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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=1265794133896"
                     
      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_358"
                     title="Poststroke Antidepressant Boosts Mental Agility (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Cardiology/Strokes/tb/18240?impressionId=1265794133896"
                     
      &lt;p&gt;Antidepressants in the first months after a stroke may aid cognitive recovery for patients without depression, according to a randomized trial analysis.&lt;/p&gt;
&lt;p&gt;Global cognitive function scores improved significantly more with escitalopram (Lexapro) than with problem-solving therapy or placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01), according to Ricardo E. Jorge, MD, of the University of Iowa in Iowa City, and colleagues.&lt;/p&gt;
&lt;p&gt;Memory scores rose significantly higher with the antidepressant as well (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01), with both effects independent of those on depression, they reported in the February &lt;em&gt;Archives of General Psychiatry&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Adjunctive restorative therapies administered during the first few months after stroke, the period with the greatest degree of spontaneous recovery, reduce the number of stroke patients with significant disability,&quot; the researchers concluded.&lt;/p&gt;
&lt;p&gt;The &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Strokes/9621&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Strokes/9621&quot; target=&quot;_blank&quot;&gt;primary analysis&lt;/a&gt; of the trial, reported in the &lt;em&gt;Journal of the American Medical Association on&lt;/em&gt; May 28, 2008, showed that prophylactic escitalopram treatment would prevent poststroke depression in one patient for every 7.2 treated &lt;em&gt;(P&lt;/em&gt;&amp;lt;0.001 compared with placebo). That article ultimately raised a controversy over an undisclosed conflict of interest.&lt;/p&gt;
&lt;p&gt;Escitalopram is a selective serotonin reuptake inhibitor (SSRI). Since serotonin plays a role in neuroplastic changes in the developing brain as well as in depression, Jorge&apos;s group analyzed whether there might be such an effect after a stroke.&lt;/p&gt;
&lt;p&gt;The study randomized patients to double-blind treatment with escitalopram (10 mg/d under age 65 or 5 mg/day age 65 and older) or placebo or unblinded problem-solving therapy (12 sessions of going through steps to arrive at a course of action for a patient-selected problem).&lt;/p&gt;
&lt;p&gt;The intent-to-treat analysis included 129 patients treated starting within the first three months after their mild to moderate severity stroke and who did not meet criteria for major or minor depression.&lt;/p&gt;
&lt;p&gt;Overall, global cognitive functioning was significantly changed between groups as measured on the Repeatable Battery for the Assessment of Neuropsychological Status (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;After controlling for change in depression score and type of stroke, escitalopram was associated with the best cognitive recovery, an adjusted mean change of 9.9 points compared with 1.9 for problem-solving therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01) and 4.0 for placebo (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;Similarly, for delayed memory scores on the same test battery, escitalopram came out on top (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;After adjustment for depression score change and stroke mechanism, the antidepressant was associated with an 11.2 point improvement in delayed memory, compared with a change of -0.7 with problem-solving therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and 3.9 with placebo (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;On test of immediate memory, escitalopram again yielded the best recovery.&lt;/p&gt;
&lt;p&gt;The researchers found mean improvement of 13.4 points with the antidepressant compared with 2.0 with problem-solving therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and 7.2 with placebo (&lt;em&gt;P&lt;/em&gt;=0.04), after adjustment for time between stroke and treatment, depression score change, and stroke type.&lt;/p&gt;
&lt;p&gt;These mental benefits appeared to have an impact on functional status as well.&lt;/p&gt;
&lt;p&gt;Cognitive domain scores on the Functional Independence Measure were better for escitalopram-treated patients than those who didn&apos;t get the drug (&lt;em&gt;P&lt;/em&gt;=0.05), as were memory domain scores on the same measure (&lt;em&gt;P&lt;/em&gt;=0.03).&lt;/p&gt;
&lt;p&gt;At baseline, the global cognitive functioning and delayed and immediate memory scores were nonsignificantly lower in the antidepressant group than in the other two groups, which could have biased the results.&lt;/p&gt;
&lt;p&gt;However, the treatment effects appeared to be real, Jorge explained in an interview.&lt;/p&gt;
&lt;p&gt;In an unpublished regression analysis, the baseline scores were not a significant covariate. &quot;If [the results were] related only to the difference in baseline, this would be significant but it wasn&apos;t,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Moreover, with an initially lower score it might have been expected that the escitalopram-treated group would have had a lower score at the end of the study than the other groups, added co-author Robert G. Robinson, MD, also of the University of Iowa.&lt;/p&gt;
