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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 26. This is the beginning of the thread.
Posted by tiopenster on July 28, 2010, at 8:02:49
I have a bad case of anxiety. I've tried just about every drug in the book. Can someone explain my response to these drugs. I do well on something for anywhere from a couple days to a week and then they stop working. This often happens on each dose increase as well. It seems to happen on every drug I try. It happens with Paxil, Lexapro, Zoloft, Buspar, Imiprimine, Zyprexa, Geodon, Lamictal, Lyrica, and Neurontin. I can't do Seroquel because of akathisia, Abilify & Risperdal did nothing for me. I believe the term for this is Tachyphylaxis, but how do I overcome it? I've been dealing with this frustration for almost 4 years. Any help?
Posted by manic666 on July 28, 2010, at 12:46:52
In reply to All my drugs work for 2-7 days then stop working, posted by tiopenster on July 28, 2010, at 8:02:49
how long do you give the trials, on all these med,s
Posted by tiopenster on July 28, 2010, at 13:54:07
In reply to Re: All my drugs work for 2-7 days then stop working, posted by manic666 on July 28, 2010, at 12:46:52
I give them several weeks, but I can never recover feeling normal.
Posted by ed_uk2010 on July 28, 2010, at 16:08:06
In reply to All my drugs work for 2-7 days then stop working, posted by tiopenster on July 28, 2010, at 8:02:49
>I believe the term for this is Tachyphylaxis, but how do I overcome it? I've been dealing with this frustration for almost 4 years. Any help?
A brief improvement after starting a new med commonly occurs due to the hopes and expectations that the treatment will work, rather than because of the drug itself.
What sort of anxiety do you suffer from?
Posted by tiopenster on July 28, 2010, at 16:21:13
In reply to Re: All my drugs work for 2-7 days then stop working, posted by ed_uk2010 on July 28, 2010, at 16:08:06
It mimics the placebo response, but the effect is quite dramatic. It's like a light switch turning on an off. I never experience the gradual improvement that would be expected. My anxiety is not physical. It's purely mental. It's a sense that something is always wrong and I have irrational fears.
Posted by ed_uk2010 on July 28, 2010, at 16:32:59
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on July 28, 2010, at 16:21:13
> It mimics the placebo response, but the effect is quite dramatic. It's like a light switch turning on an off. I never experience the gradual improvement that would be expected. My anxiety is not physical. It's purely mental. It's a sense that something is always wrong and I have irrational fears.
What sort of irrational fears?
Posted by tiopenster on July 28, 2010, at 19:21:26
In reply to Re: All my drugs work for 2-7 days then stop working, posted by ed_uk2010 on July 28, 2010, at 16:32:59
Fear of going outside, fear of going in buildings, fear of walking around the lake. Stuff like that. Plus this nagging feeling that something's wrong so I'm constantly in this constant alert that something is going to be anxiety inducing. It's this constant feedback loop so I can't just be focused on whatever I'm doing. It's really annoying.
Posted by Phillipa on July 30, 2010, at 12:22:56
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on July 28, 2010, at 19:21:26
Sounds like me. Phillipa
Posted by ed_uk2010 on July 30, 2010, at 15:22:05
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on July 28, 2010, at 19:21:26
> Fear of going outside, fear of going in buildings, fear of walking around the lake. Stuff like that.
When you're afraid, what's going through your mind? For example, do you worry that you might have a panic attack or some other symptom which might potentially make it difficult for you to 'escape' from the situation?
Posted by ed_uk2010 on July 30, 2010, at 15:23:36
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on July 28, 2010, at 19:21:26
> Fear of going outside, fear of going in buildings, fear of walking around the lake. Stuff like that. Plus this nagging feeling that something's wrong so I'm constantly in this constant alert that something is going to be anxiety inducing. It's this constant feedback loop so I can't just be focused on whatever I'm doing. It's really annoying.
Also, what is your diagnosis (if you have one)?
