Article

Age Effects on Antidepressant-Induced Manic Conversion

Child Study Center, the Department of Psychiatry, Yale University School of Medicine, New Haven, CN 06520-7900, USA.
Archives of Pediatrics and Adolescent Medicine (Impact Factor: 4.25). 09/2004; 158(8):773-80. DOI: 10.1001/archpedi.158.8.773
Source: PubMed

ABSTRACT Antidepressant drug therapy can precipitate mania in vulnerable individuals, but little is known about the effects of age on this phenomenon.
To pharmacoepidemiologically evaluate the risk of conversion to mania by antidepressant class and patient age.
Using an administrative national database of more than 7 million privately insured individuals, linked outpatient and pharmacy claims were analyzed for mental health users aged 5 to 29 years (N = 87,920).
The proportion and cumulative hazard of manic conversion were analyzed by antidepressant class and subject age among children, adolescents, and young adults with an anxiety or nonbipolar mood disorder in the United States between January 1, 1997, and December 31, 2001. Manic conversion was defined as a new diagnosis of bipolar illness.
During median follow-up of 41 weeks (range, 8-251 weeks), manic conversion occurred in 4786 patients (5.4%). Multivariate analyses using time-dependent Cox proportional hazards models indicated that an increased risk of manic conversion was associated with antidepressant category vs no antidepressant exposure (hazard ratios: 2.1 for selective serotonin reuptake inhibitors, P<.001; 3.8 for "other" antidepressants, P<.001; and 3.9 for tricyclic antidepressants, P =.002). Antidepressant x age interactions revealed inverse age effects for selective serotonin reuptake inhibitors and other antidepressants (beta = -.05; P<.001 for both) but not for tricyclic antidepressants (beta = -.02; P =.25). Peripubertal children exposed to antidepressants were at highest risk of conversion (number needed to harm: 10 [95% confidence interval, 9-12] among 10- to 14-year-olds vs 23 [95% confidence interval, 21-25] among 15- to 29-year-olds).
Patient age is an effect modifier on the risk of antidepressant-associated manic conversion. Treatment with antidepressants is associated with highest conversion hazards among children aged 10 to 14 years.

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    • "In contrast to the findings of a greater rate of conversion in younger subjects, the conversion rate from depression to BP in our study increased across the age span in a linear manner (Fig. 1). It has been reported (Lim et al., 2005; Martin et al., 2004) that the rate of antidepressant switching is greatest in younger persons . However, data on the antidepressant conversion in younger subjects is relatively limited. "
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    Journal of Affective Disorders 06/2015; 185:123-128. DOI:10.1016/j.jad.2015.06.018 · 3.71 Impact Factor
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    • "Factors including previous mood-switching during antidepressant treatment, rapid-cycling (o4 recurrences/yr ), younger onset-age, presence of co-morbid anxiety or substance-use disorders, may contribute to risk of antidepressant-associated mood-switching but require further study (Ghaemi et al., 2010 ; Perlis et al., 2010 ; Angst et al., 2011 ; Biernacka et al., 2012 ; Cazard and Ferreri, 2012 ; Post et al., 2012 ; Tondo et al., 2012 ; Valentí et al., 2012). In addition, as suggested in the present metaanalysis , tricyclic antidepressants may have a higher risk of inducing mood-switches than most modern antidepressants , at least in adults, although SRI may have a higher risk among pre-pubertal juveniles (Martin et al., 2004 ; Baldessarini et al., 2005 ; Tondo et al., 2010). The impression that bupropion may have an especially low risk of inducing mood-switches may arise from its having been marketed, for safety, with dosing limits well below those found to be effective in its initial RCTs (Baldessarini, 2013). "
    03/2015; 13(1):102-112. DOI:10.1176/appi.focus.130119
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    • "Factors including previous mood-switching during antidepressant treatment, rapid-cycling (o4 recurrences/yr ), younger onset-age, presence of co-morbid anxiety or substance-use disorders, may contribute to risk of antidepressant-associated mood-switching but require further study (Ghaemi et al., 2010 ; Perlis et al., 2010 ; Angst et al., 2011 ; Biernacka et al., 2012 ; Cazard and Ferreri, 2012 ; Post et al., 2012 ; Tondo et al., 2012 ; Valentí et al., 2012). In addition, as suggested in the present metaanalysis , tricyclic antidepressants may have a higher risk of inducing mood-switches than most modern antidepressants , at least in adults, although SRI may have a higher risk among pre-pubertal juveniles (Martin et al., 2004 ; Baldessarini et al., 2005 ; Tondo et al., 2010). The impression that bupropion may have an especially low risk of inducing mood-switches may arise from its having been marketed, for safety, with dosing limits well below those found to be effective in its initial RCTs (Baldessarini, 2013). "
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