&lt;p&gt;But that wasn&apos;t the case, he said in an interview. With regard to delayed memory, for example, &quot;the escitalopram-treated group went from the most impaired to the best performing.&quot;&lt;/p&gt;
&lt;p&gt;The researchers didn&apos;t compare end scores for the escitalopram, problem solving therapy, and placebo groups, but they were: &lt;ul&gt; &lt;li&gt;For global cognitive functioning 89.8, 89.1, and 91.0 points, respectively&lt;/li&gt; &lt;li&gt;For delayed memory, 96.6, 89.1, and 94.2, respectively&lt;/li&gt; &lt;li&gt;For immediate memory, 95.1, 94.9, and 98.5, respectively&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The treatment showed no effect on other individual cognitive measurements, including those for attention, language, and IQ. Nor were there significant differences in changes in occupational or living conditions.&lt;/p&gt;
&lt;p&gt;Although SSRIs such as escitalopram have been associated with hospitalization for GI bleeding and falls in prior studies, these complications did not occur in Jorge&apos;s study.&lt;/p&gt;
&lt;p&gt;&quot;Long-term administration of SSRIs appears to be an effective and safe treatment option to improve cognitive outcomes among patients with cerebrovascular disease,&quot; they concluded in the &lt;em&gt;Archives&lt;/em&gt; paper.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that the study was limited by lack of CT or MRI scans and the younger age of escitalopram-treated patients, compared with other groups. That may have been a source of bias, although age did not appear to be a significant factor in the trial results.&lt;/p&gt;
&lt;p&gt;In this analysis, the researchers emphasized that the trial was not financially supported in any way by any drug company  --  a declaration hinting at the controversy that brewed last year over failure of one of the authors of the original &lt;em&gt;JAMA&lt;/em&gt; article to &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/13391&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/13391&quot; target=&quot;_blank&quot;&gt;properly disclose ties&lt;/a&gt; to Forest Pharmaceuticals, which makes escitalopram.&lt;/p&gt;
&lt;p&gt;Another scientist who discovered that omission published the information in a competing journal, inducing &lt;em&gt;JAMA&lt;/em&gt; to issue a gag rule on reporting of undisclosed conflicts of interest. That policy encourages those who discover such conflicts to report them to &lt;em&gt;JAMA&apos;s&lt;/em&gt; editors but prohibits them from disclosing the conflicts publicly pending an investigation by the journal.&lt;/p&gt;
&lt;p&gt;In the current analysis, the disclosure statement indicated that co-author Robertson, had received honoraria and speakers&apos; bureau fees from Forest, with the caveat that &quot;none of the design, analysis, or expenses (including the cost of medications) of this study were supported by monies, materials, or any intellectual input from Forest Laboratories.&quot;&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 study was supported solely by a grant from the National Institute of Mental Health.&lt;/p&gt;&lt;p&gt;Jorge reported having received travel awards to participate in national meetings from the former Hamilton Pharmaceutical Company and Avanir Pharmaceutical Company.&lt;/p&gt;&lt;p&gt;Co-authors reported financial conflicts of interest with Merck, NMT Medical, Eli Lilly, Centocor, Sanofi-Bristol-Meyers-Squibb, Boerhringer-Ingelheim, Schering-Plough, AstraZeneca, and GlaxoSmithKline, the former Hamilton Pharmaceutical Company, Avanir Pharmaceutical Company, Lubeck, Forest Laboratories, and Pfizer.&lt;/p&gt;&lt;p&gt;No pharmaceutical company donated medications for or had any financial interest in the study.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_90"
                     title="Nursing Homes Overuse Antipsychotics (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Geriatrics/Depression/tb/17892?impressionId=1265794133896"
                     
      &lt;p&gt;In 2006, a year after the FDA issued mortality warnings about prescribing antipsychotic drugs for the elderly, nearly 30% of nursing home residents received the medication  --  despite the fact that a third of them had no indication for the drugs, a study revealed.&lt;/p&gt;
&lt;p&gt;In nursing homes where rates of antipsychotic drug use were highest, residents had a risk ratio of 1.37 (95% CI 1.24 to 1.51) for receiving at least one of them, compared with facilities where rates of prescribing were low, according to Yong Chen, MD, of the University of Massachusetts Medical School in Worcester, and colleagues.&lt;/p&gt;
&lt;p&gt;This elevated risk associated with facility-level prescribing was seen for patients with dementia but no psychosis (RR 1.40, 95% CI 1.23 to 1.59), and in residents with neither psychosis nor dementia (RR 1.54, 95% CI 1.24 to 1.91), the researchers reported in the Jan. 11 &lt;em&gt;Archives of Internal Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;An unrelated study, also released today, indicated that &lt;a href=&quot;http://www.medpagetoday.com/Psychiatry/Depression/17886&quot; mce_href=&quot;http://www.medpagetoday.com/Psychiatry/Depression/17886&quot; target=&quot;_blank&quot;&gt;office-based physicians were in fact cutting back on prescription of antipsychotics for dementia &lt;/a&gt;as a result of FDA warnings.&lt;/p&gt;
