Needing suggestions...

[brianjoy]

I wanted to cross post this here from the depression forum, I think it's better fitting here.  Hopefully that's okay.

 

I've struggled with anxiety, depression, social anxiety, obsessive thinking most of my adult life with some pretty severe depressive episodes in there.

I was on prozac for about 8 years, then pristiq for 1 year until I had my worst depressive episode ever (situation triggered) and went to a psychiatrist that tried all sorts of different medicines for his guess at what my condition was (said I was bipolar, schizo, psychotic depression and threw many meds at me I can't even remember). He was a big pusher of CBT, and since that didn't work with pristiq he thought it was more than just depression. I didn't agree with his diagnosis of any of those conditions and still don't. Anyway, nothing helped, he moved his practice and I self tapered myself off all the medications with no change in mood. About six months later I was depression free for about 3 years.

Then came my episode that was different from all the others, it wasn't triggered by a situation. I just slowly sank into depression and social anxiety--went on effexor 150mg with my family doctor and that lifted it for the next 3 years.

My current episode was sparked from a break up, which caused me to get mild panic attacks and situational depression, which now has lead me into a pretty deep and dark severe depression (staying in bed every second I possible can before I have to get up and face the world). Also pretty bad social anxiety, but that was mildly present before the breakup.

My family doctor up'd the effexor to 225mg and tried hydroxyzine and buspar with no effect.

Then we added xanax .5mg up to three times daily ( I never take that much, usually just one .5mg midday or none at all). That helped enormously with the panic attacks and anxiety.  I do think the next day the depression does seem to be worse though.

With the depression still pretty heavy, we added quetapine 50mg at night. I tried it for a month and some of the depression lifted but I was left in a haze and terrible drowsiness, especially in the morning. He pushed that we try it a little longer and if the drowsiness didn't go away, call in for something else.

I called in for permission to go off it and not trying anything else for a while, but the next two weeks left me in bed all day and when I was up, I was in crying spells and feeling miserable. Absolutely dreading doing anything outside of my house and being in misery while there. It's been pretty rough, but the crying spells have lifted and the depression isn't as bad now.

At my last visit, my doctor had talked about adding Wellbrutrin, but was worried it would worsen the anxiety. I mentioned adding Remeron; he wasn't very familiar with it, but said we could try it if I like. He's open to my suggestions so that's really helpful I think.  After doing some research on Remeron, it seems to also cause drowsiness so I may try and avoid it.

I have an appointment scheduled for this Friday.  What are some recommendations I can suggest?

I've been in therapy ever since the breakup, been trying meetup and other social activities because I know being social does help with my own depression, even though it takes enormous willpower to do it. I've tried to add exercise but can't find the will power to continue it.  With that said, I do spend a lot of time doing absolutely nothing and avoiding the world.  A friend popped over unexpected and that sent me into an anxiety attack (I didn't answer the door) but they came back later after the xanax calmed me down I had the house cleaned up.

Thank you so much.

[argh]

The drowsiness from remeron appears to be dose dependent. So far, for me at least, there is drowsiness at both 15 and 30mg, but much less so at 30mg.

Wellbutrin didn't make me anxious. Calmed me down actually, however there are many reports that it does increase anxiety.

Gabapentin perhaps? Also anecdotal, but calmed me down quite a bit. The evidence isn't quite there, however

"Some evidence suggests that gabapentin possesses anxiolytic properties, though few data exist for patients with generalized anxiety disorder (GAD). Gabapentin has been examined as therapy for treating social phobia, panic and somatoform disorders, anxiety in breast cancer survivors, and surgery-associated anxiety with mixed results."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732322/

so grain of salt of course.

[Iceberg]

Gabapentin might be a good idea...also maybe a long acting benzo instead of Xanax for temporary round the clock coverage 

[CeremonyNewOrder]

Maybe try a med that is outside the antidepressant category but has antidepressant properties. Sometimes a low dose antipsychotic can help and people who aren't bipolar can use lithium and lamictal.

[mikl_pls]

I would maybe try asking about a different atypical antipsychotic than quetiapine (Seroquel), like ziprasidone (Geodon) or aripiprazole (Abilify) (if you haven't already taken it) especially, even Rexulti (brexpiprazole) or Vraylar (cariprazine) (some of the newest ones), and I second Lamictal (which has a long and strict titration schedule).

