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I don't see how adding a second benzo is going to help with sleepiness unless the clobazam dose is reduced with the addition of clonazepam. That's just my thinking though.

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22 hours ago, mikl_pls said:

I don't see how adding a second benzo is going to help with sleepiness unless the clobazam dose is reduced with the addition of clonazepam. That's just my thinking though.

I have already reduced clobazam from 20mg to 15mg. Now I dont have sleepiness. I will add 0.5 clonazepam to get additional panic attack protection. After starting clonazepam, maybe I can reduce clobazam further more.

Edited by clinic

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2 hours ago, clinic said:

I have already reduced clobazam from 20mg to 15mg. Now I dont have sleepiness. I will add 0.5 clonazepam to get additional panic attack protection. After starting clonazepam, maybe I can reduce clobazam further more.

Update: I just checked my online diary where i write all my experiences with meds daily. I just found out when I used to take only single benzo(clonazepam). It has remarks that even 0.25mg clonazepam was causing daytime sedation. I'm not sure if I will add clonazepam to clobazam or not.

The problem right now is I cant tolerate risperidone on clobazam 15mg, I need clobazam 20mg to tolerate it. But i have sleepiness problem on clobazam 20mg. How about 5mg clobazam in morning and 15mg at bed time

Edited by clinic

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On 6/10/2019 at 5:45 AM, clinic said:

Update: I just checked my online diary where i write all my experiences with meds daily. I just found out when I used to take only single benzo(clonazepam). It has remarks that even 0.25mg clonazepam was causing daytime sedation. I'm not sure if I will add clonazepam to clobazam or not.

Splitting a daily dose from once a day (qd) to twice daily (bid) typically is only necessary for medications that have short half-lives, particularly when that half-life is below 24 hours, but many medications do fine with 18-24.

Clobazam has a half-life of 36-42 hours (depending on the person) and its metabolite N-desmethylclobazam has a half-life of 71-82 hours. Because of this, once daily dosing is sufficient for adequate blood levels to be maintained throughout the day. When it comes to benzos BID dosing and even TID (3 times) are more necessary with alprazolam and lorazepam because their half-lives are shorter than clonazepam but most notably, their sedative effects last for a shorter time than clonazepam (which in adults can have a sedative effect ranging from 6-12 hours). Clonazepam and clobazam can both be taken as a single evening dose for anxiety and are typically only dosed more than once daily if they're being used to treat epilepsy, mostly because a lot of people have a hard time tolerating sedation from daytime clonazepam dosing.

That being said, some people do find specifically with clonazepam that it provides better coverage when split to morning and night despite its long half-life. Because their half-lives are similar (19-60 hours for clonazepam, even more variable than clobazam), I would expect the same would be said for clobazam, but because clobazam focuses on the alpha-2 subunit of the GABA-A receptor, it will cause less sedation with daytime dosing than clonazepam would. Like I can take 0.5mg alprazolam during the day no problem but if I were to take a 0.5mg clonazepam during the day, I need to take a nap.

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The problem right now is I cant tolerate risperidone on clobazam 15mg, I need clobazam 20mg to tolerate it. But i have sleepiness problem on clobazam 20mg. How about 5mg clobazam in morning and 15mg at bed time

I want to tell you that you shouldn't get hung up on a specific dose association between risperidone and clobazam 20mg, but looking at my own cocktail, I currently have a similar interaction between Trintellix and Vyvanse. At 10mg of Trintellix and below, I can tolerate my normal Vyvanse dose of 40mg, but if I increase the Trintellix dose to 15mg or higher, I need to decrease my Vyvanse dose to 30mg. Reason being is at 40mg of Vyvanse and 15-20mg of Trintellix, I have tics. Like twitches in my face muscles and pursing or curling my lips, symptoms of dopamine over-stimulation that are expected from stimulants. I'm inclined to think that Trintellix unlike most other antidepressants actually increases dopamine output the way Vyvanse does and the two of them together are additive. Combine this with the fact that I have to balance the dopamine stimulation of Trintellix+Vyvanse against Rexulti to tone everything down and Depakote is just kind of free-moving.

