Zoloft: two pills, same dose, different experiences?
November 2, 2017 7:58 AM   Subscribe

I started taking Zoloft a month ago, and I’ve noticed a difference between taking two 50mg pills and one 100mg pill from the same manufacturer. Am I crazy?

YANMD. I am emailing him today. In the meantime, maybe you can help me think through this.

I’ve been titrating up to 100mg, in 25mg increments ~weekly. I haven’t actually had any side effects, aside from some GI issues that lasted a week and then went away.

For the first couple of weeks, I was taking these blue 50mg pills - breaking them in half, taking a whole pill, and then taking 1.5. When it was time to move to 100mg, I started taking these beige 100mg pills.

Something really interesting to me is that I noticed a positive impact on mood and anxiety at 75mg that basically evaporated as soon as I switched to the beige 100mg pills. So, yesterday, as an experiment, I took two of the blue 50mg pills (at the same time) — and, like a light switch, I felt better again.

So, the primary thing I’m curious about is why two pills of the same dose by the same manufacturer with almost identical inactive ingredients could have notably different effects. Also, I’m surprised to notice this kind of thing on a day-by-day basis, when I know that sertraline takes time to accumulate in the brain. I keep thinking "placebo!" but, who knows.

The most likely theory is that it took a week of 100mg before things stabilized again, and that just happened to be the day that I tried the blue pills. Again, the timing is just too perfect for that to make sense to me. So I’m looking for other thoughts.

(As a side note, I keep the blue pills in a small pill container that also contains dexedrine — I’m not currently taking the dexedrine, but my girlfriend theorized that the amphetamine pixie dust could be coating those pills and they could be potentiating each other. This sounds really nutty, since we’re talking about dust, but I feel like I have to mention it since it’s a meaningful distinction between the blue and beige pills.)

Interested to hear any personal experiences or well-reasoned theories. Thanks!
posted by anonymous to Health & Fitness (9 answers total) 1 user marked this as a favorite
Two pills have a bigger surface area than one pill of the same combined mass. Thus the two pills will dissolve more quickly, and have more rapid 'pharmacokinetics' -- they will hit your bloodstream faster. This is a general statement. In the specific case of Zoloft, I'm not sure this matters as much because it takes so long to reach 'steady state' concentrations in the bloodstream (e.g., why it takes a few weeks for Zoloft to become effective.)

You can test the 'surface area' idea by cutting the 100mg pill into multiple smaller pills and taking them as small pills. If that has the same effect, then there may be something to surface area of the pill for you.
posted by Doc_Sock at 8:12 AM on November 2, 2017 [3 favorites]

The rules for exactly how much active ingredient has to be in a generic drug are not as exact as you might hope. If the two pills were from different manufacturers, I think that might be a factor here. And they might might be from different sources even though they are sold under the same brand.
posted by SemiSalt at 8:23 AM on November 2, 2017

If you take the xr/time release, you cannot cut it
posted by AlexiaSky at 8:32 AM on November 2, 2017

It doesn’t come in an XR version.
posted by chesty_a_arthur at 8:57 AM on November 2, 2017

I think this is placebo.

The dip in elevated mood when you switched from 75 to 100 could have been due to a well-known effect of SSRIs, which is a sort of euphoria experienced day or weeks after starting, which then tends to settle down. The switch in dose would have been coincidence.

The reason I think this is placebo is because of how SSRIs work. They block the reuptake of serotonin, which means more serotonin is left in the synaptic cleft following a synapse. This leftover serotonin is not immediately available, however. Dendrites have to actually grow additional receptors in order to allow transfer of the additional serotonin. This takes weeks, hence the time needed for SSRIs to work. Surface area and such would have no effect on the psychopharmacology of the drug.

I also don't think the amount of dexedrine that might transfer to the surface of the pill in dust form would be noticeable to you or cause this effect.

I will point out that there is nothing wrong with placebo. In fact, a large part of the beneficial effect of SSRIs has been shown to often be placebo - but that doesn't make the effect less "real". If you are happier taking two 50s, then take two 50s.
posted by Lutoslawski at 9:03 AM on November 2, 2017 [5 favorites]

This is indirectly related, but a few years back there was a generic version of Wellbutrin that was less effective specifically in the 300mg dose - the 150mg dose by the same manufacturer was fine. It slipped through the cracks because the FDA only tested the 150mg version. I took that generic for a while, when there was research suggesting it wasn't bioequivalent but the FDA hadn't done anything about it; I could tell it wasn't helping, so I brought it up with my prescribing psychiatrist and he brushed me off. (He upped my dose instead, which ended up working because it meant adding a pill from the non-crap formulation).

I hope that's not what's happening with your Zoloft, but if you can't get a prescription specifically for two 50s, call around local pharmacies and see if you can get a 100 from a different manufacturer.
posted by Metroid Baby at 10:12 AM on November 2, 2017 [1 favorite]

So, pills are pretty much dark magic. It's not just the active ingredient that has an effect. There are experiments showing that the size of the pill, the colour, the way it's presented to you, the packaging - all have real, measurable physiological and psychological effects.

Ask anybody who's been given a generic sertraline prescription when they've been on 'the real deal' (there was a Zoloft shortage in Australia not long ago, so this was a thing that happened) and it doesn't matter how much the pharmacist says 'it's chemically identical' - they'll tell you it ain't. (For me, it's the other way around - if I take a generic version of my blood pressure meds, I don't get a night cough. If I take Famous Brand(r)(tm), I do.)

As Lutoslawski points out, technically this is the placebo effect, but you shouldn't think that 'placebo' means 'it's all in your head' / 'it's not real'. Your body really does react differently when those variables change. I really do get that cough. And your mood really does change.

So you should take whatever combination / colour pills that work best for you.
posted by obiwanwasabi at 5:32 PM on November 2, 2017 [4 favorites]

It could be placebo, or it could be that the 50mg tablets have a slightly different crystal morphology. This can cause rather large changes in pharmacokinetics resulting in a much different dose profile. I'm unsure as this is an SSRI if it would have an effect, but it might if you had been taking 100mg for a while and then took two 50mg for a day. Either way even if it is a placebo I would see if you could get a scrip for two 50mg a day if that is what works for you. A lot of CNS meds require quite large studies to demonstrate their efficacy over a placebo anyways so might as well use that to your advantage if you find something that works.
posted by koolkat at 2:28 AM on November 3, 2017 [1 favorite]

(If you figure this out, please let us know!).
posted by kitcat at 11:08 AM on November 3, 2017

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