Bipolar Support Groups.com blog

Revisions to Product Labeling

[These changes should be made to the box warning at the beginning of the package insert.]

DRUG NAME Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders.

Anyone considering the use of [Insert established name] or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older.

Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior.

Families and caregivers should be advised of the need for close observation and communication with the prescriber. [Insert Drug Name] is not approved for use in pediatric patients. [The previous sentence would be replaced with the sentence, below, for the following drugs: Prozac: Prozac is approved for use in pediatric patients with MDD and obsessive compulsive disorder (OCD). Zoloft: Zoloft is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD). Fluvoxamine: Fluvoxamine is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD).]

(See Warnings: Clinical Worsening and Suicide Risk, Precautions: Information for Patients, and Precautions: Pediatric Use) [The following changes should be made to the current language under the WARNINGS-Clinical Worsening and Suicide Risk section.]

WARNINGS-Clinical Worsening and Suicide Risk Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs.

Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a longstanding concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.

Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children,adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients.

There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table [add table number]. Table [add table number] Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated Drug-Related Increases <18 14 additional cases 18-24 5 additional cases Drug-Related Decreases 25-64 1 fewer case >65 6 fewer cases No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. [The labeling for the following drugs with discontinuation language would include the next paragraph: Celexa, Cymbalta, Effexor, Fluvoxamine, Lexapro, Paxil, Pexeva, Prozac, Sarafem, Symbyax, and Zoloft.]

If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see PRECAUTIONS and DOSAGE AND ADMINISTRATION—Discontinuation of Treatment with [Insert established name], for a description of the risks of discontinuation of [Insert established name]).

Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers.

Prescriptions for [Insert Drug Name] should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown.

However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that [Insert Drug Name] is not approved for use in treating bipolar depression. [The previous sentence would be replaced for the following drugs: Seroquel: It should be noted that Seroquel is approved for use in treating adult bipolar depression. Symbyax: It should be noted that Symbyax is approved for use in treating adult bipolar depression. [The following changes should be made in current language under the PRECAUTIONS-Information for Patients section.]

PRECAUTIONS-Information for Patients Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with [Insert Drug Name] and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for [Insert Drug Name]. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents.

Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking [Insert Drug Name]. Clinical Worsening and Suicide Risk: Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down.

Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.

Two Goals you might start with are getting well and staying well. Start by asking yourself these questions?

What am I like when I am feeling / doing well? ___________________________________________________________________________.

What are the things that help me maintain or regain the quality of life that I like?

____________________________________________________________________________

____________________________________________________________________________

___________________________________________________________________________.

What can I do to maintain my wellness?

DAILY: _____________________________________________________________________

WEEKLY: ____________________________________________________________________

MONTHLY: ___________________________________________________________________

Early warning signs

What early warning signs of my illness have I noticed or been told about by others?

FEELINGS _____________________________________________________________________

THOUGHTS _____________________________________________________________________

EMOTIONS ______________________________________________________________________

SENSATIONS ____________________________________________________________________

ACTIONS ________________________________________________________________________

WORDS __________________________________________________________________________

What can I do when these warning signs happen? 

___________________________________________________________________________

___________________________________________________________________________.

Who can help me? 

___________________________________________________________________________

How can I get in touch with them? 

___________________________________________________________________________

What should they say or do? 

____________________________________________________________________________

___________________________________________________________________________.

What are some things I can do that might help me feel better?

____________________________________________________________________________

____________________________________________________________________________

___________________________________________________________________________.

Mental Illness and the Family: Finding the Right Mental Health Care For You[/size]
If you or someone you know may benefit from a counselor or mental health center, here are some questions and guidelines to help you find the right care.

Where Can I Go For Help?

