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Increasing Prozac? Could it help this?


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I’m really struggling with zero motivation, feeling blank, and not enjoying anything really or laughing (I’m very flat emotionally). I don’t feel depressed though or sad or anything like that. My anxiety has also been high.

Could I benefit from an increase in my prozac dose from 20 mg to 40 mg if my NP agrees? Does prozac help any of what I described?

Thanks so much for any wisdom or experience! I don’t know much about AD’s or have much experience with them. 

Edited by Wonderful.Cheese
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13 hours ago, Iceberg said:

theoretically, but your on such high doses of ap that it might be tough to get a direct effect

Thank you so much. I really appreciate it!

Unfortunately I don’t think lowering or getting off any of the AAP’s I take is something that is plausible. I didn’t know that my AAP’s could be a cause of this. I thought it was negative symptoms like my tdoc said I have. So that’s interesting! Thank you for the info!

I have done so much wrong and felt such pain and worse while being under medicated. I feel it’s best I just keep taking all the meds I take and possibly be over medicated for the sake of others and myself too I suppose. 

I hope I am making sense? I’m sorry I was complaining. 

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2 minutes ago, Wonderful.Cheese said:

Thank you so much. I really appreciate it!

Unfortunately I don’t think lowering or getting off any of the AAP’s I take is something that is plausible. I didn’t know that my AAP’s could be a cause of this. I thought it was negative symptoms like my tdoc said I have. So that’s interesting! Thank you for the info!

I have done so much wrong and felt such pain and worse while being under medicated. I feel it’s best I just keep taking all the meds I take and possibly be over medicated for the sake of others and myself too I suppose. 

I hope I am making sense? I’m sorry I was complaining. 

Yes and no problem. Just because something is the right idea doesn’t mean it can’t suck 

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  • 2 months later...
On 8/4/2021 at 4:12 PM, Wonderful.Cheese said:

Unfortunately I don’t think lowering or getting off any of the AAP’s I take is something that is plausible. I didn’t know that my AAP’s could be a cause of this. I thought it was negative symptoms like my tdoc said I have. So that’s interesting! Thank you for the info!

Actually, negative symptoms in schizophrenia can be due to dopaminergic hypofunction (under-active dopamine activity) in the pre-frontal cortex. Prozac happens to be a fairly strong 5HT2C antagonist for a supposed selective SRI. This effect at 5HT2C receptors should increase norepinephrine and dopamine release in the PFC, which would help with depression, apathy, motivation, and theoretically also the negative symptoms of schizophrenia. This is why people often find Prozac to be stimulating right away after starting it, even though the full effect on mood usually isn't seen for 6-8 weeks due to its half-life.

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On 10/5/2021 at 8:26 AM, browri said:

Actually, negative symptoms in schizophrenia can be due to dopaminergic hypofunction (under-active dopamine activity) in the pre-frontal cortex. Prozac happens to be a fairly strong 5HT2C antagonist for a supposed selective SRI. This effect at 5HT2C receptors should increase norepinephrine and dopamine release in the PFC, which would help with depression, apathy, motivation, and theoretically also the negative symptoms of schizophrenia. This is why people often find Prozac to be stimulating right away after starting it, even though the full effect on mood usually isn't seen for 6-8 weeks due to its half-life.

Thank you! I didn’t know that! Very informative! This is very timely information for me. I was just thinking about this. I have put off asking my dr about a Prozac increase for too long. I am struggling still. I’m going to try to work up the nerve to email my dr about this. 

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On 10/5/2021 at 3:26 PM, browri said:

Prozac happens to be a fairly strong 5HT2C antagonist for a supposed selective SRI. This effect at 5HT2C receptors should increase norepinephrine and dopamine release in the PFC, which would help with depression, apathy, motivation, and theoretically also the negative symptoms of schizophrenia. This is why people often find Prozac to be stimulating right away after starting it, even though the full effect on mood usually isn't seen for 6-8 weeks due to its half-life.

This is interesting. I've been languishing on Prozac, and wondering about increasing it, just to see if it is more stimulating at higher dose (I assumed as an SSRI, it would bring on more apathy/lack of motivation.)

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3 hours ago, Blahblah said:

This is interesting. I've been languishing on Prozac, and wondering about increasing it, just to see if it is more stimulating at higher dose (I assumed as an SSRI, it would bring on more apathy/lack of motivation.)

Yep! My personal experience with Prozac is at the 10mg, 20mg, and 40mg doses; but it theoretically can go all the way to 80mg. I personally can't imagine what the stimulation of anything more than 40mg must be like. Prozac can certainly give you pep at 20mg, but at 40mg it's like someone hit the nitro button.

Like any SSRI, increasing the dose will further increase serotonin activity, which usually on its own has a net suppressing effect on dopamine, hence the apathy/anhedonia.

However, Prozac is such a strong 5HT2C antagonist that stimulation is often reported by patients after just the first or second dose, because direct receptor actions aren't restricted by time in the same way as actions at the transporter (time for receptor desensitization to disinhibit serotonin). In the long run, the increases in serotonin from inhibition of the transporter eventually do suppress dopamine which counterbalances this initial stimulation. This isn't to say that the effect "wears off" or anything. Prozac is still regarded next to Zoloft as one of the most stimulating SSRIs and it only gets more stimulating with dose increases and with time because of the way it inhibits its own metabolism and has to build up over several days to weeks.

