![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 25 of 28. This is the beginning of the thread.
Posted by CraigF on May 4, 2000, at 17:11:04
We've been tinkering for a while with my meds and I finally submitted to adding Risperidone/risperdal to my Serzone to augment the AD.
I'm really scared and need some advice. While paranoid ruminations and anger are often a problem for me(a good amount of the anger is caused by Serzone, I'm sure), so is a sense of vitality on my current meds.
I loved what Wellbutrin did for me in terms of overall mood, vitality, motivation...but it exacerbated the anger at times and made it very hard to concentrate at work (I'm a writer). So I cut it out.
I fear the Risp. will kill my imagination, make me groggy and scatterbrained, and send me further over the edge in general.
Does anyone have any experience with this or advice? I almost think I should titrate in an SSRI or Effexor.
HELP!!!
Posted by Cam W. on May 5, 2000, at 7:35:19
In reply to HELP!! Adding Riperidone to help Serzone, posted by CraigF on May 4, 2000, at 17:11:04
Craig - On the contrary, Risperdal should make you more alert. It may even cause insomnia. Any sedation you may feel at the start of therapy should disappear within a couple of weeks.The Risperdal works great to stop ruminations and paranoia as well. Even the much talked about EPS (movement disorder stuff) is not an issue at doses lower than 6mg per day. I believe it will work much better than adding an SSRI or Effexor. Risperdal also has some mood stabilizing propeties. The is no problem taking it with Serzone.
Although, I am not totally convinced, some studies have shown that Risperdal actually improves cognition. I'm not saying you'll be writing like Voltaire or Cervantes, but you may be able to "see" an idea clearer.
Hey, I want a copy of your first book after starting Risperdal. Good luck and keep us posted on your progress. - Cam W.
Posted by CraigF on May 5, 2000, at 13:18:11
In reply to Re: HELP!! Adding Riperidone to help Serzone, posted by Cam W. on May 5, 2000, at 7:35:19
CamW:
Thanks a million for responding. I am so afraid of dabbling in deeping drugs such as APs...My grandmother is Schizophrenic and I've seen her medicated and non (we nearly lost her to NMS). With a bi-polar dad and depressed mom, I'm always looking over my shoulder. Is this my doc trying to tell me something without upsetting me?I did some research and realized Risp. is a pretty serious drug, hitting all of the big three receptors. I worry of losing my imagination, energy, and my sense of humor (although that's been gone due to anxiety and depression for some time)I want to be able to make eye contact with my friends again.
My dreams have been strange the past two nights. Last night was probably the most horrifying, vivid nightmare (I was actually the AntiChrist)that I could not shake. Woke up several times and it returned to haunt me throughout the night (even my nine-minute snooze) Should I be concerned about this?
Also, what should I avoid in terms of recreational drugs? (i know the REAL answer), but I'm young and it happens every now and again. Ecstacy is most likely -- will that throw me over the edge?
I stopped posting here when I moved two months ago because I've been avoiding my computer. I don't recall your handle, but now you seem all over the place. Your thoughts are appreciated!
Posted by Cam W. on May 5, 2000, at 19:37:03
In reply to Re: Riperidone and terrible dreams, posted by CraigF on May 5, 2000, at 13:18:11
Craig - Nightmares are a side effect of Risperdal and usually go away (or at least lessen in intensity) as your body adjusts to the drug.Sorry, I don't know your doc, so I cannot comment on his methods. The newer "atypical" antipsychotics are much less likely to cause NMS or movement disorders than the older antipsychotics, but I won't lie; they have happened (at least in case reports). The incidence is minimal compared to the older drugs. Raise these concerns with your doc as well.
As to recreational amusements, avoid stimulants (or anything that raises dopamine levels - eg amphetamines, probably ecstasy and LSD). If you do use ANY recreational drug, do inform your doctor. Any good doc will tell you if you are going too far, and shouldn't be judgemental. After all, the seeking of pleasure is a human trait. When it becomes a habit or a vice, then it is no longer recreation. It is best to stay away from any "fun" (including alcohol and pot) at least until you are stabilized on the Risperdal. That way, if any problems arise, you can trace them to the Risperdal, without having confounding variables involved.
About me being all over the place in this room. Yeah, I know. It's starting to scare me, too. My wife isn't thrilled sometimes, also. It's just that I learn so much in here and I am opinionated and nosy (sigh).
Keep in touch - Cam W.
Posted by CraigF on May 5, 2000, at 20:30:44
In reply to Re: Riperidone and terrible dreams, posted by Cam W. on May 5, 2000, at 19:37:03
Ok, thanks again..one more question, for anyone in the know..
Weight gain is a side effect of Risperidone. Is this a function of appetite or water retention or something. I've taken .5 mg two nights in a row and I swear I came home from work with more back fat than I left the gym with last night...I've even been keeping my appetite down through diet pills, skipping dinner, and doing cardio. I traditionally respond to these steps quickly, but I've grown this tire and I want to gouge it off with a sharp spoon...I'm 28 and fit!
