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Hello Comrades,

I've been taking Sertraline (50mg daily) for 9 months now.
Reason for taking Sertraline: Depression & SAD. Maybe some GAD.

So Sertraline treats my baseline anxiety quite well, also got rid of digestion problems, but I am struggling with side effects:

  • Motor restlessness, agitation. I've always been quite "hyperactive", but Sertraline has worsened it by a good amount. I cannot sit still, I feel I have to walk, to pace. I move my fingers and toes to "release" some of the energy. Also lots of fidgeting, rocking back and forth. I have the urge to crawl out of my skin.
    _
  • Indifference, amotivation, apathy, lethargy. I get less things done on Sertraline than before Sertraline. Just want to sit around and do nothing. It is really disconcerting, because things would happen like a major car malfunction or someone f*ck*ng me over and I'd be thinking "this SHOULD piss me off, but, meh.. whatever.."! I've been doing some reading & research and there is the hypothesis that SSRI-induced-stimulation of 5HT2C & 5HT2A receptors dampens the dopaminergic transmission in the prefrontal cortex thus causing these specific SSRI side effects. Antagonism / Inverse Agonism of these receptors should theoretically resolve the problem. What medications do antagonize / inverse agonize these receptors? Are there any other reliable theories on what is causing this? And what could help?
    _
  • Sleep disturbances, f*ck*d up sleep cycle, crappy sleep. Falling asleep is difficult, shallow sleep, waking up a lot in the night => daytime fatigue. (This week I've been sleeping a lot, maybe because the body wants to compensate for last months's bad sleep?)
    _
  • Heat intolerance + hot flashes. My entire life I've been loving warmth and heat. I was the guy who could sit at the top row in the sauna for 20min @ 100°C (212 °F), but right now I cannot even stand a mild summer. And I have been getting hot flashes lasting between 10-15 mins several times a day (I am a 29 year old male, so pretty sure it is not menopause related)
    _
  • I also lost quite a bit of weight, partially due to loss of appetite, but also due to increased metabolic rate. My appetite is back to normal, but I am still not gaining any weight. BMI 20 right now.
    _
  • Palpitations (BUM BUM BUM BUM. BUM . . . BUM . . . BUM)
    _
  • mild headaches and "pressure" in my neck. Nothing bad, but very annoying in the mid and long term.

Now I don't know what to do. I need some meds with "less" side effects. I haven't tried any combination of medications yet. To my dismay my doc prefers the SSRI merry go around aka SSRI carousel. I found a new psychiatrist and I will have a first appointment in about a month, but I don't know what to suggest to him. Has anybody some experience with a similar situation? Which antidepressant would be suitable for me? If there is someone who had the same problem and found some solution: please write me. Thank you. Greetings from Germany!
 

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Welcome to CB! Thanks for the detailed post. As far as what new med to try (that's between you & your pdoc) also, like we always say here: YMMV (your mileage may very) Meds have different side effects for everyone. That being said, I think the side effects you mention are all very very common with most antidepressants and SSRIs) Each med may hit your brain in a slightly different way though, so I imagine that is why pdocs do the carousel.

Often the side effects you've mentioned go away - but that usually happens within the first 2 months, since it's been 9 months (and the above side effects are really bothering you, and intolerable - and if you feel little benefit), it may definitely be time to try a different one. Each med may have some of the common side effects you mention - but to a different degree (like Celexa for example, may cause less agitation/motor restlessness than Zoloft). So it's a bit of a weighing out what your priority is and experimenting a bit. It's a long process sometimes!

For me, SSRIs had the exact same effects you mention (including sexual dysfunction). I find SNRIs (Cymbalta and Effexor) to be better, in some regards and I have felt noticeable benefit in my mood since starting, so I am willing to compromise some comfort at the moment for more emotional stability.There are also "tweaks" in your combo - for example, I found a real apathy & lack of motivation/focus on A/D's so my pdoc was willing to add a stimulant (ritalin) which has been helpful to eliminate that unwanted side effect.

There are also many other catagories of meds (mood stabilizers, antipsychotics, Wellbutrin, etc) that may not give you the above side effects. I found Lamictal to be excellent in that regard, once I titrated to the correct dose, I only had very very minor side effect so that has been a good part of my cocktail. Good luck to you.

Edited by Blahblah
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Maybe you don't need a specific suggestion, just to explain your history and make sure he knows about the side effects u have and then let him think about it...that's what we pay them for after all hahah

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On 2/5/2018 at 6:16 AM, maxor said:

Hello Comrades,

I've been taking Sertraline (50mg daily) for 9 months now.
Reason for taking Sertraline: Depression & SAD. Maybe some GAD.