Where you go for help will depend on who has the problem (an adult or child) and the nature of the problem and/or symptoms. Often, the best place to start is your local Mental Health Association. Check your Yellow Pages for a listing or calling Mental Health America.
Other suggested resources:

• Your local health department’s Mental Health Division. These services are state funded and are obligated to first serve individuals who meet “priority population criteria” as defined by the state Mental Health Department. There may be waiting lists and not all individuals may be eligible for services. In some jurisdictions local funding is provided for additional services.
• Other mental health organizations
• Family physician
• Clergyperson
• Family services agencies, such as Catholic Charities, Family Services, or Jewish Social Services
• Educational consultants or school counselors
• Marriage and family counselors
• Child guidance counselors
• Psychiatric hospitals accredited by the Joint Commission on Accreditation of Health Care Organizations
• Hotlines, crisis centers, and emergency rooms (call 411 for Directory Assistance)

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Which Mental Health Professional Is Right For Me?

There are many types of mental health professionals. Finding the right one for you may require some research. Often it is a good idea to first describe the symptoms and/or problems to your family physician or clergy. He or she can suggest the type of mental health professional you should call.

Types of Mental Health Professionals

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• Psychiatrist – medical doctor with special training in the diagnosis and treatment of mental and emotional illnesses. Like other doctors, psychiatrists are qualified to prescribe medication.
  Qualifications: should have a state license and be board eligible or certified by the American Board of Psychiatry and Neurology.
• Child/Adolescent Psychiatrist – medical doctor with special training in the diagnosis and treatment of emotional and behavioral problems in children. Child/Adolescent psychiatrists are qualified to prescribe medication.
  Qualifications: should have a state license and be board eligible or certified by the American Board of Psychiatry and Neurology.
• Psychologist – Psychologist with a doctoral degree in psychology from an accredited/designated doctoral program in psychology and two years of supervised professional experience, including a year long internship from an approved internship. Trained to make diagnoses and provide individual and group therapy.
  Qualifications: and for some psychologists, credentialing as a health service provider in psychology.
• Clinical Social Worker – Counselor with a masters degree in social work from an accredited graduate program. Trained to make diagnoses and provide individual and group counseling.
  Qualifications: state license; may be member of the Academy of Certified Social Workers.
• Licensed Professional Counselor – Counselor with a masters degree in psychology, counseling or a related field. Trained to diagnose and provide individual and group counseling.
  Qualifications: state license
• Mental Health Counselor – Counselor with a masters degree and several years of supervised clinical work experience. Trained to diagnose and provide individual and group counseling.
  Qualifications: certification by the National Academy of Certified Clinical Mental Health Counselors.
• Certified Alcohol and Drug Abuse Counselor – Counselor with specific clinical training in alcohol and drug abuse. Trained to diagnose and provide individual and group counseling.
  Qualifications: state license
• Nurse Psychotherapist – A registered nurse who is trained in the practice of psychiatric and mental health nursing. Trained to diagnose and provide individual and group counseling.
  Qualifications: certification, state license.
• Marital and Family Therapist – A counselor with a masters degree, with special education and training in marital and family therapy. Trained to diagnose and provide individual and group counseling.
  Qualifications: state license
• Pastoral Counselor – Clergy with training in clinical pastoral education Trained to diagnose and provide individual and group counseling.
  Qualifications: Certification from American Association of Pastoral Counselors.

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You Make The Call To The Mental Health Professional…Now What Do You Do?

Spend a few minutes talking with him or her on the phone, ask about their approach to working with patients, their philosophy, whether or not they have a specialty or concentration (some psychologists for instance specialize in family counseling, or child counseling, while others specialize in divorce or coping with the loss of a loved one.) If you feel comfortable talking to the counselor or doctor, the next step is to make an appointment.
On your first visit, the counselor or the doctor, will want to get to know you and why you called him or her. The counselor will want to know– what you think the problem is, about your life, what you do, where you live, with whom you live. It is also common to be asked about your family and friends. This information helps the professional to assess your situation and develop a plan for treatment.
If you don’t feel comfortable with the professional after the first, or even several visits, talk about your feelings at your next meeting; Don’t be afraid to contact another counselor. Feeling comfortable with the professional you choose is very important to the success of your treatment.

