![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 23 to 47 of 47. Go back in thread:
Posted by SLS on January 29, 2014, at 16:47:41
In reply to Re: Switching from Abilify to Latuda, posted by Bob on January 29, 2014, at 14:17:18
> My doctor will not touch the MAOI+nortriptyline combo that you are taking. He says mixing NRIs with MAOIs is dangerous. What about stimulants, are they okay to take with an MAOI?
http://www.dr-bob.org/tips/split/TCAs-+-MAOIs.html
http://www.dr-bob.org/tips/split/MAOIs-in-high-doses-and-wi.html
:-)
- Scott
Posted by SLS on January 30, 2014, at 11:45:52
In reply to Switching from Abilify to Latuda, posted by SLS on January 27, 2014, at 21:32:51
So far, so good.
I'm 4 days into Latuda without taking any Abilify. I haven't relapsed. I like the way I feel on Latuda. It isn't magic, but it might be better than Abilify. It is early. I'm taking 40 mg/day of Latuda. There are no side effects. I was particularly concerned with cognitive blunting and zombification (not official medical nomenclature).
I am trying to be guarded in my optimism. I am failing.
- Scott
Posted by Bob on January 30, 2014, at 14:34:22
In reply to Re: Switching from Abilify to Latuda » Bob, posted by SLS on January 29, 2014, at 16:47:41
> > My doctor will not touch the MAOI+nortriptyline combo that you are taking. He says mixing NRIs with MAOIs is dangerous. What about stimulants, are they okay to take with an MAOI?
>
> http://www.dr-bob.org/tips/split/TCAs-+-MAOIs.html
>
> http://www.dr-bob.org/tips/split/MAOIs-in-high-doses-and-wi.html
>
> :-)
>
>I've shown my pdoc articles and postings about mixing the MAOIs with NRIs or stims and he isn't moved. He just isn't willing.
> - Scott
Posted by Bob on January 30, 2014, at 14:37:16
In reply to Re: Switching from Abilify to Latuda, posted by SLS on January 30, 2014, at 11:45:52
> So far, so good.
>
> I'm 4 days into Latuda without taking any Abilify. I haven't relapsed. I like the way I feel on Latuda. It isn't magic, but it might be better than Abilify. It is early. I'm taking 40 mg/day of Latuda. There are no side effects. I was particularly concerned with cognitive blunting and zombification (not official medical nomenclature).
>
> I am trying to be guarded in my optimism. I am failing.
>
>
It's stunning to hear you've had no discontinuation effects from stopping the Abilify like that! Then again you are not one to have experienced such things, correct? For me, micro-adjustments to my aripiprazole dose resulted in bad days and suicidality. My sister stopped Abilify last year and it almost took her life. She's off it now.Bob
> - Scott
Posted by Bob on January 30, 2014, at 14:40:46
In reply to Re: Switching from Abilify to Latuda » Bob, posted by SLS on January 29, 2014, at 14:02:00
>
> I hope you are experiencing a temporary setback. Who knows what your brain is up to. Have you ever tried Focalin for fatigue / brain fog? It helps me when my energy ebbs. If it is a good drug for you, you won't experience a depressive rebound when it wears off. For now, I am using it occasionally in place of caffeine. My doctor prescribed it to be taken on a daily basis in the hope that it will kick-start a robust antidepressant response. I want to see how Latuda treats me first.
>
> - Scott
>You said you are using the Focalin occasionally, so how often and under what circumstances are you taking it if not daily? How long have you been doing this?
What about Wellbutrin? I've don't remember you mentioning ever trying that or having it on your options list.
Bob
>
>
Posted by Bob on January 31, 2014, at 12:42:15
In reply to Re: Switching from Abilify to Latuda » SLS, posted by Bob on January 30, 2014, at 14:40:46
One more question Scott:I noticed you still have the minocycline on board. Do you still attribute discrete, definable benefits of your response to that med in particular? If so, what are they exactly?
Bob
Posted by SLS on January 31, 2014, at 13:39:39
In reply to Re: Switching from Abilify to Latuda » SLS, posted by Bob on January 30, 2014, at 14:37:16
> > So far, so good.