So Sertraline treats my baseline anxiety quite well, also got rid of digestion problems, but I am struggling with side effects:

  • Motor restlessness, agitation. I've always been quite "hyperactive", but Sertraline has worsened it by a good amount. I cannot sit still, I feel I have to walk, to pace. I move my fingers and toes to "release" some of the energy. Also lots of fidgeting, rocking back and forth. I have the urge to crawl out of my skin.
    _

Usually restlessness like you're describing happens to patients who take antipsychotics, which reduce activation of dopamine receptors. The akathisia results from the subsequent imbalance in acetylcholine/dopamine neurotransmission (i.e. Dopamine activity is reduced but cholinergic activity is unchanged). The way this is usually resolved is by also blocking cholinergic receptors as well which is what medications like Cogentin (benztropine) do. Additionally, antipsychotics that are less known for motor side effects like you're describing are generally moderate anticholinergics themselves so they basically automatically balance their own anti-dopaminergic activity.

However in this case, sertraline is not just a serotonin reuptake inhibitor but a dopamine reuptake inhibitor as well. In fact from an affinity standpoint, sertraline has a higher affinity for the dopamine transporter than even bupropion, but maximal doses of sertraline (~200mg) are required to achieve the same effect on the dopamine transporter as therapeutic doses of bupropion.

So you see that both overactivation and underactivation of the dopamine system can result in motor restlessness. In this particular case, though, it sounds like you may find relief with an antipsychotic that may tone down some of sertraline's dopamine activity and make it a little less activating. Will follow up on this more further down in the post.

On 2/5/2018 at 6:16 AM, maxor said:
  • Indifference, amotivation, apathy, lethargy. I get less things done on Sertraline than before Sertraline. Just want to sit around and do nothing. It is really disconcerting, because things would happen like a major car malfunction or someone f*ck*ng me over and I'd be thinking "this SHOULD piss me off, but, meh.. whatever.."! I've been doing some reading & research and there is the hypothesis that SSRI-induced-stimulation of 5HT2C & 5HT2A receptors dampens the dopaminergic transmission in the prefrontal cortex thus causing these specific SSRI side effects. Antagonism / Inverse Agonism of these receptors should theoretically resolve the problem. What medications do antagonize / inverse agonize these receptors? Are there any other reliable theories on what is causing this? And what could help?

It would seem paradoxical for sertraline. The fact that it increases dopamine activity by inhibiting the transporter should theoretically mean that sertraline would be effective in treating the symptoms that you are describing, but time and again I read other people's experiences and reference my own experience with sertraline (1 stint of 50mg for like 3 years and another for about 6-9 months), I felt like a robot usually, like I was experiencing life and not really living it and would sometimes feel like someone else was controlling my body and I was just going through the motions.

In this regard, bupropion is actually more helpful. Having experienced most of the SSRIs (the truly selective ones, not including Viibryd and Trintellix, and not including any SNRIs), bupropion actually got me MORE in touch with my emotions and pleasure. It improved my sex drive along with my motivation and interest in things. But it also made me snappy and quicker to anger. I also had a pretty steady anxiety level going all the time. I ended up going off of it because of the anxiety. However, paradoxically again, some people with anxiety find that bupropion actually helps them.

This being said, if you do have anxiety and SSRIs do effectively address your anxiety but leave you feeling apathetic/anhedonic, then augmenting with bupropion may improve your situation. In particular the escitalopram/bupropion combo is an oft-used tool in the psych's toolbox because escitalopram does a really good job for anxious depression but causes weight gain, sexual dysfunction, and general lack of motivation as well as apathy. Bupropion fairly effectively cancels out these effects in even low doses. The idea being that escitalopram is arguably the MOST selective SSRI in that it doesn't touch other monoamine transporters like how sertraline touches dopamine, and it generally doesn't bind to many receptors either. Because activation of several serotonin receptors can actually reduce dopamine levels in the brain, bupropion can help to counteract that.

To answer your question about the 5HT2 receptors, your understanding is correct. Blockade/antagonism of 5HT2A causes downstream release of dopamine in the nigrostriatum and in some other areas as well. This is an important property to the 2nd gen atypical antipsychotics because this effect reduces the incidence of akathisia/restlessness caused by dopamine receptor blocking. Antipsychotics both old and new are not very specific to the brain regions where they operate. Blocking D2 receptors in the mesocortical/mesolimbic pathway reduces psychosis, which is great. Blocking them in the nigrotriatum causes restlessness.....which isn't lol. So the idea would be to apply a general across-the-board blockade of D2 receptors and also block 5HT2A to increase dopamine release in the nigrastriatum to compensate and prevent motor side effects.