You could also always increase your Effexor XR to 300-375 mg.

As has already been said, the drowsiness from Remeron is dose-dependent. 15 mg will make you much more drowsy than 30-45 mg will, but 30-45 mg will still make you drowsy, just not as much. But it will also put quite a lot of weight on you if that's also of concern.

You could also augment the Effexor with a secondary amine tricyclic like nortriptyline (Pamelor), desipramine (Norpramin), or protriptyline (Vivactil), the latter two of which are stimulating (but not necessarily anxiety-provoking). These would boost the norepinephrine reuptake inhibition of Effexor XR and thus boost the antidepressant effect.

So just a quick list:

• Augment with Abilify, Geodon, Rexulti, or Vraylar (or some other atypical antipsychotic, but not Zyprexa, which causes type 2 diabetes)
• Augment with Lamictal
• Increase Effexor XR dose to 300-375 mg
• Augment with Remeron 30-45 mg
• Augment with Pamelor, Norpramin, or Vivactil

You can ask your doctor to do any number of these one at a time or several at once, but probably best to do one at a time because you want to know what is doing what, and what is working, etc.

Low doses of Geodon are stimulating (20-40 mg 2x/day), while high doses are sedating (60-80 mg 2x/day). It must be taken with 500 calories per dose. The same goes with Abilify, generally, except it can be taken with or without food (however, I'm on 20 mg and still being stimulated by it).

Lamictal can also be stimulating, especially when first starting up, so you might actually get a bit anxious when starting up on it, so you might need those Xanax. But that will go away once you get settled around 100-200 mg/day. The titration schedule, as per the PI sheet of Lamictal, for Lamictal for bipolar patients (which could also apply for unipolar depressed patients too, I suppose) who are not taking carbamazepine, phenytoin, phenytoin, phenobarbital primidone, or valproate, is:

• 25 mg daily x2 weeks
• 50 mg daily x2 weeks
• 100 mg daily x1 week
• 200 mg daily target dose

Usually, it's divided into two daily doses past 25 mg.

Vivactil is taken in divided doses in the day. Like 10 mg 3x/day for 30 mg.

I hope you get the relief you need!

[dtac]

Seroquel at 50mg is good for sleep, and not much else. It really doesn't affect much other than H1 until you get into the 150-200mg range. I would either titrate it up to 200mg or ditch it entirely, since you're not having problems sleeping. I took Remeron for about 2 years, started at 15mg and titrated up to 45mg over the time period. It was sedating and caused me to gain weight as well due to its' nature of blockading H1 as well. It did help my depression in bursts, but ultimately was a failure. Your body builds some tolerance to histamine sedation over time, but I found it sedating at all doses.

Perhaps Klonopin would be more useful for managing the anxiety? Starting once a day at a low dose may provide some more constant relief than Xanax, and if you stay low enough it's usually not sedating either.

Since you're on an SNRI, your choices are adding a mood stabilizer like Lamictal or an antipsychotic, like perhaps Abilify or Rexulti. Both of the latter drugs are approved as adjuncts for MDD (not saying it's your diagnosis) and can be stimulating. I think if you're already depressed and sleeping a ton and having problems getting out of bed, adding an AD that is sedating is just going to compound the problem (speaking from experience.) You could go the TCA or MAOI route, but I would put those as secondary choices due to the prevalence of side effects (not that APs are great drugs, but the newest ones are much better.)

I found Abilify extremely activating -- to the point that I couldn't sleep at doses above 2mg, but I'm an extreme case. I've been on Rexulti for almost 2 years now, and it has killed 90% of my depression --- better than any other single med -- and has practically zero side effects for me. 

[browri]

On 3/14/2018 at 2:55 PM, mikl_pls said:

I would maybe try asking about a different atypical antipsychotic than quetiapine (Seroquel), like ziprasidone (Geodon) or aripiprazole (Abilify) (if you haven't already taken it) especially, even Rexulti (brexpiprazole) or Vraylar (cariprazine) (some of the newest ones), and I second Lamictal (which has a long and strict titration schedule).

