FDA ALERT [07/2006] – Potentially Life- Threatening Serotonin Syndrome When Used With Triptan Medicines

A life-threatening condition called serotonin syndrome can happen when medicines called selective serotonin reuptake inhibitors (SSRIs), such as Celexa, and medicines used to treat migraine headaches known as 5-hydroxytryptamine receptor agonists (triptans), are used together.  Signs and symptoms of serotonin syndrome include the following:

• restlessness
• hallucinations
• loss of coordination
• fast heart beat
• increased body temperature
• fast changes in blood pressure
• overactive reflexes
• diarrhea
• coma
• nausea
• vomiting

Serotonin syndrome may be more likely to occur when starting or increasing the dose of an SSRI or a triptan.  This information comes from reports sent to FDA and knowledge of how these medicines work.  If you take migraine headache medicines, ask your healthcare professional if your medicine is a triptan.

Before you take Celexa and a triptan together, talk to your healthcare professional.  If you must take these medicines together, be aware of the possibility of serotonin syndrome, and get medical care right away if you think serotonin syndrome is happening to you.

This information reflects FDA’s current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.

FDA ALERT [07/2006] – Infant Persistent Pulmonary Hypertension

The results of a study that looked at the use of antidepressant medicines during pregnancy in  mothers of babies born with a serious condition called persistent pulmonary hypertension of the newborn (PPHN) were recently published in a medical journal.

Babies born with PPHN have abnormal blood flow through the heart and lungs and do not get enough oxygen to their bodies.  Babies with PPHN can be very sick and may die.

The study results showed that:

• babies born to mothers who took selective serotonin reuptake inhibitors (SSRIs), the family of medicines Celexa belongs to,
• 20 weeks or later in their pregnancies,
• had a higher chance (were 6 times as likely) to have persistent pulmonary hypertension (PPHN),
• than babies born to mothers who did not take  antidepressants during pregnancy.

The FDA plans to further look at the role of SSRIs in babies with PPHN.
Talk to your doctor if you are taking Celexa and are pregnant or are planning to have a baby.  You and your doctor will need to talk about the best way to treat your depression during pregnancy. 

This information reflects FDA’s current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.

What is Celexa?

Celexa is in a class of medicines called selective serotonin reuptake inhibitors (SSRIs).

Celexa tablets and oral solution are used to treat depression.

Who Should Not Take Celexa?

Never take Celexa if you are taking another drug used to treat depression, called a Monoamine Oxidase Inhibitor (MAOI), or if you have stopped taking an MAOI in the last 14 days. Taking Celexa close in time to an 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?

The following are the major potential risks and side effects of Celexa therapy.   However, this list is not complete.

• Possible life-threatening serotonin syndrome when used with triptan medicines:  See FDA Alert [07/2006] above.
  
  
• Infant persistent pulmonary hypertension:  See FDA Alert [07/2006] above.
  
  
• Suicidal thoughts or actions:Persons taking Celexa may be more likely to think about killing themselves or actually try to do so, especially when Celexa is first started or he dose is changed.  People close to persons taking Celexa can help by paying attention to changes in user’s moods or actions.   Contact your healthcare professional right away if someone using Celexa talks about or shows signs of killing him or herself.  If you are taking Celexa yourself and you start thinking about killing yourself, tell your healthcare professional about this side effect right away.
  
  
• Stopping Celexa: Do not stop taking Celexa suddenly because you could get side effects. Your healthcare professional will slowly decrease your dose.
  
  
• Bleeding problems: Celexa may cause bleeding problems, especially if taken with aspirin, NSAIDs (nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen), or other drugs that affect bleeding.
  
  
• Mania: You may become unusually hyperactive, excitable or elated.
  
  
• Seizures: You may experience a seizure (convulsion), even if you are not taking Celexa close in time with an MAOI.
  