&lt;p&gt;Recent research suggest that there&apos;s wide variation in use of antipsychotics among facilities, reflecting what the authors of the current study called &quot;an institutional prescribing culture.&quot;&lt;/p&gt;
&lt;p&gt;Previous work had suggested that facility-level factors contributed to this effect in Canada, but the extent to which these factors exist in the U.S. has been unclear.&lt;/p&gt;
&lt;p&gt;So Chen and colleagues assessed a nationwide, cross-sectional sample of 16,586 U.S. residents newly admitted to 1,257 nursing homes.&lt;/p&gt;
&lt;p&gt;The nursing homes were categorized into quintiles according to their rates of antipsychotic use, with prescribing rates in the previous year ranging from zero to 24.4% in quintile one to 43.8% to 100% in quintile five.&lt;/p&gt;
&lt;p&gt;The sample included 972 patients with psychosis, 6,188 patients with dementia but no psychosis, and 9,426 with neither dementia nor psychosis.&lt;/p&gt;
&lt;p&gt;Among residents with psychosis, 74.8% received at least one antipsychotic, as did 41.1% of those with dementia but no psychosis, and 16.4% of those with neither condition.&lt;/p&gt;
&lt;p&gt;Compared with residents in quintile five facilities, those in quintile one were more likely to be:&lt;ul&gt; &lt;li&gt;Older (&amp;gt;75 years, 75% versus 59%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;Women (69.4% versus 60.9%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;White (85% versus 71.9%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Residents in quintile one also were more likely to be frail, as determined by the Changes in Health, End-stage disease and Symptoms and Signs (CHESS) score of 3 or higher (24.7% versus 14%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), than those in quintile five.&lt;/p&gt;
&lt;p&gt;They also had better Cognitive Performance Scale scores of 0 or 1 (39.2% versus 31.4%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Conversely, compared with patients in quintile one nursing homes, those in quintile five facilities were more likely to have:&lt;ul&gt; &lt;li&gt;Moderate or severe behavioral problems (23.5% versus 12.6%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;Dementia (52.3% versus 41.4%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;Psychosis (10.3% versus 4%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Residents in quintile five had twice the unadjusted risk ratio of receiving antipsychotics compared with those in quintile one (RR 2, 95% CI 1.78 to 2.24), although this was reduced to 1.37 after adjusting for demographics, health status, and potential indication for antipsychotics.&lt;/p&gt;
&lt;p&gt;When the investigators looked at individual patient characteristics, they found that antipsychotic medication users were:&lt;ul&gt; &lt;li&gt;Younger (&amp;#8804;65, 13.7% versus 10.2%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;Male (37.6% versus 34.1%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;Less frail (CHESS score 0, 24.9% versus 17.6%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Antipsychotic users also tended to have:&lt;ul&gt; &lt;li&gt;Moderate and severe behavioral problems (32.3% versus 8.9%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;Dementia (68.8% versus 36.9%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;Psychosis (15.1% versus 2.1%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The study confirms the existence of facility-level variation in prescribing, with the likelihood of a new resident being given an antipsychotic medication being &quot;strongly and independently related to the facility-level antipsychotic prescribing rate, even after adjustment for clinical and sociodemographic characteristics,&quot; the investigators wrote.&lt;/p&gt;
&lt;p&gt;Only a small proportion of residents receiving the drugs had diagnoses of schizophrenia, bipolar disorder, or aggressive behavioral symptoms of dementia, which suggests that managing behavioral problems is an important component of facility-level decisions regarding antipsychotic medication use.&lt;/p&gt;
&lt;p&gt;The study also suggests that organizational culture plays an important role in medication prescribing in nursing homes, because in these settings, prescribing decisions often are made without direct contact between the prescriber and the patient.&lt;/p&gt;
&lt;p&gt;Among the limitations of the study were its cross-sectional design, which precludes conclusions about causality, and the use of a sole data source: a single long-term-care pharmacy provider. They also pointed out that &quot;we have excluded NHs with fewer than five residents. . . . and we further excluded short-stay residents because of their distinct characteristics from long-stay residents. Limiting our study sample therefore prevents us from extending the interpretation of our findings to smaller facilities.&quot;&lt;/p&gt;
&lt;p&gt;They further pointed out that the &quot;prevalence of psychoses in our sample was lower compared with that found in another study using medical records. Thus, we may have underestimated the prevalence of psychoses in this sample.&quot;&lt;/p&gt;