Posted by JohnL on May 6, 2000, at 4:13:40
In reply to Re: Risperidone...I'm FAT!!, posted by CraigF on May 5, 2000, at 20:30:44
Craig,
Everything Cam has mentioned is in complete agreement with my own doctor and with Dr Jensen. Both often use this drug in treating depression, either as monotherapy or as an augmentation. I was told that if I wanted similar therapy to Zyprexa, Risperdone would be similar except without the sedation and without the weight gain. Of course, we're all different, and we all know about the varying mileage thing. :-)
Sounds good to me though. I am interested in how it progresses.
JohnL
Posted by Cam W. on May 6, 2000, at 11:54:01
In reply to Re: Risperidone...I'm FAT!!, posted by CraigF on May 5, 2000, at 20:30:44
Craig - Weight gain is a side effect of Risperdal, but it is usually not as bad as with Clozaril or Zyprexa. I seriously doubt you could gain enough weight in 2 days for it to be noticeable.Also, trying to keep your weight down by skipping meals doesn't work. You should eat a fairly good meal in the morning to break the fast (breakfast) after a sleep, a moderate lunch and a light dinner. This gives your body energy throughout he day.
As well, some diet pills can counteract the effects of Risperdal, especially the prescription one. In my opinion, diet pills are 'always' a waste of money. The only way to control weight is through exercise and a good diet. You are also doomed by genetics. Look at your parents - that's you later in life. Sure, I could alter my looks with surgery (eg plastic surgery, liposuction), but I would still produce ugly kids - LOL.
The "tire" you are taking about is from age. In the last 2 years of intense (usually) karate training I went from 154 lbs to 185 lbs (& one belt notch). My middle may be bigger, but I can grab less of it. Maybe you extra weight is a result of more abdominal muscle (ie thicker).
Oh, and don't gouge it out with a spoon. Modify your vacuum cleaner with a larger engine, smaller hose, and a small guage needle. 8^)
Posted by Noa on May 7, 2000, at 12:50:27
In reply to Re: Risperidone...Craig, posted by Cam W. on May 6, 2000, at 11:54:01
Craig, I know you are sick of people telling you the "real answer" about recreational drugs, but I have to weigh in with my thoughts as I read your posts. It makes me very anxious to hear that you would take the risk of using ecstacy or other drugs while on medication. I just think it isn't worth it.
Posted by CraigF on May 17, 2000, at 19:24:51
In reply to Re: Risperidone, posted by JohnL on May 6, 2000, at 4:13:40
So, wouldn't it figure, I find that after a week or so of Risperidone (added to my Serzone, which I have decreased to 450 mgs),I feel more in touch, personable (and less reclused), and kinda happy. It's not making me fatter quite yet, but I have been getting quite ANGRY and frustrated...
It reminds me of the latter stages of Wellbutrin (added to Serzone months back and since removed), or just the Serzone at times.
My doctor thought that the WB was exacerbating the Anger caused by the Serzone metabolite. I suggested that to be the case now with the Risperidone -- it happens like clockwork every afternoon, followed by severe headache and heartburn.
My pdoc's away, so I called his colleague to suggest the Serzone metabolite was getting in the way of another helpful drug, but he doubts it. Said I'm reacting to 1 mg and need to drop back to .5 mg.
Argh!! how can an anti-psychotic make me angry??? I admit something must change. Today I felt this wave of claminess and nausea, tearing, and high emotionality (a word?)
Do these things go away? if not, Is Risperidone helpful at .5 mgs? Just Serzone is NOT. My life is starting to fall into shambles. I'm either reclused and scared or losing my temper. This is worse than me pre-medicated.
HELP!!!
PS -- I am being treated for depression and anxiety. The Risp is an adjunct...I am not Schizophrenic.
Posted by JohnL on May 18, 2000, at 2:25:50
In reply to Risperidone and Serzone and Anger (oh my), posted by CraigF on May 17, 2000, at 19:24:51
Craig,
I wish I had some kind of suggestion for you. All I can say is I know EXACTLY how you feel and the deep frustration of it all. I think it's encouraging however that you have put so much thought into the chemistries involved. In your shoes I probably wouldn't be doing anything different...just playing around with dosing looking for a sweet spot.
JohnL
Posted by Cam W. on May 18, 2000, at 2:33:48
In reply to Risperidone and Serzone and Anger (oh my), posted by CraigF on May 17, 2000, at 19:24:51
Craig - Anger, frustration and hostility are minor side effects of both of these meds, but the anger could be subsequent to you disorder as well. As John says, you and your doc may need to play with dosages to find the happy mix. Good luck - Cam
Posted by SLS on May 18, 2000, at 10:34:09
In reply to Risperidone and Serzone and Anger (oh my), posted by CraigF on May 17, 2000, at 19:24:51
> Do these things go away? if not, Is Risperidone helpful at .5 mgs? Just Serzone is NOT. My life is starting to fall into shambles. I'm either reclused and scared or losing my temper. This is worse than me pre-medicated.