Posted by tiopenster on July 30, 2010, at 16:48:18
In reply to Re: All my drugs work for 2-7 days then stop working, posted by ed_uk2010 on July 30, 2010, at 15:22:05
My diagnose is GAD/Panic Disorder. At least that's what I started out as. I stopped having panic attacks when I figured out that they weren't going to hurt me, but by then, it had turned into continuous anxiety. A fear that something was wrong with me. I started with a handlful of SSRI's but those made the anxiety so much worse. Lexapro caused me to go through switches - paranoid, manic, depressed etc. It made me scared of things like my back yard or the dark, etc. Lexapro & Zoloft essentially made me paranoid. I tried a couple others, but those would only work for a couple days. I've been off SSRI's for a while and I'm much better that I was then, but I still have residual fears. From what I've read I responded to SSRI's like a bi-polar would given the switches from normal to anxiety, but I'm not anywhere close to that diagnosis.
I haven't experience panic or anything close to in over 3 1/2 years, but I still have fears and this nagging feeling that something is wrong. It's hard to describe, but it's like I'm anxious about being anxious. I suppose I'm anxious about not being able to escape being anxious. I still have those residual fears that I acquired while on SSRI's, but this constant "hum" of anxiety riddles me throughout the day. Because of that, I am on constant alert that things will be anxiety inducing. Anything is a potential threat. I suppose that's anticipatory anxiety. Fear of fear. I hope that makes sense. Thanks for inquiring.
Posted by ed_uk2010 on July 30, 2010, at 17:11:37
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on July 30, 2010, at 16:48:18
>My diagnosis is GAD/Panic Disorder.
It sounds to me like you've developed some symptoms of agoraphobia.
Agoraphobia is an anxiety disorder characterized by fear and distress related to being in situations from which escape might be difficult or embarrassing (i.e. being on a bus or train), or in which help might not be available in the event of a panic attack or panic symptoms. In psychiatry, agoraphobia does not mean 'fear of open spaces' - an almost meaningless concept at any rate. Agoraphobia can occur with or without panic disorder. Many people experience panic-like symptoms but not full panic attacks.
GAD is normally characterized by chronic physical tension in addition to psychological symptoms. A diagnosis of GAD tends to apply to people who worry excessively about things which most people worry about to some extent eg. money problems, problems at work etc. Unusual or irrational fears are not characteristic of GAD.
How do you respond to benzodiazepines eg. clonazepam? It might be helpful for you to keep a couple of tablets of a fast-acting benzo such as Xanax or diazepam in your wallet. You don't have to take them - but you would know that they were there if you needed them for panic. This can be reassuring.
Also, how do you respond to sedating antidepressants such as trazodone?
Posted by ed_uk2010 on July 30, 2010, at 17:21:59
In reply to Re: All my drugs work for 2-7 days then stop working, posted by ed_uk2010 on July 30, 2010, at 17:11:37
Sorry, I just read one of your previous posts where you said you didn't respond well to benzos.
Perhaps you should consider phenelzine (Nardil)? Nardil can sometimes be very effective for anxiety disorders, even when other meds haven't worked. Although Nardil does effect serotonin, it effects it in a different way to SSRIs. You cannot use your response to SSRIs to predict your response to Nardil, it's a very different med.
Posted by tiopenster on July 30, 2010, at 18:05:53
In reply to Re: All my drugs work for 2-7 days then stop working, posted by ed_uk2010 on July 30, 2010, at 17:21:59
Trazadone is actually activating for me. I've only taken it a couple times for sleep, but it didn't work. Would it make me cycle/switch like the other SSRI's
Would I have to go off my Remeron and Geodon to go on Nardil? My psych didn't want to try the MAOI's because he knows how I respond to serotonin. Would it make me cycle or switch? Why do you say that it affects serotonin in a different way? I'm very intrigued by the idea of a new class of medication.
Thanks for you help!