&lt;p&gt;The investigators concluded that &quot;safety concerns continue to persist in the use of antipsychotic medications in [nursing home] residents whose benefits from these agents are unclear.&quot;&lt;/p&gt;
&lt;p&gt;They called for further research to clarify why this prescribing culture exists and to determine whether there are adverse health consequences for patients.&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 study was supported by the Robert Wood Johnson Foundation and the National Institute on Aging.&lt;/p&gt;&lt;p&gt;No financial disclosures were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_87"
                     title="Antipsychotic Use for Dementia Falls after Warnings (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Psychiatry/Depression/tb/17886?impressionId=1265794133896"
                     
      Physicians apparently heeded FDA warnings about atypical antipsychotics and significantly reduced use of the agents in older patients with dementia, according to a study of prescribing trends.&lt;br&gt;
&lt;br&gt;From 2004 to 2008, use of antipsychotics for dementia declined by 50%. However, treatment of patients with dementia still accounted for almost 10% of antipsychotic drug use during the review period, investigators reported in the January &lt;em&gt;Archives of Internal Medicine.&lt;/em&gt;&lt;br&gt;
&lt;br&gt;&quot;Without clinical data, the appropriateness of this use is uncertain,&quot; E. Ray Dorsey, MD, of the University of Rochester in New York, and colleagues wrote in conclusion.&lt;br&gt;
&lt;br&gt;&quot;The residual use in the population at risk and the decrease in the use of atypical antipsychotics in the general population, who were not targeted by the warning, raise the question as to whether the effect and specificity of FDA regulatory actions could be enhanced.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;Targeting specific segments of patients and physicians (e.g., high prescribers) and further customizing and evaluating the impact of regulatory actions may improve their impact at minimizing the risks associated with select prescription medications.&quot;&lt;/p&gt;
&lt;p&gt;Less likely to cause extrapyramidal effects than conventional antipsychotics, atypical agents have nonetheless been associated with several safety concerns. The concerns led to the following:&lt;ul&gt; &lt;li&gt;2003 Medwatch warning about an increased risk of stroke with risperidone (Risperdal) &lt;/li&gt; &lt;li&gt;2004 FDA warning about an association between atypical antipsychotics and hyperglycemia or diabetes &lt;/li&gt; &lt;li&gt;2005 FDA decision to require manufacturers of atypical antipsychotics to include a black box warning about an increased mortality risk in older patients with dementia. In 2008 the FDA extended the requirement to conventional antipsychotics.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Several studies have examined the impact of FDA warnings on the use of medications targeted by the warnings, the authors noted. A Canadian study demonstrated a slowing of the rate of increase in use of atypical and typical antipsychotics for treatment of dementia following warnings from Health Canada. However, the absolute rates of use continued to increase (&lt;em&gt;CMAJ&lt;/em&gt; 2008; 179: 438-46).&lt;/p&gt;
&lt;p&gt;To assess the impact of the 2005 black box warning among U.S. physicians, Dorsey and co-authors examined prescribing practices of a nationally representative sample of office-based physicians.&lt;/p&gt;
&lt;p&gt;Using data from a proprietary database with national representation, they evaluated use of antipsychotics in patients 65 and older with dementia from 2003 to 2008, encompassing periods before and after the FDA warnings.&lt;/p&gt;
&lt;p&gt;Overall, use of atypical antipsychotics increased annually by 34% during the period reviewed, including 16% annually in patients with dementia.&lt;/p&gt;
&lt;p&gt;In the year before the 2005 FDA advisory, prescriptions for atypical antipsychotics totaled 13.6 million, including 800,000 for patients with dementia. In the first year after the advisory, prescriptions for atypical antipsychotics decreased by 2% overall and by 19% for patients with dementia.&lt;/p&gt;
&lt;p&gt;From 2004 to 2008, atypical antipsychotics&apos; share of prescriptions for dementia therapy declined from 19% (0.8 of 4.1 million) to 9% (0.4 of 4.3 million).&lt;/p&gt;
&lt;p&gt;The investigators found that use of atypical agents for both FDA-approved and off-label indications declined through the end of the review period for all patient populations examined.&lt;/p&gt;
&lt;p&gt;Limitations of the study included the following : inability to assess whether the black box warning resulted in the decrease in prescriptions, use of drug &quot;mentions&quot; rather than individuals, sampling of physicians in ambulatory practice which decreased data on nursing home use of the drugs, and absence of clinical data on patients.&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;Dorsey disclosed current and past relationships with Medivation, Pfizer, Amarin, Avid Radiopharmaceuticals, Merck, and Lundbeck. Co-author G. Caleb Alexander disclosed relationships with IMS Health, Pfizer, Merck, and AstraZeneca.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_37"
                     title="Antidepressants Find Way to Newborn Lungs"
                     score="-0.005"
                     href="