HOWEVER, 5HT2C is a trickier subject and is a receptor better left alone unless you plan on activating it. That particular receptor subtype is associated with feeling full. When you block it, it takes more to feel full after eating. The feeling that many describe as "eating anything that isn't nailed down" could be caused by 5HT2C antagonism. Activation of this receptor on the other hand would effectively reduce your appetite.

On 2/5/2018 at 6:16 AM, maxor said:
  • Sleep disturbances, f*ck*d up sleep cycle, crappy sleep. Falling asleep is difficult, shallow sleep, waking up a lot in the night => daytime fatigue. (This week I've been sleeping a lot, maybe because the body wants to compensate for last months's bad sleep?)

Sertraline is a pretty bad one for insomnia and bupropion definitely won't help. My only recommendation here is that you take sertraline in the morning. Combining it with a low dose of an atypical antipsychotic will most likely be very helpful particularly ones that have a strong antagonist effect at 5HT2A, and 5HT7. The latter is important for circadian rhythm. Blocking 5HT7 can also reduce sexual dysfunction from SSRIs and has pro-cognitive effects.

On 2/5/2018 at 6:16 AM, maxor said:
  • Heat intolerance + hot flashes. My entire life I've been loving warmth and heat. I was the guy who could sit at the top row in the sauna for 20min @ 100°C (212 °F), but right now I cannot even stand a mild summer. And I have been getting hot flashes lasting between 10-15 mins several times a day (I am a 29 year old male, so pretty sure it is not menopause related.

Could be dopamine related. Not sure how to help with this one though.

On 2/5/2018 at 6:16 AM, maxor said:
  • I also lost quite a bit of weight, partially due to loss of appetite, but also due to increased metabolic rate. My appetite is back to normal, but I am still not gaining any weight. BMI 20 right now.

If you need to put on some weight an anxiety is a core problem for you then paroxetine or escitalopram would be good options. Both will cause some weight gain and are the go-to's for anxious depression.

On 2/5/2018 at 6:16 AM, maxor said:
  • Palpitations (BUM BUM BUM BUM. BUM . . . BUM . . . BUM

Dopamine again. Might have a way to address this below.

On 2/5/2018 at 6:16 AM, maxor said:
  • mild headaches and "pressure" in my neck. Nothing bad, but very annoying in the mid and long term.

The dopamine effect could be causing some tension.

On 2/5/2018 at 6:16 AM, maxor said:

Now I don't know what to do. I need some meds with "less" side effects. I haven't tried any combination of medications yet. To my dismay my doc prefers the SSRI merry go around aka SSRI carousel. I found a new psychiatrist and I will have a first appointment in about a month, but I don't know what to suggest to him. Has anybody some experience with a similar situation? Which antidepressant would be suitable for me? If there is someone who had the same problem and found some solution: please write me. Thank you. Greetings from Germany!
 

As I said above, paroxetine and citalopram/escitalopram are the go-to's for anxious depression. Augmenting with bupropion is generally the go-to to fight SSRI-induced side effects, particularly sexual dysfunction and anhedonia/apathy. Some notes on this though. Part of the usefulness in combining escitalopram and bupropion is that bupropion inhibits CYP2D6 and increases escitalopram's blood levels increasing effectiveness (and possibly side effects as well). However, the combination of paroxetine and bupropion is less often used because paroxetine is a strong inhibitor of CYP2B6 which metabolizes bupropion. Therefore, you would have to take the minimum dose of bupropion to reduce the risk of seizures and you would have to be very careful about increasing paroxetine. It has risk but could be robustly effective.

Alternatively, I have seen many people do something more heroic combining bupropion with an antipsychotic, specifically dopamine partial agonists to augment bupropion's effects. Like a combo of bupropion/aripiprazole. This would be both settling and activating at the same time, which some people find disconcerting. However, the newer successor to aripiprazole is brexpiprazole (Rexulti). I take it now and find it to be FAR better than aripiprazole. It isn't so agitating. It has had a really positive effect on my anxiety, and I have wondered what it would be like to go back on bupropion now that I'm taking it, but at this point I prefer Vyvanse for increasing dopamine.

Brexpiprazole is 30-50% activating at the dopamine receptors where aripiprazole is 60-70% activating. Brexpiprazole's lower amount of activation at those receptors as well as a stronger blocking effect at adrenaline receptors than aripiprazole basically makes brexpiprazole one of the best antipsychotics that I've tried. I didn't respond well to aripiprazole at all. Made me very agitated and restless.

The side effects you describe indicate to me that maybe you're a bit over-stimulated. Stimulation isn't bad as long as it's compensated for with something calming. I find Trintellix and Vyvanse to both be very activating medications. Taking Depakote and Rexulti allows me to keep my anxiety and mania in check.

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