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Starting Fluoxetine 60mg today


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My doc put me on 60mg fluoxetine for obsessive compulsions. I have read so many positive reviews and I am very encouraged.

Today is my first day on this and so far I feel nothing but I know that SSRIs are not somthing that start working right away. So my question is should I see a change in a week or a month?

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11 hours ago, the maze runner said:

My doc put me on 60mg fluoxetine for obsessive compulsions. I have read so many positive reviews and I am very encouraged.

Today is my first day on this and so far I feel nothing but I know that SSRIs are not somthing that start working right away. So my question is should I see a change in a week or a month?

I think the general refrain is 6 to 8 weeks to really get near full effect, but some people can start to feel it at 3. That’s a pretty big starting starting dose though so that might change things 

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That is quite a big dose. I think I started on 20mg and went up to 40mg after a while. But that was for depression and maybe they use different dosages for obsessive compulsions. Stopped working for me pretty soon but everyone's different. The old Russian roulette of trying meds. Not trying to sound negative and I hope they work for you. It does depend on the individual when they start working. I thought 4-6 weeks was the usual refrain to see any results, although Iceberg is talking about the full effect so we could both be right there. Also, not sure if these are the first meds you've had, but side effects will appear sooner than any benefits. These vary from person to person and usually lessen over time if you get any at all. People say not to read the leaflet which comes with them that lists all the possible side-effects. First thing I did. I don't know if you have or not but they can be quite frightening to look at. What they don't say is that common side effects means 1% of people, and the even scarier shit is even less likely.

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Yeah with Prozac there is the usual serotonin autoreceptor desensitization that you have to wait for, which can take 4-6 weeks. But Prozac also inhibits its own metabolism. So the blood level increases to steady state aren't linear. And it can take 6-8 weeks for fluoxetine and norfluoxetine to reach steady state blood levels FOLLOWED by the usual receptor desensitization. 

It is a bit strange to start out right at 60mg. If that was the target dose because the pdoc knew they were treating OCD, they would at least do 20mg for Week 1 and 40mg for Week 2 just to make sure you tolerate it. However, Prozac does take quite a bit of time to climb to steady state and this probably makes it a little bit easier to initiate at higher doses in some regards. Sometimes Prozac can be activating in the beginning though. So if you find yourself to be agitated or overstimulated for whatever reason, talk to your pdoc about maybe trying a lower dose for a week or two and then increasing again to 60mg. If your pdoc is indeed treating OCD, then you probably do want to go to 60mg or 80mg. Higher doses of Prozac (or any SSRI for that matter) are typically required to treat OCD.

 

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I am feeling a bit more loquacious and more eager to read books. Don't know the real reason behind this but whenever I start an SSRI I always gravitate towards books. Almost every time. Again, clueless as to why this is.

Last two days I finished Misery by Stephen King. 170 pages in 2 days.

 

Edited by the maze runner
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12 hours ago, the maze runner said:

For some reason I am getting alarming anxiety today. Sorry if my thoughts and posts are a bit disjointed.

Prozac is one of the more stimulating SSRIs....Anxiety can be a start-up side effect with Prozac, but it usually goes away in time.

Like @browri above,  I'm wondering why your doc didn't start lower and go up gradually to target dose.

If this "alarming" anxiety continues, I would definitely suggest discussing it with your doc.

Are you still sleeping pretty well?

Edited by CrazyRedhead
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10 hours ago, CrazyRedhead said:

Prozac is one of the more stimulating SSRIs....Anxiety can be a start-up side effect with Prozac, but it usually goes away in time.

Like @browri above,  I'm wondering why your doc didn't start lower and go up gradually to target dose.

If this "alarming" anxiety continues, I would definitely suggest discussing it with your doc.

Are you still sleeping pretty well?

My sleep is good all due to the clozapine I take. Doc has also prescribed clonazepam before bed but i do not take it. I am beginning to notice some anti depressant action of the fluoxetine if I'm not wrong.

A previous doc of mine had warned me about benzos and said that they interfere with memory consolidation. Since then I have been careful about benzos.