  
• Pregnancy: Tell your healthcare professional if you are or may be pregnant (see FDA Alert [07/2006] above).  In addition to the issue described in the alert,  babies delivered to mothers taking Celexa late in pregnancy have developed problems, such as difficulty breathing and feeding.
  
  
• Sexual problems: You may have problems with impotence (erectile dysfunction), abnormal ejaculation, difficulty reaching orgasm, or decreased libido (sexual desire).
  
  
• Other side effects include dry mouth, nausea, and sleepiness.
  
  
• Tell your healthcare professional about all your medical conditions, especially liver or kidney disease. Tell your healthcare professional if you are breast-feeding or plan to breast-feed your baby.

Are There Any Interactions With Drugs or Foods?

• Do not take Celexa with Lexapro (escitalopram), another drug used to treat depression, because they are very similar and you could get an overdose.
  
  
• Celexa may interact with medicines other than the ones already mentioned in this information sheet. These interactions can cause serious side effects. Tell your healthcare professional about all medicines, vitamins, and herbal supplements you take.
  
  
• If you plan to drink alcohol, talk to your healthcare professional.

How Do I Take Celexa?

Celexa is taken by mouth, with or without food, exactly as prescribed by your healthcare professional.

Is There Anything Else I need to Know?

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

Date this drug approved 1998
Patient Information Sheet Revised 02/2005
Patient Information Sheet Revised 07/2005
Patient Information Sheet Revised 07/2006

Date created: May 2005, Updated July 19, 2006

FDA ALERT [7/2006]: Increased Risk of Neonatal Persistent Pulmonary Hypertension

A recently published case-control study has shown that infants born to mothers who took selective serotonin reuptake inhibitors (SSRIs) after the 20th week of pregnancy were 6 times more likely to have persistent pulmonary hypertension (PPHN) than infants born to mothers who did not take antidepressants during pregnancy (see SSRI drug names at the bottom of this sheet). The background risk of a woman giving birth to an infant affected by PPHN in the general population is estimated to be about 1 to 2 infants per 1000 live births. Neonatal PPHN is associated with significant morbidity and mortality. The FDA is updating the prescribing information for all SSRIs with this new information. The FDA is also accruing data from additional sources pertaining to the potential association between SSRIs and neonatal PPHN. The FDA will provide additional information when it becomes available. In the interim, the FDA recommends that physicians carefully consider and discuss with patients the potential risks and benefits of SSRI treatment throughout pregnancy, including late pregnancy.

Considerations

Physicians should consider the benefits and risks of treating pregnant women with SSRIs, alternative treatments, or no treatment late in pregnancy.

Data Summary

A retrospective case-control study published on February 9, 2006, in the New England Journal of Medicine assessed the risk for persistent pulmonary hypertension of the newborn (PPHN) following exposure to SSRIs during pregnancy. 377 women whose infants were born with PPHN and 836 women whose infants were healthy were enrolled in the study in four United States metropolitan areas between 1998 and 2003. The study showed that infants born to mothers who took SSRIs after the completion of the 20th week of gestation were 6 times more likely to have PPHN than infants who were not exposed to antidepressants during pregnancy. 14 infants with PPHN and 6 healthy control infants had been exposed to an SSRI after the 20th week of gestation. There were too few cases of PPHN with each individual SSRI to compare risks for PPHN with individual SSRIs. The study did not find an association between exposure to SSRIs during the first 20 weeks of gestation and PPHN.

Exposure to non-SSRI antidepressants did not appear to be associated with an increased risk of PPHN, although the number of infants with exposure to non-SSRI antidepressants was too small to permit a reliable risk estimate or comparison with the risk observed for SSRIs.

In weighing the risks and benefits of treatment with SSRIs and other antidepressants during pregnancy for individual patients, physicians should also note the recent publication of a prospective longitudinal study of 201 pregnant women with a history of major depression in the February 1, 2006, issue of JAMA. In this study, women who discontinued antidepressant medication during pregnancy had a higher risk of relapse of major depression during pregnancy (68%) than women who maintained antidepressant medication throughout pregnancy (26%).

