endogenously and three non-endogenously depressed hospitalized patients. Four endogenously depressed patients dropped out due to deterioration early in the treatment period. The remainin...
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1993-01-01 00:00:00
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更新日期:2006-09-01 00:00:00
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