Posted by ed_uk2010 on July 31, 2010, at 14:34:52
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on July 30, 2010, at 18:05:53
>Would I have to go off my Remeron and Geodon to go on Nardil?
Difficult one. The safety of combining these drugs with MAOIs is not clear (due to lack of study). One potential problem is that Geodon is a weak serotonin reuptake inhibitor. SRIs can cause serious reactions when combined with MAOIs.
>My psych didn't want to try the MAOI's because he knows how I respond to serotonin.
When you react badly to an SSRI, you are not 'responding to serotonin', you are responding to potent serotonin reuptake inhibition ie. the blockage of serotonin reuptake from the synaptic cleft into the presynaptic neuron. Reuptake is the process which terminates the effects of serotonin at the synapse.
Serotonin is a vital neurotransmitter which is of great relevance to a wide variety of psychiatric problems. Most psych drugs affect serotonin neurotransmission, some directly, some indirectly. The important thing to bear in mind is that serotonin neurotransmission is affected differently by different classes of drugs. We all need serotonin, you can't say 'serotonin is bad for me'. What you can say is that 'potent serotonin reuptake inhibitors cause problems for me, but other drugs affecting serotonin neurotransmission in different ways might be beneficial'.
At the moment, you are on two drugs which substantially affect serotonin neurotransmission: mirtazapine and ziprasidone. Both drugs affect serotonin function in a different way to SSRIs.
Mirtazapine:
Mirtazapine blocks certain serotonin receptors, notably 5-HT2 and 5-HT3 subtypes. It is claimed to indirectly increase serotonin neurotransmission via 5-HT1a receptors - although I am not sure to what extent this occurs in reality.
Ziprasidone:
Ziprasidone blocks certain serotonin receptors, especially 5-HT2 and 5-HT1d. It stimulates 5-HT1a receptors and weakly inhibits serotonin reuptake.
>Why do you say that it affects serotonin in a different way? I'm very intrigued by the idea of a new class of medication.
MAOIs certainly have a different mechanism of action to SSRIs: this is one of the reasons that they are often useful in treatment-resistant depression and severe anxiety disorders. Unlike SSRIs, they do not prevent serotonin from being removed from the synapse by the reuptake pump. As I explained above, reuptake is the process which terminates the effect of serotonin at the synapse. In contrast, MAOIs inhibit the metabolism (breakdown) of serotonin inside the pre-synaptic neuron. This increases the amount of serotonin which is available for release. In addition, MAOIs inhibit the breakdown of norepinephrine, dopamine and trace amines. Phenelzine (Nardil) increases levels of GABA by interfering with its metabolism; this may contribute to Nardil's effectiveness in anxiety disorders. Parnate does not have this effect, but it does have some additional stimulant-like properties which Nardil lacks. The MAOIs really are a complex group of drugs. I know you are concerned about the possibility of an adverse reaction to MAOIs due to 'increased serotonin'.... but to be perfectly honest, you can't predict what your response to MAOIs will be based on your response to SSRIs and related drugs. There are just so many differences between MAOIs and SSRIs.
>Thanks for you help!You're welcome.
The worst thing about Nardil is that it does cause side effects very frequently. You also have to educate yourself about the necessary dietary restrictions and drug interactions. The best thing about Nardil is its efficacy. It's really not a drug for mild depression or mild anxiety. For severe cases it can make a huge impact.
If you do decide to try Nardil, you will need to start with a low dose and increase gradually. It certainly can be a difficult process - but it's worth the hassle if it gets rid of your anxiety.
In order to take Nardil safety, you do need a psychiatrist who is experienced with the use of MAOIs. They are not easy drugs to use, and many psychiatrists lack the knowledge and confidence to use them safely. Younger psychiatrists in particular may never have prescribed them. Some may believe that they are 'bad, dangerous drugs'. This type of comment tends to come from psychiatrists who are not familiar with MAOIs and have (usually) never used them. Steer clear of this type of doctor, they are usually the same ones who think the latest 'wonder drugs' can treat everyone. If only that were true!