Types Of Treatment

Psychotherapy is a method of talking face-to-face with a therapist. The following are a few of the types of available therapy:
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• Behavior Therapy – Includes stress management, biofeedback and relaxation training to change thinking patterns and behavior.
• Psychoanalysis – Long-term therapy meant to “uncover” unconscious motivations and early patterns to resolve issues and to become aware of how those motivations influence present actions and feelings.
• Cognitive Therapy – Seeks to identify and correct thinking patterns that can lead to troublesome feelings and behavior.
• Family Therapy – Includes discussion and problem-solving sessions with every member of the family.
• Movement/Art/Music Therapy – These methods include the use of movement, art or music to express emotions. Effective for persons who cannot otherwise express feelings.
• Group Therapy – Includes a small group of people who, with the guidance of a trained therapist, discuss individual issues and help each other with problems.

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Drug Therapy–Drugs can be beneficial to some persons with mental or emotional disorders. The patient should ask about risk, possible side-effects and interaction with certain foods, alcohol and other medications. Medication should be taken in the prescribed dosage and at prescribed intervals and should be monitored daily.
Electric Convulsive Treatment (ECT) — Used to treat some cases of major depression, delusions, and hallucinations, or life-threatening sleep and eating disorders that can not be effectively treated with drugs and/or psychotherapy. Discuss with your physician about the risks and side effects of ECT.

Am I Getting The Care I Need?

As you progress through the therapeutic process, you should begin to feel gradual relief from your distress, to develop self assurance, and have a greater ability to make decisions and increased comfort in your relationship with others. Therapy may be painful and uncomfortable at times but episodes of discomfort occur during the most successful therapy sessions. Mental health treatment should help you cope with your feelings more effectively.
If you feel you are not getting results, it may be because the treatment you are receiving is not the one best suited to your specific needs. If you feel there are problems, discuss them with your therapist. A competent therapist will be eager to discuss your reactions to therapy and respond to your feeling about the process. If you are still dissatisfied, a consultation with another therapist may help you and your therapist evaluate your work together.

What About Self-Help/Support Groups?

Self-help support groups bring together people with common experiences. Participants share experiences, provide understanding and support and help each other find new ways to cope with problems.
There are support groups for almost any concern including alcoholism, overeating, the loss of a child, co-dependency, grand parenting, various mental illnesses, cancer, parenting, and many, many others.

Mental illness in the family is Hospitalization Necessary:

Of the 5.4 million people who sought mental health treatment in 1990, less than 7% required hospitalization. More than half of those who needed inpatient-care had schizophrenia, one of the most severe forms of mental illness. If you or someone you know may have a mental illness, the chances are that you will not need hospitalization. But, if you do, the following information will help assure you of the best care possible.

Questions To Ask:

• Has the person been professionally evaluated? By whom? Do I understand the diagnosis?
• If the patient has not been evaluated, why am I seeking admission for the person? a) A doctor’s recommendation? b) Need to have patient removed from family situation? Why? Because of behavioral problems? c) What are they? Because family cannot care for him or her? Why? d) What symptoms is the patient exhibiting which cause concern?

The Hospital/Treatment Center At Check-In:

• Does your facility treat patients only for this specific diagnosis?
• If the patient has other health or emotional problems will he/she receive treatment for these problems also?
• Does your facility require tests when admitted? If so, what are they?
• Who will perform these tests?
• Who will evaluate the patient when he/she is admitted?
• What are the person’s qualifications/ title?
• Will this person continue to treat the patient?
• Will the patient be seen by this professional on a regular basis?
• When will the initial evaluation take place?