> >
> > I'm 4 days into Latuda without taking any Abilify. I haven't relapsed. I like the way I feel on Latuda. It isn't magic, but it might be better than Abilify. It is early. I'm taking 40 mg/day of Latuda. There are no side effects. I was particularly concerned with cognitive blunting and zombification (not official medical nomenclature).
> >
> > I am trying to be guarded in my optimism. I am failing.
> >
> >
>
>
> It's stunning to hear you've had no discontinuation effects from stopping the Abilify like that! Then again you are not one to have experienced such things, correct?Not really. Although I need and can tolerate high dosages of many drugs, that doesn't seem to indicate that withdrawal effects are significantly reduced whenever I discontinue a medication. The last time I attempted to discontinue Abilify by tapering, I still experienced a wicked withdrawal depressive rebound that lasted for a few days before evening out. This time, I stopped the Abilify abruptly and began taking Latuda at 40 mg/day on the same day. I felt only a slight loss of antidepressant activity on day 3 that lasted for about 6 hours. I could "feel" the Latuda breaking my fall (speculation, I know). It is important to note that the half-life of Abilify is 3 days. So, blood levels of Abilify came down more slowly than what would be seen with most other psychotropic medications.
> For me, micro-adjustments to my aripiprazole dose resulted in bad days and suicidality. My sister stopped Abilify last year and it almost took her life. She's off it now.
In many cases, the depressive/anxiogenic rebound effect from discontinuing a psychotropic is transient, but can be mitigated by performing a gradual taper. Even this doesn't always work to prevent entirely the withdrawal effects. However, it should reduce their in duration and magnitude.
- Scott
Posted by SLS on January 31, 2014, at 13:53:00
In reply to Re: Switching from Abilify to Latuda » SLS, posted by Bob on January 30, 2014, at 14:40:46
> > I hope you are experiencing a temporary setback. Who knows what your brain is up to. Have you ever tried Focalin for fatigue / brain fog? It helps me when my energy ebbs. If it is a good drug for you, you won't experience a depressive rebound when it wears off. For now, I am using it occasionally in place of caffeine. My doctor prescribed it to be taken on a daily basis in the hope that it will kick-start a robust antidepressant response. I want to see how Latuda treats me first.
> You said you are using the Focalin occasionally, so how often and under what circumstances are you taking it if not daily? How long have you been doing this?
Focalin helps with mental and physical energy, but not with depression per se. However, with more mental resources to work with, the depression is easier to negotiate and tolerate. I was prescribed Focalin to be taken twice a day, every day. He said that if I got euphoric and suffered a depressive crash, it was the wrong drug for me. We hoped that it might kick-start the other medications to begin working better. Ideally, I would then be able to discontinue the Focalin at some point.
Focalin worked for me the way my doctor was hoping it would at first, but just not to a degree that I was satisfied with. I therefore decided to use it more as a PRN and remain flexible. I would say that there was some tolerance that developed at the dosage I used, but it was not a complete waste of time to take it. I thought that to use Focalin acutely only for particularly difficult days would preserve a more robust stimulant effect than taking it continuously.
> What about Wellbutrin? I've don't remember you mentioning ever trying that or having it on your options list.I have tried Wellbutrin several times beginning in 1983 at dosages as high as 900 mg/day. Each time, it made me feel moderately worse, even when combined with Parnate.
- Scott
Posted by SLS on January 31, 2014, at 14:11:49
In reply to Re: Switching from Abilify to Latuda » Bob, posted by Bob on January 31, 2014, at 12:42:15
> One more question Scott:
Yeah sure...
:-)
> I noticed you still have the minocycline on board. Do you still attribute discrete, definable benefits of your response to that med in particular? If so, what are they exactly?
I tried to discontinue minocycline once. I had been taking it for 6 months at that time. I relapsed within two days. Fortunately, I felt better quickly after restarting it. The scope of the improvements produced by minocycline are more global than being selective of only a few symptoms.
Get well!!!
- Scott
Posted by Bob on January 31, 2014, at 14:15:36
In reply to Re: Switching from Abilify to Latuda » Bob, posted by SLS on January 31, 2014, at 14:11:49
Thanks for answering all those questions Scott!
