I have been on Lexapro 10 mg for about four weeks now. Since the third day I began taking it, I've been experiencing fatigue, tiredness, and strong sleepiness throughout (but not the whole) day. I take Lexapro at night and this seems to help a little.

I had similar sleepiness side effects with Cymbalta 60 mg when I took it for over a year.

I'm afraid of raising my dose to 20 mg Lexapro because of the possibility of an increase in this side effect, but 10 mg is not working very well for my depression. At least Cymbalta was effective!

My doctor prescribed 450 mg of Wellbutrin XL because it is supposed to be an "energizing" antidepressant. I, however, found that it does not help at all.

I'm at a loss as to what else I can do. Right now, I have to take naps during the day, and I accomplish less each day. The sleepiness is not going away. Ironically, fatigue and lethargy are some of the symptoms of my depression to begin with.

Besides Wellbutrin, I don't know what other options are out there. I highly doubt my doctor will prescribe schedule II stimulants for this. Maybe Provigil is an option, but that would be prescribed off label too.

I know this is a very common problem, but I haven't been able to find a solution. Any ideas? Any medications I may want to speak to my doctor about?

Thanks

I feel for you because I felt the same on it and didn't find anything that worked - although I didn't try very had in fairness. There may be some vitamins etc that work - ones that are supposed to boost your energy and vitality. I took a vitamin B complex but it didn't seem to help. I feel SO much more alive and full of energy since coming off my meds (I'm not suggesting you do this). I had forgotten what it was like to feel normal instead of exhausted all the time. Have a chat to the doc, maybe there are other things apart from Wellbutrin that can help?

xx

Hi data,

It is a bit of a battlefield trying to find the right combination of meds that are eventually going to be effective for you.

I know it is not fun running through the gauntlet of different meds, coming off and going on again, suffering the side effects.

Talk with your Doctor about any alternatives for sleep. I doubt if he will use schedule 2 meds at this stage.

Best of Luck

Jim Bow

Thanks for the replies guys. I've tried different vitamins and supplements, and none of them put a dent in the sleepiness caused by Lexapro.

I wish there was a general "all-antidepressants" section here so I could find out how people on meds other than Lexapro deal with SSRI sedation.

What's strange is that I know some people who take higher dosages of Lexapro and don't experience this side effect at all.

When I was on Paxil and very sedated, my doc put me on Provigil. It worked great. Then my insurance quit covering it so he put me on Ritalin. That worked great too but eventually the Paxil quit working, he weaned me off, put me on Welbutrin and I went manic. Luckily the fatigue from the Lexapro is wearing off because I tried Provigil again and started to go manic again. :(

Thanks for the reply Tovah.

Provigil sounds like a promising solution, but I think I should try switching to another AD before that, especially since I feel no benefit from Lexapro anyway.

I have previously taken Cymbalta and Prozac. Prozac did not cause nearly as significant fatigue as either Lexapro or Cymbalta.

Paxil and Zoloft have a reputation for being sedating; Effexor\Pristiq less so. My doctor does not believe in prescribing MAOIs, so those are not an option.

In your opinion guys, what is the least sedating AD you have been on (besides Wellbutrin).

Hi all

One possibility not mentioned here is L-acetyl carnitine. This is a precursor to Acetyl-choline, another of the neurotransmitters which the SSRI's incidently affect. Acetyl-choline is the primary driver of the majority of the body systems. In particular, as far as SSRIs go, low levels of acetyl choline can be related to fatigue, sexual performance and weight gain. Also an anti-oxidant. Also used medically in Alzheimer's and depression.

L-acetyl carnitine is generally used as a dietry supplement, energy booster, mind stimulator and body building supplement. Very safe and not needing a prescription.

Without going into my usual long winded analysis of the biophysiology (which is fascinating), it is well worth a go. From what I see it has the potential to strongly improve the more long-term side effects of the SSRI as well as reduce the withdrawal syndrome when stopping the drugs.

Personal experience with it supports this.

This post has been edited by Herald: Sep 27 2009, 02:38 PM

Thanks for your input Herald. I too am familiar with the benefits of acetylcholine.

In fact, every day:
I take an Acetylcholine precursor salt.
I take Huperzine A, an Acetylcholinesterase inhibitor.
Occasionally I take Piracetam, a supplement likely active as a cholinergic.

I am convinced these supplements are beneficial for overall health, and even improve memory and cognition.