Take care,
Ed_UK
Posted by bleauberry on August 2, 2010, at 20:20:41
In reply to All my drugs work for 2-7 days then stop working, posted by tiopenster on July 28, 2010, at 8:02:49
Maybe you are like some of us that cannot take drugs continuously every day. You can take it once every other day, once every three days, whatever, never allowing the genes to catch on to what you are doing. Take the drug every day and they can figure it out pretty fast, what, a week at the most, and then send out their instructions to undo what the drug is trying to do. Keep the genetic instruction guys confused. As soon as they figure out what you are doing by taking a drug regularly, they have all kinds of ways to undo it.
For example. Let's say the genes have instructions for a certain amount of serotonin at the synapse. You then start lexapro. Within a week the genes are sending out warning flags to everybody....too much serotonin, not in our instructions, you guys who turn tryptophan into serotonin STOP. You guys in the MAO department need to step up your pace and chew up all the serotonin because for some strange reason the reuptake guys are blocked and we got a flood of serotonin here.
Keep the genes on the run. Which means you can't take a drug more than 2 or 3 days in row. You might have to switch back and forth between several different meds you find helpful so as to keep the genes in total confusion so they don't mess things up.
I know that sounds bizarre. But hey, whatever you gotta do, right? It works for me and other people.
Someone else might instead say you gotta increase the dose more and more until you reach a point where the good effect stays, which could be double or triple the maximum dose normally prescribed. Again, whatever you gotta do. I remember for example reading about a lady with Lyme disease who had intermittent response to Lexapro but didn't get a sustained response until the dose hit 60mg. That is way above the usual maximum dose.
If someone had an answer to your question they could make millions.
Posted by tiopenster on August 3, 2010, at 8:31:44
In reply to Re: All my drugs work for 2-7 days then stop working » tiopenster, posted by ed_uk2010 on July 31, 2010, at 14:34:52
Wow, what a great explanation. Where did you learn all that. You sound like a psychiatrist. I can't believe you're so willing to help me.
I have to say I'm scared to go off all my meds to try Nardil, but it may be worth a shot.
Thank you so much for your help.
Posted by ed_uk2010 on August 3, 2010, at 14:47:40
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on August 3, 2010, at 8:31:44
>I have to say I'm scared to go off all my meds to try Nardil, but it may be worth a shot.
How bad do you feel right now? To what extent are your current meds helping?
Ed
Posted by tiopenster on August 3, 2010, at 15:55:56
In reply to Re: All my drugs work for 2-7 days then stop working » tiopenster, posted by ed_uk2010 on August 3, 2010, at 14:47:40
Hi Ed,
My current regimen gives me average of about 80% relief and that's with 5 drugs! I don't have any anxiety or panic attacks, but I still have the constant sense that something is wrong and I have certain phobic reactions - what you described as agoraphobia. i.e. getting in the shower, going outside, going in buildings, flying, etc.
Currently, I seem to bounce around. I think the Geodon and Remeron makes me unstable from day to day. Some days I feel half way decent, but then I'll switch to feeling bad - sometimes in the middle of the day. It's like a light switch. So my drug regimen helps (I think), but it changes every day. I chart on my calendar every day how I feel in percentages and it's like I'm an ultra rapid cycler except I don't have depression. I just cycle from normal to anxiety.
I did feel stable for about 6 months when I was on Lyrica, Neurontin, Depakote, Lamictal, Remeron and Geodon, but I felt apathatic, fatigued and emotionless. I weaned off Remeron and Geodon and all hell broke loose. I was stable, but only because I was consistently anxious and nauseous. I went back on all Remeron and Geodon, but have not been able to regain the same stability. That's after 8 weeks.