Posted by SLS on February 16, 2014, at 14:36:37
In reply to Re: Switching from Abilify to Latuda » SLS, posted by Bob on January 31, 2014, at 14:15:36
Well, Latuda was a failed treatment for me. Despite an encouraging improvement in symptoms during the first few days, Latuda made me feel very much worse over time and upon a dosage increase to 60 mg/day. I had to fight thoughts of suicide. Not fun. I have been feeling better since discontinuing Latuda two days ago. It is my suspicion that my bipolar depression was made worse by the ability of Latuda to block NE alpha-2a receptors. Other drugs with this property have exacerbated my depression in the past, including Remeron and idazoxan. My guess is that more people will profit from the 5-HT7 antagonism exerted by Latuda in the treatment of depression than will suffer an exacerbation of that illness.
Good luck to everyone being treated with Latuda!
- Scott
Posted by Bob on February 16, 2014, at 14:41:20
In reply to Switching from Abilify to Latuda - Failed, posted by SLS on February 16, 2014, at 14:36:37
> Well, Latuda was a failed treatment for me. Despite an encouraging improvement in symptoms during the first few days, Latuda made me feel very much worse over time and upon a dosage increase to 60 mg/day. I had to fight thoughts of suicide. Not fun. I have been feeling better since discontinuing Latuda two days ago. It is my suspicion that my bipolar depression was made worse by the ability of Latuda to block NE alpha-2a receptors. Other drugs with this property have exacerbated my depression in the past, including Remeron and idazoxan. My guess is that more people will profit from the 5-HT7 antagonism exerted by Latuda in the treatment of depression than will suffer an exacerbation of that illness.
>
> Good luck to everyone being treated with Latuda!
>
>
> - Scott
So are you back on Abilify then?-Bob
Posted by SLS on February 16, 2014, at 18:30:46
In reply to Re: Switching from Abilify to Latuda - Failed » SLS, posted by Bob on February 16, 2014, at 14:41:20
> > Well, Latuda was a failed treatment for me. Despite an encouraging improvement in symptoms during the first few days, Latuda made me feel very much worse over time and upon a dosage increase to 60 mg/day. I had to fight thoughts of suicide. Not fun. I have been feeling better since discontinuing Latuda two days ago. It is my suspicion that my bipolar depression was made worse by the ability of Latuda to block NE alpha-2a receptors. Other drugs with this property have exacerbated my depression in the past, including Remeron and idazoxan. My guess is that more people will profit from the 5-HT7 antagonism exerted by Latuda in the treatment of depression than will suffer an exacerbation of that illness.
> >
> > Good luck to everyone being treated with Latuda!
> So are you back on Abilify then?I have restarted Abilify using a loading dose of 30 mg to get things going. I am going to request of my doctor to try Saphris (asenapine). It is a fairly potent antagonist of 5-HT7 receptors - more so than Abilify. I might even lose weight on it.
- Scott
Posted by Phillipa on February 16, 2014, at 20:08:09
In reply to Switching from Abilify to Latuda - Failed, posted by SLS on February 16, 2014, at 14:36:37
Scott I'm sorry it didn't work for you. So back to Abilify? No others other than saphris? Poo PJ
Posted by herpills on February 17, 2014, at 14:14:13
In reply to Re: Switching from Abilify to Latuda - Failed » Bob, posted by SLS on February 16, 2014, at 18:30:46
>
> I have restarted Abilify using a loading dose of 30 mg to get things going. I am going to request of my doctor to try Saphris (asenapine). It is a fairly potent antagonist of 5-HT7 receptors - more so than Abilify. I might even lose weight on it.
>
>
> - ScottScott, I'm sorry to hear that Latuda didn't work out. My trial of Latuda was also a failure unfortunately. I hope that Saphris will help you. I liked Saphris better than Abilify. I did have a slight gain in weight on it, but not as much as when I was on Abilify. herpills
Posted by Bob on February 17, 2014, at 14:36:10
In reply to Re: Switching from Abilify to Latuda - Failed » SLS, posted by herpills on February 17, 2014, at 14:14:13
>
> >
> > I have restarted Abilify using a loading dose of 30 mg to get things going. I am going to request of my doctor to try Saphris (asenapine). It is a fairly potent antagonist of 5-HT7 receptors - more so than Abilify. I might even lose weight on it.
