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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_450"
                     title="SSRI and Tamoxifen Increase Mortality Risk (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/18376?impressionId=1265778303677"
                     
      Overlapping use of tamoxifen and the antidepressant paroxetine (Paxil) significantly increases the risk of breast cancer mortality, data from a large cohort of breast cancer patients showed.&lt;br&gt;
&lt;br&gt;The excess breast-cancer mortality risk ranged as high as 91%, depending on the duration of simultaneous use, researchers reported online in &lt;em&gt;BMJ.&lt;/em&gt;&lt;br&gt;
&lt;br&gt;Women taking other antidepressants with tamoxifen, including other selective serotonin reuptake inhibitors (SSRIs), did not have an increased risk of breast cancer death.&lt;br&gt;
&lt;br&gt;&quot;We estimate that use of paroxetine for 41% of tamoxifen treatment (the median overlap in our sample) would result in one additional breast cancer death within five years of cessation of tamoxifen for every 19.7 patients so treated; the risk with more extensive overlap would be greater,&quot; David Juurlink, MD, PhD, of Sunnybrook Health Sciences Center in Toronto, and colleagues concluded.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;The findings add to an accumulation of evidence suggesting that inhibition of the cytochrome P450 2D6 isozyme (CYP2D6) may adversely affect outcomes in breast cancer patients taking tamoxifen. CYP2D6 is the principle catalyst for converting tamoxifen into endoxifen, a metabolite with 100-fold greater affinity for the estrogen receptor.&lt;/p&gt;
&lt;p&gt;Multiple studies have shown that women who have a poor-metabolizer phenotype have lower levels of endoxifen, as do women treated with drugs that inhibit CYP2D6.&lt;/p&gt;
&lt;p&gt;&quot;Indeed, in patients who receive tamoxifen in addition to a CYP2D6 inhibitor, endoxifen concentrations vary inversely with the degree of CYP2D6 inhibition,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Paroxetine is used to treat depression and vasomotor symptoms in breast cancer patients treated with tamoxifen. Paroxetine is not the only SSRI antidepressant used by breast cancer patients, but it is the only SSRI that irreversibly inhibits CYP2D6.&lt;/p&gt;
&lt;p&gt;Whether the metabolic effects of CYP2D6 inhibition translated into adverse breast cancer outcomes had not been determined.&lt;/p&gt;
&lt;p&gt;To examine the issue, Juurlink and colleagues compared prescribing data with clinical records of 24,430 breast cancer patients, ages 66 and older, who initiated tamoxifen therapy from 1993 to 2005. Of those, 7,500 also received an antidepressant.&lt;/p&gt;
&lt;p&gt;Ultimately, the investigators narrowed the study population to 2,430 women who took a single SSRI during tamoxifen therapy. The most commonly prescribed SSRI was paroxetine (25.9%), followed by sertraline (22.3%), citalopram (19.2%), venlafaxine (15%), fluoxetine (10.4%), and fluvoxamine (7.2%).&lt;/p&gt;
&lt;p&gt;During a mean follow-up of 2.38 years, 1,074 patients died, including 374 breast cancer deaths.&lt;/p&gt;
&lt;p&gt;The analysis showed an increased risk of breast cancer death only among women taking paroxetine.&lt;/p&gt;
&lt;p&gt;The breast cancer mortality risk increased with the duration of concomitant use of paroxetine and tamoxifen. As the duration of therapeutic overlap increased from 25%, to 50%, to 75% of time on tamoxifen, the excess risk of breast cancer death increased from 24%, to 54%, to 91%.&lt;/p&gt;
&lt;p&gt;Investigators repeated the analysis, using death from any cause. Overlapping treatment with tamoxifen and paroxetine led to an increased mortality risk of 13%, 28%, and 46% as the duration of overlap increased from 25% to 75%.&lt;/p&gt;
&lt;p&gt;The results suggest clear implications for use of SSRIs in breast cancer patients on tamoxifen, Frank Andersohn, MD, and Stefan Willich, MD, of Charite University in Berlin, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;&quot;The straightforward answer is to avoid prescribing strong CYP2D6-inhibiting SSRIs (such as paroxetine or fluoxetine) for women with breast cancer who are prescribed tamoxifen, and to consider instead drugs with low potential to inhibit CYP2D6 (such as citalopram or venlafaxine),&quot; they wrote.&lt;/p&gt;
&lt;p&gt;For women who are already taking a potent inhibitor of CYP2D6, doctors should consider switching to a drug that does not inhibit the enzyme, they added. However, any switch should be accomplished gradually, as abrupt discontinuation of an antidepressant confers risk, as well, they noted.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Co-author Kathleen Pritchard disclosed relationships with sanofi-aventis, AstraZeneca, Roche, Pfizer, Ortho-Biotech, YM Biosciences, Novartis, Abraxis, Amgen, GlaxoSmithKline, Bristol Myers Squibb, and Roche&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_412"
                     title="Depression During Pregnancy Linked to Kids&apos; Behavior Problems (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/Psychiatry/Depression/tb/18321?impressionId=1265778303677"
                     
      &lt;p&gt;Children born to mothers who were depressed during pregnancy were more than twice as likely to display antisocial behavior by age 16 as children whose mothers had not been depressed, researchers found.&lt;/p&gt;
&lt;p&gt;Of 120 mothers from South London who were followed from pregnancy through their children&apos;s teen years, 31% had depression during pregnancy, according to Dale Hay, PhD, of Cardiff University in Wales, and colleagues.&lt;/p&gt;
