The Antidepressant Fluoxetine (Prozac) and Suicidal Ideation — Déjà vu 1991

Fourteen years ago, in May 1991, the Health Research Group petitioned the Food and Drug Administration (FDA) to require a warning in the professional product labeling, or package insert, of fluoxetine (PROZAC) concerning the risk of suicidal impulses in patients using the drug. Fluoxetine belongs to the family of antidepressants known as selective serotonin re-uptake inhibitors, or SSRIs.

Our petition was based on a number of published case reports of people who had developed self-injurious thoughts and behavior, often not long after starting to use fluoxetine. At the time we filed our petition, other widely prescribed SSRIs such as sertraline (ZOLOFT) or paroxetine (PAXIL) were not on the market.

The warning we sought said:

“A small minority of persons taking fluoxetine have experienced intense, violent, suicidal thoughts, agitation, and impulsivity after starting treatment with the drug. Some of the people involved had no prior history of depression or suicidal thoughts and were being treated with fluoxetine for other problems (e.g. obsessive-compulsive disorder). Whether development of such symptoms is coincidental or drug-related is still under investigation. Fluoxetine should only be used under careful medical supervision, and patients are advised to consider alerting relatives and friends to their use of fluoxetine and the risk of suicidal obsession and self-injurious behavior.”

On March 22, 2004, the FDA issued a Public Health Advisory on the use of antidepressants in children and adults warning that close observation of these patients is needed because of the possibility of worsening depression or the emergence of suicidal thoughts. The drugs included in the warning were bupropion (WELLBUTRIN), citalopram (CELEXA), fluoxetine, fluvoxamine (LUVOX), mirtazapine (REMERON), nefazodone (SERZONE), paroxetine, sertraline, escitalopram (LEXAPRO) and venlafaxine (EFFEXOR). It should be noted that the only drug that has received approval for use in children with major depressive disorder is fluoxetine (Prozac). Several of these drugs are approved for the treatment of obsessive-compulsive disorder in pediatric patients, for example, sertraline, fluoxetine, and fluvoxamine. Fluvoxamine is not approved as an antidepressant in the U.S.

The FDA has requested changes to the professional product labeling, or package inserts, for these drugs to reflect the Public Health Advisory. The labeling changes are consistent with recommendations made to the FDA at a meeting of the Psychopharmacological Drugs Advisory Committee (PDAC) and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee, held on February 2, 2004. The possibility of suicidality associated with the use of antidepressant drug products in the pediatric population was also the subject of two previous FDA communications on June 19, 2003, and on October 27, 2003.

Other warnings included in the FDA’s March 22nd advisory were:

• Health care providers should carefully monitor patients receiving antidepressants for possible worsening of depression or suicidality, especially at the beginning of therapy or when the dose either increases or decreases. Although FDA has not concluded that these drugs cause worsening depression or suicidality, health care providers should be aware that worsening of symptoms could be due to the underlying disease or might be a result of drug therapy.
• Health care providers should carefully evaluate patients in whom depression persistently worsens, or emergent suicidality is severe, abrupt in onset, or was not part of the presenting symptoms, to determine what intervention, including discontinuing or modifying the current drug therapy, is indicated.
• Anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (severe 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 the FDA has not concluded that these symptoms are a precursor to either worsening of depression or the emergence of suicidal impulses, there is concern that patients who experience one or more of these symptoms may be at increased risk for worsening depression or suicidality. Therefore, therapy should be evaluated and medications may need to be discontinued when symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
• If a decision is made to discontinue treatment, certain of these medications should be tapered rather than stopped abruptly (the professional labels for these drugs give specific details).
• Because antidepressants are believed to have the potential for inducing manic episodes in patients with bipolar disorder, there is a concern about using antidepressants alone in this population. Therefore, patients should be adequately screened to determine if they are at risk for bipolar disorder before initiating antidepressant treatment so that they can be appropriately monitored during treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.
• Health care providers should instruct patients, their families and their caregivers to be alert for the emergence of agitation, irritability, and the other symptoms described above, as well as the emergence of suicidality and worsening depression, and to report such symptoms immediately to their health care provider.

What You Can Do

DO NOT ABRUPTLY DISCONTINUE ANY OF THE ANTIDEPRESSANTS MENTIONED IN THIS ARTICLE —DISCONTINUATION OF THESE DRUGS SHOULD TAKE PLACE ONLY UNDER MEDICAL SUPERVISION.

Patients and parents whose children are using any of the drugs mentioned above should consult the prescribing physician immediately.