> >
> >
> > - Scott
>
> Scott, I'm sorry to hear that Latuda didn't work out. My trial of Latuda was also a failure unfortunately. I hope that Saphris will help you. I liked Saphris better than Abilify. I did have a slight gain in weight on it, but not as much as when I was on Abilify. herpills
>
Let us know how you do When you try Saphris Scott. Good luck!- Bob
Posted by LouisianaSportsman on February 19, 2014, at 23:39:57
In reply to Switching from Abilify to Latuda - Failed, posted by SLS on February 16, 2014, at 14:36:37
Scott,
I am sorry to hear that you failed with Latuda.
As I mentioned, I had a bad experience when I switched from Abilify to Latuda as well-- I believe I mentioned severe depression as well in an earlier post kinda warning you about this. I thought it was specific to just my case, but it seems like it happened to you too. I must report, however, that the malaise associated with the lurasidone persisted for about two weeks-- extremely bad for some of the duration-- and now it is the most efficacious AP I have ever been on somehow. I am sorry it was not a good medicine for you. Good luck with asenapine!
Posted by SLS on February 20, 2014, at 3:41:31
In reply to Re: Switching from Abilify to Latuda - Failed, posted by LouisianaSportsman on February 19, 2014, at 23:39:57
Everyone - thanks for the good advice and well-wishes. We are definitely a nice group of people.
Saphris might make me feel worse, but I don't think it makes sense for me to skip over it. My doctor wants me to take 5 mg/day.
While we are on the subject...
Abilify, Latuda, and Saphris are all serotonin 5-HT7 receptor antagonists; Latuda being the most potent. Experiments indicate that 5-HT7 receptors are involved in depression and the therapeutic action of certain drugs. However, Latuda and Saphris are also antagonists of norepinephrine NE alpha-2 receptors, and thus acts like higher dosages of Remeron. Remeron and idazoxan (an experimental NE alpha-2 antagonist) both severely exacerbate my depression. Therefore, Latuda will have been the third drug with this action to make me feel worse. Unfortunately, this leaves open the possibility that Saphris will make me feel worse, too. I try not to exclude drugs from consideration based upon my silly little personal theories. Too little is understood about how drugs operate to treat depression, and I try to avoid being presumptuous. For example, it is only recently that the significance of 5-HT7 receptors in depression has been recognized. I would not have taken this into account previously.
One other concern of mine with Saphris is that it is a full antagonist at serotonin 5-HT1a receptors. This compares to the partial agonist properties of Geodon, Abilify, and Latuda, as well as Viibryd and Brintellix (also a 5-HT7 antagonist). 5-HT1a partial agonism does not seem to make me feel worse and might actually help. Saphris might produce an exacerbation of my depression because it operates on these receptors in the opposite manner.
Saphris might make me feel worse:1. 5-HT7 receptor antagonists have antidepressant properties.
2. Abilify, Latuda, and Saphris are all 5-HT7 antagonists.
3. NE alpha-2 receptor antagonists make me feel worse (idazoxan and Remeron).
4. Latuda and Saphris are both NE alpha-2 antagonists. Abilify is not.
5. Latuda makes me feel worse.
6. 5-HT1a receptor agonists have antidepressant properties.
7. 5-HT1a receptor partial agonists that made me feel better include Abilify, Geodon, and Viibryd.
8. Saphris is a 5-HT1a antagonist and operates in a manner opposite to the drugs that helped me.
* I don't think that Brintellix (vortioxetine) should be ignored in the treatment of depression. In addition to its SSRI-like inhibition of serotonin reuptake, it is also a 5-HT1a agonist and a 5-HT7 antagonist. It is also a 5-HT3a receptor antagonist, but I don't know the clinical significance of this. I would make Brintellix my next drug to try if I were not already taking Parnate. Serotonin syndrome would result were these two drugs to be combined.