>
> HELP!!!
>
> PS -- I am being treated for depression and anxiety. The Risp is an adjunct...I am not Schizophrenic.
I bet your anger and state of frustration appear as a result of the drop in blood (and brain) level of Risperidone, as its half-life is only about 6 hours. Perhaps more frequent dosing would help. An alternative would be to use a neuroleptic with a longer half-life. Zyprexa has a half-life of about 35 hours.I get the feeling that Zyprexa offers a greater potential to exert an antidepressant effect. Currently, there are investigations evaluating the efficacy of combining Zyprexa with an SSRI to treat depression.
I hope you can resolve this situation using one of the suggestions you find here. If you are convinced that risperidone is helpful, I would stick with using one of three neuroleptics: Zyprexa, Seroquel, or Risperdal.
Serzone sounds like it may be hurting you more than it is helping. Your doctor is probably right about the metabolite, mCPP, causing some problems. It can be really nasty sometimes. It may be that Risperdal masks the mCPP-induced anger. As the level of Risperdal ebbs between dosing, this anger might may be uncovered.
Good luck.
- Scott
Posted by Liz on May 18, 2000, at 13:36:58
In reply to Risperidone and Serzone and Anger (oh my), posted by CraigF on May 17, 2000, at 19:24:51
Sorry you have to go through this. My p-doc decided to switch me to Serzone after a wash-out from Effexor because he felt I needed more sleep. It only took 2 days of Serzone to make me hostile and nasty to my friends and family. I couldn't stand the sound of human voices, they made me jump. When a friend called, all I wanted to do was hang up; I couldn't stand talking or listening to her. My husband told me I was rude after I hung up. It was a horrible experience. I only lasted 6 days on Serzone.
My recommendation is to only change one drug at a time so you know what's happening.Best wishes
Posted by CraigF on May 18, 2000, at 14:04:12
In reply to Re: Risperidone and Serzone and Anger (oh my), posted by Liz on May 18, 2000, at 13:36:58
Thanks, everyone, for your input!
I took .5 mg last evening. I have to say it was a pretty bad day overall. In addition to feeling physcially sick, I felt desperate and so uncomfortable around people.
I woke up feeling peachy today, however. I had 1.5 beers Tuesday night watching Buffy w/friends. I know how sensative Risperidone is in terms of sedation with alcohol, but could this sudden physical sickness and panic be related?
I really do feel OK today
Posted by PeterJ on May 19, 2000, at 2:36:56
In reply to Re: Risperidone and Serzone and Anger (oh my), posted by CraigF on May 18, 2000, at 14:04:12
Drug interactions are of two types. Pharmacokinetic interactions occur when one drug affects the levels of the other drug or its metabolites in your body. Pharmacodynamic interactions occur when the effects of one drug add of subtract from the effects of another drug.Combining risperidone and nefazadone has the potential of both kinds of interactions. It's not necessarily a bad combination, but it's a complicated one and it may explain your anger symptoms.
Nefazadone is metabolized by an enzyme called Cytochrome p450 3A. This enzyme converts the Nefazodone to another compound call mCPP (meta-chlorophenylpiperazine). mCPP is a metabolite of several psychiatric drugs and has unique and powerful effects on the brain which have been extensively studied. These studies (mostly at the National Insitututes of Health and also at Yale and other universities) involve giving people mCPP intravenously or orally and noting the effects in various conditions. One observation that has been made is that intravenous infusion of mCPP often causes feelings of anger. This is particularly common in people with certain anxiety disorders. Oral ingestion of mCPP is not as potent but may induce anger as well. If someone is taking Nefazodone and is experiencing unexpected anger, it is very possible that mCPP is the cause.
There has been no study of the effects of risperidone on the levels of mCPP produced by nefazadone, but the underlying biochemistry does suggest the possibility of an interaction.
First of all, while the enzyme that produces mCPP is Cytochrome P450 3A (known as CYP 3A for short) the enzyme that gets rid of the mCPP is another Cytochrome called P450 2D6 (CYP 2D6).
Nefazodone---[by CYP 3A]---> mCPP ----[by CYP 2D6]---> Inactive Metabolites
The important fact is that risperidone inhhibits CYP 2D6. So by taking risperidone you could block the breakdown of the anger-causing mCPP. Now risperidone is not a very powerful 2D6 inhibitor, and you are taking a small dose, so the effects might not be pronounced. But there is another drug interaction to take into acount as well. Not only would the risperidone increase the levels of mCPP, but the nefazodone may increase the levels of the risperidone.
Risperidone's metabolism is very complicated and would take me several pages to explain. In a nutshell, risperidone is metabolized by both the CYP 3A enzyme and the CYP 2D6 enzyme. However the 2D6 enzyme mainly converts risperidone to another compound (OH)-risperidone that has the same effects as risperidone itself. To set in motion the process of actually deactivating risperidone you need the 3A enzyme. This 3A enzyeme takes the dumbell shaped risperidone molecule and literally breaks it in half. But, and here is the key, nefazodone is a very potent inhibitor of CYP 3A. So taking nefazodone slows down the breakdown of risperidone.