My present doc seems to favor stuff like tofisopam and etizolam for anxiety. Tofisopam basically does not do anything and etizolam is very highly detrimental to short term memory.

 

Edited by the maze runner
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10 hours ago, the maze runner said:

My sleep is good all due to the clozapine I take. Doc has also prescribed clonazepam before bed but i do not take it. I am beginning to notice some anti depressant action of the fluoxetine if I'm not wrong.

Glad you are noticing some positive effects from the Prozac.....That's great...!!

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On 11/3/2021 at 10:16 AM, the maze runner said:

@browri I didn't know about the auto receptor desensitization. Is this something like what amisulpride does to dopamine auto receptors.

Actually the opposite. Starting with the basics, heteroreceptors are receptors that a neurotransmitter binds to in order to control the flow of OTHER neurotransmitters. Autoreceptors are receptors that a neurotransmitter binds to in order to control itself. 

So for dopamine receptors, pre-synaptic D2 receptors are auto-receptors, and they, along with other receptors, control the outflow of dopamine. When dopamine is released from a sending neuron (the pre-synaptic neuron) it activates dopamine auto-receptors on the sending neuron to reduce dopamine release. This makes a negative feedback loop to rebalance neurotransmitter communication after a firing event. In the case of amisulpride, it is a dopamine receptor antagonist, but at low doses it more strongly blocks the pre-synaptic dopamine auto-receptors and less potently the post-synaptic dopamine heteroreceptors. This results in increased dopamine release but not an appreciable blockade of that extra dopamine release from activating the receiving/post-synaptic neuron.

For serotonin, the major pre-synaptic auto-receptor is 5HT1A. If this receptor is activated by serotonin, it reduces serotonin outflow. This is what happens with an SSRI. From the first dose of an SSRI, serum and plasma levels of serotonin and its metabolites are immediately increased, but the effect on mood is often delayed at least 2 weeks, if not 4. This is because the SSRI causes an activation of 5HT1A and subsequent reduction in serotonin release. After a few weeks, these receptors become desensitized to this activation, and the inhibitory effect that this activation has on serotonin release is reduced. It's about this time that people start reporting improvements in mood.

With Prozac, the long half-life also means a very long climb to plasma steady state and the CYP2D6 inhibition leads to further increases in fluoxetine blood levels, which is why the half-life of fluoxetine after a single dose is 1 to 3 days but after multiple dosing is more like 4-6 days. Norfluoxetine is anywhere from 4-16 days. So this means steady state of fluoxetine alone would take anywhere from 22 to 33 days. Norfluoxetine could potentially take 88 days. And one should reasonably expect to see improvement for another 2 weeks after reaching steady state on any antidepressant. 

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13 hours ago, browri said:

Actually the opposite. Starting with the basics, heteroreceptors are receptors that a neurotransmitter binds to in order to control the flow of OTHER neurotransmitters. Autoreceptors are receptors that a neurotransmitter binds to in order to control itself. 

So for dopamine receptors, pre-synaptic D2 receptors are auto-receptors, and they, along with other receptors, control the outflow of dopamine. When dopamine is released from a sending neuron (the pre-synaptic neuron) it activates dopamine auto-receptors on the sending neuron to reduce dopamine release. This makes a negative feedback loop to rebalance neurotransmitter communication after a firing event. In the case of amisulpride, it is a dopamine receptor antagonist, but at low doses it more strongly blocks the pre-synaptic dopamine auto-receptors and less potently the post-synaptic dopamine heteroreceptors. This results in increased dopamine release but not an appreciable blockade of that extra dopamine release from activating the receiving/post-synaptic neuron.

For serotonin, the major pre-synaptic auto-receptor is 5HT1A. If this receptor is activated by serotonin, it reduces serotonin outflow. This is what happens with an SSRI. From the first dose of an SSRI, serum and plasma levels of serotonin and its metabolites are immediately increased, but the effect on mood is often delayed at least 2 weeks, if not 4. This is because the SSRI causes an activation of 5HT1A and subsequent reduction in serotonin release. After a few weeks, these receptors become desensitized to this activation, and the inhibitory effect that this activation has on serotonin release is reduced. It's about this time that people start reporting improvements in mood.

