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    <recommendedItem id="20090101_19_1056"
                     title="FDA Review Questions Cardiac, Suicide Risks for Investigational Antipsychotic"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Psychiatry/Schizophrenia/tb/13619?impressionId=1265798389370"
                     
       WASHINGTON, April 6 -- Investigational antipsychotic drug sertindole (Serdolect) is effective at treating schizophrenia, but it may lead to sudden cardiac death, according to an FDA review. 
              &lt;p&gt; 
              &lt;p&gt;The agency released its review in advance of Tuesday&apos;s meeting of the Psychopharmacologic Drugs Advisory Committee, which will decide if the drug&apos;s cardiovascular risk is an obstacle to FDA approval. 
              &lt;p&gt; 
              &lt;p&gt;The advisory panel will also consider the sponsor&apos;s suicide prevention claim, and whether to recommend to the FDA that the drug is safe and effective. The vote will effectively amount to a recommendation of approval or denial.
              &lt;p&gt; 
              &lt;p&gt;Sertindole is already used in other countries to treat schizophrenia. 
              &lt;p&gt; 
              &lt;p&gt;According to the FDA review, led by psychiatrist Phillip Kronstein, M.D., sertindole is effective in treating schizophrenia, but concerns remain about the drug&apos;s potential to prolong the heart&apos;s QT interval, which can lead to sudden cardiac death. That same cardiac risk has been seen in other antipsychotic drugs similar to sertindole. 
              &lt;p&gt; 
              &lt;p&gt;Sertindole is a so-called atypical antipsychotic drug, Its specific mechanism appears to be to inhibit spontaneously active dopamine neurons in the mesolimbic ventral tegmental area without affecting dopamine neurons in the substantial nigra compacta. 
              &lt;p&gt; 
              &lt;p&gt;A recent study found that atypical antipsychotics carry a risk of sudden cardiac death similar to that associated with older schizophrenia drugs.  (See: &lt;a href=&quot;http://www.medpagetoday.com/Psychiatry/Schizophrenia/12453&quot; target=&quot;blank&quot;&gt;Risk of Sudden Death No Less Likely with Atypical Antipsychotics&lt;/a&gt;) 
              &lt;p&gt; 
              &lt;p&gt;Sertindole has been approved in the U.K. since 1996. But use of the drug was temporarily suspended after an online database indicated that sertindole might cause more deaths than risperidone (Risperdal). The drug&apos;s manufacturer, Lundbeck, agreed to perform a large randomized parallel-group study comparing all-cause death, cardiac death, and suicide for sertindole versus risperidone.
              &lt;p&gt; 
              &lt;p&gt;Based on results from that nearly 10,000-patient study, which did not show an increase in all-cause mortality with sertindole, the restrictions on the drug were lifted. 
              &lt;p&gt; 
              &lt;p&gt;But in Lundbeck&apos;s analyses to prepare for U.S. approval, the FDA reviewers didn&apos;t think the comparable all-cause mortality data was exactly a home run for sertindole, &quot;given the relatively higher mortality in this population from multiple causes,&quot; Dr. Kronstein said. 
              &lt;p&gt; 
              &lt;p&gt;More relevant are the cardiac deaths, in light of sertindole&apos;s connection to heart problems, he said. The FDA review found that patients taking sertindole had a significantly higher risk of cardiac death compared with those taking risperidone (&lt;em&gt;P&lt;/em&gt;=0.002). 
              &lt;p&gt; 
              &lt;p&gt;Thirteen patients died suddenly from cardiac causes in the sertindole group, compared with three who were taking risperidone. 
              &lt;p&gt; 
              &lt;p&gt;&quot;This is a significant and concerning result, indicating that sertindole-treated patients had an approximately five times higher risk of sudden cardiac death,&quot; according to the review.
              &lt;p&gt; 
              &lt;p&gt;The other major question for the committee is whether Lundbeck can justifiably claim that sertindole prevents suicidality better than other antipsychotic drugs.