This is the theoretical basis of the interaction. There has only been one published case I have seen that actually looked at levels of risperidone in someone taking nefazodone. That paper estimated that nefazodone doubled the levels of risperidone in the blood. However, this paper, which also described other interactions of risperidone, did not give much detail, such as the amount of nefazodone taken, and the amount of mCPP was not studied at all.
So that's the pharmacokinetic interaction. Nefazodone may increase the levels of risperidone and risperidone may increase the levels of mCPP.
There is also a possible pharmacodynamic interaction. Both risperidone and nefazodone interact with a number of receptors in the brain. Risperidone blocks serotonin and dopamine receptors, and may also block certain adrenergic receptors. Nefazodone blocks serotonin recoptors and uptake sites, and also blocks adrenergic receptors. mCPP stimulates serotonin receptors and may block some adrenergic receptors. There's a lot going on there, but the end result is any of these drugs can cause some degree of stimulation which could in some situations manifest itself as anger. (I could try to figure out which receptor specifically involved, but honestly there are so many involved that anyone picking one out as the cause would be guessing.) Risperidone can be used to treat psychosis, that does not mean it is not an activating drug. It can be activating, especially in low doses.
So what's the bottom line of all this? Well, I think you did the right thing in lowering the risperidone dose. Since risperidone and nefazodone can potentially increase each other's levels (and that of mCPP) and intensify each other's effects you may have been getting more of each than it seemed from your dose levels. Judging from the one published case, dropping the dose by 1/2 is about right.
You were concerned about whether such a low dose of risperidone could be effective. Risperidone can actually be surprisingly effective in small doses. While schizophrenic patients may need 6-8mg or more, people with anxiety and mood disorders like you have often respond to less. 0.5mg is a low dose, but there are reports of effectivnesss of such doses in bipolar patients. Elderly people and people with Parkinson's also repsond to very low doses (0.25mg and up). In your case, the drug interactions might mean that 0.5mg is as powerful as 1 or 2 mg would be. If the anger goes away you could try going back to 1mg in the future if needed.
So the short term answer is to cut back the dose of either the risperidone or the nefazodone. Hopefully you will be able to find a dose which relieves your depression without exacerbating anger. If you can't find such a dose, the next step would be to consider other antidepressants such as SSRIs or other anti-anger medications such as Lithium, propranolol, clonidine, etc. While some antidepressants may cause transient anger as they activate a person, this almost always goes away with time. Be cautious with the drug Trazodone as it also produces mCPP, and with Buspirone, as it produces a similar compound called 1-PP which can cause anxiety and agitation.
I am confident you will be able to find a treatment that will help in the long run causing excessive anger. It may be hard to hold on in the meanwhile, but you can do it.
P.S. You and your doctor did a good job of suggesting mCPP as a possible factor in the anger. Very few doctors are familiar with these studies. I happen to know about it because I did research into this area after experiencing mCPP and 1-PP related side effects years ago. I also have done studies on risperidone metabolism although I have not taken that drug. I know several of the world's leading authorities on mCPP and risperidone metabolism and in fact I can remember suggesting the possibility of a risperidone-nefazodone interaction before it was actually reported in the literature. (I'm here mainly as someone who is also ill, but I also have an academic background in biochemistry which comes in handy sometimes.)
Peter.
Posted by CraigF on May 20, 2000, at 20:12:52
In reply to Re: Risperidone and Serzone and Anger (oh my), posted by PeterJ on May 19, 2000, at 2:36:56
Thanks, Peter, I'm definitely printing this info out for my doctor.
Here's kind of a technical question...the fat and the anger are combining to make for a terrible Saturday night...
Does Risperidone result in weight gain as a function of appetite? or does it cause some metabolic change?
I work out almost religiously and have shrunk to nearly a 30 inch waist (from a 34 two years ago) This small waist is important because of my weak shoulders and small stature.
Despite cardio 3-4 times per week in the past two weeks I have developed a significant tire. I look silly in the clothes I recently bought.
I asked this before and got a pat response about diet and exercize being key to fitness. I know that. If i have to curb my appetite with pills, I will, but not if the weight gain is a metabolic thing...can anything be done? I don't want to die alone!! (just joking, but this is a sensitive topic for me.) At least I had a body to lure people to me even though my baggage drives people back away.
A factual answer minus prostheletizing would be great...Thanks.
Posted by Cindy W on May 21, 2000, at 1:35:40
In reply to Re: Rather not die alone (Risperidone), posted by CraigF on May 20, 2000, at 20:12:52
> Thanks, Peter, I'm definitely printing this info out for my doctor.
>
> Here's kind of a technical question...the fat and the anger are combining to make for a terrible Saturday night...
>
> Does Risperidone result in weight gain as a function of appetite? or does it cause some metabolic change?