With Prozac, the long half-life also means a very long climb to plasma steady state and the CYP2D6 inhibition leads to further increases in fluoxetine blood levels, which is why the half-life of fluoxetine after a single dose is 1 to 3 days but after multiple dosing is more like 4-6 days. Norfluoxetine is anywhere from 4-16 days. So this means steady state of fluoxetine alone would take anywhere from 22 to 33 days. Norfluoxetine could potentially take 88 days. And one should reasonably expect to see improvement for another 2 weeks after reaching steady state on any antidepressant. 

Thanks for the explanation. I have a few questions though. I think I feel better already after one week. Why do you think that is. Also do I need to worry about tolerance like with many other drugs. I have noticed the phenomenon of tolerance most markedly with modafinil. What is tolerance and how does one beat it. Thanks in advance.

Edited by the maze runner
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10 hours ago, the maze runner said:

Thanks for the explanation. I have a few questions though. I think I feel better already after one week. Why do you think that is. Also do I need to worry about tolerance like with many other drugs. I have noticed the phenomenon of tolerance most markedly with modafinil. What is tolerance and how does one beat it. Thanks in advance.

Fluoxetine is primarily an inhibitor of the serotonin transporter (SERT), but fluoxetine and its metabolite, norfluoxetine, also have a moderate affinity for the 5HT2C receptor as antagonists at higher concentrations (60mg+). Blocking this receptor tends to cause increased release of norepinephrine and dopamine in the prefrontal cortex (PFC), which can have a stimulating effect. Additionally, norfluoxetine may be a modest inhibitor of the dopamine transporter at higher doses, and fluoxetine may modestly inhibit the norepinephrine transporter. Both compounds may even mildly antagonize the 5HT2A receptors at higher doses.

Largely though, fluoxetine is considered to be an SRI and 5HT2C antagonist, and the latter action is usually why fluoxetine is activating in the beginning (1-2 weeks), even before the actions on SERT have an opportunity to set in (4-8 weeks).

As for tolerance, I wouldn't expect that to be an issue with fluoxetine. Unless of course we're talking about antidepressant tachyphylaxis ("poop-out") which can happen with any antidepressant. I suppose it depends on what you're building a tolerance to.

Generally tolerance is defined as requiring higher dosing to achieve the same effect. So if we talk about amphetamine stimulants and ADHD, when you initiate a drug like Adderall, there is an initial period of increased motivation and energy, maybe some euphoria, but those aren't the target of the stimulant, even if they are inadvertently affected. Even if some of that initial energy and motivation subsides, stimulants should still improve focus/concentration and overall executive functioning. If they continue to do this even when the initial motivation and energy has worn off, this is not developing a tolerance. The drug is still fundamentally doing what it's supposed to do. Some people do find over time that they require dose increases to achieve the same effect. It is possible that some of these may be patients who don't know to separate motivation and energy from focus/concentration and executive function, but it is certainly the case that many do in fact need dose increases over time to maintain therapeutic effects on focus and concentration.

In the case of modafinil, its purpose is generally to induce wakefulness. As long as it continues to do this, then a tolerance hasn't been developed. If you noticed increased motivation and energy when initiating modafinil or after dose increases that eventually wears off after a week or two, it is possible this was a TEAS (treatment-emergent affective switch). But as long as you aren't falling asleep, then generally modafinil is doing its job.

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12 hours ago, the maze runner said:

What is tolerance and how does one beat it.

this is a big topic but i'll try. There is a process in your body called down-regulation that basically causes some sites in the body to become less sensitive when exposed to constantly high levels of a signaling neurotransmitter. It is a function of maintaining homeostasis in the body and keeping rates/amplitude of chemical responses level (it can work the other way too.) The result is that over time the same amount of transmitter will result in a gradually smaller effect. This is isn't a given for all people or all meds, but basically your body is teaching itself to tolerate new stimuli. In the case of SSRIs this can be helpful initially, because it helps to make uncomfortable start-up side effects to go away with time. It is true that people sometimes need higher and higher doses of SSRI, but its not one of the usual suspects when you think about meds that gain significant tolerance. shorter-term tolerance is more often in play with things like opioids, stims and benzos. Since you have to take the med every day, there isn't really a definite strategy to fight potential tolerance other than monitoring symptoms. I will say that it is not unheard of for SSRIs to give out randomly but thats not something I'd worry about right now