- Scott
Posted by SLS on February 24, 2014, at 22:03:06
In reply to Returned to Abilify. Adding Saphris., posted by SLS on February 20, 2014, at 3:41:31
The first few days of my taking Saphris produced a great deal of somnolence. This effect is abating, though. I am experiencing a subtle, but recognizable improvement in depression. We'll have to see if it persists beyond three weeks. It usually doesn't persist beyond three days.
- Scott
Posted by SLS on February 25, 2014, at 5:33:15
In reply to Re: Returned to Abilify. Adding Saphris., posted by SLS on February 24, 2014, at 22:03:06
> The first few days of my taking Saphris produced a great deal of somnolence. This effect is abating, though. I am experiencing a subtle, but recognizable improvement in depression. We'll have to see if it persists beyond three weeks. It usually doesn't persist beyond three days.
I am on my fifth day of taking Saphris. I raised the dosage to 10 mg/day (5 mg b.i.d.) yesterday. I have lost most of the antidepressant effect that appeared a few days ago while taking 5 mg/day. I am still expecting Saphris to make me feel worse in a way similar to Latuda, Remeron, and idazoxan. I suspect that NE alpha-2a receptor antagonism is responsible for this.
- Scott
Posted by johnLA on February 25, 2014, at 10:57:13
In reply to Re: Returned to Abilify. Adding Saphris., posted by SLS on February 25, 2014, at 5:33:15
scott-
i am curious as to your response to remeron.
could you put it in 'laymen's' terms, if you have the time? it's mode of action and your specific response? i am not knowledgeable on the specific receptors you guys often talk about. i'm curious.
i was taking remeron for a long time. not sure it did anything really. i am wondering now if it made my depression worse as well.
thanks for any reply.
john
Posted by SLS on February 25, 2014, at 12:21:33
In reply to Re: Returned to Abilify. Adding Saphris. » SLS, posted by johnLA on February 25, 2014, at 10:57:13
Hi John.
> i am curious as to your response to remeron.
>
> could you put it in 'laymen's' termsDon't I always?
;-)
> it's mode of action and your specific response?
Gosh. It is so hard to describe depression. With Remeron and idazoxan, I felt an anxious depression. I wanted it to end. I was, for the most part, motionless. I was too vegetative to think. Suicide was out of the question, as I didn't have the energy or wits to do it. It was actually painful. I just wanted to be left alone, yet, I was dependent on others to survive. The depression was hideous. It had no beginning and had no end.
5-HT = serotoin
NE = norepinephrine (noradrenalin)
H = histamineRemeron binds to and acts as an antagonist at receptors of several different neurotransmitters. These are a few of them.
1. 5-HT2a
2. 5-HT2b
3. 5-HT3
4. NE alpha-2a
5. H1A neurotransmitter is like a key that fits into a lock; the lock being the receptor. Generally speaking, a receptor is specific for one neurotransmitter.
* Agonist = a substance that binds to a receptor and stimulates it to perform its duties.
* Antagonist = a substance that binds to a receptor and blocks it from being stimulated.
* Inverse agonist = a substance that binds to a receptor and fools the receptor complex into acting in a manner opposite to that produced by an agonist.
Remeron is an antagonist at the five receptors listed above.
1. When stimulated, 5-HT2a and 5-HT2c receptors antagonize (inhibit) the release of excitatory neurotransmitters like dopamine in several brain structures. Remeron is very "sticky" and will bind to these same receptors tighter than serotonin does, thus inhibiting the action of serotonin. So, Remeron is inhibiting the inhibiting function of serotonin receptors on dopamine release. This is what is known as disinhibition. Confusing, I know. The bottom line is that to block 5-HT2a/c receptors releases more dopamine.
2. When stimulated, NE alpha-2a receptors increase the synthesis and release of NE. They are located on the terminal presynaptic membrane, and act as autoreceptors. (self-recognition). When NE levels decrease, the number of autoreceptors being stimulated by NE also decreases. This is a signal to the presynaptic neuron terminal to make more and release more NE. This is what it is known as a negative-feedback loop. So, when Remeron blocks the NE alpha-2a receptors, it is as if a blindfold was placed over them. They don't "see" the NE floating around in the synapse. The presynaptic neuron is therefore fooled into thinking it is time to make more and release more NE. The bottom line is that Remeron increases NE activity.
