View Full Version : Why do anti depressants poop out?


Fuzzy12
08-19-13, 12:44 PM
So apparently, people with BP are often resistant to anti depressants or after an initial response stop responding. The latter is me.

I seem to be hypersensitive whenever I start a med, especially Sertraline. It worked wonders last year for the first few weeks. I actually felt a noticeably difference within a few days. Then the effect reduced and I kept increasing the dose gradually, with no effect whatsoever. Duloxetine and Venlafaxine did nothing for me.

When I started lamotrigine, I did feel more stable for 1-2 days. But after that it only seemed to stabilise my euphoria. I.e. I couldn't feel euphoric anymore but was just steadily depressed.

I read that the initial response to meds might be due to the placebo effect but I think that's unlikely to be the case with me. When I started Sertraline, I had no hope whatsoever that it would work. I couldn't imagine it and I definitely didn't expect it to start working so soon. But then I very quickly felt both the side effects and an elevation in my mood.

Now, I'm back on Sertraline. I felt much better for about a day when I increased my dose to 150, then the effect pooped out. Similarly, when yesterday I increased the dose to 200mg, I felt pretty good for about 12 hours.

Any idea why this might be happening? Do I just get used to the meds and dose increases so quickly? Do my neurons just get saturated so quickly?

Raye
08-19-13, 12:52 PM
Good question. I've always been anti-d resistant.

Sorry I can't answer your question, I don't want to sound stupid, but what is the 'placebo effect?'

Fuzzy12
08-19-13, 12:56 PM
Good question. I've always been anti-d resistant.

When I reached 200mg of Lamictal, it quit working... I was off it for a bit and now back on it, and it seems to be working again.

Sorry I can't answer your question, but what is the 'placebo effect?'

I think, it's just that when you start taking meds you feel better because you expect to feel better with the medication. So, it's not actually the med helping you but your faith in the med.

I read a paper (about lamotrine for BP II) I think, where the authors said that a lot of people who respond and improve initially but then the medication gradually stops working. They said that it's likely that most of these actually did not clinically respond to lamotrigine but were just helped by the placebo effect.

Raye
08-19-13, 01:31 PM
Thanks for explaining that. It makes alot of sense.

heytheredelilah
08-19-13, 05:25 PM
So apparently, people with BP are often resistant to anti depressants or after an initial response stop responding. The latter is me.

I seem to be hypersensitive whenever I start a med, especially Sertraline. It worked wonders last year for the first few weeks. I actually felt a noticeably difference within a few days. Then the effect reduced and I kept increasing the dose gradually, with no effect whatsoever. Duloxetine and Venlafaxine did nothing for me.

When I started lamotrigine, I did feel more stable for 1-2 days. But after that it only seemed to stabilise my euphoria. I.e. I couldn't feel euphoric anymore but was just steadily depressed.

I read that the initial response to meds might be due to the placebo effect but I think that's unlikely to be the case with me. When I started Sertraline, I had no hope whatsoever that it would work. I couldn't imagine it and I definitely didn't expect it to start working so soon. But then I very quickly felt both the side effects and an elevation in my mood.

Now, I'm back on Sertraline. I felt much better for about a day when I increased my dose to 150, then the effect pooped out. Similarly, when yesterday I increased the dose to 200mg, I felt pretty good for about 12 hours.

Any idea why this might be happening? Do I just get used to the meds and dose increases so quickly? Do my neurons just get saturated so quickly?

Do you think you may have believed you would feel better despite other thoughts that you would not?

I've tried effexor for my depression and came off when it did not work. Ironically, I experienced a lot of happiness and euphoria on the second day I took the pill. I skipped class, called some friends and made plans, then got asked out by a very charming stranger who said he felt attracted to my confidence. I'm usually shy...

I think it only lasted either that one day or the next day as well. Then it was done...

When I told my therapist, she said the med would not have had time to make a difference in my mood, which makes little sense to me. But she said it would not be in my bloodstream?

I have not been diagnosed with bipolar.