During the Patient’s Stay:

• When can I (or another family member) talk to the therapist or doctor?
• Will we be able to discuss treatment with the doctor or therapist? When? How often?
• When can family members visit? For how long?
• Will the patient be allowed to receive phone calls?
• Will the patient have a daily schedule of activities or treatments?
• If so, what activities will the patient be involved in?
• Is therapy group or private and is it part of the treatment plan?
• What clothes should the patient bring?
• How long will the patient be at the facility?
• Who makes this decision?
• Will the family be advised of changes in treatment?
• Who will make the evaluation for discharging the patient? When will this happen?

Leaving The Hospital:

• Will someone advise the patient and family about adjustment concerns such as the need for further counseling or a medication schedule?
• What can we expect when the patient is discharged?
• Will he/she be on medications? Which ones?
• How will these medications help? Are they habit-forming? What are the side effects? What is the dosage?
• How long will the patient have to take this medication?
• If the patient leaves the hospital without permission how will the hospital handle this?
• If this occurs, what is the parent or family’s responsibility?
• Will the patient be able to continue school work while in the hospital? Or how soon after he or she is discharged?
• If classes are offered to patients, what are they and who teaches them?
• What follow-up treatment or support group options should the family and patient consider?

Financial And Insurance Issues:

Ask the treatment center and/or insurance company the following questions:

• Does the hospital accept this type of insurance? If not, what are the alternatives? If it does, what is covered?
• Can coverage be reviewed with a member of the staff?
• Are there separate charges and how much are they for physicians, therapists or caretakers? What may these separate charges be?
• How are fees assessed?
• When will billing occur?
• If insurance only covers part of the cost, what other arrangements can be made for payments?
• Is there other assistance available? Will the facility accept partial payments or payments on a schedule?

Ask The Therapist:

• What can the patient and family expect during the treatment process?
• What can be the expected reactions/behaviors of the patient?
• How should the family respond?
• How can the patient and family prepare for unexpected behavior and possible setbacks?

Read the Medication Guide that comes with you or your family member’s antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. Talk to your, or your family member’s, healthcare provider about:

• all risks and benefits of treatment with antidepressant medicines

• all treatment choices for depression or other serious mental illness

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?

1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults when the medicine is first started.

2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.

3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member? • Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

This is very important when an antidepressant medicine is first started or when the dose is changed.

• Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.

• Keep all follow-up visits with the healthcare provider as scheduled.

Call the healthcare provider between visits as needed, especially if you have concerns about symptoms. Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying

• attempts to commit suicide

• new or worse depression

• new or worse anxiety

• feeling very agitated or restless

• panic attacks

• trouble sleeping (insomnia)

• new or worse irritability

• acting aggressive, being angry, or violent

• acting on dangerous impulses

• an extreme increase in activity and talking (mania)

• other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

• Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.

• Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.

• Antidepressant medicines have other side effects.

Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.

• Antidepressant medicines can interact with other medicines.

Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.

• Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child’s healthcare provider for more information.

This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.

FDA Drug Safety Communication:

FDA reporting mental health drug ziprasidone (Geodon) associated with rare but potentially fatal skin reactions Safety Announcement [12-11-2014]

The U.S. Food and Drug Administration (FDA) is warning that the antipsychotic drug ziprasidone (marketed under the brand name, Geodon, and its generics) is associated with a rare but serious skin reaction that can progress to affect other parts of the body.

A new warning has been added to the Geodon drug label to describe the serious condition known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Patients who have a fever with a rash and/or swollen lymph glands should seek urgent medical care. Health care professionals should immediately stop treatment with ziprasidone if DRESS is suspected. Ziprasidone is an antipsychotic drug used to treat the serious mental health disorders schizophrenia and bipolar I disorder.

Ziprasidone helps restore certain natural substances in the brain and can decrease hallucinations, delusions, other psychotic symptoms, and mania. To work properly, ziprasidone should be taken every day as prescribed. Patients should not stop taking their medicine or change their dose without first talking to their health care professional. DRESS may start as a rash that can spread to all parts of the body.