SSRI Drug Names

• Celexa (citalopram)
• Fluvoxamine
• Lexapro (escitalopram)
• Paxil (paroxetine)
• Prozac (fluoxetine)
• Symbyax (olanzepine/fluoxetine)
• Zoloft (sertraline)

  FDA ALERT [7/2006]: Potentially Life-Threatening Serotonin Syndrome with Combined Use of SSRIs or SNRIs and Triptan Medications

  There is the potential for life-threatening serotonin syndrome (a syndrome of changes in mental status, autonomic instability, neuromuscular abnormalities, and gastrointestinal symptoms) in patients taking 5-hydroxytryptamine receptor agonists (triptans) and selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) concomitantly (see drug names at the bottom of this sheet). This information is based on reports of serotonin syndrome occurring in patients treated with triptans and SSRIs/SNRIs, and the biological plausibility of such a reaction in persons receiving two serotonergic medications. The FDA recommends that patients treated concomitantly with a triptan and an SSRI/SNRI be informed of the possibility of serotonin syndrome (which may be more likely to occur when starting or increasing the dose of an SSRI, SNRI, or triptan) and be carefully followed.

• Considerations

  • Weigh the potential risk of concomitant SSRI/SNRI and triptan use with the benefit expected from using each drug, prior to prescribing these drugs together.
  • When prescribing an SSRI or a triptan, physicians should discuss the possibility of serotonin syndrome with patients if an SSRI and a triptan will be used concomitantly. Healthcare providers should keep in mind that triptans are often used intermittently, and that the SSRI, SNRI, or triptan may be prescribed by a different healthcare provider.
  • Healthcare providers should be alert to the highly variable signs and symptoms of serotonin syndrome. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
  • If concomitant treatment with an SSRI or SNRI and triptan is clinically warranted, the patient should be carefully observed, particularly during treatment initiation and dose increases.

  Data Summary
  
  The FDA has reviewed 27 reports of serotonin syndrome reported in association with concomitant SSRI or SNRI and triptan use. Two reports described life-threatening events and 13 reports stated that the patients required hospitalization. Some of the cases occurred in patients who had previously used concomitant SSRIs or SNRIs and triptans without experiencing serotonin syndrome. The reported signs and symptoms of serotonin syndrome were highly variable and included respiratory failure, coma, mania, hallucinations, confusion, dizziness, hyperthermia, hypertension, sweating, trembling, weakness, and ataxia. In 8 cases, recent dose increases or addition of another serotonergic drug to an SSRI/triptan or SNRI/triptan combination were temporally related to symptom onset. The median time to onset subsequent to the addition of another serotonergic drug or dose increase of a serotonergic drug was 1 day, with a range of 10 minutes to 6 days.
  
  Serotonin syndrome following concomitant SSRI or SNRI and triptan use is biologically plausible. SSRIs, SNRIs, and triptans independently increase serotonin levels. Therefore, it is expected that concomitant use of SSRIs or SNRIs and triptans would result in higher serotonin levels than the serotonin levels observed with the use of SSRIs, SNRIs, or triptans alone, potentially leading to serotonin syndrome.

  SSRIs and a Combination Drug Containing an SSRI	SNRIs	Triptans
  Celexa (citalopram) Fluvoxamine Lexapro (escitalopram) Paxil (paroxetine) Prozac (fluoxetine) Symbyax (olanzapine/fluoxetine) Zoloft (sertraline)	Cymbalta (duloxetine) Effexor (venlafaxine)	Amerge (naratriptan) Axert (almotriptan) Frova (frovatriptan) Imitrex (sumatriptan) Maxalt and Maxalt-MLT (rizatriptan) Relpax (eletriptan Zomig and Zomig ZMT(zolmitriptan)