In addition to being approved by the FDA for major depressive disorder, or MDD, various SSRIs are also approved to treat obsessive-complusive disorder, bulimia, panic disorder, social anxiety disorder, and posttraumatic stress disorder. Fluoxetine, better known as Prozac, is also sold as Sarafem to treat a condition known as premenstrual dysphoric disorder. Women taking Prozac should not be taking Sarafem.
The SSRIs may reduce the risk of suicide in depressed adult patients. However, there have been a few reports that Prozac may actually induce suicidal thoughts in selected patients, although this has not been confirmed. Our Research Group petitioned the FDA in 1991 to require a box warning in the professional product labeling for Prozac warning doctors that a small minority of persons taking the drug have experienced intense, violent, suicidal thoughts; agitation; and impulsivity after starting treatment with the drug. In October 2004 the FDA issued a public health advisory requiring manufacturers to add a black-box warning to its professional product labeling or package insert of all antidepressants. This black-box warning is shown below. A black-box warning is the strongest type of warning that the FDA can require. The FDA also requires that a Patient Medication Guide be given to patients receiving this drug advising them of the risk and precautions that can be taken. You should not take this drug for mild depression or anxiety, or as a sleeping pill.
The FDA-approved professional product labeling for antidepressant drugs sold in the United States carries the following statement:
Suicide: The possibility of a suicide attempt is inherent in major depressive disorder and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy. Prescriptions for Drug X should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Only Prozac is approved for use in children less than 18 years of age for major depressive disorder.
A review of 64 randomized controlled trials comparing SSRIs to the older tricyclic antidepressants such as imipramine (TOFRANIL) found similar benefit from the new and older drugs. When the results of many clinical trials were pooled, called a meta-analysis, no clear benefit was found for the new drugs over the older antidepressants. The adverse effects of the new and old antidepressants have little in common except for withdrawal symptoms. For example, SSRIs are less likely than the tricyclic drugs to cause sedation, anticholinergic effects, and heart rhythm disturbances. On the other hand, SSRIs’ adverse effects commonly affect the gastrointestinal tract, especially causing nausea and diarrhea, and may also cause insomnia, agitation, extrapyramidal symptoms (drug-induced parkinsonism), and withdrawal effects.
One group of adverse effects is traded for another between the SSRIs and tricyclic antidepressants, and there does not appear to be any difference in the proportion of people who can tolerate these two groups of antidepressants. When the number of people who stopped taking an antidepressant in 58 clinical trials were studied, there was no clinically significant difference between the SSRIs and the tricyclic and related antidepressants.
A large meta-analysis commissioned by the U.S. Department of Health and Human Services through the Agency for Health Care Policy and Research in 1999 found that in general there were no significant differences in the effectiveness of the newer antidepressants such as the SSRIs and the older agents such as the tricyclic antidepressants. In terms of adverse drug reactions, there was no significant difference between the new and old antidepressants in overall discontinuation rates of use of these drugs by patients. Drug discontinuation rates can be used to compare adverse reactions between drugs.
When you take these medicines you may experience some adverse effects. The most frequently reported include nausea, anxiety, headache, and insomnia. These adverse effects tend to be worst at the start of treatment and improve over a few weeks. Akathisia—symptoms of restlessness, constant pacing, and purposeless movements of the feet and legs—may also occur. Dry mouth, sweating, diarrhea, tremor, loss of appetite, and dizziness are also common adverse effects.
The length of time it takes an antidepressant to work can overlap with the time of spontaneous recovery, especially if the depression is situational—caused by a death or other external circumstances. The majority of people lift themselves out of depression with friends, spiritual resources, or activities such as exercise, work, reading, play, art, and travel. If depression is not overcome by these measures, seek help from mental health professionals, such as therapists or psychiatrists. Antidepressant drugs should be reserved for depression that is major and does not respond to psychotherapy alone.
In March 2005, the FDA amended the professional product label of fluvoxamine to include warnings about its use together with tizanidine (ZANAFLEX), a drug used for spasticity, and alosetron (LOTRONEX), a Do Not Use drug used to treat Irritable Bowel Syndrome. Fluvoxamine can increase the amounts of each of these drugs that is present in the bloodstream to dangerous levels.
In July 2006 the FDA notified healthcare professionals and consumers that there may be additional, though rare, risks of taking SSRI medications during pregnancy. This study focused on newborn babies with persistent pulmonary hypertension (PPHN), which is a serious and life-threatening lung condition that occurs soon after birth. Babies born with PPHN have high pressure in their lung blood vessels and are not able to get enough oxygen into their bloodstream.
Additionally, the labeling for paroxetine (PAXIL) was recently changed to add information about findings in an epidemiologic study that suggests that exposure to the drug in the first trimester of pregnancy may be associated with an increased risk of cardiac birth defects.
In July 2006 the FDA also issued a public health advisory warning consumers about the possibility of life-threatening reactions — such as nausea, changes in blood pressure or hallucinations — that may be caused by the interaction of migraine headache drugs, called “triptans,” and certain antidepressants.
When triptans are taken in combination with antidepressants known as selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs), a condition called serotonin syndrome may result.
Signs and symptoms of serotonin syndrome include the following:
Restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhea, coma, nausea and vomiting.
FDA BLACK BOX WARNING
Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in short term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Antidepressant’s Name] or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be 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. [Antidepressant’s Name] is not approved for use in pediatric patients except for patients with [Any approved pediatric claims here].
Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of nine 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 on drug was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.