>
> I work out almost religiously and have shrunk to nearly a 30 inch waist (from a 34 two years ago) This small waist is important because of my weak shoulders and small stature.
>
> Despite cardio 3-4 times per week in the past two weeks I have developed a significant tire. I look silly in the clothes I recently bought.
>
> I asked this before and got a pat response about diet and exercize being key to fitness. I know that. If i have to curb my appetite with pills, I will, but not if the weight gain is a metabolic thing...can anything be done? I don't want to die alone!! (just joking, but this is a sensitive topic for me.) At least I had a body to lure people to me even though my baggage drives people back away.
>
> A factual answer minus prostheletizing would be great...Thanks.
Craig, I can relate to what you say about not wanting to die alone. Also, I don't want to LIVE alone!!!--Cindy W
Posted by SLS on May 21, 2000, at 12:08:16
In reply to Re: Rather not die alone (Risperidone), posted by CraigF on May 20, 2000, at 20:12:52
Craig,
You scared the hell out of me. I'm glad to see that things are cool for now.
> Thanks, Peter, I'm definitely printing this info out for my doctor.
Peter's answer was brilliant. Mine sucked. I hope you and your doctor can figure out what's going on.
I am still curious, though. You mentioned that your anger seemed to emerge during the afternoon. Is this the only time you experience anger? When do you take your doses of Risperdal?
> Here's kind of a technical question...the fat and the anger are combining to make for a terrible Saturday night...
>
> Does Risperidone result in weight gain as a function of appetite? or does it cause some metabolic change?I'm sure PeterJ will answer this question better than I will, but I have some time to kill.
I have encountered some pretty contradictory stuff regarding Risperdal specifically. It has been claimed that it carries the least risk of weight-gain of the atypical neuroleptics. There are even a few reported incidents of weight-loss. The only other neuroleptic I have read about for which this is also observed is Stelazine, although I don't know if this drug is applicable to your case. Risperdal, more often than not, produces weight gain.
I find that the drug companies, along with the research teams they pay to investigate their drugs, are often full of crap. Their denial of weight gain as a side effect of the SSRIs is probably the biggest farce in modern psychiatry.
Yes. Risperdal and the other neuroleptics do cause changes in metabolism. These drugs block the dopamine D2 receptor. These receptors seem to control various metabolisms and functions associated with regulation of body weight. Perhaps the most obvious changes occur in glucose/insulin dynamics. Neuroleptics reduce the body's sensitivity to insulin. This allows for higher levels of glucose in the blood stream, which the body then converts to fat stores.
> I work out almost religiously and have shrunk to nearly a 30 inch waist (from a 34 two years ago) This small waist is important because of my weak shoulders and small stature.
>
> Despite cardio 3-4 times per week in the past two weeks I have developed a significant tire. I look silly in the clothes I recently bought.
>
> I asked this before and got a pat response about diet and exercize being key to fitness. I know that. If i have to curb my appetite with pills, I will, but not if the weight gain is a metabolic thing...can anything be done? I don't want to die alone!! (just joking, but this is a sensitive topic for me.) At least I had a body to lure people to me even though my baggage drives people back away.I know this feeling. When I was in my early twenties, I was responsible for giving a lot of young women whiplash whenever I walked down Wall Street.
Because my depression has been so severe and vegetative, I have spent the last decade confined to either a bed or a couch. This is not an exaggeration. The only reason I'm here on Babble is because taking Lamictal has moderated the depression somewhat. I have lost most of the muscle I gained through bodybuilding. On top of inactivity, I have put on 40lbs as a result of the weight-gain associated with tricyclics (histamine H1 receptor blockade). This is also produced by changes in metabolism. I can eat like a bird and not lose a single pound.
> A factual answer minus prostheletizing would be great...Thanks.
Just exercise more and eat right.
:-)
:-(
- Scott
Posted by PeterJ on May 22, 2000, at 0:43:42
In reply to Re: Rather not die alone (Risperidone), posted by CraigF on May 20, 2000, at 20:12:52
> Does Risperidone result in weight gain as a function of appetite? or does it cause some metabolic change?Risperidone can cause weight gain by both mechanisms. Risperidone blocks histamine, serotonin and dopamine receptors. This results in an increase in appetite, which is difficult to control. There is also some metabolic effect due to the increase in the hormone prolactin which may occur. The metabolic effect is probably relatively small at the dose you are taking, but it can be a factor.
Nefazodone can cause weght gain or loss depending on the individual.
The effects of risperidone may, to some extent, be counteracted, by diet and exercise, but it isn't easy. The appetite-increasing effect of the drug tells your body it needs more food, and it is hard to work against this.
Weight lifting (in addition to cardio) may be helpful as at least some of the added weight may be muscle instead of fat.
Appetite suppresant pills are not a good way to go, as nearly all of them can make someone more angry and will just undo the benefits of the risperidone. I'm not saying that to be preachy, it's just an unfortunate fact.
