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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
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
Posted by mars on January 16, 2001, at 5:11:12
In reply to Celebrex aggravating depression! WHY?, posted by nhgrandma on January 15, 2001, at 21:09:59
Hi nhgrandma -
I went to www.google.com and searched on "celebrex" and "depression". (Unfortunately, if you add in the term "celexa" you pull up a bunch of pages about how people are confusing the names of Celebrex and Celexa.) I did see some reports of depression beginning or increasing after starting Celebrex. I think you should look at them. Have you spoken to your doctor? Are there any other NSAIDs you can take?
best,
mary
> 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
Posted by Ted R on January 22, 2001, at 21:59:59
In reply to Re: Celebrex aggravating depression! WHY?, posted by mars on January 16, 2001, at 5:11:12
> Hi nhgrandma -
>
> I went to www.google.com and searched on "celebrex" and "depression". (Unfortunately, if you add in the term "celexa" you pull up a bunch of pages about how people are confusing the names of Celebrex and Celexa.) I did see some reports of depression beginning or increasing after starting Celebrex. I think you should look at them. Have you spoken to your doctor? Are there any other NSAIDs you can take?
>
> best,
>
> mary
>
> > 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
> Celebrex is a new specific inhibitor of pain and inflammation, safer than the older meds like Ibuprofen or Naprosyn, because it spares important prostaglandins in the stomach, and is very unlikely to cause ulcers. However Celebrex is
pretty highly lipophilic, and achieves high levels in the brain, thus affecting and reducing the level of certain prostaglandins in the brain. For most people, mood should not be affected, but as with the older meds, some people like yourself, may complain of worsening of mood or bad dreams etc. or other CNS side effects, probably occuring as a result of the reduced prostaglandin levels in the brain. These side effects may be transient, but often times patients are sensitive to the change in brain levels of these mediators of inflammation, and depression can be a result. The good news is that Celebrex is being looked at, for the prevention of Alzheimers, because of the role that an excess of prostaglandins in the brain may play, in the development of the disease. Hope that helps.
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
============================================
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.
Posted by Ted R on January 25, 2001, at 21:53:57
In reply to Re: Celebrex aggravating depression! WHY? » nhgrandma, posted by Sunnely on January 25, 2001, at 20:05:28
> > 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
>
> ============================================
>
> 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.
> I really believe that you have overstated the potential or depressive response that can occur probably idiosyncratically with NSAIds. If you are talking about DMARDS, really aggressive anti-inflammatories used for severe immune response diseases such as Rheumatoid Arthritis, then you might be on to something. As these types of Drugs, such as methotrexate or some of the really potent corticosteroids, most effectively and primarily impact cytokines, TNF bodies, and macrophages, and not your simpler and purer prostaglandin inhibitors such as Celebrex or Naprosyn. The FDA for what it is worth, has always stated "causal relationship not established" for NSAids and the occurence of depression. I am curious as to what references or studies, that you are citing....TEdR
Posted by Sunnely on January 26, 2001, at 0:26:09
In reply to Re: Celebrex aggravating depression! WHY?, posted by Ted R on January 25, 2001, at 21:53:57
> > I really believe that you have overstated the potential or depressive response that can occur probably idiosyncratically with NSAIds. If you are talking about DMARDS, really aggressive anti-inflammatories used for severe immune response diseases such as Rheumatoid Arthritis, then you might be on to something. As these types of Drugs, such as methotrexate or some of the really potent corticosteroids, most effectively and primarily impact cytokines, TNF bodies, and macrophages, and not your simpler and purer prostaglandin inhibitors such as Celebrex or Naprosyn. The FDA for what it is worth, has always stated "causal relationship not established" for NSAids and the occurence of depression. I am curious as to what references or studies, that you are citing....TEdR
>+++++++++++++++++++++++++++++++++++++++
Hi TedR,
Here's the source of my response:
Sussman N, Magid S: Psychiatric manifestations of nonsteroidal anti-inflammatory drugs. Primary Psychiatry 2000;7(9):26-30.
Posted by nhgrandma on January 26, 2001, at 12:31:04
In reply to Re: Celebrex aggravating depression! WHY? » Ted R, posted by Sunnely on January 26, 2001, at 0:26:09
>
> Hi TedR,
>
> Here's the source of my response:
>
> Sussman N, Magid S: Psychiatric manifestations of nonsteroidal anti-inflammatory drugs. Primary Psychiatry 2000;7(9):26-30.I haven't read the article but my experience confirms to me that there is some connection. I have searched for the answer and I appreciate the input. Right now the dosage of Celexa has been increased and the dosage of Celebrex has been reduced. We'll see what happens. nhgrandma
Posted by SLS on January 30, 2001, at 16:46:42
In reply to Re: Celebrex aggravating depression! WHY? » nhgrandma, posted by Sunnely on January 25, 2001, at 20:05:28
Dear Sunnely,
Your post was wonderfully executed, and I profitted from it greatly. I will need to reread it a few times yet. I interpret your wording that the various cytokines can either enhance or suppress the immune system. Is this true?
Would low dosages of Elavil h.s. be a reasonable remedy for both the neck pain and the Celebrex-induced exacerbation of depression?
I work real hard not to ask you what background or profession you are involved with to be so knowledgeable and objective. I won't ask that question now. Make believe I never brought it up.
I would like to extend to you a sincere "thank you" for your contributions. I am appreciative of the time it must take to compose such wonderful posts.
Again, make believe I never asked.
- Scott> > 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
============================================
> 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.
This is the end of the thread.
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