What I'm getting at though is that splitting your clobazam dose bid (5mg AM + 15mg PM) and then trying to reintroduce 0.25mg of risperidone with your evening clobazam dose (all under your doctor's supervision) would be worth trying before adding in a 4th agent (clonazepam) as you've already indicated that 0.25mg of clonazepam caused you enough sedation to be bothersome in the past, but 0.25mg is unlikely to yield the same kind of sedation into the daytime having a shorter half-life than clonazepam, a shorter effect window than clonazepam, as well as an intermediate receptor dissociation profile.

Edited by browri

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I second what @browri said. He said literally everything I was struggling to put into words.

There are some exceptions to some benzos with long half-lives needing to be dosed more than once a day; e.g., diazepam, which has almost the longest half lives of any benzo in the US. My pdoc said never to take more than 10 mg at a time. I've seen where some people have taken 20 mg at a time without any problem. But you would never want to take all 40 mg in one dose if you were on that dose (max dose). You would dose it 10 mg qid. Same for chlordiazepoxide and clorazepate, which, btw, are other options for you, @clinic.

I think you should also focus on one thing at a time. First figure out how to rid yourself of the daytime sleepiness, then worry about cognition.

Speaking of Vyvanse, that could also be an option. I know anything that increases dopamine causes psychosis, but perhaps Vyvanse 10 mg wouldn't. Or Adderall 2.5-5 mg, or dextroamphetamine 2.5 mg. Or possibly go with methylphenidate with 5 mg, or dexmethylphenidate 2.5 mg. Though if modafinil and armodafinil made you psychotic (which is strange seeing as though they work mostly on orexin and histamine over dopamine), the classic stimulants may not be an option. What dose of modafinil and armodafinil did you take? Do you remember?

 

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14 hours ago, browri said:

What I'm getting at though is that splitting your clobazam dose bid (5mg AM + 15mg PM) and then trying to reintroduce 0.25mg of risperidone with your evening clobazam dose (all under your doctor's supervision) would be worth trying before adding in a 4th agent (clonazepam) as you've already indicated that 0.25mg of clonazepam caused you enough sedation to be bothersome in the past, but 0.25mg is unlikely to yield the same kind of sedation into the daytime having a shorter half-life than clonazepam, a shorter effect window than clonazepam, as well as an intermediate receptor dissociation profile.

My sedation and tiredness r back again. I will need to reduce clobazam to 10mg/day from 15mg. Then maybe try taking 10mg in am and 10mg in pm. Right now I'm sleeping till 2pm then sedation goes away. Arms and legs are the most painful parts when I'm tired.

I think I was wrong about that clonazepam causing sedation. I think I took clonazepam for only few days like 2-3 and made conclusion that it was causing sedation. Usually tolerance develops to sedation.

Edited by clinic

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6 hours ago, mikl_pls said:

Speaking of Vyvanse, that could also be an option. I know anything that increases dopamine causes psychosis, but perhaps Vyvanse 10 mg wouldn't. Or Adderall 2.5-5 mg, or dextroamphetamine 2.5 mg. Or possibly go with methylphenidate with 5 mg, or dexmethylphenidate 2.5 mg. Though if modafinil and armodafinil made you psychotic (which is strange seeing as though they work mostly on orexin and histamine over dopamine), the classic stimulants may not be an option. What dose of modafinil and armodafinil did you take? Do you remember?

 

I have tried methylphenidate(20-30mg) and I got psychotic and agggresive/angry on it. I have tried both modafinil and armodafinil both causing psychosis as well. In terms of dose I have tried 50mg and 100mg modafinil max.

My illness started in 2013 when I was hospitalized for psychosis. You will be stunned to know that I actually took modafinil 100mg for 2 years(2013-2015) without any problems but after my 1st relapse in 2016 things changed. I cant even tolerate even 50mg modafinil now.