Also, I thought that my reaction to effexor was a good indicator that I was indeed not bipolar despite some suspicions from my pdoc and people from here.

If it's a norepinephrine reuptake inhibitor and that neurotransmitter is partly responsible for mania/hypomania in people with bipolar disorder, would it not have made me manic or hypomanic (and for longer than a day...)?

Also, did you try adjusting the doses with the antidepressants?

keliza
08-19-13, 06:07 PM
Good question. I've always been anti-d resistant.

Sorry I can't answer your question, I don't want to sound stupid, but what is the 'placebo effect?'

Not a stupid question at all Raye! Fuzzy answered it pretty well. I just wanted to add onto her answer.

The 'placebo effect' was initially named after the psychological effect that researchers saw when they were performing drug trials (not just psych drugs). In drug trials, blind tests are given to test groups to evaluate the efficacy of a treatment, such as a medication. One group will be given the actual medicine, and the other will be given a placebo, a place holder that has no medicinal properties at all. They are often just plain sugar pills. The test subjects do not know who is getting medicine and who is getting a placebo, they all look the same.

In double-blind trials, the researchers do not know what they are giving the test subjects either. A separate group knows what label A and B mean - neither the subjects nor the ones administering the medicine know which is which. That helps remove any bias that the researchers might have unintentionally when giving what they know to be real medicine or placebo (body language, word choice, facial expressions, etc.)

What researchers have found is that there is almost always a response to the placebo medication, even though it is not actually any kind of medicinal treatment at all. We'll use Tylenol for headaches as an example. One group would be given Tylenol, and they would have, say, an 80% response rate. That would mean that 80% of patients saw a reduction in head pain when they took Tylenol. The other group would be given a placebo that looked like Tylenol but had no medicinal properties. The placebo group might see a 20% response rate. That means 20% of test subjects who received placebos would experience a reduction in head pain, even though they did not actually receive any medication.

That 20% response is the placebo effect. It means that they perceived that they had a reduction in pain symptoms, even though they were not actually given any medication to relieve the pain. It's a very complex reaction that seems to prove that, at least for some people, what you believe can have a very real impact on how you respond to treatment. Their reduction in pain was very real, it just wasn't caused by the medication. Nobody is exactly sure how the placebo effect works with various medications, only that it is fairly reliable.

Fuzzy, it's entirely possible that your temporary response to medication is a placebo effect. It's also possible that you are acclimating to the medications too quickly for them to be useful. I think it's more likely to be the placebo effect. Even if outwardly you doubt that these medications will help, you may still on some subconscious level hope that they will work, and so for a brief period of time, they do. It's impossible to say exactly what is going on.

Raye
08-19-13, 06:20 PM
Keliza,

you ROCK! :grouphug:

daveddd
08-19-13, 08:02 PM
ssris improve depression through mood enhancement

as with all mood enhancement drugs, you can gain a tolerance


its part of the issue i have with making everything completely biological (only biological , there is biology involved), it can lead to a long journey of switching and trying meds and ultimately fail

anti ds are great for temporary relief to motivate yourself for therapy(which one is best, i dont know)

its why i get nervous when i see "miracle drug?" type threads or things that are similar

ive had quite a few of those moments and even a one or two of those threads

Rebelyell
08-19-13, 09:05 PM
Crappy formulation?

fracturedstory
08-20-13, 04:03 AM
My placebo effect lasted 6 months. Sarcasm.

Anti-d's worked well in me but then the anxiety and depression just came back and I'm pretty sure I had my first manic experience on them. I thought it was a meltdown but from then on I've been sensitive around strobes. Like really. My brain goes crazy sped up fast and I think I could either have a seizure or a great high.

Fuzzy12
08-20-13, 07:27 AM
It could be just the placebo effect but not necessarily, I think. When I felt Sertraline kicking in, it felt very physical. First came the side effects (which I didn't expect so soon), then I got extremely restless and then I started feeling all right.

Physiologically, is it possible to feel an effect from meds in the first few days (or first few weeks) and then nothing? Why are BPs supposed to be often non responsive to anti depressants?

