Study: Use of antipsychotic drugs improves life expectancy for individuals with schizophrenia

Results of a Johns Hopkins study suggest that individuals with schizophrenia are significantly more likely to live longer if they take their antipsychotic drugs on schedule, avoid extremely high doses and also regularly see a mental health professional. Psychiatrists have long known that people with schizophrenia who stick to a drug regimen have fewer of the debilitating delusions and hallucinations that are hallmarks of this illness. But there have been concerns about whether some of the known side effects of the medications — increased risk of cardiovascular disease and diabetes, for example — carry higher mortality risks, the researchers say. "We know that antipsychotic medications reduce symptoms, and our study shows that staying on reasonable, recommended doses is associated with longer life," says Bernadette A. Cullen, M.B., B.Ch., B.A.O., MRCPsych, an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, and leader of the study published in Schizophrenia Bulletin. "The same is true for going to see a psychiatrist or therapist," she says, noting that regular visits to a mental health professional are one way to monitor and encourage drug-use compliance, but also in and of themselves increased survival in this vulnerable population. Cullen and her colleagues analyzed data collected between 1994 through 2004 on 2,132 adult Maryland Medicaid beneficiaries with schizophrenia. The researchers reviewed how much medication the patients took, how regularly they took it and how often they visited a mental health professional. The goal of the study was to review how adherence to the 2009 pharmacological Schizophrenia Patient Outcomes Research Team (PORT) guidelines was associated with mortality in this population. Comparing data from year to year, the researchers found that among those patients who had 90 percent or better compliance with their medication schedules, the risk of death was 25 percent lower compared to those who were less than 10 percent compliant. Over the decade-long study period, taking medication did not increase the risk of death and there was a trend towards reducing the mortality rate. In addition, the researchers found that each additional visit per year to a mental health professional was linked to a 5 percent reduction in risk of death overall LSW Continuing Education Cullen's study did not rule out all links between increased mortality and antipsychotic drugs. For example, her team found that people who took high doses of first-generation antipsychotic medication daily (1500 mg or greater chlorpromazine equivalents) were 88 percent more likely to die. She says mortality rates possibly increased in this group because first-generation antipsychotics have been associated with cardiac disease risks, and among those who died while taking the larger doses, 53 percent died of cardiovascular disease. "These drugs work very well, but there is clearly a point of diminishing returns," she says. "You rarely need to be on extremely high doses." Among those whose information was reviewed, the most common cause of death was cardiovascular disease (28 percent); unintended harm, including suicide, was responsible for 8 percent. "If people are taking their medications, they usually have fewer symptoms and are able to be more organized in other areas of their lives," says Cullen, director of community psychiatry at The Johns Hopkins Hospital. "We believe they are then more likely to make appointments with their primary care doctors, to stay on top of other illnesses they may have and to regularly take diabetes, blood pressure or cholesterol medication that they may require to stay healthy. We also believe that they are more likely to be socially engaged and have a healthier lifestyle." "If your illness is under control, you can do a lot more," she adds. Cullen says the study clearly lays out the value of mental health providers to individuals with schizophrenia. Those who saw therapists or psychiatrists were more likely to survive, regardless of whether the individual also took his or her antipsychotic medication on a regular basis, she says. This finding is crucial, she says, given that Maryland Medicaid officials are considering capping the number of mental health visits allowed each year, something the data now suggest is potentially detrimental to survival. Cullen notes that adherence to a medication regimen and moderate first-generation antipsychotic dosing are both part of the 2009 PORT recommendations designed to guide treatment. ### The study was supported by a grant from the National Institutes of Health's National Institute of Mental Health (R01MH074070). Other Johns Hopkins researchers involved in the study include Emma E. McGinty, M.S.; Yiyi Zhang, Ph.D.; Susan dos Reis, Ph.D.; Donald M. Steinwachs, Ph.D.; Eliseo Guallar, M.D., Dr.PH.; and Gail L. Daumit, M.D., M.H.S. For more information: http://www.hopkinsmedicine.org/psychiatry/specialty_areas/community_psych/