However, they do nothing for my AD induced fatigue.

BTW... Paroxetine (Paxil) is the only SSRI\SNRI with significant anticholinergic activity. People on Paxil or about to go on Paxil may want to do some research about this fact.

NOTE- please talk to your doctor before combining any supplements with psychopharmaceuticals.

BTW... a bit of news. After explaining my unendurable sleepiness, my doctor switched me back to Cymbalta. If that doesn't work, we have to look at further options.

Excellent. Thank you Data.

With that armory of ACh enhancers if it were going to help with fatigue they probably would have. Either that, or you would be even more tired without them. As with all these neurochemicals it seems the pathways of how they work are still so undefined that much is trial, error and individual response which leads the way to what does or doesn't work.

Apart from my own personal interest in these drugs my father has recently developed Mild Cognitive Impairment (possible pre-cursor to Alzheimer's Disease with a primary cause as lack of ACh ). I had a thorough discussion with the neurologist about the part ACh enhancement takes in the disease process. I was already on to the carnitine and Vitamin B supplements. (Didn't see that Vitamin B was also linked as a ACh precursor molecule - not surprised though). Similarly the enzyme inhibitor. His is scripted. Very interesting to see that Huperzine, apparently with as good a potency as the scripted one and in at least Phase IV clinical trials, is an over the counter herbal remedy.

I agree with your thoughts on the ACh supplements. I wonder if they will become the next disprin and everyone (over the age of X) take some.

What are your thoughts on the fairly simplistic look at this pathway with respect to the longer term effects of depression? - Increase mind based ACh, stimulates peripheral receptors to release Adrenalin --> improve fatigue, sexual performance issues.

Just realised this is off the central issue of what might work best for your fatigue.

You said: Maybe Provigil is an option, but that would be prescribed off label too

Wikipedia : Modafinil shows potential effectiveness in the treatment of depression,[9] .... shift worker's sleep disorder, [13] and disease-related fatigue.[14][15

Sounds like worth a try

This post has been edited by Herald: Oct 2 2009, 03:19 PM

First off, I'm sorry to hear about your dad's condition and I wish him the best of health.



I have often pondered the same question: Why aren't cholinergics used as adjuncts to antidepressants? From my own experience, cholinergics improve mood and energy slightly and also have positive cognitive effects, something that is very beneficial in many kinds of depression. I also believe the anxiogenic and peripheral (sweating, etc.) side effects are minimal.

The surprise is that some of the research I have read points to lower acetylcholine activity as being beneficial in depression. Some people even find anticholinergic side effects euphoric. The mechanism of tricyclic antidepressants may in part be mediated by their effect on acetylcholine. Acetylcholine concentration in parts of the brain seems to play a part in Dopamine release, and the two neurotransmitters seem to have a quantitative relationship that is very important in depression. There are many fascinating articles online on this subject. I'm currently working on a biology degree and this kind of stuff interests me, but much of it is too advanced for me.

Anyway, just another example of how people's bodies are different, in this case their reaction to cholinergics.

Hey Data

Thank you for your thoughts on Dad. We are on track with doing all that can be done. There is a brand new Phase II clinical trial of a new drug with a log of promise (all relative) that we are working on getting him into in 6 months.



Agreed. It makes it very hard to get the right balance.

Further to the issue of fatigue - your comments reminded me of the following post by Deepster. This was one of the posts that took me off on the path of ACh. Deepster found Pristiq worked. Looks fairly new (post 2007) and the part that got me was the norepinephrine re-uptake in additon to the serotonin and the fact that Deepster was so badly affected by normal SSRI and coped well with this one. Major difference for Deepster and a very significant from the cholinergic point of view. It may be that external supplementation to affect the pool of ACh neurotransmitters is not enough. It may need a more direct influence in the CNS, ie on the re-uptake inhibitiors, in the same way as serotonin. Might be worth your considering with your doc?

Deepster - are you there for comments?

From Deepster's post August 19th 2009 - on post How Long Did The "can't keep going with these side effect last for you" Topic



This post has been edited by iowa: Oct 3 2009, 06:33 PM

Yep, still around and still just as pleased with Pristiq as I can be. Never tried cymbalta or effexor as Pristiq was the new SNRI kid on the block at the time it was Rx'd. I have heard of some people who had bad experiences on either SSRIs or other SNRIs not encountering the same problems with Pristiq. I have had no issues with fatigue while on pristiq, and I have even added trazodone at night to help with the sleep issues. Of course, trazodone is somewhat notorious for causing(in some people) the "trazodone hangover". So, if one is already experiencing fatigue SEs from whatever med they are on, trazodone might not be an option. I added this last part just because I am curious, Data. Are getting sufficient and "proper" sleep at night?

