Definitely having a depression blip week 5. Ugh

[MissyMischief]

Well, the first four weeks were pretty okay as far as side effects go. I had a handful of good and pretty okay days in there, which was so, so nice. In the entire month of December, I only took 3 Xanax, whereas, in previous months I was taking one tablet every single morning just to get by.

Tonight will be dose three into week 5, and damn, I have been feeling SO depressed and weepy. My anxiety is not too bad to begin with, but I do start to feel anxious about being depressed, asking myself why I'm depressed, if this means the meds aren't actually working etc...etc...depression is a very depressing state to be in.

I'm trying to tell myself it's just a blip. I've read a bunch of Fluox-users on here reporting a major blip in weeks 5 and 6. I read that Fluox takes 30 to 60 days to stabilize in your blood plasma. Other antidepressants only take 7-14 days, so I'm assuming the meds are just trying to stabilize.

Anyone out there to give me some reassurance? I'm trying really hard to distract myself and not think the worst, but it's a struggle.

[MyNameIsTerry]

It's got a chronic half life of 4-6 days.

The basic pharmacokinetic calculation for any drug is 5 half lives to reach "steady-state" (as much going in as coming out).

So, on the basic calcs you get:

4 days = 96 hours = 480 hours = 20 days (4*24*5/24)
6 days = 144 hours = 720 hours = 30 days (6*24*5/24)

If you want to work it to 100% accuracy, it's 7 half lives instead of 5 but this is beyond being stable in blood plasma.

Other antidepressants can take varied amounts, it depends on the half life. Some are so short it can take days, others it takes more like 8 days because they are longer. There is always a Mean average and those who are outliers (like the day 4 people or day 6 people) may have factors involved e.g. children tend to metabolize quicker, old people take longer, renal insufficiency makes it longer, drinking lots of water makes it quicker, etc). You are likely the Mean but in looking at side effects it can be helpful to wait out the outlier periods to be sure as you (and your doctors) can never know as it's completely individual.

There is a good piece on Wiki that explains these unique issues with this med...and thank god you are not on norfluoxetine, eh?

Pharmacokinetics

The bioavailability of fluoxetine is relatively high (72%), and peak plasma concentrations are reached in 6–8 hours. It is highly bound to plasma proteins, mostly albumin and α1-glycoprotein.[3] Fluoxetine is metabolized in the liver by isoenzymes of the cytochrome P450 system, including CYP2D6.[70] The role of CYP2D6 in the metabolism of fluoxetine may be clinically important, as there is great genetic variability in the function of this enzyme among people. CYP2D6 is responsible for converting fluoxetine to its only active metabolite, norfluoxetine.[71] Both drugs are also potent inhibitors of CYP2D6.[72]

The extremely slow elimination of fluoxetine and its active metabolite norfluoxetine from the body distinguishes it from other antidepressants. With time, fluoxetine and norfluoxetine inhibit their own metabolism, so fluoxetine elimination half-life changes from 1 to 3 days, after a single dose, to 4 to 6 days, after long-term use.[3] Similarly, the half-life of norfluoxetine is longer (16 days) after long-term use.[70][73][74] Therefore, the concentration of the drug and its active metabolite in the blood continues to grow through the first few weeks of treatment, and their steady concentration in the blood is achieved only after four weeks.[75][76] Moreover, the brain concentration of fluoxetine and its metabolites keeps increasing through at least the first five weeks of treatment.[77] That means that the full benefits of the current dose a patient receives are not realized for at least a month since its initiation. For example, in one 6-week study, the median time to achieving consistent response was 29 days.[75] Likewise, complete excretion of the drug may take several weeks. During the first week after the treatment discontinuation, the brain concentration of fluoxetine decreases only by 50%,[77] The blood level of norfluoxetine 4 weeks after the treatment discontinuation is about 80% of the level registered by the end of the first treatment week, and 7 weeks after the discontinuation norfluoxetine is still detectable in the blood


Are you managing to do any jogging? Exercise might help with the depression but I know it's damn hard to do much of anything in these side effect windows, they always hit me hard.

I wouldn't worry about the 60 day thing unless their is a professional source for it, users can not always know why things are happening and assume it's the drug. It took me 2-3 months to feel Citalopram working for me yet I would have been stable on my dose within 8 days as started straight on 20mg (which I wouldn't recommend, stupid GP!) and some people may see that as the lead time but it doesn't stack up in pharmacokinetics.

[MissyMischief]

Hi Terry!

Thanks for responding! You are very kind .

So, I guess technically I'm at the "steady state", since this is day 32 for me on the full 20mg. I did wean myself onto the full dose over about a three week period, though. Not sure what effect that had.