I wonder if it's my lifestyle that's limiting the effect. Both Sertraline and lamotrigine reduce my appetite drastically. The more I increase the dose, the less I eat. Could the lack of nutrition make them less efficient?

Also, when I first started Sertraline, I wasn't smoking. I started smoking again about 2 months after starting Sertraline. By that time the effect had already reduced but I wonder if nicotine made it even more ineffective. I read somewhere that smoking interferes with the beneficial properties of some anti depressants.

Delilah, yes, with every med, I start at a very low dose and then gradually increase the dose. I only increase the dose though if I feel that the med isn't working or isn't working anymore. Right now, I'm taking 200mg of Sertraline, the maximum recommended dose I think. I do feel slightly better but I'm worried that it will stop working again.

keliza
08-21-13, 04:51 PM
It is certainly possible to feel a physiological response from a medication within the first few days or weeks. The reason is because the physiological response is your body's reaction to taking the medication. The psychological response (the antidepressant qualities), on the other hand, are the result of more long-term changes to your neurons and brain chemistry that develop over time, weeks or months.

Does that make sense? Nobody is entirely sure HOW antidepressants work, but their efficacy appears to potentially be caused by changes in grey matter volumes in certain parts of the brain (neurogenesis), changes in the way certain receptors behave (blocking serotonin and/or norepinephrine reuptake, for example), MAO inhibition (blocking the enzyme monoamine oxidase from taking serotonin, norepinephrine, and dopamine out of the brain), etc. All of these processes take time to show long-term effects and improvement. So you won't see TRUE antidepressant qualities until weeks later, because the brain has to adjust, both structurally and chemically.

On the other hand, physiological responses are immediate because they are related to the way the rest of your body processes the actual medication. The chemicals introduced in the medication may cause insomnia, changes to the metabolism, changes to libido, etc. and those things are more immediate. They don't require long-term changes to the brain to be experienced, so they are experienced more immediately.

I think it's possible that the medication causes you to feel a slight bump in mood due to some physiological response you're having, not because of the actual antidepressant properties. The actual changes in the brain that cause long-term alleviation of depression have not occurred yet, and won't for several weeks.

Why are people with bipolar disorder less responsive to antidepressants? Nobody knows. Based on current research, bipolar depression is not all that different from unipolar depression, with one interesting difference measured by research:

"Despite the many parallels, one set of striking differences emerges. Studies of both intracellular mechanisms and sleep deprivation suggest that people with a lifetime history of mania may have deficits in the ability to regulate neurotransmitters in the face of a challenge. Such regulatory deficits would be expected to be manifested in more rapid course changes, as well as increased vulnerability to environmental challenges." (x (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2850601/))

But as far as bran imaging studies, levels of neurotransmitters during depressive episodes, etc. it looks like the brains of people with major depressive disorder (MDD) vs BP are fairly similar. So why are antidepressants so much less effective in BP patients than MDD patients? Like I said... nobody knows.

There are some patterns. Antidepressants are less effective and more likely to cause manic switching in patients who have bipolar I disorder, rapid cycling, mixed episodes, a history of substance abuse, or who use older classes of antidepressants (TCAs). Patients with BPII, no rapid cycling, no substance abuse, no mixed episodes, and who use newer classes of antidepressants are less likely to have a manic switch and are more likely to have a positive response to antidepressants.

The info in the above paragraph comes from this (http://bipolarnews.org/?p=1298) interesting article that compiles a lot of recent data (up to 2012) about antidepressants in MDD vs. BP depression. This (http://www.ncbi.nlm.nih.gov/pubmed/23121222) is an excellent study about the use of antidepressants in bipolar I, II, and MDD patients. Their conclusion: "Selective use of antidepressants with or without mood stabilizers in non-agitated, depressed bipolar disorder patients for short periods was effective with moderate risk of potentially dangerous, manic mood elevation."

So basically they found that antidepressants can be used in NON-AGITATED depressed bipolar patients for short periods of time, and there is still a moderate risk of potential manic mood elevation. Doesn't sound like a great gamble, but if someone is suicidally depressed I suppose it's a calculated risk a person might have to take.