@brianjoy The sedation from Seroquel starts to lessen after 200mg. Additionally, sometimes switching to the XR can make a big difference in sedation according to a lot of people's reports. It may also improve the weight gain problem for some people. @mikl_pls's suggestions above are definitely good ones. I have personally never tried ziprasidone, but he has and it's definitely going to be more activating at the lower doses and sedating at the higher ones. Only frustrating thing is that every time you take it, you have to take it with 500 calories, and it has to be taken twice a day. Although you can take larger doses all at once at night.

Abilify will definitely be activating, although for some that starts to smooth out after getting to 10-15mg. I personally never made it past 7.5mg. I found it to be too agitating. Rexulti, however, has been awesome. Don't let anyone tell you that Rexulti is pharmaceutical evergreening and that it's just "the new Abilify". While it was fully intended to replace Abilify, it is definitely a different medication. I actually find it to be more sedating, and I take it at night, but it doesn't make me feel tired during the day and I think it provides a little bit of extra stimulation to the Vyvanse. Since starting Rexulti, I've gone from taking Xanax 2-3 times a week to taking it once a month or less. And it has a very strong antidepressant effect. Works really well with the Trintellix.

Vraylar would definitely be more stimulating like Abilify. Although I've heard plenty of people find it makes them feel tired in the beginning even if they take it in the morning. So your mileage may vary there.

Lamictal is also a great option for both bipolar and unipolar depression, although there are some that would disagree.

On 3/14/2018 at 2:55 PM, mikl_pls said:

You could also always increase your Effexor XR to 300-375 mg.

Could definitely work if you need more stimulation. Effexor starts to hit dopamine at these higher doses which might help to enervate you a bit.

On 3/14/2018 at 2:55 PM, mikl_pls said:

As has already been said, the drowsiness from Remeron is dose-dependent. 15 mg will make you much more drowsy than 30-45 mg will, but 30-45 mg will still make you drowsy, just not as much. But it will also put quite a lot of weight on you if that's also of concern.

Interestingly enough, the dose-dependence of Remeron's sedation could be fundamentally altered in the presence of Effexor if they are being taken together. Effexor, especially at 225mg, will have a fairly strong effect on norepinephrine reuptake inhibition. Remeron's blockade of adrenergic receptors should amplify this activity to make Effexor more stimulating. Even going along with the last suggestion, 300mg venlafaxine ER + 30mg mirtazapine would be one helluva combo.

On 3/14/2018 at 2:55 PM, mikl_pls said:

You could also augment the Effexor with a secondary amine tricyclic like nortriptyline (Pamelor), desipramine (Norpramin), or protriptyline (Vivactil), the latter two of which are stimulating (but not necessarily anxiety-provoking). These would boost the norepinephrine reuptake inhibition of Effexor XR and thus boost the antidepressant effect.

Also great options, although doctors are less receptive to augmentation of SSRI/SNRIs/SMSs with tricyclics because of serotonin syndrome. However, all of the above suggested tricyclics are actually not very serotonergic. nortriptyline is a metabolite of amitriptyline and while amitriptyline is regarded as one of the most serotonergic tricyclics, nortriptyline is quite the opposite, much more noradrenergic. Desipramine is the metabolite of imipramine and shares a similar relationship with its parent as nortriptyline does to amitriptyline. And protripyline is a different beast altogether in that it's the most dopaminergic. Low dose protriptyline would mean you wouldn't have to go to 300-375mg on Effexor to get the dopamine effects.

On 3/14/2018 at 2:55 PM, mikl_pls said:

So just a quick list:

• Augment with Abilify, Geodon, Rexulti, or Vraylar (or some other atypical antipsychotic, but not Zyprexa, which causes type 2 diabetes)
• Augment with Lamictal
• Increase Effexor XR dose to 300-375 mg
• Augment with Remeron 30-45 mg
• Augment with Pamelor, Norpramin, or Vivactil

You can ask your doctor to do any number of these one at a time or several at once, but probably best to do one at a time because you want to know what is doing what, and what is working, etc.

Low doses of Geodon are stimulating (20-40 mg 2x/day), while high doses are sedating (60-80 mg 2x/day). It must be taken with 500 calories per dose. The same goes with Abilify, generally, except it can be taken with or without food (however, I'm on 20 mg and still being stimulated by it).