Edited by clinic

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2 hours ago, clinic said:

My sedation and tiredness r back again. I will need to reduce clobazam to 10mg/day from 15mg. Then maybe try taking 10mg in am and 10mg in pm. Right now I'm sleeping till 2pm then sedation goes away. Arms and legs are the most painful parts when I'm tired.

I think I was wrong about that clonazepam causing sedation. I think I took clonazepam for only few days like 2-3 and made conclusion that it was causing sedation. Usually tolerance develops to sedation.

Dividing the dose makes sense to me. I'm not sure if it will reduce sedation though after all is said and done. But it's definitely worth a try.

Another thing, do you take your clozapine all at once or in split doses? Also, when do you take your paroxetine CR?

1 hour ago, clinic said:

I have tried methylphenidate(20-30mg) and I got psychotic and agggresive/angry on it. I have tried both modafinil and armodafinil both causing psychosis as well. In terms of dose I have tried 50mg and 100mg modafinil max.

My illness started in 2013 when I was hospitalized for psychosis. You will be stunned to know that I actually took modafinil 100mg for 2 years(2013-2015) without any problems but after my 1st relapse in 2016 things changed. I cant even tolerate even 50mg modafinil now.

That's a typical starting dose of methylphenidate, but I was thinking about just a tiny, tiny dose of it. But I have a feeling you wouldn't tolerate it. :( 

Ok that's what I was actually going to suggest was to try just 50 mg modafinil or 50 mg armodafinil (which is more potent than modafinil).

That is rather odd.

Ok, I'm trying to get creative here. I see you've tried blonanserin, which is available in Japan and Korea; do you live in either of these countries? If so, you have a whole different set of drugs available to you than we do in the US.

Have you tried any of the following in lieu of clozapine?:

  • clocapramine
  • mosapramine
  • timiperone (may not be a good idea)
  • sulpiride
  • sultopride
  • zotepine
  • nemonapride
  • pipamperone
  • perospirone

I don't know much about the pharmacology of these meds, so bare with me if I've made bad suggestions.

Have you tried amantadine with your clozapine? It is dopaminergic, but it might be just right and not cause psychosis.

What about augmenting your clozapine with low-dose aripiprazole?

Edited by mikl_pls

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38 minutes ago, mikl_pls said:

Another thing, do you take your clozapine all at once or in split doses? Also, when do you take your paroxetine CR?

I take 200mg clozapine all at bedtime. I take paroxetine 12.5 in morning and 25mg in evening

Well sertraline took away all sedation at 50mg, but i got paranoid on it

Edited by clinic

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1 hour ago, clinic said:

I take 200mg clozapine all at bedtime. I take paroxetine 12.5 in morning and 25mg in evening

Well sertraline took away all sedation at 50mg, but i got paranoid on it

I would recommend taking all of your paroxetine at bedtime. It can be sedating for many and the 12.5mg morning dose could be part of your sedation.

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1 minute ago, browri said:

I would recommend taking all of your paroxetine at bedtime. It can be sedating for many and the 12.5mg morning dose could be part of your sedation.

No im taking this dose pattern since 2 years, morning 12.5 does not cause sedation. Taking whole 37.5mg at once causes anxiety and restless, hence the divided dose

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2 hours ago, mikl_pls said:

Ok, I'm trying to get creative here. I see you've tried blonanserin, which is available in Japan and Korea; do you live in either of these countries? If so, you have a whole different set of drugs available to you than we do in the US.

Have you tried any of the following in lieu of clozapine?:

  • clocapramine
  • mosapramine
  • timiperone (may not be a good idea)
  • sulpiride
  • sultopride
  • zotepine
  • nemonapride
  • pipamperone
  • perospirone

I don't know much about the pharmacology of these meds, so bare with me if I've made bad suggestions.

Have you tried amantadine with your clozapine? It is dopaminergic, but it might be just right and not cause psychosis.

What about augmenting your clozapine with low-dose aripiprazole?

Abilify causes psychosis at any dose. Pdoc said i cant take amantadine.

I live in India.