&lt;p&gt;Children born to these women were significantly more likely to display antisocial behavior (OR 2.46, 95% CI 1.10 to 5.48) and commit violent acts (OR 4.36, 95% CI 1.54 to 12.41) before age 16, the researchers reported in the January/February issue of &lt;em&gt;Child Development&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The associations were magnified in women who also had a history of behavior problems when they were children.&lt;/p&gt;
&lt;p&gt;&quot;A focus on mothers&apos; history of conduct problems and depression during pregnancy, as opposed to broader measures of the social environment, would hold promise for more targeted early interventions to prevent the development of serious antisocial behavior,&quot; Hay&apos;s group wrote.&lt;/p&gt;
&lt;p&gt;Previous studies have linked mothers&apos; mental health problems in pregnancy with disruptive behaviors in their children, but it&apos;s unclear what explains the relationship, according to the researchers.&lt;/p&gt;
&lt;p&gt;To explore the issue, they turned to the South London Child Development Study, which prospectively followed 120 pregnant women and their children into the teenage years.&lt;/p&gt;
&lt;p&gt;All families came from a relatively disadvantaged urban area. These families were more likely to belong to the working class and to be from ethnic minority groups than the general U.K. population.&lt;/p&gt;
&lt;p&gt;One-third of the children had been arrested or diagnosed with a conduct disorder by age 16. Of these 88.9% had been arrested and 45% had committed violent acts, including theft from a person, violent disorder, fighting, carrying a weapon, and assault.&lt;/p&gt;
&lt;p&gt;The association between maternal depression during pregnancy and risk of antisocial behavior remained relatively constant in analyses controlling for family environment, a child&apos;s exposure to maternal depression after birth, mothers&apos; substance use during pregnancy, and parental antisocial behavior.&lt;/p&gt;
&lt;p&gt;None of the factors fully explained the relationship. Neither did the arrest history of the biological father.&lt;/p&gt;
&lt;p&gt;But, the researchers wrote in the paper, &quot;it would be unwise to conclude that paternal risk factors are unimportant, given that we did not have more detailed information about the father&apos;s own history of conduct disorders.&quot;&lt;/p&gt;
&lt;p&gt;They explored several potential mechanisms for the link between maternal depression and a child&apos;s behavior problems: &lt;ul&gt; &lt;li&gt;Direct effects on the fetus from biological correlates of the mothers&apos; depressive symptoms&lt;/li&gt; &lt;li&gt;Depression in pregnancy as a sign of environmental adversity&lt;/li&gt; &lt;li&gt;Re-exposure to maternal depression after birth&lt;/li&gt; &lt;li&gt;Indirect effects of depression on the developing fetus driven by mothers&apos; smoking, drinking, and drug taking during pregnancy &lt;/li&gt; &lt;li&gt;A genetic explanation whereby women who experience depression in pregnancy may also have a greater genetic risk for antisocial behavior, which they pass on to their offspring &lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Hay and her colleagues noted that these explanations are not necessarily mutually exclusive.&lt;/p&gt;
&lt;p&gt;They also acknowledged some limitations of the study, including the lack of information about fetal growth and neuroendocrine measures on the mother and child and the relatively small sample size.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The SLCDS has been funded by U.K. project grants from the Medical Research Council, by the Psychiatric Research Trust, and by the South West G.P. Trust. The current analysis was partially supported by an Economic and Social Research Council studentship to one of Hay&apos;s co-authors and by a Medical Research Council U.K. Program Grant.&lt;/p&gt;&lt;p&gt;The authors did not report any conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_405"
                     title="Difficult Childhood Lingers in the Mind (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/Psychiatry/GeneralPsychiatry/tb/18312?impressionId=1265778303677"
                     
      &lt;p&gt;Adversities faced in childhood have effects on mental health far into the future, researchers affirmed.&lt;/p&gt;
&lt;p&gt;Mental illness in adulthood was increasingly likely the more traumas faced in childhood, Ronald C. Kessler, PhD, of Harvard, and colleagues reported in the February issue of the &lt;em&gt;Archives of General Psychiatry&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Childhood difficulties potentially explained 32.4% of all the psychiatric disorders examined, they said, based on analyses of the National Comorbidity Survey Replication.&lt;/p&gt;
&lt;p&gt;Adversities relating to family dysfunction  --  substance-abusing parents, sexual or physical abuse in the home, neglect, etc.  --  appeared to have the strongest link to onset and persistence of psychiatric disorders, they reported.&lt;/p&gt;
&lt;p&gt;These findings match folk wisdom and decades of research into the negative effects of child maltreatment, commented John McGrath, MD, PhD, of the Queensland Centre for Mental Health Research in Wacol, Australia, and colleagues in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;But the lack of specificity between certain exposures to particular mental health outcomes  --  such as the death of one&apos;s mother leading to depression  --  was notable, the editorialists said.&lt;/p&gt;