If weight gain continues to be a problem, you might want to ask your doctor to look into the drug topiramate (Topamax). It's an anticonvulsant that is being tried in mood disorders. It's said to be particularly good for people with irritablity and anger. And it causes weight loss. You can read more at these URLs:
http://www.dr-bob.org/tips/split/Topiramate.html
http://www.psycom.net/depression.central.topiramate.html
Also, there is a new antipsychotic being reviewed for approval called Ziprasidone, which may not cause weight gain. The FDA is still reviewing its safety at the moment.
Many of the new antipsychotics such as olanzepine and clozapine cause more weight gain than risperidone does. There are older antipsychotics which don't cause weight gain. Molindone is one. But these drugs are more likely than Risperidone to cause movement disorders (tardive dyskinesia).
Peter
Posted by SLS on May 22, 2000, at 14:15:53
In reply to Re: Rather not die alone (Risperidone), posted by PeterJ on May 22, 2000, at 0:43:42
> > Does Risperidone result in weight gain as a function of appetite? or does it cause some metabolic change?
> Risperidone can cause weight gain by both mechanisms. Risperidone blocks histamine, serotonin and dopamine receptors. This results in an increase in appetite, which is difficult to control. There is also some metabolic effect due to the increase in the hormone prolactin which may occur. The metabolic effect is probably relatively small at the dose you are taking, but it can be a factor.
By what metabolic mechanisms do neuroleptics cause weight-gain?
> The effects of risperidone may, to some extent, be counteracted, by diet and exercise, but it isn't easy. The appetite-increasing effect of the drug tells your body it needs more food, and it is hard to work against this.
Is leptin involved in this?
> Weight lifting (in addition to cardio) may be helpful as at least some of the added weight may be muscle instead of fat.
--------------------------------------------------------
Weight-lifting can help to reduce body fat (not simply shunt calories to muscle through anabolism) in three ways:1. Testosterone is secreted in response to the intensity of the exercise.
2. Growth-hormone (GH) is secreted during moderate to intense exercise.
* Question for PeterJ: Do neuroleptics inhibit the release of exercise-induced GH secretion?
Both of these hormones are lipolytic - they promote the burning of fat. In addition, these hormones act synergistically to promote an increase in whole body metabolism.
3. The release of adrenalin and norepinephrine during exercise directly stimulates adipose tissue to burn of fat.
Very often, a person who is bodybuilding can reduce his percentage of body fat down to %10 without jogging a single mile. This fat loss is not attributable simply to the number of calories burned from the exercise itself.
The basal metabolism rate (BMR) is increased. (Sometimes the term "resting metabolism rate" - RMR is used). You begin to burn more calories per hour, even while you are sitting on your butt doing nothing.
"Cardiovascular" or aerobic exercise - increasing your heart-rate to between 60 - 85 percent of your maximum (220 minus your age) for twenty minutes or more - will also promote an increase in growth-hormone release and BMR. However, to simply burn calories, walking does the trick very nicely. Weight-lifting and walking make a good combination. Jogging, a high-impact exercise, can ruin knees and ankles.
It is recommended that for maximum fat burning, exercise be performed at a moderate level (60%) for a more extended period of time, for example: walking for forty minutes versus running for twenty minutes.
Circuit-training is counterproductive.
- Scott
Posted by CraigF on May 22, 2000, at 17:53:13
In reply to Re: Rather not die at all (Risperidone) - Exercise, posted by SLS on May 22, 2000, at 14:15:53
Thanks, everyone.
What an informative thread this has been! One last question, I think...Does the inability to concentrate (so distractable at work) fade over time? My productivity is almost half of previous levels.
Posted by Jade on May 22, 2000, at 22:21:25
In reply to Re: Rather not die alone (Risperidone), posted by PeterJ on May 22, 2000, at 0:43:42
>
> > Does Risperidone result in weight gain as a function of appetite? or does it cause some metabolic change?
>
>
>
> Risperidone can cause weight gain by both mechanisms. Risperidone blocks histamine, serotonin and dopamine receptors. This results in an increase in appetite, which is difficult to control. There is also some metabolic effect due to the increase in the hormone prolactin which may occur. The metabolic effect is probably relatively small at the dose you are taking, but it can be a factor.
>
> Many of the new antipsychotics such as olanzepine and clozapine cause more weight gain than risperidone does. There are older antipsychotics which don't cause weight gain. Molindone is one. But these drugs are more likely than Risperidone to cause movement disorders (tardive dyskinesia).
>
> PeterI am a student who is curious about why some individuals do not experience weight gain on these medications.
Have animal studies been done re: weight gain and antipsychotics?
Do the percentages vary with each drug?
Can someone guide me to resources for the above questions?
Thank you
Jade
Posted by Cam W. on May 23, 2000, at 7:09:06
In reply to Re: Rather not die alone (Risperidone), posted by Jade on May 22, 2000, at 22:21:25
>
> I am a student who is curious about why some individuals do not experience weight gain on these medications.Most people only have personal experience. The reasons are not yet clear why there is weight gain, but many theories are popping up in the literature, lately.