It can include fever, swollen lymph nodes, and inflammation of organs such as the liver, kidney, lungs, heart, or pancreas. DRESS also causes a higher-than-normal number of a particular type of white blood cell called eosinophils in the blood. DRESS can lead to death.

FDA reviewed information from six patients in whom the signs and symptoms of DRESS appeared between 11 and 30 days after ziprasidone treatment was started. None of these patients died (see Data Summary). Based on this information, FDA required the manufacturer of Geodon to add a new warning for DRESS to the Warnings and Precautions section of the drug labels for the capsule, oral suspension, and injection formulations.

We urge health care professionals and patients to report side effects involving ziprasidone to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.

Facts about ziprasidone (Geodon)

• Ziprasidone is an atypical antipsychotic drug used to treat schizophrenia and bipolar I disorder.
• Ziprasidone is marketed under the brand name Geodon, and as generics.
• During 2013, approximately 2.5 million prescriptions for oral formulations of ziprasidone were dispensed, and approximately 353,000 patients received a prescription for an oral formulation of ziprasidone through U.S. outpatient retail pharmacies.1 Additional Information for Patients
• Treatment with ziprasidone may cause you to have a rash.
The rash can be severe, covering much of the body. You may also have a fever and other symptoms associated with a serious condition known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
• Call your health care professional(s) and seek immediate care if you develop any of the following signs or symptoms: o Skin rash o Fever o Swollen face o Swollen lymph glands
• For ziprasidone to work properly, it should be taken every day as prescribed.
• Do not stop taking ziprasidone or change your dose without first talking to your health care professional.
• Discuss any questions or concerns about ziprasidone with your health care professional.
• Report any side effects you experience to your health care professional and the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.

Additional Information for Health Care Professionals
• Make sure your patients know that rash may occur with ziprasidone treatment and may progress to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
• Explain the signs and symptoms of severe skin reactions to your patients and tell them when to seek immediate care. • DRESS consists of three or more of the following: o cutaneous reaction (such as rash or exfoliative dermatitis) o eosinophilia o fever o lymphadenopathy, and o one or more systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, pericarditis, and pancreatitis.
• If DRESS is suspected, ziprasidone treatment should be stopped immediately.
• Report adverse reactions involving ziprasidone to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.

1 Source: IMS Health, National Prescription Audit (NPA™) and Total Patient Tracker (TPT). Year 2013, data extracted October 2014 Data Summary FDA reviewed six worldwide cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with ziprasidone use and reported to the FDA Adverse Event Reporting System (FAERS).

The six cases were temporally associated with ziprasidone, with a time to onset of symptoms from 11 days to one month after ziprasidone initiation. In three cases, a recurrence of symptoms was reported following the discontinuation and re-initiation of ziprasidone, with a faster time to onset following the re-initiation. Three of the cases reported concomitant use of drugs associated with DRESS. The cases reported serious outcomes, including hospitalization. There were no cases reporting death.

The FAERS cases support an association between ziprasidone and the development of DRESS because of the consistency of the case characteristics to the signs and symptoms of DRESS, the temporal relationship between ziprasidone initiation and the onset of symptoms, and reportedcases of positive re-challenge. Although there were no fatalities among the reported cases, DRESS is a potentially fatal drug reaction with a mortality rate of up to 10%.2

The pathogenesis of DRESS is unclear; however, it is thought to be the result of a combination of genetic and immunologic factors, such as detoxification defects in the drug metabolism pathway, resulting in toxic metabolite formation and an immune response. Reactivation of viral infections (herpes virus [HHV-6, HHV-7] or Epstein-Barr Virus [EBV]) may also play a role by inducing or amplifying the immune reaction. There is currently no specific treatment for DRESS.

The keys to managing DRESS are early recognition of the syndrome, discontinuation of the offending agent as soon as possible, and supportive care. Treatment with systemic corticosteroids should be considered in cases with extensive organ involvement.