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Re: Celebrex aggravating depression! WHY? » nhgrandma

Posted by Sunnely on January 25, 2001, at 20:05:28

In reply to Celebrex aggravating depression! WHY?, posted by nhgrandma on January 15, 2001, at 21:09:59

> Why do anti-inflamatory medications (the latest being Celebrex) aggravate depression? I am currently on 20 mg Celexa and .50 mg Clonazepam for sleep. The combo has been working great until I added Celebrex for neck pain. I have experimented over the last 3 months and have found a definite correlation between Celebrex and increased depression. But the pain diminishes. Bummer. I do not understand. Is there any reason or answer for this problem? Thanks

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Hi nhgrandma,

NSAIDs (nonsteroidal antiinflammatory drugs) including the new ones called selective COX-2 inhibitors such as celecoxib (Celebrex) and refocoxib (Vioxx) have been reported to cause different psychiatric symptoms including depression. (COX stands for cyclooxygenase, comprised of COX-1 and COX-2). Other psychiatric disturbances reported include catatonia, psychosis (paranoia, hallucinations), mania, and depersonalization.

The exact mechanism (reason) as to how or why NSAIDs can cause or aggravate depression is not known. However, there is considerable evidence supporting the presence of abnormalities in immunes system and inflammatory response in some psychiatric conditions. There is also evidence that NSAIDs may act directly on brain functions.

One potential compound that may form the basis of explanation at least in NSAID-induced depression is the compound called "cytokines." Cytokines are peptides that mediate inflammatory and immune responses, which are major focus of theories on how mechanisms of inflammatory response are involved in psychiatric disturbances. NSAIDs fit into these models because they influence cytokine production.

The activity of cytokines is complex. There are neumerous cytokines that act either to promote inflammation or to diminish the immune response. They act as neuromodulators ie., influence the action of other brain chemicals, and have far-reaching effects on other systems including the neurotransmitters presumed to be involved in psychiatric disorders, and on the mechanisms of most psychotropic drugs.

Several authors have hypothesized that those depressions in which the patients experience malaise, or feel sick rather than sad, may have cytokine-mediated symptoms. In the case of serious medical illnesses - such as infection or cancer - apathy, fatigue, hypersomnia (increased sleep), decreased sexual drive, and loss of appetite may represent an adaptive mechanism. This complex behaviors associated with serious illness has been referred to as "sickness behavior" or the "malaise theory of depression" - for example, patients with infectioins often experience increased sleepiness, decreased appetite, and decreased sexual drive.

It was postulated that antidepressants exert their beneficial effects through an analgesic (pain relieving) effect on cytokine-induced dysphoric symptoms. Antidepressants have been shown to modify cytokine function. Treatment with cytokines (e.g., Interferon or INF) is sometimes associated with the development of mood and cognitive changes. Interferon is notorious for causing dramatic mood changes such as depression, anxiety, irritability, manic symptoms, and suicidal behavior; as well as cognitive changes such as hallucinations, paranoia, decreased concentration, confusion, and delirium. In clinical practice, pretreatment with antidepressants significantly reduces the anxiety provoking effect and depressive-like actions of INF, allowing patients to maintain INF treatment.

To conlude, the main issue is not whether patients with psychiatric disorders should avoid using NSAIDs; instead, given the available evidence, anti-inflammatory drugs warrant heightened scrutiny for their potential effects on the way they affect mood, cognition, and behavior. Indeed, NSAIDs do in fact appear to be "emotion-modulating drugs." In this regard, they may have effects similar to corticosteroids. Therefore, clinicians and patients alike must be aware of potential adverse psychiatric events with the use of these drugs.


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