>
> Have animal studies been done re: weight gain and antipsychotics?Animal studies on this subject are difficult. Some have been done, but no conclusive evidence, that I have heard.
>
> Do the percentages vary with each drug?The weight gain is very individualized, but the percentages are much higher than the drug companies report. It seems that the better an antipsychotic is, the more potential there is for weight gain (eg Clozaril > Zyprexa > Risperdal). Slimmer people at baseline seem to gain more weight than people who are overweight. The better the atypical antipsychotic works for an individual, the more weight seems to be gained. The weight gain seems to plateau eventually (approx. at 8 mos.). Weight gain may be tied to increased leptin levels, decreased metabolism, increased carbohydrate craving, none of the above or all of the above.
>
> Can someone guide me to resources for the above questions?There are several papers by the Wirshings (Donna and Bill) out of UC Berkley. Check PubMed, Google, Metacrawler, etc. with combinations of weight gain with the different antipsychotics.
>
Many of the older atypical antipsychotics also caused weight gain, but the potential for EPS and TD overshadowed any weight gain increases.It is also easier to try to keep the weight off than try to lose it once it has been gained (diligent control of diet and vigorous exercise). The weight gain usually plateaus within a year, so this can be seen as a relatively short term problem.
The gains from these meds far outweigh (pun intended) any weight gain, for the most part. Most people do not stop the medications because of weight gain.
Hope this helps - Cam
Posted by Jade on May 24, 2000, at 0:08:08
In reply to Re: Rather not die alone (Risperidone), posted by Cam W. on May 23, 2000, at 7:09:06
Cam,
Thank you for the response. I will look for those papers.
Jade
Posted by Adam on May 25, 2000, at 15:07:16
In reply to Re: Risperidone and Serzone and Anger (oh my), posted by PeterJ on May 19, 2000, at 2:36:56
I have been so busy lately that I scan Psychobabble pretty much based on the "new" flags, and often find myself going back to earlier dates first (before I scroll down) to follow a thread.
So I feel a bit like a clod to see a thread discussing almost precisely the same thing I'm talking about in another, totally unrealated thread.
Anyway, Peter, the stuff I've read is in almost complete accord with what you have discussed here. I have also considered the effects of Welbutrin, since I was taking that shortly before I was taking Serzone (nefazodone). However, for instance, most of what I have read seems to indicate that while risperidone is a 2D6 substrate, it shouldn't inhibit 2D6. It is true that the conventional wisdom on such interactions isn't always up to date with the science, but I couldn't find evidence that risperidone would raise the levels of mCPP. Serzone, as you have said, is thought to inhibit CYP450-3A, which metabolizes 9-hydroxyrisperidone (RISP > 9-OH-RISP via 2D6). Inhibition of 3A might be a problem vis a vis risperidone if risperidone concentrations are not closely monitored. I read also that RISP and 9-OH-RISP have about the same pharmacologic activity. I remember that one paper, where the author hypothesised that genetic differences in CYP450-2D6 could cause wide variations in the RISP to 9-OH-RISP ratio, but since both compounds do about the same thing, clinical outcome isn't as highly affected as one would expect by such deficiencies.
Also, it is true that RISP blocks certain serotonin receptors, but at lower doses, it blocks primarily certain dopamine receptors (D4 is the biggie, I think). I'm not sure if it is known what blood level of RISP correlates with dopamine receptor specific doses, and if such a thing could be carefully titrated in the case of drug interactions. Do you know?If one were, say, deficient in CYP450-2D6 (and about 10% of the caucasian population is thought to be), and were taking both nefazodone and risperidone, that could be a really bad thing. If one is responding poorly to nefazodone (a potential indicator of 2D6 deficiency?), and then throws risperidone into the mix, it seems you've got an anxiogenic drug mixed with a higher risk for extrapyramidal symptoms from the other. A dangerous coctail, perhaps?
What do you think? This actually didn't dawn on me until just now. It would blow my "risperidone+nefazodone is better than clozipine+nefazodone" theory right out of the water (if there aren't other holes in it) at least in some circumstances.
>
> Drug interactions are of two types. Pharmacokinetic interactions occur when one drug affects the levels of the other drug or its metabolites in your body. Pharmacodynamic interactions occur when the effects of one drug add of subtract from the effects of another drug.
>
> Combining risperidone and nefazadone has the potential of both kinds of interactions. It's not necessarily a bad combination, but it's a complicated one and it may explain your anger symptoms.
>
> Nefazadone is metabolized by an enzyme called Cytochrome p450 3A. This enzyme converts the Nefazodone to another compound call mCPP (meta-chlorophenylpiperazine). mCPP is a metabolite of several psychiatric drugs and has unique and powerful effects on the brain which have been extensively studied. These studies (mostly at the National Insitututes of Health and also at Yale and other universities) involve giving people mCPP intravenously or orally and noting the effects in various conditions. One observation that has been made is that intravenous infusion of mCPP often causes feelings of anger. This is particularly common in people with certain anxiety disorders. Oral ingestion of mCPP is not as potent but may induce anger as well. If someone is taking Nefazodone and is experiencing unexpected anger, it is very possible that mCPP is the cause.