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What I will say about Prozac is that, ultimately, it is an SSRI because it has a strong affinity for the serotonin transporter primarily (1nM for fluoxetine and 19nM for norfluoxetine, the metabolite), and its 5HT2C antagonism (and subsequent norepinephrine and dopamine release) are less, but potent enough to matter (receptor affinity of 72.6nM for fluoxetine and 91.2 for norfluoxetine). Prozac generally significantly inhibits the SERT at all doses because of its affinity with 20mg usually being sufficient for 60% SERT occupance (I believe), but its antagonism of 5HT2C is escalating with the dose, which is why dose increases become more stimulating due to the escalating norepinephrine/dopamine release. On top of all this, fluoxetine is also a weak norepinephrine reuptake inhibitor itself (660nM), and norfluoxetine is an even stronger dopamine reuptake inhibitor (420nM). So at 80mg, those extra effects at the other transporters may actually play a role. To elicit an antidepressant effect, SERT occupancy/inhibition typically needs to be at least 60% if not closer to 80%. However, for DAT in particular, all evidence we have indicates that level of occupancy is not only not necessary to elicit similar antidepressant effect, but occupancy that high at DAT is generally only seen in illicit substances like cocaine and usually has addictive qualities. And without a significant amount of the DAT in the PFC, even the slightest DAT inhibition can elicit a big effect, which is why Wellbutrin still works really well for a lot of people despite being an extremely weak DAT inhibitor, itself.

Looking at your signature @Blahblah and I forgot that you're on a tall dose of Ritalin too on top of the Prozac. I say this all because Prozac should be synergistic Ritalin due to this noradrenergic and dopaminergic "overlap" between the two medications.

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On 10/8/2021 at 2:57 PM, browri said:

Looking at your signature @Blahblah and I forgot that you're on a tall dose of Ritalin too on top of the Prozac. I say this all because Prozac should be synergistic Ritalin due to this noradrenergic and dopaminergic "overlap" between the two medications.

Yeah, I was hesitant to increase an SSRI when it seems my lingering symptoms are more related to lack of dopamine.

So overall, you think increasing Prozac to 30mg/day could work more synergistically with Ritalin (and not further dampen out the dopamine effects?) I've also debated on going back to Effexor, but I don't know. I'm pretty fed up with trialing things multiple times and attempting to parse out what med is actually making a noticeable, positive difference.

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15 hours ago, Blahblah said:

Yeah, I was hesitant to increase an SSRI when it seems my lingering symptoms are more related to lack of dopamine.

Have you ever paired antidepressants before? For example, I see that you've tried Zoloft, Prozac, Celexa, Lexapro, Trintellix, Wellbutrin, Cymbalta, and Effexor. Have any of those ever been combined? The first combination that comes to mind really is the combination of Remeron with either Cymbalta or Effexor. But another combination would be Lexpro+Wellbutrin.

From what I've been reading, though, the real dopamine kicker is actually Zoloft+Wellbutrin. This particular combination is a bit more multi-faceted, but I wonder if it would work well for you. Sertraline is predominantly an SRI with modest DRI activity. Bupropion is an NDRI, but it is limited by the fact that it is rapidly broken down to metabolites that are NRIs with very little DRI activity. This makes Wellbutrin as a medication overall at steady state mostly an NRI with only modest DRI activity. So when they are put together, this makes the combination a very potent SNRI as well as more potent of a DRI than either medication would be alone.

In addition to the complementary pharmacological activity at the dopamine transporter, they have supplementary pharmacokinetic interactions, which further enhances the dopaminergic effect. As indicated previously, while bupropion is a fairly strong DRI, it is rapidly broken down by the enzyme CYP2B6 to metabolites that do not have significant DRI activity. Sertraline inhibits CYP2B6, making more bupropion available at steady state and increasing Wellbutrin's inhibitory effect on the dopamine transporter, further complementing sertraline's DRI activity. On top of this, bupropion and its metabolites are all CYP2D6 inhibitors, which is responsible for breaking down sertraline and its metabolites. This of course has the effect of increasing blood levels of sertraline and some metabolites.

The net result is that both Zoloft and Wellbutrin could be dosed lower and still have far more significant stimulating effects than either would alone, even at higher doses.

15 hours ago, Blahblah said:

So overall, you think increasing Prozac to 30mg/day could work more synergistically with Ritalin (and not further dampen out the dopamine effects?) I've also debated on going back to Effexor, but I don't know. I'm pretty fed up with trialing things multiple times and attempting to parse out what med is actually making a noticeable, positive difference.

Going back to Effexor would really only be worth it if you went to at least 150mg, but I'm pretty sure that was a standard dose for you, and you couldn't go any further than that. Correct me if I'm wrong. To really dig into norepinephrine and dopamine, you generally have to go to 225mg if not to 300mg. But at that rate, it would be safer to go to Cymbalta, because it'll have less of an effect on blood pressure than Effexor or Pristiq.

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