Paxil News

What is PAXIL?
The drug PAXIL (paroxetine hydrochloride) is a psychotropic drug manufactured by the company GlaxoSmithKline (GSK, formerly SmithKline Beecham). Broadly, a psychotropic drug is any drug that has the capability of affecting the mind, emotions, or behavior. More specifically, it belongs to a class of prescription drugs called SSRIs (selective serotonin reuptake inhibitors). SSRIs are antidepressants that affect the way the nerves in the brain transmit signals (or messages) to one another. A message is passed from one nerve to another by the release of a chemical messenger called a neurotransmitter. The neurotransmitter is then taken up by another nerve, thus passing on the signal. If there are neurotransmitters that are not taken up by other nerves, they are then typically reabsorbed by the nerve that emitted them. This is called reuptake. SSRIs alter this process by inhibiting the reuptake of serotonin, a neurotransmitter linked to moods and depression. By inhibiting the reuptake of serotonin, SSRIs act to increase the level of serotonin that is available to be taken up by other nerves.

What are the label prescribed uses of PAXIL?
According to the prescribing information provided by GSK and approved by the FDA (Food and Drug Administration), PAXIL received approval for the treatment of depression in 1989, and then subsequent approval for the treatment of several psychiatric disorders from 1999 to 2002. These psychiatric disorders are: major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder (PD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD).

The length of treatment with PAXIL and relevant dosage are dependent on the disorder and patient being treated. For example, elderly patients and those with liver damage or disease have a lower recommended initial dose than the typical adult patient. Indeed, PAXIL may not be suitable for all patients. GSK notes in the prescribing information that the safety and effectiveness in pediatric patients is not known and the FDA specifically states that PAXIL is not FDA approved for pediatric use. Thus use in children is not considered a label prescribed use.

With the original approval of PAXIL came a Category C pregnancy labeling. A drug receives such a labeling when either there is not enough information to determine the risk to a fetus; or animal testing has demonstrated adverse effects, but there are not enough human studies to determine the effects of a drug on the fetus. In either case, healthcare professionals are urged to weigh the possible risks to the fetus with the benefits to the mother before prescribing the drug. Recent studies, however, have shed more light on the possible effects of PAXIL to a fetus, prompting the FDA to change the pregnancy category from C to D. This means that studies in pregnant women have demonstrated a risk to the fetus and healthcare professionals should consider discontinuing or switching to a different antidepressant if a patient is pregnant or intends to become pregnant. The labeling information of PAXIL has been subsequently changed to reflect such information.

What are the off-label prescribed uses of PAXIL?
Although PAXIL is FDA approved only for certain psychiatric disorders, this does not mean that these are the only instances where it can be prescribed. Doctors can legally prescribe a drug for uses not mentioned in the approved labeling, and this is known as off-label prescribing. Healthcare providers obtain information about the off-label uses of drugs through avenues such as journal articles and professional meetings. The FDA's policies on the off-label use of drugs are such that, while parties other than the drug company are not prohibited from discussing or distributing materials regarding them, the drug company itself is prohibited from promoting off-label uses of its products. The FDA also recognizes that off-label uses of drugs are often appropriate and at the discretion of informed healthcare professionals.

Many off-label uses of PAXIL have been reported in medical and psychiatric journals. The following are some of the conditions for which PAXIL has been prescribed that are not included in the FDA-approved labeling: depression in pediatric patients, eating disorders such as bulimia (binge eating), menopausal hot flashes, neuropathic pain (chronic pain due to nervous system injury), premature ejaculation, migraine prevention, diabetic neuropathy (numbness, pain, and weakness in hands, feet, and legs of patients with diabetes), fibromyalgia (chronic pain and stiffness of muscles, tendons, and joints without inflammation), neurocardiogenic syncope (a temporary failing of the body to regulate blood pressure and heart rate resulting in a drop in blood pressure which in turn causes fainting), premenstrual syndrom,multiple chemical sensitivities (adverse physical reaction to common chemicals), irritable bowel syndrome (gastrointestinal disorder involving abnormal stomach contractions), and Tourette disorder (a tic disorder characterized by chronic vocal and motor tics).

