Duloxetine - what to combine with it?

[amskray]

Hi everybody.  I am taking Duloxetine and am in a mood slump right now combined with increased anxiety.  I don't want to up the dose bc that makes me sleepy and lethargic. Can anyone give me ideas of meds that could work with duloxetine? Maybe only temporarily until winter's over? 

I'dappreciate any ideas! Thanks!

[dumbdoo]

Hello there,

I am taking Duloxetine also (120mg for 10 months now), and I have severe mood swings (cycling between feeling normal and feeling depressed), intrusive thoughts and increased anxiety.

Quetiapine XR (300mg), when added to the mix, made my depression a hundred times worse, so I wouldn't recommend it to anyone. I also tried Abilify (up to 5mg), which worked fine in the beginning (raised my energy level and my mood), but suddenly stopped to help me after two months. It is at least worth a shot.

[Blahblah]

@amskray Is there a particular symptom that is not being helped by the Duloxetine?

Abilify is often used as an add-on. It didn't help me particularly, but it's worth trying. I take Ritalin as an add-on to my antidepressant because along with my depression, I still deal with severe apathy/low motivation/lethargy symptoms.

[amskray]

 

3 hours ago, Blahblah said:

Is there a particular symptom that is not being helped by the Duloxetine?

Just the usual...feeling like life has no meaning, like people don't like me,anxiety about my kids...low energy, lack of motivation. 

[CeremonyNewOrder]

I take Clozapine, lithium, and Adderall with my cymbalta and it has been a miracle combination for me.

[amskray]

@Blahblah how are the doctors in France about prescribing Ritalin off label?

@mikl_pls If you see this would you be willing to comment? You are very knowledgeable about meds. I have an appointment with my psychiatrist on Thursday and I want to suggest something to him. I live in Germany and they tend to prescribe meds very conservatively so it may be an uphill battle. 

[Blahblah]

@amskray Stimulants like Ritalin are extremely controlled here (and taboo as an add-on or off-label), probably also difficult to get in Germany. Here, they only want to prescribe it in severe cases for kids with clear-cut ADHD diagnosis and hyperactivity. (BTW they would never Rx it if there's any indication you are Bipolar) I was on Ritalin for a short trial previously in the US (with benefit) so they took that into consideration and I've had ADD/inattentive symptoms along with my depression. I was referred to a hospital pdoc, because I could only get it through a direct hospital prescription, not just any pdoc here. There are definitely more hoops to jump through, but worth trying if you are resistant to other meds or have ADD-related symptoms.

[mikl_pls]

@amskray I think everyone has mentioned pretty much everything. The antidepressant Remeron goes well with SNRIs, but you have to watch out for sedation and weight gain. Higher doses are better as an antidepressant.

I am doing well with a combo of Abilify 15 mg, Cymbalta 120 mg, Dexedrine 30 mg, plus other meds like Trileptal 1200 mg, and titrating up on Topamax (Trokendi XR). But the core I think are the Abilify, Cymbalta, and Dexedrine. I was on this combo two summers ago when a bout of anhedonia hit me like a ton of bricks. I could tell it was doing something to try to get me out of it, but that's more than I can say about anything else I tried.

[amskray]

Okay. Thanks everyone! So...the summary is:

1)Ritalin (pretty sure he won't be willing to try it )

2)Abilify  (which scares me bc it's an antipsychotic which just sounds scary to me)

3)Remeron (i don't know anything about it )

 

[amskray]

What about wellbutrin?

 

[dumbdoo]

23 minutes ago, amskray said:

3)Remeron (i don't know anything about it )

It was on my schedule in 2014, and worked reasonably well, but I've put on weight easily (and I mean "a lot of weight") in that time and had to deal with serious water retention. Both are very common side effects of Mirtazapine. But I don't want to scare you, I know a bunch of people who are doing well with Mirtazapine. Plus it's efficiency is well backed by research I think.

 

[Lady Krazy Kat]

How about lamictal? When I used to take Zoloft and it didn’t quite work, I added lamictal and the combo helped tremendously. Don’t have be bipolar for lamictal to work. 

If you just need it for winter, Wellbutrin is approved for seasonal depression.

 

Edited December 13, 2017 by Lady Krazy Kat

[amskray]

I'll look into Lamictal.  

Thanks for all the ideas everyone! 

[Gearhead]

I do well on lamotrigine an duloxetine.

[BrianOCD]

On 12/12/2017 at 1:57 PM, amskray said:

What about wellbutrin?

 

I'm on Wellbutrin, just went up today to 300mg

I can feel it helping a little bit but it's pretty early.

My depression hasn't quite lifted yet either, and you get that jittery/anxious feeling too that I hate from antidepressants...

But I've been told Wellbutrin is remarkably safe, and can be added on and taken away easily so it might work as an add-on for ya.