3. H1 receptors are one type of histamine receptor. They are involved in wakefulness, perceived energy, immune system activation, and appetite. H1 antagonist antihistamines like Remeron reduce wakefulness, cause fatigue, inhibit metabolism, inhibit immune activity, and increase appetite.
So, where does this leave you?
I don't know. Remeron can poop out just like SSRIs do, although I doubt it occurs as often. You could try adding a SRI drug (SSRI or SNRI) first, and then attempt to discontinue the Remeron if you feel better. You might need both drugs. You might not do well with them at all.
What are your main symptoms?
If you have to ask whether or not you are feeling well, then you probably aren't.
Sorry for any mistakes. I don't have the energy to proofread this. :-(
- Scott
Posted by johnLA on February 25, 2014, at 19:40:20
In reply to Re: Returned to Abilify. Adding Saphris. » johnLA, posted by SLS on February 25, 2014, at 12:21:33
thanks so much scott.
i really appreciate you taking the time to walk me thru all that stuff.
i will need to read it a few times. :)
my main symptoms are anergia, anhedonia, ruminating negative thoughts. you know the drill.
i am only on klonopin right now. super med sensitive. i am not giving-up on meds. but, after 4 years now i'm tired of the way they make me feel. ironically i feel better right now than i have on all the med trials. still, i am far from well.
anyway, thanks again so much for the lesson. i will read it several times like i said. you did a very nice job of explaining a complex subject matter.
wishing you good health scott.
john
Posted by SLS on February 25, 2014, at 20:52:43
In reply to Re: Returned to Abilify. Adding Saphris. » johnLA, posted by SLS on February 25, 2014, at 12:21:33
Sorry!!!
How very silly of me.
I should have proofread this. I wish I could just copy-and-paste directly from my brain. On second thought, that could be dangerous.
> 2. When stimulated, NE alpha-2a receptors increase the synthesis and release of NE.
This should read:
2. When stimulated, NE alpha-2a receptors DECREASE the synthesis and release of NE.
- Scott
Posted by SLS on February 26, 2014, at 1:04:18
In reply to Re: Returned to Abilify. Adding Saphris. » SLS, posted by johnLA on February 25, 2014, at 19:40:20
> wishing you good health scott.
Thanks John.
I apologize for the mistake I made in my explanation.
It is extremely important to understand the concept of feedback loops and homeostasis.
The method by which most neurons manage how much neurotransmitter to synthesize and release is to monitor how much is floating around outside the cell. In the case of the synapse, the sensors that do the monitoring are called autoreceptors, and are located presynaptically on the first (sending) neuron. When most of these receptors are occupied by the neurotransmitter molecule as concentrations grow, it tells the presynaptic cell to stop making so much of it and to reduce its release. Thus the concentration of neurotransmitter in the synapse begins to decrease. When it gets too low, most of the autoreceptors are empty. The drop in autoreceptor occupancy signals the neuron to then increase the synthesis and release of neurotransmitter. This is an example of a negative feedback loop. It facilitates the maintenance of consistency in synaptic neurotransmission. This is an example of homeostasis.
Remeron (mirtazapine) acts to block the presynaptic autoreceptors from detecting norepinephrine (NE) in the synapse. It occupies the autoreceptor, but does not stimulate it. This is called receptor antagonism, with Remeron being the antagonist. As far as the presynaptic neuron is concerned, the concentration of NE is too low, so it keeps synthesizing and releasing NE, even while synaptic concentrations continue to rise. The homeostasis is disrupted.
The NE autoreceptor that Remeron blocks is of the subtype NE alpha-2. It is therefore an antagonist of that receptor. Remeron is selective because it does not bind to other subtypes of NE receptors. Postsynaptic NE receptors located on the second (receiving) neuron remain available to be stimulated by the increasing synaptic concentrations of neurotransmitter. Overall NE activity increases, at least for awhile. However, in order for this to happen, dosages of Remeron must be high enough. This probably accounts for why higher dosages of Remeron (45 - 90 mg/day) become less sedating and more antidepressant.
- Scott
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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