How long does Risperidone affect brain?

[Ralph]

I'm trying to taper off Seroquel because it is too sedating for me (understatement) and my doc prescribed risperidone to manage any flare ups during this process. I have two major worries about risperidone:

1. Reports I have read indicate that people feel at least if not more sluggish/cognitively impaired in risperidone as with Seroquel. Am I switching from the frying pan to the fire?

2. Pharmacology documentation of risperidone shows this drug is an irreversible 5HT7 antagonist. I'm freaking out over the irreversible part; is this mutilating my brain? :eek::eek:

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More info in case clarification would help -

My understanding is that an irreversible antagonist permanently inactivates the receptor until the neuron basically recycles the proteins and grows a new receptor. How long does this endocytosis-exocytosis cycle take?

My diagnosis is MDD or unipolar depression. I was prescribed antipsychotic (APs) because SSRI's didn't help me although Wellbutrin gets me from severe to moderate depression. According to pdoc APs can augment Antidepressants. After getting worse over time, I have my doubts about the efficacy of AP+AD therapy for unipolar depression.

I am really, really scared to take something that will continue to affect me well after the med is discontinued. In other words I don't want to be permanently or even slightly long term lobotomized just cause my pdoc is committed to a certain regimen.

Yet as far as I understand at present 5HT7 receptor antagonism may be responsible for the antidepressant effects of certain atypical APs, and blocking this receptor is hypothesized to reduce the level of a neurotransmitter (cAMP) that inhibits the prefrontal cortex, which I am inferring might help overcome the brain fog and personality loss that came with Seroquel.

I have considered taking these questions to my pdoc but she is not the most responsive in my experience and frankly has been rude to me in the past when I asked questions. I'm working on finding a new one.

[Luna-]

Hi Ralph

I know a place you could go to ask these questions and have a chance at an answer. PM me for details as it is another forum.

[malign]

And although I'm not medical, I can give you a convincing bit of mathematical reasoning on the subject. I would suggest that whatever the dosage rate is, for maintenance of a patient on Risperidone, that rate should be close to the half-life for receptor replacement.

Here's my thinking: once the patient has ramped up to their maintenance dose, some receptors are blocked and some aren't. Now, no matter what the precise maintenance dose is (I don't know), if a higher amount were given, more and more receptors would get blocked, and the patient wouldn't be "maintained". On the other hand, if the dose were lower, the body would replace the receptors faster than they became blocked, and the effects would decrease. Thus, whatever the maintenance dosage rate is (once a day, three times a day, once a week ...), that must be approximately the half-life for receptor replacement.

As for the body recycling proteins, it is believed that we do this all the time, due to naturally-occuring chemical damage. We simply digest the old proteins and build new ones.

[Luna-]

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Biologist.

[Ralph]

...if a higher amount were given, more and more receptors would get blocked, and the patient wouldn't be "maintained". On the other hand, if the dose were lower, the body would replace the receptors faster than they became blocked, and the effects would decrease. Thus, whatever the maintenance dosage rate is (once a day, three times a day, once a week ...), that must be approximately the half-life for receptor replacement.

That is brilliant. The overall reasoning is irrefutable and should give a good ballpark figure. I'd also like to get the medical info but this is a great way to extract information without wading into too much of a neuroscience course.

Luna, I sent a PM. Thanks.

[malign]

Gotta love math.

Unless you hate it. ;-)

[Ralph]

I love math. :cool: The first "a-ha" moment I ever had was when I finally figured out the fundamental theorem of calculus. That seems so long ago now. Especially fascinating are the patterns that repeat in nature, e.g., Fibonacci series, golden ratio, etc.

[Luna-]

And fractals! Gotta love fractals.

[Ralph]

Fractals are repeating patterns of repeating patterns of repeating patterns of...

Yeah, they are endlessly fascinating as well.

[Luna-]

There's just one problem with the above theory. It doesn't take variability into account. People metabolise fast or slowly, well or poorly. Any other meds/OTCs influence absorption because the drugs which use the enzymes involved in metabolising them are in competition with each other for that enzyme. Some fruit juices, notably grapefruit juice, affect absorption as do caffeine consumption and exercise. In clinical trials, to get a baseline metabolism, a wash-out period of these factors takes place before the drug is given and blood levels monitored. (I used to work in this field.)