              &lt;p&gt; 
              &lt;p&gt;Lundbeck has proposed to include such a claim in the product&apos;s label. In the company&apos;s trials, there were 14 suicide deaths among sertindole patients and 21 in the risperidone group.
              &lt;p&gt; 
              &lt;p&gt;But the FDA&apos;s staff review disagreed with the way Lundbeck examined suicide risk, and requested that the company analyze all suicide attempts instead of only those that succeeded.
              &lt;p&gt; 
              &lt;p&gt;According to the briefing documents for the meeting, this second analysis found that 46 patients attempted suicide during treatment and up to 30 days after in the sertindole group, compared with 62 in the risperidone group, with the difference failing to reach statistical significance.
              &lt;p&gt; 
              &lt;p&gt;The panel is to vote on whether the data show that sertindole reduces suicidality in schizophrenic patients.
              &lt;p&gt; 
              &lt;p&gt;As for the drug&apos;s efficacy in schizophrenia symptoms, two clinical trials have adequately proved the short-term antipsychotic efficacy of between 12 mg and 20 mg daily doses of sertindole, according to the FDA&apos;s Dr. Kronstein. 
              &lt;p&gt; 
              &lt;p&gt;There are no adequate and well-controlled data to address long-term efficacy, he said. 
              &lt;p&gt; 
              &lt;p&gt;The FDA does not have to follow the advice of the panels, but it usually does.
    </recommendedItem>
    <recommendedItem id="20090101_19_1073"
                     title="FDA Concerned About Expanding Quetiapine Use for Mood Disorders"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Psychiatry/Depression/tb/13635?impressionId=1265798389370"
                     
      WASHINGTON, April 7 -- An FDA staff review expressed worries about adding new indications for the antipsychotic drug quetiapine (Seroquel) because of increased risks for metabolic problems.
              &lt;p&gt; 
              &lt;p&gt;The drug&apos;s manufacturer, AstraZeneca, is seeking to have the drug approved for generalized anxiety disorder and major depression.
              &lt;p&gt; 
              &lt;p&gt;Quetiapine is currently marketed for treatment of schizophrenia, acute bipolar depression and mania, and for maintenance therapy of bipolar disorder as an adjunct to lithium or divalproex (Depakote).
              &lt;p&gt; 
              &lt;p&gt;The staff review was released in advance of this Wednesday&apos;s meeting of the FDA&apos;s Psychopharmacologic Drugs Advisory Committee, which will vote on whether to recommend approval for the new indications. 
              &lt;p&gt; 
              &lt;p&gt;Agency staff said that, while the drug has been shown to be an effective treatment for people with anxiety disorder and depression, expanding the drug&apos;s indication could put millions of additional patients at risk for metabolic and cardiovascular problems such as weight gain, diabetes, and sudden cardiac death.   
              &lt;p&gt; 
              &lt;p&gt;The FDA review team also said it was concerned about tardive dyskinesia, an involuntary movement that is considered an &quot;accepted risk in schizophrenia and bipolar patients,&quot; according to Thomas P. Laughren, M.D. director of Division of Psychiatry Products at the FDA. 
              &lt;p&gt; 
              &lt;p&gt;Atypical antipsychotic drugs such as quetiapine were thought to reduce the risk of tardive dyskinesia compared with older schizophrenia drugs such as chlorpromazine (Thorazine). But Dr. Laughren said AstraZeneca had not addressed the risks for tardive dyskinesia in the new patient populations covered by its application.
              &lt;p&gt; 
              &lt;p&gt;Quetiapine may also be associated with sudden cardiac death -- a risk seen in both atypical antipsychotics as well as older drugs. (See: &lt;a href=&quot;http://www.medpagetoday.com/Psychiatry/Schizophrenia/12453&quot; target=&quot;blank&quot;&gt;Risk of Sudden Death No Less Likely with Atypical Antipsychotics&lt;/a&gt;)
              &lt;p&gt; 
              &lt;p&gt;The FDA reviewers said these risks could likely be &quot;adequately characterized in labeling.&quot; They pointed out that the risks are not unique to quetiapine and are seen in the entire class of atypical antipsychotic drugs. 