I used the term tachyphylaxis as a description of how I do well for a short amount of time on a new drug or a new dosage and then it goes bad. Here's the article that I got the term from. It's a brilliant article because it describes me exactly (except that I'm not bi-polar) - something no one has been able to do. http://www.psychiatrictimes.com/display/article/10168/51906 The authors describe several responses to SSRIs. Tachyphylaxis is one of them. Not only did that happen to me on SSRI's, but also Tricyclics, Neurontin, Lyrica, Lamictal, Geodon, Zyprexa & Buspar. I actually drove 4 hours to meet with the author of the article - Dr Coplan. He was great, but he just said to take more Lamictal, which didn't do the trick. He stopped responding to my follow up emails probably because he didn't know what to do. Now I can't afford to see him any more even if I was willing to drive up to New York.
My local psychiatrist doesn't know what to do. (I've been through an internist and 2 psychiatrists.) As I mentioned previously, he didn't want to do MAOI's because I "react poorly to serotonin." But as you said, this could simply be the reuptake inhibition mechanism.
I can't remember if I mentioned it earlier, but benzos don't do anything for my anxiety.
What do you think my best option would be? Nardil? I'm only worried about side effects and the 2 months that would be required for a fair trial and the fact that I'd have to go off Remeron. I did a drug interaction test here and it seems that I could keep all my other meds (although I don't know how much they're doing) http://www.medscape.com/druginfo/druginterchecker I was surprised that there was no counter indication for Geodon. Maybe it's wrong.
Again, thank you Ed for taking an interest in my situation. It's very helpful considering the fact that I feel lonely because I'm a medical mystery! I knew I was one when my pdoc told me about potential drug trials that NIMH was always doing.
Posted by ed_uk2010 on August 4, 2010, at 15:08:27
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on August 3, 2010, at 15:55:56
Hi Tio,
So what is your exact regimen at the moment? eg. all your meds, including doses, times of day taken etc. Will reply to your above post soon.
Also, do you have any non-psych medical conditions?
Posted by tiopenster on August 4, 2010, at 15:40:05
In reply to Re: All my drugs work for 2-7 days then stop working » tiopenster, posted by ed_uk2010 on August 4, 2010, at 15:08:27
Hi Ed,
I take the following all at night
Psych meds:
Geodon 80mg (20, 40, 60, and 80 started to work for a couple days then they'd poop out, so there's no need going higher)
Remeron 15mg (I don't notice any different with higher doses)
Lamictal 50mg (more or less than that doesn't seem to help any)
Neurontin 900mg (I was on up to 3000mg, but it all stops working after a couple days)
Lyrica 225mg (I was on higher, but again, that stopped working after a week)Non-psych meds:
Axid 150mg or Prevacid 30mg for acid reflux
Glucophage (Metrformin) 500mg for insulin resistance and weight loss
Zocor 40mg for high cholesterol. I just stopped this because it was giving me slightly elevated liver enzymesVitamins:
Lovaza (Fish Oil)
Probiotics
Vitamin D
Multiivitamin
Calcium/MagnesiumJust curious where your knowledge comes from for all this. You seem like you're a doctor. I'm not assuming that, but you are meticulous, knowledgeable and inquisitive. I love it. Or perhaps you're personally using an MAOI and can speak from personal experience. I'm curious.
Thanks Ed
Posted by ed_uk2010 on August 4, 2010, at 16:02:26
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on August 4, 2010, at 15:40:05
So, at the moment, do you think most of the benefit is coming from Remeron or something else?
It is very unusual to take Lyrica and Neurontin together, since these drugs have the same mechanism of action. Lyrica will probably displace Neurontin from receptors since it is more potent. I think it would be best just to take Lyrica on its own.
About the Zocor. Statins occasionally induce depression and other psychiatric disturbances eg. sleep disturbances, sexual disturbances and reduced memory function. These are not common side effects - it's just something to consider. Have you been on Zocor for a long time?
