14 replies to this topic

[YoungSchizo]

I've been quite obsessed/interested in this med for a while now and most likely will push my pdoc to give me a chance in trying it, the depression/negative symptoms are so damn crippling, this might be the drug that may pull me out of at least the depression I suffer from for the past 12 years.

However, I can't seem to find ONE SINGLE article or user experience that it has been prescribed to schizophrenics.. Is it because of the dopaminergic agonism that it's not suited for schizophrenics or what's the deal? Also, will Nardil interact with antipsychotics (Latuda and Zyprexa)?

[Mind_Paralysis]

It increases the activity of both serotonin and dopamine at the same time, such  drugs are known to trigger psychosis, so yes, possibly.

 

But hey, mate, have you tried a combo of this, instead?

 

 

Brexpiprazole

Reboxetine

Ondansetron (5ht3-antagonists are supposed to help specifically with negative symptoms, which is your primary problem)

 

All of the following have some evidence of effects on negative symptoms - Brexpiprazole and RBX could help with depressive symptoms as well. Brex is, as some may know, the first SDAM - Serotonin Dopamine Activity Modulator, which is cleared by the FDA for the treatment of Depression specifically - other drugs with antipsychotic effects are not.

[YoungSchizo]

It increases the activity of both serotonin and dopamine at the same time, such drugs are known to trigger psychosis, so yes, possibly.

But hey, mate, have you tried a combo of this, instead?


Brexpiprazole
Reboxetine
Ondansetron (5ht3-antagonists are supposed to help specifically with negative symptoms, which is your primary problem)

All of the following have some evidence of effects on negative symptoms - Brexpiprazole and RBX could help with depressive symptoms as well. Brex is, as some may know, the first SDAM - Serotonin Dopamine Activity Modulator, which is cleared by the FDA for the treatment of Depression specifically - other drugs with antipsychotic effects are not.

Would raising serotonin really hurt? (Since most antidepressants raise it also without affecting symptoms). Nardil also raises GABA, couldn't that sorta "level" things?

Brexi I'm unable to obtain because it's far away from approval in Europe.. I will have a look into Reboxetine and Ondansetron but those I'm almost 90% sure I'm unable to get prescribed off label..

But about Nardil, why are there zero study's done on schizophrenia? What's your take on it?

[jaiho]

It's true Nardil has a risk of aggravating positive symptoms due to it increasing limbic dopamine levels.

But, if you add a dopamine modulator such as Abilify with Nardil, you should get a very robust effect on negative symptoms as well as positives.

Ive read a few reports of people have immense success on negative symptoms using broad range meds like SSRI + NRI.

MAOIs use the same reasoning of broad range neurotransmission increase.

[YoungSchizo]

It's true Nardil has a risk of aggravating positive symptoms due to it increasing limbic dopamine levels.
But, if you add a dopamine modulator such as Abilify with Nardil, you should get a very robust effect on negative symptoms as well as positives.
Ive read a few reports of people have immense success on negative symptoms using broad range meds like SSRI + NRI.
MAOIs use the same reasoning of broad range neurotransmission increase.

I'm on the smallest dose of Latuda (37mg) and Zyprexa (2,5mg), can I mix it with those?
Do you recall any of the SSRI + NRI mixes?

I've also read Nardil activates dopamine and serotonin neurotransmission in the PFC, isn't that effect positive for schizophrenics?

[jaiho]

 

It's true Nardil has a risk of aggravating positive symptoms due to it increasing limbic dopamine levels.
But, if you add a dopamine modulator such as Abilify with Nardil, you should get a very robust effect on negative symptoms as well as positives.
Ive read a few reports of people have immense success on negative symptoms using broad range meds like SSRI + NRI.
MAOIs use the same reasoning of broad range neurotransmission increase.

I'm on the smallest dose of Latuda (37mg) and Zyprexa (2,5mg), can I mix it with those?
Do you recall any of the SSRI + NRI mixes?