I see most of the atypicals are serotonin - dopamine antagonist. Is anti-serotonin properties, the cause of my anxiety ? I can stop clozapine and shift to olanzapine + risperidone. Risperidone is just for cognition. I know a friend who has completed his graduation on combination of clozapine + risperidone. Even latuda helps cognition but i can't take that cuz it is not that as effective as olanzapine. I have seen studies in favor of risperidone in regards to cognition. My memory was super solid on brief period i tried risperidone.

We have amisulpride here which is 2nd best antipsychotic after clozapine(1st best). The problem with amisulpride is it raises prolactin so high even on low doses + it highly prolongs qtc interval. It is classified as dopamine stabilizer and dopamine partial agonist, so i dont think it will cause anxiety and i wont need benzo on amisulpride.. But i would not prefer amisulpride. I hope olanzapine also does not raise anxiety as severe that i would need a benzo.

Man, it takes so much time to find a stable cocktail. Once u become stable, even then suddenly another problem emerges like me becoming super sedated on clobazam 20mg which did not happen before. You fix 1 problem in mental illness, then 2nd one emerges....fuckin hell

Edited by clinic
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31 minutes ago, clinic said:

Abilify causes psychosis at any dose. Pdoc said i cant take amantadine.

I live in India.

I see most of the atypicals are serotonin - dopamine antagonist. Is anti-serotonin properties, the cause of my anxiety ? I can stop clozapine and shift to olanzapine + risperidone. Risperidone is just for cognition. I know a friend who has completed his graduation on combination of clozapine + risperidone. Even latuda helps cognition but i can't take that cuz it is not that as effective as olanzapine. I have seen studies in favor of risperidone in regards to cognition. My memory was super solid on brief period i tried risperidone.

We have amisulpride here which is 2nd best antipsychotic after clozapine(1st best). The problem with amisulpride is it raises prolactin so high even on low doses + it highly prolongs qtc interval. It is classified as dopamine stabilizer and dopamine partial agonist, so i dont think it will cause anxiety and i wont need benzo on amisulpride.. But i would not prefer amisulpride. I hope olanzapine also does not raise anxiety as severe that i would need a benzo.

Man, it takes so much time to find a stable cocktail. Once u become stable, even then suddenly another problem emerges like me becoming super sedated on clobazam 20mg which did not happen before. You fix 1 problem in mental illness, then 2nd one emerges....fuckin hell

I would expect olanzapine would improve anxiety. It did for me, and it's structurally very similar to clozapine.

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29 minutes ago, clinic said:

Abilify causes psychosis at any dose. Pdoc said i cant take amantadine.

I see... Well let's strike those options... lol

30 minutes ago, clinic said:

I live in India.

Oh ok, so you have like, a bunch of meds available to you. I'm not familiar with India's market of medication either, but I can do some research.

31 minutes ago, clinic said:

I see most of the atypicals are serotonin - dopamine antagonist. Is anti-serotonin properties, the cause of my anxiety ? I can stop clozapine and shift to olanzapine + risperidone. Risperidone is just for cognition. I know a friend who has completed his graduation on combination of clozapine + risperidone. Even latuda helps cognition but i can't take that cuz it is not that as effective as olanzapine. I have seen studies in favor of risperidone in regards to cognition. My memory was super solid on brief period i tried risperidone.

Yes, that's what makes them "atypical." I don't believe the antiserotonergic properties are responsible for anxiety; rather, the opposite should be occurring. 5-HT2A antagonism should be anxiolytic, as should 5-HT1A partial agonism. 5-HT2C antagonism mainly is antidepressant and pro-cognitive, as is 5-HT6 and 5-HT7 antagonism.

I would admit that I would feel better about you being on olanzapine because of its being safer and more tolerable. Like @browri said, olanzapine is closely structurally related to clozapine. It would also cause a little less weight gain and would be slightly less likely to cause diabetes, but would still be highly likely to cause both. Olanzapine, though, is not a 5-HT1A partial agonist I don't believe. I could be wrong, but from what I've read, it isn't. Maybe you don't need that property though. But paroxetine is going to stimulate those receptors indirectly anyway via increased serotonin in the synapse.