I jogged a couple of days ago, but right now, my motivation is about zero. I didn't sleep well, and am feeling a bit anxious this morning. Ugh, gotta love side effects.

Thanks again, Terry!!

This is the website where I got the 30 to 60 day info.
http://www.emedexpert.com/compare/ssris.shtml

[MyNameIsTerry]

Well if you started straight on 10mg or 20mg, steady state calculation is the same. It's not dose dependent. However, increasing means moving into steady state at the new level and this means your blood plasma goes through the same process to reach it at the increased dose.

With your med there is also the additional factor with brain concentration. So, it makes sense that will also re-occur with a dosage change.

For me, I add the periods together to determine when I think I would be out of the side effect windows. Normally it's pretty quick with meds but this med is such a long one. The 5-6 week issue you will have seen on the threads is probably that brain adjustment issue coming to the forefront.

SSRI's work by increasing Serotonin in the gap, which they start doing quickly but their longer term action is also to prevent the re-uptake and they do this by plugging the holes in the receptor so there are less. I've read studies of other SSRI's where this takes a month so I would expect it will take a bit longer with yours. When you increase a dose, it should follow that more Serotonin will flood the gap and more holes with eventually be plugged.

From following some of the people who taper on Citalopram, they get hit with side effects often at both the 10mg and 20mg stages but the latter seems to be where it hits them the worst. I wonder if this is the issue you currently face with yours?

According to Drugs.com professional section it states the following:

Accumulation and slow elimination
The relatively slow elimination of Fluoxetine (elimination half-life of 1 to 3 days after acute administration and 4 to 6 days after chronic administration) and its active metabolite, norFluoxetine (elimination half-life of 4 to 16 days after acute and chronic administration), leads to significant accumulation of these active species in chronic use and delayed attainment of steady state, even when a fixed dose is used. After 30 days of dosing at 40 mg/day, plasma concentrations of Fluoxetine in the range of 91 to 302 ng/mL and norFluoxetine in the range of 72 to 258 ng/mL have been observed. Plasma concentrations of Fluoxetine were higher than those predicted by single-dose studies, because Fluoxetine's metabolism is not proportional to dose. NorFluoxetine, however, appears to have linear pharmacokinetics. Its mean terminal half-life after a single dose was 8.6 days and after multiple dosing was 9.3 days. Steady-state levels after prolonged dosing are similar to levels seen at 4 to 5 weeks.


So, I'm not sure where they get the 60 days from. They, and another site I just saw, also don't have the correct accepted half lives either so I don't know where they get their from but Drugs.com is a large professional website. Your site is also pretty light on side effect profiles as if it's been gathered so that might be a clue I guess otherwise it looks a good site. Bare in mind my calculation was a basic one, not tailored so the info off Wiki & Drugs.com is to be used as it has been observed via clinical trials. My 20 day calc probably doesn't work because the drug and it's active metabolite actually inhibit each other after a certain amount of chronic use causing the half lives to be affected and longer so my calc wouldn't handle this. This is partly why I tend to go for the longer times to be safe.

[MissyMischief]

Thanks again, Terry!

Got a better night sleep last night. Anxious this morning, but propranolol helps. Going to see my counselor today, which always leaves me in an optimistic mood.

I do hope I turn a corner soon. Fingers crossed.

[MissyMischief]

Well, shit really does pass in time! Today I feel so cheerful and energized. I woke up this way, and I'm truly surprised. A little anxious but not worried about it in the slightest. Just cheery, cheery, cheery! And it's pouring rain outside! I just thought I'd post a happy post, considering when I posted originally, I was feeling so crappy. Tomorrow is day one of 7 weeks.

Enjoying it while it lasts! Yay!

[Magic]

Lets hope you feel the same tomorrow Genoire .

[MissyMischief]

Lets hope you feel the same tomorrow Genoire .

Thank you, Magic!! Me too ! And I hope you are doing well!!

[MissyMischief]

Well, another pretty good morning. Let my dogs out, but in a groggy state, managed to accidentally take another Fluox tab (I took the last one last night, before bed). Argh! Silly me. I guess that means I'll skip my usual dose tonight??? Hope this doesn't make me feel too bad or anything. Well, today is the start of week 7.

[MissyMischief]

Yesterday, I was a bit anxious into the afternoon. Finally got fed up and took 1/2 Xanax, which helped a lot. The rest of the day was good. I updated my resume and worked on some craft projects. Woke up this morning feeling kind of depressed for some reason, but got up and it faded really fast. I think I might go for a jog, since there is a break in the rain right now.

Really looking forward to consistency here, soon, I hope. Today is day 44. Two days into week 7.