I've also read Nardil activates dopamine and serotonin neurotransmission in the PFC, isn't that effect positive for schizophrenics?

 

 

You can mix with those. MAOIs dont interact with most drugs except for when they inhibit SERT to a significant degree.

 

Increasing dopamine & serotonin in the PFC is useful for negative symptoms, which is the mesocortical dopamine pathway. A TCA such as Nortriptyline is useful for negs for this reason, and works even better with an SSRI or MAOI.

 

It's when dopamine is increased too much in the meso limbic pathway that it's problematic for positive symptoms, which your anti psychotics are handling with antagonism.

 

I suggest following this algorithim if you want the best chances of treating the negs.

 

The added benefit also, of keeping Nortriptyline as a backbone of your treatment, is that it also blocks the tyramine response (Which is why MAOIs require a special diet)

Edited by jaiho, 05 August 2017 - 01:16 AM.

[Finn]

https://www.ncbi.nlm...les/PMC1885050/

 

An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid.

 

(phenelzine (Nardil) and isoniazid belong to Hydrazine class)

 

Hydrazine MAO inhibitors generally exhibited greater inhibition of CYP following preincubation, whereas this was less frequent for the propargylamines, and tranylcypromine and moclobemide. Phenelzine (Nardil) and isoniazid inactivated all CYP but were most potent toward CYP3A and CYP2C19.

 

Lurasidone (Latuda) is apparently substrate of CYP3A4.

 

Tranylcypromine (Parnate) in addition to having apparently generally lower CYP-inhibition conflicts, is also more researched for schizophrenia based on Google Scholar search with terms like

 

allintitle: phenelzine OR tranylcypromine schizophrenia OR schizophrenics

 

allintitle: monoamine oxidase inhibitor OR inhibitors schizophrenia

 

Of those hits only 1 is for phenelzine and that article has not been cited and doesn't seem to be easily accessible and is probably written in Italian. 

 

 

 

 

 

http://www.sciencedi...924977X17302304

 

Tranylcypromine in mind (Part II): Review of clinical pharmacology and meta-analysis of controlled studies in depression

 

3.4. Tranylcypromine adjuvant to antipsychotic drugs in negative syndrome of schizophrenia

 

The use of TCP as a “psychic energizer” and an adjuvant to antipsychotic drugs, mainly trifluoperazine, has been reported in so-called defect schizophrenia as early as 1960 (Kruse, 1960; Singh and Free, 1960). A pharmacoepidemiologic study in two German university clinics revealed in 1994 that 8% of TCP patients were suffering from schizophrenia (Schmidt et al., 1994). This approach has been supported on a clinical and theoretical basis by the observation that atypical depression shares some characteristics with schizophrenia with negative symptoms (Parker et al., 2002) and by the hypothesis of dopaminergic and norepinephrinergic hypofrontality (Da Silva et al., 2008). TCP is expected to improve negative schizophrenia by increasing prefrontal cortex dopamine and norepinephrine neurotransmission.

 

A controlled study published in 1987 included 30 chronic schizophrenic outpatients with predominant emotional withdrawal, motor retardation, and blunted affect and only minimal positive symptoms. Patients were treated with 300 mg/day chlorpromazine, whereas half each received adjuvant 20 mg/day TCP or placebo over 4 months. Improvement was observed in 11 patients on TCP (73%) and no patients on placebo. After switching the placebo group to TCP for an additional 4 months, 13 patients (87%) showed improvement. Taking into account 10 previous studies, including 6 controlled (Buffaloe and Sandifer, 1961; Hedberg et al., 1971; Hordern et al., 1962; Mena et al., 1964; Schiele et al., 1963; Vogt, 1961) and 4 open (Barsa and Saunders, 1962; Bucci, 1969; Kruse, 1960; Singh and Free, 1960) studies, the authors concluded that labelling TCP only as an antidepressant is misleading (Bucci, 1987).