22 minutes ago, browri said:

Fluoxetine is primarily an inhibitor of the serotonin transporter (SERT), but fluoxetine and its metabolite, norfluoxetine, also have a moderate affinity for the 5HT2C receptor as antagonists at higher concentrations (60mg+). Blocking this receptor tends to cause increased release of norepinephrine and dopamine in the prefrontal cortex (PFC), which can have a stimulating effect. Additionally, norfluoxetine may be a modest inhibitor of the dopamine transporter at higher doses, and fluoxetine may modestly inhibit the norepinephrine transporter. Both compounds may even mildly antagonize the 5HT2A receptors at higher doses.

Largely though, fluoxetine is considered to be an SRI and 5HT2C antagonist, and the latter action is usually why fluoxetine is activating in the beginning (1-2 weeks), even before the actions on SERT have an opportunity to set in (4-8 weeks).

As for tolerance, I wouldn't expect that to be an issue with fluoxetine. Unless of course we're talking about antidepressant tachyphylaxis ("poop-out") which can happen with any antidepressant. I suppose it depends on what you're building a tolerance to.

Generally tolerance is defined as requiring higher dosing to achieve the same effect. So if we talk about amphetamine stimulants and ADHD, when you initiate a drug like Adderall, there is an initial period of increased motivation and energy, maybe some euphoria, but those aren't the target of the stimulant, even if they are inadvertently affected. Even if some of that initial energy and motivation subsides, stimulants should still improve focus/concentration and overall executive functioning. If they continue to do this even when the initial motivation and energy has worn off, this is not developing a tolerance. The drug is still fundamentally doing what it's supposed to do. Some people do find over time that they require dose increases to achieve the same effect. It is possible that some of these may be patients who don't know to separate motivation and energy from focus/concentration and executive function, but it is certainly the case that many do in fact need dose increases over time to maintain therapeutic effects on focus and concentration.

In the case of modafinil, its purpose is generally to induce wakefulness. As long as it continues to do this, then a tolerance hasn't been developed. If you noticed increased motivation and energy when initiating modafinil or after dose increases that eventually wears off after a week or two, it is possible this was a TEAS (treatment-emergent affective switch). But as long as you aren't falling asleep, then generally modafinil is doing its job.

Damnit @browri you beat me by one minute😝

Edited by Iceberg
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21 hours ago, Iceberg said:

Damnit @browri you beat me by one minute😝

Lol maybe, but you did highlight a good point that I missed on receptor desensitization. There is a downregulation process that happens. It's postulated that low serotonin can lead to upregulation or increased expression of the HTR1A gene that encodes the 5HT1A receptor. This is the brain state in depression. So an inhibitor of the transporter would prevent serotonin from being cleared from the synapse, which leads to increased activation of the 5HT1A receptors. The brain compensates by reducing expression of the HTR1A gene, which results in fewer 5HT1A receptors, a process known as downregulation. With fewer 5HT1A receptors to activate, downstream serotonin release is disinhibited, hence the antidepressant effect.

Lots of different genes code for different receptor proteins and enzymes. Any impact on the 5HT1A receptor could lead to downstream alterations in gene expression (i.e. changes in the expression of genes OTHER than HTR1A). For example, a serotonin reuptake inhibitor can lead to reduced dopamine firing over time. This might lead to an upregulation of dopamine receptors. Additionally, the time scale for this downstream impact can stretch out for much longer periods of time than just a few weeks. This may be why some people need to increase the dose of an antidepressant not too long after starting it. It may also possibly be why antidepressants "poop out" (tachyphylaxis) after being on them for a long time.