Whatever the reason, research has found that antidepressants definitely work differently in BP brains vs. MDD brains. Why is unclear. Knowing that, it's probably more prudent to look into treatment with mood stabilizers and/or antipsychotic medications instead of antidepressants.

daveddd
08-21-13, 06:45 PM
people in certain schools of thought overcomplicated everything

there unsure because they arent going to find what they are looking for

seratonin -happy chemical, ssris keep it around in your brain, its really pretty simple

most people are depressed for a reason, and the brain will usually give you hints in the form of rumination

keliza
08-22-13, 11:40 AM
Dave, it would be great if brain chemistry was that simple. Serotonin works primarily in your gut, actually. It also has ties to mood and depression, but so do dopamine, norepinephrine, and many other chemicals. Some people don't respond to serotonin agonists, so it's not quite as simple as "add more serotonin and you'll be happier." Some people go wildly manic on serotonin agonist drugs. Some people take SSRIs at very high doses and experience no improvement, but do on drugs that target different chemicals. Some people's brains have structural abnormalities, either causing or caused by depression, that contribute to the illness. There's a lot more to it than more serotonin = more happy.

You're right, everyone is depressed for a reason. Sometimes that reason is trauma. Sometimes that reason is many small things building up in life that make a person unhappy. Sometimes that reason is that the brain is out of whack and can't synthesize or utilize neurotransmitters properly. Usually it is a combination of many reasons. Even the "outside" reasons become "inside" reasons with time, though. Your brain chemistry changes after a traumatic event, so the depression is never purely internal or external. One influences the other, which influences the other, it feeds itself over time.

Studies show repeatedly that for moderate to severe depression, you have to attack it from both directions - medication and therapy - to see the best results. And when it comes to bipolar disorder, you are dealing with an illness that is almost guaranteed to repeat itself many times throughout a person's life, so prophylactic meds are a staple for many people's continued remission. And those meds often have nothing to do with serotonin.

daveddd
08-22-13, 01:08 PM
i get that brain chemistry is complicated

the point, meds dont "fix" why your depressed, they enhance your mood

maybe in bipolar lower sensitivity levels that lead to episodes when facing adversity

what i dont agree with, is like the quote you posted

"bipolar people have trouble regulating neurotransmitters "

people dont regulate their neuro transmitters

they regulate their emotions with conscious actions called executive function

the neurotransmitters are to follow

in barkleys newest book, he has a section called "the missing self in executive functions", where he complains how the 'self' is being ignored in neurological reductionism (his words), he talks about this

im not against meds, they just arent "fixing" anything

daveddd
08-22-13, 02:48 PM
Ok my heads a mess today I didn't explain much

I meant when meds lift your depression with out fixing the cause that's just enhancing your mood

Without fixing the cause that won't cut it for long

I'm generally in agreement with your post though

keliza
08-22-13, 02:55 PM
Ok my heads a mess today I didn't explain much

I meant when meds lift your depression with out fixing the cause that's just enhancing your mood

Without fixing the cause that won't cut it for long

I'm generally in agreement with your post though

Okay, yes, we do agree on that then. I agree that if you don't address the emotional and environmental causes of depression, the meds aren't going to help you much. It's got to come from all directions, otherwise the meds are like a bandaid over a bullet hole.

DmxDex
09-25-13, 08:10 AM
If you do your research most of us who are poorly likely damaged our guts or have very poor nutrition. Coffee is very bad as is sugar. Sugar causes huge amounts of problems to the gut.

the old saying is true you are what you eat.

saying that I recently read that when a female was having mania her throids where pumping out high levels of hormone.

VeryTired
09-25-13, 10:28 AM
This is a thread about diminishing effects of medications. But I do wonder if perhaps another explanation for the phenomenon could be that the meds are working on some of the symptoms and their causes, but not all. It feels positive to get that partial benefit at first but over time, the un-treated symptoms become more apparent and the overall effect is that the medication is working less well. Just a thought.