NSAIDs, or Non Steroidal Anti-Inflammatory Drugs, are one of the most prescribed of all medications, accounting for 5 to 10 percent of all prescriptions in western countries. Over 100 million prescriptions are written for NSAIDs in the United States each year with many of these types of drugs available over the counter. NSAIDs are most commonly used for arthritic diseases, degenerative joint diseases, and acute or chronic pain.
NSAIDs are associated with an increased risk of adverse events and can result in hospitalizations and deaths. In the United States, it is estimated that over 100,000 hospitalizations and over 16,500 deaths are attributable to NSAID related gastrointestinal complications in arthritis patients alone. In the United States, approximately 21% of all adverse events reported to the FDA are associated with NSAID use. Usual complications are associated with gastrointestinal bleeding, but there are also complications relating to the liver, kidneys, and heart.
The December 2004 issue of the journal Drugs, the authors of a study examine the less common neuropsychiatric adverse effects that may occur with the use of NSAIDs. Specifically, “these neuropsychiatric symptoms include changes in cognition, mood and even precipitation or exacerbation of pre-existing psychiatric conditions.”
The authors note that one recent population study examined the New Zealand Medicine Adverse Reaction Committee over a 20-year period. During that period, 150 psychiatric adverse events associated with NSAIDs were reported including: confusion, depression, hallucination, lethargy, sleep disturbance, and malaise. Other less common events included: anxiety, amnesia, emotional liability, abnormal thinking, psychosis, and delirium.
Another study reviewed the records of patients experiencing postpartum complications over a 5-year period in a Canadian university hospital to identify adverse drug reactions associated with the NSAID indometacin. The authors of that study identified psychiatric events in 32 patients. The most common symptoms were dizziness, agitation, and anxiety. A few patients reported fear, dyspnoea (difficult or labored respiration), dysphoria (an unpleasant mood, such as sadness, anxiety, or irritability), depersonalization, panic, fear of dying, hallucinations, and abnormal movements.
A 2003 study reviewed the Australian Adverse Drug Reactions Advisory Committee. That study examined the psychiatric events associated with the newer selective COX-2 NSAIDs. The committee reported 142 neuropsychiatric events associated with celecoxib (Celebrex) and 49 with rofecoxib (Vioxx). The most common events with Celebrex were found to be confusion, somnolence, and insomnia. Hallucinations were more reported with Vioxx than with Celebrex.
The authors note that in all these studies the data was largely based on voluntary reporting systems. These systems are generally acknowledged as only reporting a small fraction of the actual adverse events and as such these studies may not reflect the total number of events that have occurred.
NSAIDS block the production of prostaglandins by inhibiting the activity of COX (cyclooxygenase). COX-2 is the most abundant form found in the central nervous system (CNS) and has specifically been found in the neocortex, hippocampus, and other locations. COX-2 is upregulated by nerve activity and is located in cells that are involved in synaptic signaling. Evidence also suggests that inhibition of prostaglandins by NSAIDs can increase dopamine levels in the brain.
Additionally, NSAID use and psychiatric disturbances may involve the role of fatty acids, which are precursors to prostaglandins. “In particular, depression, affective disorders, attention-deficit hyperactivity disorder (ADHD), psychological stress and schizophrenia have been related to fatty acid metabolism.”
The authors conclude that, “psychiatric symptoms are a rare but relevant complication of NSAID use. This effect is probably a consequence of impairment in the neurotransmission modulated by prostaglandins when NSAIDs are used by susceptible individuals. These drugs should be used with caution in high-risk individuals with pre-existing psychiatric illness and caution may also be advisable in the postpartum period. Prescribers should consider warning patients of the possibility of an acute neuropsychiatric event when traditional NSAIDs or selective COX-2 inhibitors are prescribed.”
Source: Drugs; 64 (23) December 2004