@the maze runner regarding problems with anxiety, expect some of those effects to take time to resolve. It truly may be at least 4 weeks before you see any benefit on mood or anxiety. And I think benefits for anxiety can oftentimes take longer than other mood benefits. When did you start fluoxetine? Was this pre-existing anxiety that has gotten worse, or new anxiety since starting fluoxetine? If it is pre-existing and worsened after starting fluoxetine but isn't getting progressively worse, or if it's new anxiety that started not too long after starting fluoxetine but similarly isn't getting progressively worse, that is likely the 5HT2C antagonism, which is felt pretty quickly after starting fluoxetine. My advice in those cases would be to stick it out. However if in either case of pre-existing or new anxiety, if it is getting progressively worse, then you probably want to talk to your pdoc to make sure you're being monitored and that you aren't overwhelmed. Again, that may be the effect of starting fluoxetine right at 60mg, because you usually start patients at 20mg for a week before increasing to 40mg if needed and then 60mg or 80mg depending on tolerability and efficacy. Like I said in a previous post, for anxiety and OCD, higher dosing of any SSRI is typically needed. Fluoxetine would normally be dosed 60-80mg for OCD, but fluoxetine's stimulating effects on startup are known to somewhat hinder its use in some anxiety patients. Specifically, you often have to go slowly with fluoxetine in anxious patients, and fluoxetine is already slowed down by its long time to steady state (4-6 weeks).

Looks like your first post was October 31st, which would put you at ~2 weeks now on fluoxetine 60mg. If you find the anxiety to be intolerable or worsening in a bad way, then definitely talk to your pdoc about backing down the dose to 40mg. At this point, there's probably no use in backing all the way down to 20mg, because from a blood concentration perspective, after 2 weeks of 60mg, you may have already exceeded blood levels consistent with a 20mg dose, which may mean that 20mg may be knocking it too far down.

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The anxiety is there but I feel it is manageable. Don't know if doc anticipated it and that's why he prescribed clonazepam at bed time. But I don't take it. One previous pdoc said it causes memory consolidation problems.

I am also on methylphenidate 10 mg once in morning and once in afternoon. It gives me a boost both in the morning and in the afternoon. This is actually a reduced dose from what I was taking before.

I already feel quite good even though it's been only one and a half to two weeks.

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23 hours ago, the maze runner said:

The anxiety is there but I feel it is manageable. Don't know if doc anticipated it and that's why he prescribed clonazepam at bed time. But I don't take it. One previous pdoc said it causes memory consolidation problems.

I am also on methylphenidate 10 mg once in morning and once in afternoon. It gives me a boost both in the morning and in the afternoon. This is actually a reduced dose from what I was taking before.

I already feel quite good even though it's been only one and a half to two weeks.

Okay, well if it's manageable for now, then try to stick it out as long as you can. Like I said, the 5HT2C antagonism will even have effect in the beginning and cause norepinephrine and dopamine release. Pointing out that you take methylphenidate is pretty relevant because it's a norepinephrine/dopamine reuptake inhibitor. So fluoxetine and methylphenidate will actually enhance each other in a complementary way.

Interesting that you noted the clonazepam. I do believe I've heard some studies regarding clonazepam and its effects on cognition over time, but if it's used in the short term, clonazepam shouldn't be causing that kind of problem. It's best to keep our use of benzos to a minimum anyway.

However, in this case, taking adjunctive benzo like clonazepam for the first few weeks while starting an antidepressant to help calm some of the initial activation is actually pretty normal practice. Possible but less likely your pdoc's intent was to keep you on clonazepam long term. And starting you out at 60mg of fluoxetine instead of titrating you up explains why they added the clonazepam in the first place. They probably expected the high starting dose of fluoxetine to be too intense and told you to take the clonazepam while you adjust to it, then at a future appt, they would discontinue it.

At this point though, if you're nearly 2 weeks through and you're managing well enough, then it might not make sense to start the clonazepam now if there's nothing particularly wrong. However, you shouldn't be scared of using something like clonazepam in the short-term to help ease into a new situation if you find you are struggling. If anything becomes a problem, talk to your pdoc about it. It's been about 2 weeks, when do you see them again?

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