              &lt;p&gt; 
              &lt;p&gt;But the analysis suggested stronger concerns about the metabolic effects.
              &lt;p&gt; 
              &lt;p&gt;In responding to the company&apos;s application, the FDA requested and received additional data from AstraZeneca on metabolic changes seen in its clinical studies.
              &lt;p&gt; 
              &lt;p&gt;According to the agency&apos;s analysis of that data, patients taking quetiapine gained an average of 2.6 pounds at 43 days median exposure, while the placebo group gained an average of less than half of a pound. There was some suggestion that weight gain increased over time. 
              &lt;p&gt; 
              &lt;p&gt;Patients receiving quetiapine also had a significant increase in fasting blood glucose and total cholesterol. 
              &lt;p&gt; 
              &lt;p&gt;AstraZeneca recently came under fire when court documents revealed that the drugmaker allegedly tried to minimize the risk of diabetes and weight gain associated with quetiapine in part by cherry-picking data for publication. (See: &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/13064&quot; target=&quot;blank&quot;&gt;Negative Data on Seroquel Allegedly Suppressed by Drugmaker&lt;/a&gt;) 
              &lt;p&gt; 
              &lt;p&gt;According to the FDA review, three clinical studies proved quetiapine is an effective monotherapy, while two studies suggested the drug is an effective adjunctive therapy to an antidepressant. One study showed quetiapine is an effective maintenance therapy, according to the FDA&apos;s clinical review. 
              &lt;p&gt; 
              &lt;p&gt;The FDA does not have to follow its advisory panels&apos; recommendations, but it usually does.
       
    </recommendedItem>
    <recommendedItem id="20090101_19_1098"
                     title="FDA Panel Splits on New Uses for Atypical Antipsychotic"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Psychiatry/Depression/tb/13667?impressionId=1265798389370"
                     
       SILVER SPRING, Md., April 8 -- An FDA advisory committee today was reluctant to recommend approval of more indications for the antipsychotic drug quetiapine (Seroquel), with studies showing substantial metabolic and cardiovascular risks.
              &lt;p&gt; 
              &lt;p&gt;Consequently, the Psychopharmacologic Drugs Advisory Committee voted down a request to market the drug for generalized anxiety disorder.
              &lt;p&gt; 
              &lt;p&gt;It gave assent to the drug for major depression, but only when patients have failed other treatments and only in combination with another antidepressant.
              &lt;p&gt; 
              &lt;p&gt;Quetiapine&apos;s manufacturer, AstraZeneca, is seeking approval for the drug as a first-line therapy for both conditions.
              &lt;p&gt; 
              &lt;p&gt;A psychiatrist on the panel said at least 10% of the U.S. population will experience either major depression or anxiety disorder in their lifetimes -- a huge number of people who could potentially receive the drug if approved as first-line therapy.
              &lt;p&gt; 
              &lt;p&gt;Panel members said expanding quetiapine to such a large population was too big of a gamble given the increased risk for weight gain, high glucose levels, and tardive dyskinesia -- persistent, involuntary, and sometimes disfiguring movements -- associated with the drug.
              &lt;p&gt; 
              &lt;p&gt;The panel agreed that AstraZeneca&apos;s trials were too short to prove that quetiapine doesn&apos;t increase the risk of sudden cardiac death. In addition, members were concerned about the risk of tardive dyskinesia with quetiapine, an issue for all antipsychotic drugs.
              &lt;p&gt; 
              &lt;p&gt;The drug&apos;s efficacy in these conditions was not much in question, with the panel voting 9 to 1 that the drug is effective in major depression, and 7 to 2 (with one abstention) that it relieves generalized anxiety disorder.