>
> There has been no study of the effects of risperidone on the levels of mCPP produced by nefazadone, but the underlying biochemistry does suggest the possibility of an interaction.
>
> First of all, while the enzyme that produces mCPP is Cytochrome P450 3A (known as CYP 3A for short) the enzyme that gets rid of the mCPP is another Cytochrome called P450 2D6 (CYP 2D6).
>
> Nefazodone---[by CYP 3A]---> mCPP ----[by CYP 2D6]---> Inactive Metabolites
>
> The important fact is that risperidone inhhibits CYP 2D6. So by taking risperidone you could block the breakdown of the anger-causing mCPP. Now risperidone is not a very powerful 2D6 inhibitor, and you are taking a small dose, so the effects might not be pronounced. But there is another drug interaction to take into acount as well. Not only would the risperidone increase the levels of mCPP, but the nefazodone may increase the levels of the risperidone.
>
> Risperidone's metabolism is very complicated and would take me several pages to explain. In a nutshell, risperidone is metabolized by both the CYP 3A enzyme and the CYP 2D6 enzyme. However the 2D6 enzyme mainly converts risperidone to another compound (OH)-risperidone that has the same effects as risperidone itself. To set in motion the process of actually deactivating risperidone you need the 3A enzyme. This 3A enzyeme takes the dumbell shaped risperidone molecule and literally breaks it in half. But, and here is the key, nefazodone is a very potent inhibitor of CYP 3A. So taking nefazodone slows down the breakdown of risperidone.
>
> This is the theoretical basis of the interaction. There has only been one published case I have seen that actually looked at levels of risperidone in someone taking nefazodone. That paper estimated that nefazodone doubled the levels of risperidone in the blood. However, this paper, which also described other interactions of risperidone, did not give much detail, such as the amount of nefazodone taken, and the amount of mCPP was not studied at all.
>
> So that's the pharmacokinetic interaction. Nefazodone may increase the levels of risperidone and risperidone may increase the levels of mCPP.
>
> There is also a possible pharmacodynamic interaction. Both risperidone and nefazodone interact with a number of receptors in the brain. Risperidone blocks serotonin and dopamine receptors, and may also block certain adrenergic receptors. Nefazodone blocks serotonin recoptors and uptake sites, and also blocks adrenergic receptors. mCPP stimulates serotonin receptors and may block some adrenergic receptors. There's a lot going on there, but the end result is any of these drugs can cause some degree of stimulation which could in some situations manifest itself as anger. (I could try to figure out which receptor specifically involved, but honestly there are so many involved that anyone picking one out as the cause would be guessing.) Risperidone can be used to treat psychosis, that does not mean it is not an activating drug. It can be activating, especially in low doses.
>
> So what's the bottom line of all this? Well, I think you did the right thing in lowering the risperidone dose. Since risperidone and nefazodone can potentially increase each other's levels (and that of mCPP) and intensify each other's effects you may have been getting more of each than it seemed from your dose levels. Judging from the one published case, dropping the dose by 1/2 is about right.
>
> You were concerned about whether such a low dose of risperidone could be effective. Risperidone can actually be surprisingly effective in small doses. While schizophrenic patients may need 6-8mg or more, people with anxiety and mood disorders like you have often respond to less. 0.5mg is a low dose, but there are reports of effectivnesss of such doses in bipolar patients. Elderly people and people with Parkinson's also repsond to very low doses (0.25mg and up). In your case, the drug interactions might mean that 0.5mg is as powerful as 1 or 2 mg would be. If the anger goes away you could try going back to 1mg in the future if needed.
>
> So the short term answer is to cut back the dose of either the risperidone or the nefazodone. Hopefully you will be able to find a dose which relieves your depression without exacerbating anger. If you can't find such a dose, the next step would be to consider other antidepressants such as SSRIs or other anti-anger medications such as Lithium, propranolol, clonidine, etc. While some antidepressants may cause transient anger as they activate a person, this almost always goes away with time. Be cautious with the drug Trazodone as it also produces mCPP, and with Buspirone, as it produces a similar compound called 1-PP which can cause anxiety and agitation.
>
> I am confident you will be able to find a treatment that will help in the long run causing excessive anger. It may be hard to hold on in the meanwhile, but you can do it.
>
> P.S. You and your doctor did a good job of suggesting mCPP as a possible factor in the anger. Very few doctors are familiar with these studies. I happen to know about it because I did research into this area after experiencing mCPP and 1-PP related side effects years ago. I also have done studies on risperidone metabolism although I have not taken that drug. I know several of the world's leading authorities on mCPP and risperidone metabolism and in fact I can remember suggesting the possibility of a risperidone-nefazodone interaction before it was actually reported in the literature. (I'm here mainly as someone who is also ill, but I also have an academic background in biochemistry which comes in handy sometimes.)
>
> Peter.
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