I would try the olanzapine on its own first before adding low-dose risperidone.

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21 minutes ago, mikl_pls said:

I would try the olanzapine on its own first before adding low-dose risperidone.

Yes, I will force pdoc to give me olanzapine and reduce clozapine. I need his approval first.

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57 minutes ago, mikl_pls said:

Olanzapine, though, is not a 5-HT1A partial agonist I don't believe. I could be wrong, but from what I've read, it isn't. Maybe you don't need that property though. But paroxetine is going to stimulate those receptors indirectly anyway via increased serotonin in the synapse.

I would try the olanzapine on its own first before adding low-dose risperidone.

Olanzapine has very low affinity for the 5HT1A receptor and acts as an antagonist. However, as you said, central 5HT1 family activation would happen via paroxetine's reuptake inhibition of serotonin.

While olanzapine doesn't have any intrinsic activity at 5HT1A, it does have a low-moderate affinity for the alpha-2C agrenergic receptor which is postulated to indirectly increase serotonin output and thus indirectly increase central 5HT1 activation. I believe scientists arrived at this conclusion due to mirtazapine's ability to treat depression solely with it's antagonism of the serotonin-2 and alpha/adrenergic-2 receptor families. The same can be said for risperidone.

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1 hour ago, browri said:

The same can be said for risperidone.

Didn't you also say that risperidone, at specifically at low doses, preferentially antagonizes the presynaptic dopamine autoreceptors, increasing dopamine release? Or did I dream that up? lol

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2 hours ago, clinic said:

Yes, I will force pdoc to give me olanzapine and reduce clozapine. I need his approval first.

Well, I wouldn't force him do to anything. I would provide good evidence in your favor for switching to olanzapine. For instance, olanzapine is less sedating than clozapine, so you may be able to get the same therapeutic effect with olanzapine without as much sedation. Also, clozapine has a higher incidence of blood dyscrasias compared to olanzapine, so you'd be safer with olanzapine, assuming you could get the same protection from your psychosis.

You could cross-titrate between clozapine and olanzapine (I believe the -pine's require cross titration...), rather than remaining on clozapine indefinitely.

Eventually you could commence the risperidone under your pdoc's supervision if he sees it fit.

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35 minutes ago, mikl_pls said:

Didn't you also say that risperidone, at specifically at low doses, preferentially antagonizes the presynaptic dopamine autoreceptors, increasing dopamine release? Or did I dream that up? lol

Yes that would be correct and by low doses I mean <1mg/d. What I was meaning to say in my last post was that, like olanzapine, while risperidone itself has low affinity for 5HT1A and is an antagonist there, it still increases 5HT1 activation overall via antagonism of the alpha-2 adrenergic receptor family.

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3 minutes ago, mikl_pls said:

(I believe the -pine's require cross titration...)

The -pines do require cross-titration when moving to the -dones, the -pips and the -rip. However when moving between -pines it is less necessary. Stahl's reasoning for this is the propensity for the -pines to be anti-cholinergic as an AAP sub-class and therefore when switching to other chemical groups that aren't as potent anti-cholinergic agents, it should be done with a 1-2 week overlap because:

A. Anti-cholinergic withdrawal can be rough all on its own.

B. Anti-cholinergic activity of the -pines effectively fends off akathisia that precipitates from dopamine antagonism and dopamine's subsequent imbalance against acetylcholine in the brain, hence why -pines generally have a lower propensity for EPS/akathisia relative to the other chemical groups. With this in mind, switching from a -pine to another class too rapidly could precipitate sudden treatment-emergent akathisia which can be distressing to the patient during a med transition

3 minutes ago, mikl_pls said:

Eventually you could commence the risperidone under your pdoc's supervision if he sees it fit.

If he sees fit is the important part. Forcing ideas on your pdoc can be seen as agitation or aggression. You can certainly bring the evidence and have a debate with your pdoc. I do at most appointments lol. But your pdoc ultimately makes the decision.

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