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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=1265785126601"
                     
       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=1265785126601"
                     
      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_1082"
                     title="FDA Panel Recommends Limited Use of Investigational Antipsychotic"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Psychiatry/Schizophrenia/tb/13646?impressionId=1265785126601"
                     
       SILVER SPRING, Md., April 7 -- An FDA advisory panel voted to recommend FDA approval for sertindole (Serdolect) to treat schizophrenia, but only for a subgroup of patients that the agency would have to define.
              &lt;p&gt; 
              &lt;p&gt;The lukewarm backing came in part because of studies showing that patients taking sertindole were more than four times as likely to die suddenly, compared with another atypical antipsychotic, risperidone (Risperdal). 
              &lt;p&gt; 
              &lt;p&gt;In fact, the Psychopharmacologic Drugs Advisory Committee voted 12 to 1 that the drug is not &quot;acceptably safe&quot; for the general schizophrenic population.  
              &lt;p&gt; 
              &lt;p&gt;But the panel unanimously agreed the drug is effective and then voted 8 to 2, with three members abstaining, that some patients might benefit from having sertindole as an option. 
              &lt;p&gt; 
              &lt;p&gt;The committee did not clearly identify those patients, however, leaving it to the FDA to decide which patients, if any, should receive the drug, manufactured by Lundbeck and currently marketed in other countries.
              &lt;p&gt; 
              &lt;p&gt;One panelist suggested that sertindole only be prescribed for schizophrenics who have not responded to other drugs, and another suggested performing cardiac tests to give some hint of whether a patient might be at increased risk for heart problems. 
              &lt;p&gt; 
              &lt;p&gt;&quot;I would hope this is a treatment of last resort,&quot; said Gail Griffith, M.S., the consumer representative on the panel.
              &lt;p&gt; 
              &lt;p&gt;Sertindole prolongs the heart&apos;s QT interval, which may lead to major cardiac problems, including sudden death. In the sponsor&apos;s trial, there were 13 sudden cardiac deaths among patients taking sertindole and three among patients taking risperidone (&lt;em&gt;P&lt;/em&gt;=0.002).
              &lt;p&gt; 
              &lt;p&gt;&quot;The cardiovascular risk is real, but I think that is counterbalanced by the need for other treatment,&quot; said Sheryl Kelsey, Ph.D., professor of epidemiology at University of Pittsburgh. Kelsey is a temporary member of the Cardiovascular and Renal Drugs Advisory Committee, which had three of its members voting on Tuesday&apos;s panel. 
              &lt;p&gt; 
              &lt;p&gt;Sudden cardiac death has been seen in other antipsychotic drugs similar to sertindole.
              &lt;p&gt; 
              &lt;p&gt;(See: &lt;a href=&quot;http://www.medpagetoday.com/Psychiatry/Schizophrenia/12453&quot; taraget=&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 also swatted away Lundbeck&apos;s proposed claim that sertindole could help prevent suicide among schizophrenic patients. About half of all schizophrenic patients attempt suicide, according to the drugmaker. 
              &lt;p&gt; 
              &lt;p&gt;But the committee voted 12 to 1 that patients taking sertindole are no less likely to contemplate, attempt, or succeed in taking their lives, compared with those taking antischizophrenia drug risperidone.  
              &lt;p&gt; 
              &lt;p&gt;An FDA analysis found that 36 sertindole-treated patients attempted suicide, compared with 54 in the risperidone group, but the difference failed to reach statistical significance.
              &lt;p&gt; 
              &lt;p&gt;The efficacy data on which the panel based its vote came from the sponsor&apos;s trials involving more than 10,000 patients.
              &lt;p&gt; 
              &lt;p&gt;These studies adequately proved the short-term antipsychotic efficacy of 12- to 20-mg daily doses of sertindole, according to the lead FDA staff reviewer, psychiatrist Phillip Kronstein, M.D.
              &lt;p&gt; 
              &lt;p&gt;The FDA does not have to follow the advice of its advisory panels, but it usually does.  
              &lt;p&gt; 
              &lt;p&gt;(See: &lt;a href=&quot;http://www.medpagetoday.com/Psychiatry/Schizophrenia/13619&quot; target=&quot;blank&quot;&gt;FDA Review Questions Cardiac, Suicide Risks for Investigational Antipsychotic&lt;/a&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=1265785126601"
                     
      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>
    <recommendedItem id="20090101_19_2457"
                     title="FDA Okays First Monthly Antipsychotic Drug"
                     score="-0.005"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/15391?impressionId=1265785126601"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has approved the injectable maintenance drug paliperidone palmitate (Invega Sustenna), making it the first once-monthly, atypical antipsychotic for schizophrenia.&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;The long-acting drug is approved for both acute and maintenance treatment.&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;The parent drug  --  paliperidone in a once-daily tablet  --  is an active metabolite of an old pharmaceutical, the atypical antipsychotic risperidone (Risperdal). (See &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/4741&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/4741&quot; target=&quot;_blank&quot;&gt;Invega (paliperidone), Son of Risperdal (risperidone), Wins FDA Okay for Schizophrenia&lt;/a&gt;)&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;Researchers see once-monthly dosing as a potential solution for the medication adherence problems common in schizophrenia, noted Henry A. Nasrallah, MD, of the University of Cincinnati, an investigator in the paliperidone palmitate clinical trials.&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;&quot;Inconsistent compliance with medications is arguably one of the single greatest impediments to managing the symptoms of schizophrenia and delaying the time to relapse,&quot; he said in a prepared statement.&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;Approval of the new, once-monthly formulation was based on four studies of acute symptom control and a longer-term, placebo-controlled maintenance study.&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;The maintenance study found significantly longer time-to-first relapse (the primary endpoint) among patients receiving paliperidone palmitate, compared with placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;During the double-blind phase of the study, relapse rates were 10% and 34%, respectively. (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/APA/9371&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/APA/9371&quot; target=&quot;_blank&quot;&gt;APA: Injectable Atypical Drug Slows Schizophrenia Recurrence&lt;/a&gt;)&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;Paliperidone palmitate comes in prefilled syringes. Recommended dosing starts with 234 mg and 156 mg injections into the deltoid muscle one week apart, followed by monthly 117 mg doses in the deltoid or gluteal muscle.&lt;/p&gt;&lt;p class=&quot;MsoNormal&quot;&gt;Paliperidone palmitate is not approved for treating dementia-related psychosis in the elderly, as clinical studies showed an increased likelihood of death.&lt;/p&gt;&lt;p&gt;Other potential negative side effects include weight gain, hyperglycemia, &lt;span&gt; &lt;/span&gt;neuroleptic malignant syndrome, altered heart rhythm, and tardive dyskinesia.&lt;/p&gt;&lt;p&gt;The drug is manufactured by Janssen Pharmaceurticals of Titusville, N.J.&lt;/p&gt;
    </recommendedItem>
</recommendedContent>