Reducing off-label use of antipsychotic medications may save money

Reducing the non-FDA-approved use of antipsychotic drugs may be a way to save money while having little effect on patient care, according to a Penn State College of Medicine study. Researchers say that 57.6 percent of patients prescribed antipsychotic medications in data from 2003 did not have schizophrenia or bipolar disorder, the conditions for which the drugs were approved for use. Use of medication for treatments that is not FDA-approved is called off-label use. "Given healthcare reform and widespread crisis in state revenues, state Medicaid programs will be under pressure to serve larger patient populations, increasing their fiscal stress," said Douglass L. Leslie, Ph.D., professor of public health sciences. "Medicaid prescription drug programs covered 75 percent of all antipsychotic prescription medications in the United States in 2002. Reducing off-label antipsychotic use may generate savings with little impact on patient outcomes." Researchers looked at data for 42 states from 2003, the latest data available at the time of analysis, from the Centers for Medicare & Medicaid Services. They report their results in a recent issue of American Journal of Managed Care. Patients in a Medicaid fee-for-service plan for the entire year were chosen using de-identified patient information that could not be traced to the individuals. The researchers chose patients without a diagnosis of either schizophrenia or bipolar disorder during 2003 who received an antipsychotic medication. During 2003, 372,038 patients received an antipsychotic medication. Of these patients, 214,113, or 57.6 percent, did not have a diagnosis of schizophrenia or bipolar disorder. Diagnoses included other mental disorders: 35 percent, minor depression -- 25.4 percent, major depression -- 23.2 percent, no mental disorder -- 18.8 percent, conduct disorder -- 18.8 percent, and anxiety disorder -- 16.2 percent. "A high rate of off-label antipsychotic use would not necessarily be of concern if there were scientific evidence supporting the effectiveness of these medications for conditions other than schizophrenia and bipolar disorder," Leslie said. Off-label use is supported in the medical community, with the American Academy of Neurology endorsing the use of quinine for treatment-resistant leg cramps, for example. Since 2003, some of the antipsychotic medications have been approved by the FDA for the treatment of other conditions, including irritability in autism and treatment-resistant depression. However, at the time the data were collected they were considered off-label. The rate of off-label use of antipsychotics is high compared to other medications. Other studies have shown off-label medication use includes cardiovascular drugs: 46 percent, anticonvulsants -- 46 percent, and antiasthmatics -- 42 percent. "Antipsychotics were the highest selling medication class at $14.6 billion in 2009," Leslie said. "Medicaid bears a significant proportion of these costs. Hence, off-label use may be responsible for a considerable portion of state Medicaid budgets, with little or no documented clinical benefit and a substantial risk of adverse effects. Off-label use may be an area of potential savings with little impact on patient outcomes." The newest antipsychotic drugs can cost up to $10 per day at doses recommended for patients with schizophrenia. According to the researchers, more research is needed to determine if off-label use of antipsychotic medications yields substantial clinical benefit and to identify how doctors decide to prescribe these drugs for non-FDA approved conditions. Reasons why drugs may be prescribed off-label include a lack of research results showing the drug's effectiveness in certain patients or for other conditions, or that the drugs may be used as a last resort for those patients who have not responded to other treatments. Further research is needed on the decision-making process of doctors to prescribe off-label. "Where there is limited evidence of clinical benefit, greater caution should probably be used before prescribing these drugs off-label because they can have hazardous side effects," Leslie said. ### This study was funded in part by a grant from the National Institute of Mental Health and by the Department of Veterans Affairs Mental Illness Research, Education and Clinical Center. Researchers are continuing their analysis by incorporating newer data that was recently released. Also part of this study is Robert Rosenheck, M.D., Yale School of Medicine. Continuing Education for Social Workers

Dual medications for depression increases costs, side effects with no benefit to patients

Taking two medications for depression does not hasten recovery from the condition that affects 19 million Americans each year, researchers at UT Southwestern Medical Center have found in a national study. "Clinicians should not rush to prescribe combinations of antidepressant medications as first-line treatment for patients with major depressive disorder," said Dr. Madhukar H. Trivedi, professor of psychiatry and chief of the division of mood disorders at UT Southwestern and principal investigator of the study, which is available online today and is scheduled for publication in an upcoming issue of the American Journal of Psychiatry. "The clinical implications are very clear – the extra cost and burden of two medications is not worthwhile as a first treatment step," he said. In the Combining Medication to Enhance Depression Outcomes, or CO-MED, study, researchers at 15 sites across the country studied 665 patients ages 18 to 75 with major depressive disorder. Three treatment groups were formed and prescribed antidepressant medications already approved by the Food and Drug Administration. One group received escitalopram (a selective serotonin reuptake inhibitor, or SSRI) and a placebo; the second group received the same SSRI paired with bupropion (a non-tricyclic antidepressant); and a third group took different antidepressants: venlafaxine (a tetracyclic antidepressant) and mirtazapine (a serotonin norepinephrine reuptake inhibitor). The study was conducted from March 2008 through February 2009 LSW Continuing Education After 12 weeks of treatment, remission and response rates were similar across the three groups: 39 percent, 39 percent and 38 percent, respectively, for remission, and about 52 percent in all three groups for response. After seven months of treatment, remission and response rates across the three groups remained similar, but side effects were more frequent in the third group. Only about 33 percent of depressed patients go into remission in the first 12 weeks of treatment with antidepressant medication, as Dr. Trivedi and colleagues previously reported from the Sequenced Treatment Alternatives to Relieve Depression, or STAR*D, study. STAR*D was the largest study ever undertaken on the treatment of major depressive disorder and is considered a benchmark in the field of depression research. That six-year, $33 million study initially included more than 4,000 patients from sites across the country. Dr. Trivedi was a co-principal investigator of STAR*D. The next step, Dr. Trivedi said, is to study biological markers of depression to see if researchers can predict response to antidepressant medication and, thus, improve overall outcomes. ### Other UT Southwestern researchers involved in the study were Drs. Benji Kurian and David Morris, assistant professors of psychiatry; Dr. Diane Warden, associate professor of psychiatry; and Dr. Mustafa Husain, professor of psychiatry, internal medicine, and neurology and neurotherapeutics. Former UT Southwestern professor Dr. A. John Rush, now with the Duke-NUS Graduate Medical School in Singapore, and researchers from the University of Pittsburgh; Massachusetts General Hospital; Columbia University College of Physicians and Surgeons; the University of California, Los Angeles; Vanderbilt University; Harbor-UCLA Medical Center; Virginia Commonwealth University; and Columbia University Medical Center also contributed. The study was funded by the National Institute of Mental Health. Forest Pharmaceuticals, GlaxoSmithKline, Organon and Wyeth Pharmaceuticals provided the medications. Visit http://www.utsouthwestern.org/neurosciences to learn more about UT Southwestern's clinical services in neurosciences, including psychiatry. This news release is available on our World Wide Web home page at www.utsouthwestern.edu/home/news/index.html To automatically receive news releases from UT Southwestern via email, subscribe at www.utsouthwestern.edu/receivenews