So the biochemistry of each individual varies. What you're talking about is called the 'therapeutic index' - the min and max blood levels of the drug needed to do the job. Therapeutic indices are generalisations. Depending on your own biochemistry, on how quickly or slowly you metabolise the drug, yours could be higher or lower. So recommended dosages cover what is considered the therapeutic index for the majority of people. This doesn't guarantee it's correct for you.

Hope I'm not injecting doubt into taking drugs here. Statistically, the recommended dosage is likely to put you within the therapeutic index.

As to any permanent effects of drugs, bear in mind that the brain is neuroplastic. It can make new receptors and new neural connections. Once a drug is withdrawn, homeostasis tends to bring the brain/body back into equilibrium. (There are some side-effects that can become permanent, but this requires repeated dosing over a period of time.) As an example, taken regularly, benzodiazepines cause structural changes in the brain, which, once the benzo is withdrawn, slowly return to the natural state (In some, slower than in others, in the worst case, years.) Where did you read that Risperdal causes permanent changes? I wonder if that is so.

I'm not advocating for or against drugs. I'm just into information, like you.

[Luna-]

The AD + AP combo is apparently gathering evidence of efficacy in MDD. Interestingly, my pdoc told me that the primary recommendation now (here in SA, at least) is to augment the AD with lithium in MDD. (Not popular with patients because of the blood monitoring needed, but apparently it's effective.)

And yes, risperidone may affect cognition just like Sero-dum-dum. I know I lost many IQ points on SQ. Less so, on Geodon, ie it came back. I would imagine Risperdal is much like SQ. I've never tried it.

[Guest ASchwartz]

Ralph,

Have you asked your psychiatrist about this?

Allan

[Ralph]

There's just one problem with the above theory. It doesn't take variability into account.

In my effort to be brief I didn't mention this, but I was tacitly taking variability into account, which is why I used the term "ballpark". Biodiversity and other confounding factors means that any point estimate would admit of a wide confidence interval. Nonetheless, knowing that for example, the drug is usually given twice a day vs. once a week tells that the replacement cycle is closer to a matter of days rather than months or longer.

Thanks for pointing this out, as this may be of benefit to other readers.

Where did you read that Risperdal causes permanent changes? I wonder if that is so.

I didn't read that it causes permanent changes - but it is an irreversible antagonist of 5HT7 receptors, meaning the drug permanently blocks the receptor from being activated by serotonin until the receptor is replaced by the body.

My worry was that if these receptors take a long time to regrow, then the drug would continue to affect me well after it left my system. I don't yet know enough about receptors to understand how quickly or not they are replaced. AFAIK humans don't grow any new brain cells after reaching adulthood. Existing neurons can become longer to fill in for cells killed by neurotoxins such as alcohol, though. This may be urban legend; I'm still a newbie in this area. I wasn't sure if neuroreceptors are also like that but it looks like they regrow fairly easily.

[Ralph]

Ralph,

Have you asked your psychiatrist about this?

Allan

No - my pdoc doesn't give me the time to ask questions and in the past has received my curiosity coldly to put it mildly. This has trained me to seek info elsewhere.

[Ralph]

The AD + AP combo is apparently gathering evidence of efficacy in MDD.

And yes, risperidone may affect cognition just like Sero-dum-dum. I know I lost many IQ points on SQ.

I wonder if this evidence is based on controlled studies or self reports from patients prescribed APs off-label. The reason this would be significant is that at least in my experience, the AP didn't relieve my symptoms so much as leave me so spaced out that I was unable/unwilling to complain.

OTOH I have come to doubt whether MDD is really my problem or is this the long term result of a deeper issue. I fit the depression criteria symptomatically, but at this time I think this is because ADHD or something like it causes me to mismanage my life, which leads to experiences and (lack of) relationships that a normal person would respond to with disruptions in sleep, appetite, ambition, will to live, etc. I don't know; I'm still trying to figure it out.