 

A recent non-interventional surveillance study of 53 patients investigated this approach for adjuvant TCP with second generation antipsychotic drugs. Improved impulse in 20 patients was found as a minor benefit of adjuvant TCP after ineffective trials with adjuvant SSRIs. The optimum treatment was defined for negative schizophrenic patients with no or minimal positive symptoms, TCP dose no more than 40 mg/day, antipsychotics at medium dose, no benzodiazepines, and a minimum duration of treatment of 2 to 3 months. The risk of exacerbation of positive symptoms was found to be very low and patients were considered to be compliant with the tyramine-restricted diet (Roesch-Ely et al., 2011). Nevertheless, controlled trials are needed for a better definition of the benefit-risk ratio of TCP in negative schizophrenia.

 

 

Edited by Finn, 05 August 2017 - 05:46 AM.

[YoungSchizo]

Thanks for the responses. I didn't looked into Parnate much because people say it metabolizes into amphetamine in the brain, is that true? (I've tried Ritalin but it aggravated positive symptoms)

[Finn]

https://www.biopsych...lcypromine.html

 

Failure to detect amphetamine or 1-amino-3-phenylpropane in humans or rats receiving the MAO inhibitor tranylcypromine

[YoungSchizo]

https://www.biopsych...lcypromine.html

Failure to detect amphetamine or 1-amino-3-phenylpropane in humans or rats receiving the MAO inhibitor tranylcypromine

Thanks for clarifying. Now I can consider trying Parnate also.

[mateusbrasil]

English is not my native language.

 

unfortunately I have no experience with MAOI's synthetic / prescription drug.

but I have experience with other MAOIs that may be useful to you.

 

I believe you will make a big deal.

I also plan to add a MAOI´s to my "stack" against schizophrenia / negative symptoms, so it would be very interesting if you could share your negative or positive experiences here.

 

here are some researches, and anecdotal / personal experiences:

 

Looking at the literature, inhibition of MAO appears to be one of the most reliable / effective ways to increase dopamine in PFC, since DAT unlike in the mesolimbic pathway does not seem to play a role in the "emptying" of dopamine in the PFC in a effective way, therefore 'MAO', 'NET' and 'COMT' have a proeminete control in the availability of dopamine in the PFC.

 

then it makes sense that studies using selegiline have found reductions in negative symptoms, without worsening

of the positives symptoms compared to a DRI - which more potently increases dopamine in the mesolimbic pathway vs. PFC.

 

since I have not yet experienced selegiline (yet) my experiences of the benefits of inhibiting MAOb comes from when I was a smoker - smokers have an activity of 30 to 40% less MAOb in the brain.

 

the evidence of the benefits of inhibiting MAOb (and perhaps MAOa) comes from the fact that when I quit smoking many improvements I had made in my negative / cognitive symptoms (apathy, avolition, long term memory, verbal memory, memory work, articulate speech)

was lost - although I was still using nicotine (snuff)

but of course!, part of these benefit could also be due to improvement in my ADHD.

 

as cigarette smoking may also have negative effects on schizophrenia (eg oxidative stress, NMDA redox imbalance), and inhibition may be suboptimal 30 to 40%, and in the long term appears to increase MAOb activity or at least resume baseline: "" "" We found that smoking induced an epigenetic regulation of MAOB, ie a reduction of its gene promoter methylation, resulting in high MAO protein concentrations that persist long after (over 10 years) quitting smoking.

I believe my "negative symptoms" would have improved more and, more consistently, if instead of using the cigarette I had used a more potent MAO-B inhibitor

for example: selegiline,neuravena(?)...

 

 

in my experience inhibiting MAO-A does not have the same benefits as MAO-B. and although an inhibition ("very potent") makes me very "happy" at the beginning in the long run makes me melancholic, and I suspect that it worsens the positive symptoms - but I'm not sure, also have to take into account that I got these experiences with turmeric (curcumin) that may also have other active substances.