In general, SSRIs seem to be used for a variety of different conditions outside of the psychiatric conditions for which they were intended. This may be due to their apparent "safety, tolerability, and demonstrated efficacy across a broad range of clinical conditions."

What are the side effects of taking PAXIL?

GSK reports that PAXIL is "one of the leading treatments for depression and anxiety disorders in the country" and states that it is "safe and effective with fewer side effects than other types of antidepressants." This does not mean that there are no side effects. In fact, the prescribing information lists several, some more severe than others, and some that are typical with antidepressants or SSRIs. For example, taking the drug can cause mania or hypomania (a less severe form of mania) and akathisia (an inner sense of restlessness and inability to sit or stand still). Both of these effects have also been noted with other antidepressants and SSRIs. Patients taking SSRIs also have the potential to develop serotonin syndrome, the symptoms of which include agitation, confusion, diaphoresis (sweating), hallucinations, hyperreflexia (reaction of the involuntary nervous system to over-stimulation), myoclonus (abnormal contractions of the muscles), shivering, tachycardia (rapid heart rate), and tremors.

Although antidepressants are prescribed to treat depression, the prescribing information and the FDA warn that taking antidepressants may cause an increase in suicidal thoughts and actions in people 18 years or younger. For this reason, the FDA has not approved PAXIL for use in pediatric patients. The FDA also notes that several recent scientific publications suggest there is an increase in the risk for suicidal behavior in adults taking antidepressants. Thus, patients being treated for depression and other disorders need to be carefully monitored for worsening symptoms, suicidal tendencies, or unusual behavior changes.

In addition to the side effects of antidepressants and SSRIs in general, PAXIL use has been associated with other side effects. It has been known to cause seizures, and it is warned that individuals with a history of seizures, or who develop seizers while on the medication, not use the drug. There is a potential for upper gastrointestinal bleeding (esophagus, stomach, small intestines) and so PAXIL should not be taken with drugs that affect blood clotting such as NSAIDs or aspirin. Elderly patients are typically started on a lower dosage because of their inability to clear the drug as rapidly from their systems as the average patient. Several cases of hyponatremia (abnormally low concentration of sodium in the blood) have been reported in elderly patients. PAXIL can cause negative sexual side effects in both men and women, although these side effects were seen more frequently in men than women. This includes decreased libido, ejaculatory disturbance, and impotence in men; and decreased libido and orgasmic disturbance in women. During clinical trials, patients frequently reported the following negative effects: hypertension (high blood pressure), tachycardia (rapid heart rate), weight gain, joint pain, emotional instability, dizziness, itching, and ringing of the ears.

Aside from the side effects of actually taking the drug, patients are warned that discontinuation of treatment with PAXIL should be gradual because of the potential for negative effects. The negative affects of discontinuation (especially when sudden) include dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional instability, insomnia, and hypomania.

One of the most recently reported—and serious—side effects of taking PAXIL was found in women who were treated with the drug within the first three months of pregnancy. New studies suggest that the drug increases the risk for birth defects, particularly heart defects, when women take the drug during the first trimester of pregnancy. The studies showed that these women were one and a half to two times as likely to have a baby with a heart defect as women who received other antidepressants or the general population. Most of the defects were holes in the walls of the chambers of the heart and ranged in severity from those that may resolve without treatment to those needing to be repaired surgically.

The FDA requires that the known side effects of a drug be provided with the prescribing information and label. The FDA also reports new developments and warnings about the negative effects of drugs on its website www.fda.gov. Both consumers and healthcare professionals are encouraged to report the negative effects of a drug on MedWatch (www.fda.gov/medwatch/index.html).