Out of curiosity, have you even been on trimipramine (Surmontil)? It's a rather unique tricyclic antidepressant because it doesn't inhibit the reuptake of serotonin or NE, but does potently block various serotonin receptors.
>
> Non-psych meds:
> Axid 150mg or Prevacid 30mg for acid reflux
> Glucophage (Metrformin) 500mg for insulin resistance and weight loss
> Zocor 40mg for high cholesterol. I just stopped this because it was giving me slightly elevated liver enzymes
>
> Vitamins:
> Lovaza (Fish Oil)
> Probiotics
> Vitamin D
> Multiivitamin
> Calcium/Magnesium
>
> Just curious where your knowledge comes from for all this. You seem like you're a doctor. I'm not assuming that, but you are meticulous, knowledgeable and inquisitive. I love it. Or perhaps you're personally using an MAOI and can speak from personal experience. I'm curious.
>
> Thanks Ed
Posted by tiopenster on August 4, 2010, at 16:28:52
In reply to Re: All my drugs work for 2-7 days then stop working, posted by ed_uk2010 on August 4, 2010, at 16:02:26
Yes, I think most of the benefit comes from Remeron although it does make me unstable. I have gone off Lyrica and didn't do so well, so it has to be helping some. I've also gone off Geodon alone and I struggled a bit. It seems there is some synergy in what I'm using now, but it's not getting me where I need to be. I should probably try to get off Neurontin and see what happens. I have tried Remeron by itself, but it seems to require some of these other drugs to get it's most effect.
I had read about some of those Zocor side effects. That's why I went off (in addition to the liver problem) I was on Zocor from Sept 27, 2009 until about 3 weeks ago.
I've never heard of trimipramine (Surmontil) let alone use it. The only TCA I've used is Pamelor, but it gave me the 2 good days, then bad again problem. Below is a quote from wikipedia in reference to Surmontil. How can it be a weak inhibitor of serotonin and yet have a strong antagonism for 5ht2. Isn't that a contradiction? Is inhibition different from antagonism?
"Trimipramine's mechanism of action differs from other TCAs. It is only a moderate reuptake inhibitor of norepinephrine, and a weak reuptake inhibitor of serotonin and dopamine. Its main effects are due to considerable receptor antagonism as follows:
Strong: 5-HT2, mACh, H1, H2, α1-adrenergic
Moderate: D2
Weak: 5-HT1, a2-adrenergic"Would you recommend switching out Remeron & Geodon for Surmontil or merely adding it?
Posted by ed_uk2010 on August 4, 2010, at 16:49:52
In reply to Re: All my drugs work for 2-7 days then stop working, posted by tiopenster on August 4, 2010, at 16:28:52
>How can it be a weak inhibitor of serotonin and yet have a strong antagonism for 5ht2. Isn't that a contradiction? Is inhibition different from antagonism?
It's just saying that it's got weak activity at 5-HT(1) receptors, but strong antagonism at 5-HT(2) receptors. Antagonism means that a receptor is 'blocked' - preventing it from being stimulated.
>Would you recommend switching out Remeron & Geodon for Surmontil or merely adding it?
It was only a suggestion. First of all, you would need to discuss it with your doctor. He may not think that it is suitable.
If you do decide to try it, I do think that you should stop Neurontin first. You can't just keep on adding meds! Surmontil should be started at a low dose and increased gradually, anticholinergic side effects such as dry mouth can be bothersome. After starting Surmontil, I would suggest reducing Geodon first then Remeron later. Once you have increased up to a therapeutic dose of Surmontil, you may be able to stop both Remeron and Geodon.
I can't promise that Surmontil will be a good med for you. It does cause side effects very frequently eg. drowsiness, dry mouth, constipation, dizziness etc. I was just thinking that its serotonin receptor blocking effects might be useful, and that it's a bit different to anything you've tried before.