 

Now, one interesting thing about inhibiting MAO-A is that it is synergistic with nicotine, when I am about MAO-AI´s

all the positive effects of nicotine is "potentiated"

although it also increases reward effects (and I have to use nicotine/snuff more often), and it also seems to cause a greater increase in heart rate - so be very careful!

 

another important thing to keep in mind is that an acute withdrawal of MAOIs (mainly non-selective and irreversible)

can make you out of reality in a few days, especially if you already have schizophrenia and are not on an antipsychotic (or your tolerance for it is high).

these increases in psychotic symptoms are not specific for schizophrenics - since healthy people can also go "crazy" in a withdrawal of MAOIs.

 

I was not aware of this, and I almost lost a friend in a cigarette withdrawal (irreversible MAOb), although at first I seemed to be "well", as the days went on I became more and more paranoid and delirious, thinking that my friend wanted to "pull a fast one on me."

 

 

 

[YoungSchizo]

That MAOI's increase PFC dopamine was the final desicion for me to trying Nardil since I mainly suffer from negative symptoms and I literally feel a weakness in that part of my brain (it really feels that my front right part of my brain is dysfunctional.. I literally feel that part of my brain is dysfunctional). I also am addicted to nicotine, only through vaping it though. So I have no idea how the MAO "inhibition" will affect me but I'll find out soon.

[YoungSchizo]

Today I called my pharmacy about my prescription for Nardil and got bad news. I've been told Nardil is not available on the Dutch market and that they informed my pdoc about this. I've looked it up and Nardil can only be prescribed with a doctor's statement to the manufacturer of the drug. Since my doc didn't do this (automatically) but told the pharmacy she would contact me I'm guessing she will give me bad news (I made a phone appointment with her tomorrow). Should I just let it go if she gives me bad news or should I take measures if she's not willing to prescribe it to me?

 

I have no idea what to expect from Nardil but this really sucks.

[Finn]

Parnate should be trialed first due to Nardil CYP450 enzyme issues anyway, when trying to treat negative symptoms while taking antipsychotics. 

 

In continental Europe it is pretty common that tranylcypromine (Parnate) is the only irreversible MAOI available, this seems to be so in Netherlands also. 

 

https://www.medicijn...=14828&niveau=1

 

Nardil's better "internet reputation" is mostly due to social anxiety people probably benefiting of Nardil's metabolite inhibiting GABA-T, this isn't going be that useful for negative symptoms

 

There is a reason why you can find easily data of Parnate used for negative symptoms but you can't find anything for Nardil.

 

Apparently Parnate doesn't destroy CYP450 enzymes, p450 inhibition is apparently mild and reversible.

 

Nardil destroys CYP450 enzymes, the p450 system slow down can accumulate to really high levels. It could really screw up your Latuda and Zyprexa levels. 

 

 

Old filler ingredients helped Nardil to tolerate room temperature, but some of  those filler ingredients have fallen out of grace with regulators. Many modern versions of Nardil need to be kept in fridge temperatures as much as possible. So if you don't get full compensation for importing unregistered drugs, fridge importing could be really expensive, or since it would be handled a lot by people who are not aware of Nardil at all or at least recent changes in fridge requirement for it, imported Nardil could end up spending quite a lot of time in room temperature anyway.

 

 

Edited by Finn, 05 September 2017 - 04:30 AM.

[YoungSchizo]

Had my appointment today, I was told by my pdoc Nardil is harder to get by and my doc luckily was willing to prescribe me Parnate instead, so I will be starting that in a couple of days.

 

Thanks for the informative info @Finn . I had no idea about the enzyme issues. What do you mean with "screw up your Latuda and Zyprexa levels".. Would Nardil make them less potent or the opposite?  

My preference for Nardil was based upon it's "better" internet reputation but also because of it's inhibition of GABA-T, I react very good (especially positive symptoms) to drugs that raise GABA levels.