Regards,
Deepster

This post has been edited by iowa: Oct 3 2009, 06:39 PM

Thank you Deepster

On a side note one of the related topics (on another forum within here) relating to sexual side effects I found another supplement someone is trying (Tongat ali). Topic: Could This "magic Jungle Root" Be The Answer To The Sexual Side Effects Of Effexor And Other Ad Meds????!!! No suprises to me that the google search shows an acetylcholine component to the action.

Google search:

"Powerful Male Tonic Supplement with TONGKAT ALI. Philippines - 1316965
Vitamins / Supplements Pasay City Metro Manila tongkat ali, ... It stimulates
the acetylcholine receptors, which relax the blood vessels leading to the ...

Thanks for the replies herald and deepster. I appreciate it.

That's a tough one. Lexapro screwed up my sleep cycle; I would wake up at 2 AM and not be able to fall asleep- something that rarely happens to me. I generally have trouble falling asleep. I take a Z class hypnotic for that. Also, I participated in a sleep study, but for a reason I won't get in to, I am unable to get my results.

I do get enough sleep at night, though I'm not sure of the quality. Problem is, the fatigue is only present when I'm on certain ADs. This summer, I was off medication for a while and the fatigue went away.

I stopped Lexapro more than a week ago and feel much less tired, and no longer have to take naps during the day. I'm back on Cymbalta 30 mg right now, which so far hasn't caused significant fatigue, though today I felt sleepy and lacked concentration, so it might be coming. Also, 60 mg is the dose that's helped me in the past, and is also the one that caused sedation for me in the past.

I'll keep you guys informed.

I've heard about this stuff. Seems people get mixed results with it, but intersting about the acetylcholine. Sexual side effects are my other major side effect from ADs. I've tried some supplements for it with not much success.

An update: this is my second week on Cymbalta 30 mg, and I am beginning to experience levels of fatigue and sleepiness almost as bad as on Lexapro 10 mg. This is very frustrating because when I was on Cymbalta 30 mg back in 2007, I experienced NO fatigue from it. What happened in those two years? I'm beginning to realize that even though being on ADs makes me more fatigued, I am, starting around 2009, more fatigued even when I am unmedicated.

My doctor put me on Provigil this week. Unfortunately, 200 mg does nothing for me. Yesterday, I took 200 mg at noon, and an hour later, I fell asleep into a three-hour-long nap!

I believe there might be something hormonally wrong. I had blood work done this spring, which my family doctor said showed nothing unusual. It seems that another thorough blood test is in order. My symptoms are beginning to look similar to hypothyroidism.

What do you guys think?

HI Data,

I also wondered if I might have this as I have many of the symptoms. But I thought that when they did a standard blood test, something would have showed up which showed this may be a possibility. When I got blood tests, they never said what they were testing for but they said everything was fine so I assumed it wasn't a possibility. So wouldn't your blood work have shown up something if this was the case? Or am I just putting too much faith in the medical profession?!

I am constantly fatigued - much better since coming off ADs but it's still noticeable. Can I ask what the Provigil is supposed to do?

If you're worried then I think it's always worth going to the doctor and getting checked out. Especially as this is an easily fixed problem. If you do go, let me know how you get on.

PRT xx

Hey Data

(Having written this, and from another of your posts, I see you are already on to the dopamine possiblity)- never the less, will leave it.

Looks like it may be worth checking out dopamine deficiency. Below is an extract from just one discussion. There looks as if there might be a way to get an clinical diagnosis or at least an indication - it talks about urine neurotransmitter evaluation. Probably a fairly specialist test but worthwhile if it gives an answer to your condition. I have left out discussion of do it yourself remedies, primarily nutritional. There are also some drugs.