Edited December 14, 2017 by BrianOCD

[amskray]

The doctor prescribed a very small dose of venlafaxine to go with my duloxetine. Any thoughts about that?

[mikl_pls]

7 hours ago, amskray said:

The doctor prescribed a very small dose of venlafaxine to go with my duloxetine. Any thoughts about that?

That's.... odd to me... A small dose of venlafaxine only acts on serotonin. Never really heard of taking two SNRIs concomitantly unless you're cross-tapering between one to another.

[amskray]

23 minutes ago, mikl_pls said:

small dose of venlafaxine only acts on serotonin. 

@mikl_plswould a higher dose  make any more sense or do you think it's just a goofy combination? 

 

[Iceberg]

Hmmm that's an interesting strategy 

[amskray]

Man...I really am not feeling very confident about this doctor. 

Can anyone think of ANY good reason to prescribe this combination? 

[Iceberg]

Well one possibility is this has worked for that dr before with other patients 

[mikl_pls]

On 12/14/2017 at 2:37 PM, amskray said:

 

A higher dose of venlafaxine would work on both serotonin and norepinephrine, but Cymbalta is already doing that, and this could be achieved by increasing the Cymbalta dose (unless you're maxed out at 120 mg...).

On 12/14/2017 at 3:01 PM, amskray said:

Man...I really am not feeling very confident about this doctor. 

Can anyone think of ANY good reason to prescribe this combination? 

Not really, unless...

On 12/15/2017 at 11:57 AM, Iceberg said:

Well one possibility is this has worked for that dr before with other patients 

...unless this is the case.

[amskray]

Well,I don't really know what to do.  I think I am going to get through Christmas with Duloxetine supplemented with alprazolam if I can't tolerate the anxiety.  Then I  will see...

[BrianOCD]

On 12/18/2017 at 4:19 AM, amskray said:

Well,I don't really know what to do.  I think I am going to get through Christmas with Duloxetine supplemented with alprazolam if I can't tolerate the anxiety.  Then I  will see...

I remember when I was still feeling depressed on 300mg of effexor my PDoc added Deplin which helped a lot, seemed to make the effexor work better.

[mikl_pls]

3 hours ago, BrianOCD said:

I remember when I was still feeling depressed on 300mg of effexor my PDoc added Deplin which helped a lot, seemed to make the effexor work better.

I can second Deplin. I have the MTHFR genetic mutations and Deplin helped immensely. Then my insurance revoked coverage of it...  There are "semi-pseudo-equivalent" products out there, but otherwise, if your insurance won't pay for it, you can get it directly from the pharmaceutical company but for a high dollar price.

[dumbdoo]

On 18.12.2017 at 11:19 AM, amskray said:

Well,I don't really know what to do.  I think I am going to get through Christmas with Duloxetine supplemented with alprazolam if I can't tolerate the anxiety.  Then I  will see...

Hi amskray,

since we both take duloxetine and still have harsh times with relapsing symptoms of depression, I want to give you a short update on my situation. My pdoc put me also on Valdoxan/Agomelatine, a 5ht2c antagonist, which makes perfect sense to me from a pharmacological point of view. It is expected to enhance the release of dopamine (and NE) in different parts of the brain. On the other hand the SSRIs mechanism of action on the 5ht2c receptors inhibits the release of dopamine, so this could possibly contribute to our feelings of low mood, tiredness and so on. Maybe agomelatine is another option you could discuss with your pdoc?

Edited December 20, 2017 by dumbdoo

[protectmepls]

3 hours ago, dumbdoo said:

Hi amskray,

since we both take duloxetine and still have harsh times with relapsing symptoms of depression, I want to give you a short update on my situation. My pdoc put me also on Valdoxan/Agomelatine, a 5ht2c antagonist, which makes perfect sense to me from a pharmacological point of view. It is expected to enhance the release of dopamine (and NE) in different parts of the brain. On the other hand the SSRIs mechanism of action on the 5ht2c receptors inhibits the release of dopamine, so this could possibly contribute to our feelings of low mood, tiredness and so on. Maybe agomelatine is another option you could discuss with your pdoc?

What dose of Duloxetine and Agomelatine are you taking? Is it safe to take both?

[dumbdoo]

3 hours ago, cryinginmoscow said:

What dose of Duloxetine and Agomelatine are you taking? Is it safe to take both?

My doc put me on 25mg agomelatine and I’m still taking 120mg duloxetine. In theory they are both safe together, because they have completely different mechanisms of action. Unfortunately agomelatine can be harmful to your liver, so you have to get your liver checked on a regular basis.

[amskray]

Hi. I haven't been on here in awhile.  Things got better and now they're worse. I am going to make an appointment with the doctor and give him these ideas. 

Thanks, everybody! 