              &lt;p&gt; 
              &lt;p&gt;Instead, safety issues occupied most of the panel&apos;s attention.
              &lt;p&gt; 
              &lt;p&gt;The FDA has never approved an antipsychotic as a monotherapy for depression, said Robert Temple, M.D., director of the Office of Drug Evaluation at the FDA.
              &lt;p&gt; 
              &lt;p&gt;The panel failed to endorse the safety of the drug when used as a stand-alone treatment for depression by a vote of 4 to 4, with one panelist abstaining.
              &lt;p&gt; 
              &lt;p&gt;But the committee voted 6 to 3 that quetiapine is acceptably safe when used in addition to another drug to treat depression that has not responded to previous therapy.
              &lt;p&gt; 
              &lt;p&gt;It also voted 6 to 2, with one member abstaining, to reject the safety claim of the drug as a monotherapy to treat anxiety.
              &lt;p&gt; 
              &lt;p&gt;&quot;It&apos;s not as clear we need the alternatives as much as we do for cases of depression,&quot; said Wayne Goodman, M.D., chairman of the committee. &quot;I don&apos;t see that there&apos;s a clear advantage for this.&quot;
              &lt;p&gt; 
              &lt;p&gt;Weight gain associated with quetiapine was a major concern.
              &lt;p&gt; 
              &lt;p&gt;According to the agency&apos;s analysis of AstraZeneca&apos;s clinical trials, patients taking quetiapine gained an average of 2.6 pounds at 43 days median exposure, while the placebo group gained an average of less than half of a pound. There was some suggestion that weight gain increased over time.
              &lt;p&gt; 
              &lt;p&gt;That might seem like an inconsequential weight gain, but, said Frank Greenway, M.D., medical director Pennington Biomedical Research Center, Baton Rouge, La., &quot;it&apos;s remarkable how a small amount of weight gain can be detrimental in terms of diabetes.&quot;
              &lt;p&gt; 
              &lt;p&gt;Patients receiving quetiapine also had a significant increase in fasting blood glucose and total cholesterol.
              &lt;p&gt; 
              &lt;p&gt;The panel also worried that quetiapine may carry a risk of sudden cardiac death, apparently a class effect of atypical antipsychotics.
              &lt;p&gt; 
              &lt;p&gt;(See: &lt;a href=&quot;http://www.medpagetoday.com/Psychiatry/Schizophrenia/12453&quot; target=&quot;blank&quot;&gt;Risk of Sudden Death No Less Likely with Atypical Antipsychotics&lt;/a&gt;)
              &lt;p&gt; 
              &lt;p&gt;The panel seemed troubled as well by the 1.7% risk for tardive dyskinesia  observed in the trial.
              &lt;p&gt; 
              &lt;p&gt;&quot;When you look at the unanswered questions about tardive dyskinesia, diabetes, and sudden cardiac death, you need to answer those questions before approving, especially when there are other drugs that are safer,&quot; according to Diana Zuckerman, Ph.D., president of the National Research Center for Women and Families, who spoke during the meeting&apos;s public comment period.
              &lt;p&gt; 
              &lt;p&gt;The panel also heard tearful testimony from several spouses and parents of Iraq veterans whose loved ones either died or experienced severe side effects while taking quetiapine along with other drugs for treatment of post-traumatic stress disorder. Quetiapine is not approved for the condition.
              &lt;p&gt; 
              &lt;p&gt;Quetiapine is currently approved for treatment of schizophrenia, acute bipolar depression and mania, and for maintenance therapy of bipolar disorder as an adjunct to lithium or divalproex (Depakote).
              &lt;p&gt; 
              &lt;p&gt;The FDA does not have to follow its advisory panels&apos; recommendations, but it usually does. 
