FDA ALERT [7/2005] – Suicidal Thoughts or Actions in Children and Adults

Patients with depression or other mental illnesses often think about or attempt suicide. Closely watch anyone taking antidepressants, especially early in treatment or when the dose is changed. Patients who become irritable or anxious, or have new or increased thoughts of suicide or other changes in mood or behavior (or their care givers) should contact their healthcare professional right away.

Children

Taking antidepressants may increase suicidal thoughts and actions in about 1 out of 50 people 18 years or younger. Although nefazodone is prescribed for children, FDA has not approved nefazodone for use in children.

Adults

Several recent scientific publications report the possibility of an increased risk for suicidal behavior in adults who are being treated with antidepressant medications. Even before these reports became available, FDA began a complete review of all available data to determine whether there is an increased risk of suicidal thinking or behavior in adults being treated with antidepressant medications. It is expected that this review will take a year or longer to complete. In the meantime, FDA is highlighting that adults being treated with antidepressant medication, particularly those being treated for depression, should be watched closely for worsening of depression and for increased suicidal thinking or behavior.

FDA approved labeling for nefazodone contains a serious warning about the risk of liver failure

WARNING: LIFE THREATENING LIVER FAILURE
Nefazodone may cause serious liver problems, which may lead to death. Patients with active liver disease or with high levels on liver function tests should not take nefazodone. Call your healthcare professional right away if you get any of the following symptoms while taking nefazodone because you may be getting a liver problem:

• Yellowing of the skin or whites of eyes (jaundice)
• Unusually dark urine
• Loss of appetite that lasts several days or longer
• Nausea or lower stomach (abdominal) pain

What Is Nefazodone?

Nefazodone is a medicine that is used to treat depression.

Who Should Not Take Nefazodone?

Never take nefazodone if you:

• Have liver problems
• Are allergic to the medicine Desyrel (trazodone)
• Take the following medicines:
  • Halcion (triazolam), a drug to treat trouble sleeping. Nefazodone can increase the amount of Halcion in your body, causing serious side effects.
  • Orap (pimozide), a drug to treat Tourette’s syndrome, because it can result in serious heartbeat problems.
  • Tegretol (carbamazepine), a drug to control seizures. Tegretol can reduce the amount of nefazodone in your body so that it does not help your depression.
• Take another drug used to treat depression, called a Monoamine Oxidase Inhibitor (MAOI), or if you have stopped taking a MAOI in the last 14 days. Taking nefazodone close in time to a MAOI can result in serious, sometimes fatal, reactions, including:
  • High body temperature
  • Coma
  • Seizures (convulsions)

MAOI drugs include Nardil (phenelzine sulfate), Parnate (tranylcypromine sulfate), Marplan (isocarboxazid), and other brands.

What Are The Risks?

• Life-threatening liver failure. See Warning.
• Suicidal thought or actions. See FDA Alert.
• Low blood pressure (postural hypotension) and fainting. Low blood pressure can be serious for people with heart problems, strokes, dehydration, and who take medicines to control blood pressure.
• Mania: You may become hyperactive, excitable or elated.
• Seizures. You may have a seizure (convulsion), even if you are not taking nefazodone close in time with a MAOI.
• An erection that won't go away (priapism). Get medical help right away for an erection that lasts for more than 4 hours.
• Other side effects include sleepiness, dry mouth, nausea, dizziness, constipation, weakness, lightheadedness, vision problems, and confusion
• Tell your healthcare professional about all your medical conditions especially if you have or have had heart problems, a heart attack, a stroke, or mania; if you are pregnant or plan to become pregnant; or if you are breast-feeding or plan to breast-feed your baby.

Are There Any Interactions With Medicines Or Foods?

• Nefazodone can interact with Xanax (alprazolam), an anti-anxiety medicine. Your dose of Xanax should be decreased if used with nefazodone.
• Nefazodone may interact with medicines other than the ones already mentioned in this information sheet, causing serious side effects. Tell your healthcare professional about all the medicines, vitamins, and herbal supplements you take, especially medicines for mental illness, depression, seizures, and immunosuppressants.
• If you plan to drink alcohol, talk to your healthcare professional.

How Do I Take Nefazodone?

Nefazodone is taken by mouth, with or without food, twice a day.

Is There Anything Else I Need To Know?

You can get more information about antidepressants at: www.fda.gov/cder/drug/antidepressants/default.htm

FDA Alert [7/2005]: Suicidality in Pediatric and Adult Patients

All patients being treated with any type of antidepressants should be observed closely for clinical worsening and suicidality especially during the first few months of therapy and when the dose is modified.

Pediatrics

FDA has concluded that suicidal thinking or behavior may increase in pediatric patients treated with any type of antidepressant, especially early in treatment. Increases in suicidal thinking or behavior due to drug can be expected in about 1 out of 50 treated pediatric patients. Note that, although nefazodone is prescribed for pediatric patients, it is not approved by FDA for use in pediatric patients.

Adults

Several recent scientific publications report the possibility of an increased risk for suicidal behavior in adults who are being treated with antidepressant medications. Even before these reports became available, FDA began a complete review of all available data to determine whether there is an increased risk of suicidality (suicidal thinking or behavior) in adults being treated with any type of antidepressant medication. It is expected that this review will require a year or longer to complete. In the meantime, FDA is highlighting that adults being treated with any type of antidepressant medication, particularly those being treated for depression, should be watched closely for worsening of depression and for increased suicidal thinking or behavior.

Recommendations

All patients being treated with any type of antidepressant for any indication should be 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. For pediatric patients, such observation would generally include at least weekly face-to-face contact with patients or their family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks. Additional contact by telephone may be appropriate between face-to-face visits. Adults whose symptoms worsen while being treated with antidepressant medications, including an increase in suicidal thinking or behavior, should be evaluated by their healthcare professional.

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.

Data Summary

Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4 percent, twice the placebo risk of 2 percent. No suicides occurred in these trials; however, the duration of treatment was limited. Spontaneous post-marketing reports of suicide-related events associated with the use of SSRIs, including suicidal ideation, suicide attempt, self-mutilation and completed suicide have been received. Because these events may also be related to underlying psychiatric illness, definitive evaluation of the effects of SSRIs on suicide related events from post-marketing reports alone is not possible, and the data from controlled clinical trials is more informative.

Although there are no similar comprehensive data linking the use of antidepressant medications and an increased risk of suicidality in adults, FDA has initiated a complete review of all available data. FDA has asked the manufacturers of all marketed antidepressants to identify all placebo-controlled clinical trials conducted in adults in their development programs for their antidepressant products, regardless of the indication studied, and to provide information from these trials to FDA. Manufacturers are being asked to use a similar approach to assembling this information as was used in evaluating the risk of suicidality in placebo-controlled trials in pediatric patients treated with antidepressant medications.

Date created: May 2005, updated May 9, 2007