[Blahblah]

Hi @amskray Sorry to hear things are going downhill. I've been maintaining I suppose, still with deep dips every month and a whole lot of anhedonia. I can barely get myself to do anything - even "pleasant" things. I just want to lay around in my pjs, unshowered and I'm spending too much time online again, avoiding chores. I'm doing the bare minimum.

Are you just taking Cymbalta? Will you go off or add something else? I've been on Effexor about 4-5 months and not having a big difference. I really don't want to take more than 3-4 meds per day. I'm so over this.

[amskray]

 @Blahblah    I just take Duloxetine.  I want to add something to it. When I tried to switch last summer I had horrible withdrawal symptoms and ended up in the hospital. So I want to avoid that!

I've narrowed it down to 2 meds that I will ask my doctor about:Agomelatine and Bupropion. 

[Blahblah]

What is Agomelatine? Never heard of that. Is it everywhere in Europe? Good luck with Buproprion. I did 2 separate trials of it, and luckily it had no side effects, but I went over 300mg and it didn't do anything at all. Bizarre because most meds have some kind of side effect!

[browri]

On 12/20/2017 at 7:31 AM, dumbdoo said:

On the other hand the SSRIs mechanism of action on the 5ht2c receptors inhibits the release of dopamine, so this could possibly contribute to our feelings of low mood, tiredness and so on.

@amskray He makes a good point, when you take duloxetine, it indiscriminately increases serotonin and norepinephrine in the synapse without directly modulating any receptors. Activation of serotonin receptors can be associated with a decrease in dopamine release, among other neurotransmitters. Blocking them can increase release, keeping in mind that it is different from subtype to subtype. For example, blocking 5HT₃ receptors causes massive downstream release of norepinephrine, dopamine, histamine, acetylcholine, and glutamate as well as inhibiting GABA firing, and it causes upstream release of more serotonin. On the flip-side, activation of 5HT_1A receptors causes downstream release of dopamine while also desensitizing the receptor and accelerating the time-to-effect of the antidepressant. So theoretically a combination of Lexapro+Zofran+Buspar would be FAR more effective FAR more quickly than Lexapro alone.

One of the things you mentioned in your first post was prominent anxiety combined with fatigue/lethargy. This could mean too much norepinephrine activity. Your doctor could address this by going down on duloxetine (and potentially make your depression worse by also reducing serotonin activity), or he could add Rexulti (brexpiprazole). It has some pretty potent blockade of adrenergic receptors that might help to quell that tense, nervous feeling. It's helped a lot for me. In fact my current combo of Depakote+Trintellix+Rexulti+Vyvanse is my absolute favorite combo of meds I've taken and is now my signature/go-to. However, I would even recommend a basic combination of Trintellix+Rexulti to start based on my own experience. Trintellix is generally stimulating at all doses for me, Rexulti is more sedating at lower doses and became more stimulating after 0.75mg+. I'm at 1mg at the time of this writing. 10mg of Trintellix. However I go up on the Trintellix in the Fall/Winter to 20mg and down on the Rexulti to 0.5mg to address it in more of a seasonal affective kind of way.

One of the things that took me aback was that your doctor prescribed venlafaxine on top of duloxetine. Like it was said, it must have worked for him in other patients, but at this point we do know that introducing two different compounds with an identical mechanism of action will essentially "cap" out in that it doesn't have a synergistic effect. Antidepressant effect is usually correlated to the transporter "occupancy" meaning how much of your SERT is "occupied" by a medication or "bound" to it. For antidepressant effect, most SSRIs and SNRIs need to be around 60-85% occupancy. However, if you've already achieved 85% occupancy with one antidepressant, adding another doesn't have an additive effect from a biological perspective the way you would expect. This is why once you get to 85-90% occupancy, if there are still prominent mood symptoms, you need to add in other targets to continue increasing serotonin levels. Proof that this is the case can be seen by the effect of 5mg and 10mg of Trintellix having a SERT occupancy of 40-45% and 55-60%, respectively, yet still managing to increase serotonin levels throughout the body more efficiently than first-gen SSRIs/SNRIs and also having an antidepressant effect where other ADs wouldn't having much of an effect at those occupancy levels.

[amskray]

So....I did go to the doctor and I presented him with my research. He agreed to prescribe Agomelatine.  I just need to get a liver test . I have put the whole thing on hold bc I am making a last minute trip to the US to visit my mother.  She has dementia and has really started deteriorating in the past few weeks.  Very sad. 

On the other hand, I am feeling good,oddly enough.  I finally found 2 therapists that I like after searching fora long time.  Now I actually have to choose!  For awhile I couldn't find any!

[amskray]

@Blahblah.:Agomelatine is an atypical antidepressant which has few of the typical side effects  (no weight gain). It can cause liver problems.  It can help with the quality of sleep.