Posted by tiopenster on August 4, 2010, at 23:33:36
In reply to Re: All my drugs work for 2-7 days then stop working, posted by ed_uk2010 on August 4, 2010, at 16:49:52
Hi Ed,
I assume you're from the homeland of Britain. We love you chaps out there across the pond. I was just photographing a political conference tonight (that's my day job) and I sat next to 3 Young Britons. There were 20 at the conference total. They were so nice and interesting. I love your kind.
Back to business.
A few follow up questions If you don't mind. I suggest taking this offline, but there has to be one poor soul that will benefit from the conversation in 10 years.I do seem to have a problem specifically with the 5ht1 receptor, hence all my problems with SSRIs. They's what they hone in on. My worst reaction was to Lexapro and that's because it's laser like focus on serotonin and nothing else. The was the devil for me. I've never been depressred or manic before I was put on that drug. It needs an exorcist.
I've had moderate success with Remeron, probably because it doesn't touch 5ht1 directly and this it "modulates" as opposed to doing RI. And Geodon focuses on 5ht2
Below is what wikipedia says about Geodon: If you can understand what it's says, I wondered if you could compare it to what wikipedia says about Surmontil: The fact that they both antagonize at the 5ht receptor indicates some sort of similarity. I wonder if I'm reading it all wrong.
"Trimipramine's mechanism of action differs from other TCAs. It is only a moderate reuptake inhibitor of norepinephrine, and a weak reuptake inhibitor of serotonin and dopamine. Its main effects are due to considerable receptor antagonism as follows:
Strong: 5-HT2, mACh, H1, H2, α1-adrenergic
Moderate: D2
Weak: 5-HT1, a2-adrenergic""
"Ziprasidone has a high affinity for dopamine, serotonin, and alpha-adrenergic receptors and a moderate affinity for histamine receptors, where it is believed to act as an antagonist.[2] Ziprasidone also displays some inhibition of synaptic reuptake of serotonin and norepinephrine[2][3], although the clinical significance of this is unknown. The mechanism of action of ziprasidone is unknown. However it has been theorized that its antipsychotic activity is mediated primarily by antagonism at dopamine receptors, specifically D2. Serotonin antagonism may also play a role in the effectiveness of ziprasidone, but the significance of 5-HT2A antagonism is debated among researchers.[4] Ziprasidone has perhaps the most selective affinity for 5-HT2A receptors relative to D2 and 5-HT2C receptors of any neuroleptic.[5][6] Antagonism at histaminic and alpha adrenergic receptors likely explains some of the side effects of ziprasidone, such as sedation and orthostasis.And furthermore, this is what it says about Remeron: Mirtazapine is an antagonist/inverse agonist at the following receptors:[71][72]
▪5-HT2A receptor (Ki = 69 nM)
▪5-HT2B receptor (Ki = ? (~20-fold lower than for 5-HT2A/2C))[73]
▪5-HT2C receptor (Ki = 39 nM)
▪5-HT3 receptor (Ki = ? (similar to 5-HT2A/2C))[74]
▪5-HT7 receptor (Ki = 265 nM)
▪a1-adrenergic receptor (Ki = 608 nM)
▪a2A-adrenergic receptor (Ki = 20 nM)
▪a2C-adrenergic receptor (Ki = 18 nM)
▪H1 receptor (Ki = 1.6 nM)
▪mACh receptors (Ki = 794 nM)
Covers every serotonin receptor except 5ht1. Maybe that's why I've done half way decent on it.My psch clued into the fact that it was the 5ht1 that I don't do well on.
I should note, that I had moderate success on Zyprexa. Not sure what that acts on. It made me eat like a horse, my blood surgar levels were increased and I was so fatigued all the time. That was a deal breaker for me. I had to be on 10mg for the anti-anxiety to kick it It gave me this 3 days good, 2 days bad. I could switch from normal to anxious on the flip of a switch.
So my final questions is whether I should talk to my doctor about Trimipramine or Nardil. I'm game for both. The former sounds easier than the latter.
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