    </recommendedItem>
    <recommendedItem id="20090101_19_2565"
                     title="FDA Okays New Antipsychotic for Schizophrenia, Bipolar Disorder"
                     score="-0.005"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/15537?impressionId=1265798389370"
                     
      &lt;p&gt;WASHINGTON  --  The FDA approved the atypical antipsychotic asenapine (Saphris) for schizophrenia and bipolar disorder in adults, making it the first psychotropic drug to gain initial approval for both conditions.&lt;/p&gt;
&lt;p&gt;The drug is indicated for first-line use in acute treatment of schizophrenia and of manic or mixed episodes in bipolar I disorder, with or without psychotic features.&lt;/p&gt;
&lt;p&gt;FDA approval was based on data from more than 3,000 patients showing statistically significant efficacy versus placebo in acute schizophrenia trials and statistically significant reduction of bipolar mania symptoms versus placebo.&lt;/p&gt;
&lt;p&gt;The drug showed signs of treating negative schizophrenia symptoms better than risperidone (Risperdal) in early clinical trials, but the advantage was not subsequently confirmed against olanzapine (Zyprexa, Zydis). (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/APA/14371&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/APA/14371&quot; target=&quot;_blank&quot;&gt;APA: New Drug No Better for Negative Schizophrenia Symptoms&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Like other atypical antipsychotics, asenapine&apos;s side effects include sedation, weight gain, tardive dyskinesia, and diabetes risks. However, a clinical trial showed that asenapine&apos;s rate of weight gain was significantly lower than that experienced with olanzapine, a similar antipsychotic.&lt;/p&gt;
&lt;p&gt;Atypical antipsychotics also show an increased likelihood of death in elderly patients treated for dementia-related psychosis.&lt;/p&gt;
&lt;p&gt;The tablets are available in five and 10 mg doses and should be taken twice daily.&lt;/p&gt;
&lt;p&gt;Manufacturer Schering-Plough said it plans to make the drug available in the fourth quarter of 2009.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20090101_19_1411"
                     title="FDA Approves Iloperidone for Schizophrenia"
                     score="-0.005"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/14094?impressionId=1265798389370"
                     
      WASHINGTON, May 7 -- The FDA has cleared the long-delayed antipsychotic drug iloperidone (Fanapt) for marketing as therapy for adult schizophrenia.
              &lt;p&gt; 
              &lt;p&gt;Iloperidone is a mixed dopamine D2/serotonin 5-HT2A receptor antagonist and is a member of the atypical antipsychotic drug class.
              &lt;p&gt; 
              &lt;p&gt;The agent had been dropped from development a decade ago after initial clinical trial results indicated it was less effective than other schizophrenia medications including risperidone (Risperdal) and haloperidol (Haldol).
              &lt;p&gt; 
              &lt;p&gt;Rights to the drug were sold to Vanda Pharmaceuticals, which conducted new trials including ziprasidone (Geodon) as the active comparator.
              &lt;p&gt; 
              &lt;p&gt;In the pivotal 593-patient, four-week trial leading to the new approval, iloperidone matched ziprasidone in improving scores on the Positive and Negative Syndrome Scale (PANSS) and both drugs were significantly better than placebo. (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/APA/9376&quot; target=&quot;blank&quot;&gt;APA: Sidelined Schizophrenia Drug Makes a Comeback&lt;/a&gt;)
              &lt;p&gt; 
              &lt;p&gt;Iloperidone also demonstrated efficacy in a separate placebo-controlled trial that lasted six weeks.
              &lt;p&gt; 
              &lt;p&gt;The recommended target dose range is 12 to 24 mg/day.
              &lt;p&gt; 
              &lt;p&gt;The most common adverse reactions in iloperidone&apos;s clinical trials were dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, drowsiness, tachycardia, and weight increase.
              &lt;p&gt; 
              &lt;p&gt;As with other atypical antipsychotics, iloperidone may affect the cardiac QTc interval, so physicians may consider prescribing iloperidone after other antipsychotics are tried first, according to the company.
              &lt;p&gt; 
              &lt;p&gt;Iloperidone will not be commercially available until later this year. 
             
    </recommendedItem>
</recommendedContent>