"the “other neurotransmitter” which is also very important but is much less well known: dopamine...dopamine effect can be diminished by interference from the serotonin effects of the SSRI class of drugs. One goes up the other goes down...Using SSRI drugs or nutrients that increase serotonin may lead to depletion of dopamine with its associated symptoms....we should be aware of the earlier manifestations of the loss of dopaminergic neurons. Loss of drive and vitality is the clearest signal, along with poor motivation, loss of joy generally, low sex drive, diminished sexual performance and pleasure from sexual activity, and lessened intensity of orgasms are common. Another, even earlier, sign of trouble is the inability to remember one’s dreams, or a complete discontinuation of dream activity. ...Overall dopamine works as a natural amphetamine that controls your energy, excitement and motivation. It is also related to blood pressure, metabolism, digestion, voluntary movement, intelligence, abstract thought, setting goals, and long-term planning....

"Dopamine deficiencies can lead to some of the following symptoms... (left in the ones you have mentioned, plenty of others)

Low sex drive and/or difficulty achieving orgasm
Thyroid disorders
Excessive sleep

Physical signs of dopamine deficiency will be fatigue, sleeping long hours and still not feeling rested, your mind wandering, difficulty making decisions, craving caffeine, sexual dysfunction. Unconsciously you will try to compensate by avoiding stressful situations, drinking coffee to give you energy and drinking alcohol to bring you down...

Dopamine is a crucially important brain neurotransmitter. Deficiencies or imbalances can be diagnosed by clinical symptoms and urine neurotransmitter evaluation."

This post has been edited by Herald: Oct 15 2009, 02:51 AM

Hi again Data

Something occured to me last night after considering again your comment here which was on one of your previous posts

[quote]BTW, I take l-Tyrosine daily [/unquote]

I wondered if your Pdoc knows which, and all, the supplements you are taking and what answer she/he would give if asked "Could all these supplements be causing the symptoms I am having?"

Thanks for the replies and advice PRT and Herald.
That's what I thought. Maybe something has changed since my last blood test. Or maybe my internist, who evaluated the blood work, was too busy looking at my cholesterol numbers, which most gp's seem obsessed with.
Provigil is supposedly a novel kind of stimulant that does not have as many side effects or the abuse potential of classic stimulants like amphetamine. It's described as a "walefullness-promoting-agent," and is indicated for narcolepsy, among a few other things. The wikipedia article on provigil (generic name modafinil) is pretty good.

Herald, I agree with you about the importance of Dopamine. In fact, my understanding is that it is generally agreed upon, to varying degrees in the medical community, that Dopamine regulation plays a significant role in the Pathophysiology of depression and other disorders like Schizophrenia.

This is an interesting idea. I remember reading something similar. However, I also remember reading that one of the ways SSRI's are supposed to work is by an indirect positive affect on Dopamine regulation. Anyway, Dopamine release and synaptic expression, as induced by stimulants like Amphetamine and Cocaine, certainly seem to temporarily relieve unipolar depression and cause euphoria. The drugs were used as early "antidepressants" of sorts, at the turn of the last century. Unfortunately, the consequences of such a mechanism of action make these agents incompatible as medicines for depression.

Somehow, the new generation of antidepressants must be able to positively regulate Dopamine slowly and without desensitizing neurons. From my research, potential agents that work on the glutamate system, indirectly affecting Dopamine, seem promising.

Excluding the MAOI's, there is only one FDA indicated antidepressant that I am aware of that supposedly has a direct effect on DA. That's Wellbutrin. I do not like Wellbutrin, and although it really seems to help people, I wager that its benefits are not mediated by Dopamine. I elaborated on this in my last post in this thread:
http://www.depressionforums.org/forums/Wel...cts-t33987.html

Having experienced bad unease and dysphoria on a higher dosage of Wellbutrin, I wouldn't be surprised if Wellbutrin causes Norepinephrine to "displace" Dopamine at certain common synapses. This is similar to what you mention about SSRI's.

DA deficiency, as you describe it seems to present itself clinically more as Parkinson's disease than depression. What's more, proponents of the DA theory of Schizophrenia believe that an excess DA in parts of the brain is responsible for at least some of its causes.
Dopamine is such a ubiquitous presence in the nervous system, and has such varying and seemingly paradoxical roles depending on which piece of anatomy you are dealing with (DA receptors are present in the emetic center of the brain!), that it may be too broad of a target for a medicine.

He does, and they should not be a problem. I periodically stop taking supplements to see if they cause any problems. The only mechanism that I can think of that the mild supplements I take could cause symptoms is through some kind of enzyme inhibition, etc in relation to RX meds.