&lt;p&gt;&quot;Thus, childhood trauma upsets the orderly psychological and biological cascades of development, leaving the affected individual at increased risk of a wide range of adverse mental health outcomes,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Rather than continue to rehash the epidemiology, it&apos;s time to focus on prevention and intervention, McGrath&apos;s group emphasized.&lt;/p&gt;
&lt;p&gt;&quot;It is unrealistic to think that we could protect all children from all adversities, but can we identify factors that bolster resilience and focus our efforts on the most vulnerable subgroups?&quot; they asked.&lt;/p&gt;
&lt;p&gt;The researchers examined joint associations of 12 retrospectively reported childhood adversities with lifetime incidence of disorders meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria in the National Comorbidity Survey Replication I, a cross-sectional survey of a nationally-representative sample of adults in 9,282 American households.&lt;/p&gt;
&lt;p&gt;Among the respondents, 53.4% reported at least one childhood adversity, most commonly parental divorce (17.5%), family violence (14.0%), family economic problems (10.6%), and parental mental illness (10.3%).&lt;/p&gt;
&lt;p&gt;These adversities were all individually and significantly linked to first onset of psychiatric disorders with odds ratios of 1.5 to 1.9 for dysfunctional family factors (physical abuse, sexual abuse, neglect, parental mental illness, parental substance abuse, parental criminality, or family violence) and 1.0 to 1.5 for other factors like life-threatening childhood physical illness, extreme poverty, parental divorce, or loss of or separation from parents.&lt;/p&gt;
&lt;p&gt;Despite some apparent but not significantly meaningful variation in type of adversity with type of psychiatric disorder, the researchers said they could rule out that all types were the same for future mental health risk (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Problems tended to cluster, though. Among people who faced one adversity in childhood, 51.2% to 95.1% faced others as well, depending on the adversity.&lt;/p&gt;
&lt;p&gt;Risk of mental illness rose with number of issues faced in childhood from an odds ratio of 1.3 for one up to 3.4 for six and 3.2 for seven or more adversities.&lt;/p&gt;
&lt;p&gt;&quot;This subadditive pattern has important implications for intervention because it means that prevention or amelioration of only a single childhood adversity in youths exposed to many childhood adversities is unlikely to have important preventive effects,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;Overall, childhood adversities were projected to account for 44.6% of childhood-onset disorders, 32.0% of adolescent-onset disorders, and 28.6% of adult-onset disorders.&lt;/p&gt;
&lt;p&gt;The researchers also looked at persistence through the second part of the National Comorbidity Survey Replication which went beyond just core diagnostic assessment in 5,692 respondents.&lt;/p&gt;
&lt;p&gt;In a complex multivariate interactive analysis, childhood adversity from dysfunctional family factors appeared significantly linked to persistence in a given year (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) whereas the number of factors was not significant.&lt;/p&gt;
&lt;p&gt;These significant factors were parental mental illness, physical abuse, sexual abuse, and neglect, but they carried modest effects individually with odds ratios of 1.2.&lt;/p&gt;
&lt;p&gt;But in one simulation, not being exposed to childhood trauma would only increase the time since the most recent episode of psychiatric illness by 1.6%, suggesting &quot;quite modest&quot; substantive importance in determining persistence.&lt;/p&gt;
&lt;p&gt;&quot;These results indirectly suggest that the public health implications of childhood adversities are greater for primary than for secondary prevention because the associations of childhood adversities with disorder onset are much stronger than the associations with persistence,&quot; Kessler&apos;s group wrote.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that recall bias may have limited their study such that the results could be considered an &quot;upper bound&quot; for the real association and that the study could not prove causality.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The National Comorbidity Survey Replication is supported by a grant from the National Institute of Mental Health with supplemental support from the National Institute on Drug Abuse, the Substance Abuse and Mental Health Services Administration, a grant from the Robert Wood Johnson Foundation, and the John W. Alden Trust.&lt;/p&gt;&lt;p&gt;The analyses were supported by a grant from the NIMH; the John D. and Catherine T. MacArthur Foundation; the Pfizer Foundation; grants from the U.S. Public Health Service; an award from the Fogarty International Center; the Pan American Health Organization; Eli Lilly; Ortho-McNeil Pharmaceutical; GlaxoSmithKline; and Bristol-Myers Squibb.&lt;/p&gt;&lt;p&gt;Kessler reported financial conflicts of interest with GlaxoSmithKline, Kaiser Permanente, Pfizer, sanofi-aventis, Shire Pharmaceuticals, Wyeth-Ayerst, Eli Lilly, Bristol-Myers Squibb, Johnson &amp;amp; Johnson Pharmaceuticals, and Ortho-McNeil Pharmaceutical.&lt;/p&gt;&lt;p&gt;The editorialists reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_3_442"
                     title="AACAP: Black Box Warnings Decreased Pediatric Antidepressant Use"
                     score="-0.005"
                     href="