Lamictal can also be stimulating, especially when first starting up, so you might actually get a bit anxious when starting up on it, so you might need those Xanax. But that will go away once you get settled around 100-200 mg/day. The titration schedule, as per the PI sheet of Lamictal, for Lamictal for bipolar patients (which could also apply for unipolar depressed patients too, I suppose) who are not taking carbamazepine, phenytoin, phenytoin, phenobarbital primidone, or valproate, is:

• 25 mg daily x2 weeks
• 50 mg daily x2 weeks
• 100 mg daily x1 week
• 200 mg daily target dose

Usually, it's divided into two daily doses past 25 mg.

Vivactil is taken in divided doses in the day. Like 10 mg 3x/day for 30 mg.

I hope you get the relief you need!

All of these are great suggestions, @brianjoy. So comparing their pros and cons is all that's really left.

Increasing the Effexor to 300-375mg will likely be the least intrusive as it's a medication you're already on and something your body is already mostly adjusted to. However, it isn't a very "complete" or "well-rounded" approach if you've been shown to be treatment-resistant historically and your condition has an array of symptoms ranging from depression (either situational or endogenous), to social anxiety, to obsessions. Effexor has shown to be one of the more effective antidepressants for treatment-resistant depression.....if it works for you. If it works partially, sometimes switching to Pristiq can make a difference.

Augmenting with Remeron is a very appealing combination because it has repeatedly demonstrated positive efficacy in clinical practice. Dr. Stephen Stahl calls Effexor+Remeron "California Rocket Fuel". Downsides would be sedation and weight gain. However, at least from Remeron's perspective, a lot of weight gain does come from an increased appetite. So with some discipline the includes a diet and exercise you may be able to avoid some of the weight gain. Additionally, the more potent adrenergic effects combined with Effexor at the top end may help to fend off some of that weight gain and sedation. It would really depend on whether or not Effexor on its own has caused you to gain or lose weight.

The other two augmenting options being tricyclics or Lamictal. I don't have any experience myself with tricyclics, so I can't comment much there except to say that pdocs will be more wary prescribing two antidepressants than they would be prescribing a combo of Effexor+Remeron or Effexor+Lamictal. Some pdocs, however, may be receptive, and if they're feeling adventurous, I would recommend that you go with it. The two downsides to Lamictal are that it takes a while to get titrated up and the titration itself can be a bit rocky. After increasing the dose, you may feel some anxiety, which may go away and you'll feel fine for a few days, then you might get depressed for a few days. After 1-2 weeks at the same dose it always levels out and that whole process is lessened after you get past 100mg. The only real deal-breaker with Lamictal is whether or not you get the rash. But if you don't get it, then Lamictal can be a very useful medication.

Thinking like a pdoc, if I felt that you really weren't bipolar or psychotic in any way, I would be hesitant to go to antipsychotics as a FIRST augmentation strategy simply because they will carry more risks than other augmentation options like lamotrigine (Lamictal), tricyclics, mirtazapine (Remeron). However, if I had ruled out Lamictal and Remeron, I would go right to some of the atypicals that were mentioned here because they have demonstrated positive efficacy as antidepressant adjuncts with the most compelling evidence going to Abilify and Rexulti. Additionally, I've found that I require for depression and mood stabilization far lower doses of Rexulti than the prescribing information calls for. I started for the first 2 weeks at 0.5mg and by the end of the two weeks it was just too much and I couldn't tolerate it. So I dropped down to 0.25mg and stayed there for a few months. I just went back up to 0.5mg about two weeks ago and it feels totally different this time around, and I LOVE IT. Prescribing information though calls for a target dose of 2mg. Rexulti is by far my FAVORITE AAP of all the ones I've tried with Zyprexa coming in second. I know @mikl_pls did mention the risk of type 2 diabetes with Zyprexa. It is by far the riskiest AP when it comes to metabolic side effects. However, if you don't already have a family history of type 2 diabetes and you maintain a good diet and physical activity, Zyprexa is an option you should consider if other augmentation options don't work out. At even 2.5mg I found it to be very calming and good for depression. I never went higher than 5mg. I did gain a bit of weight and my blood glucose and triglycerides did increase. However, I did not take my own advice and eat better and work out while I was taking it. The Zydis form (sublingual) can sometimes cause less weight gain.

On 3/14/2018 at 5:18 PM, dtac said:

Perhaps Klonopin would be more useful for managing the anxiety? Starting once a day at a low dose may provide some more constant relief than Xanax, and if you stay low enough it's usually not sedating either.

I would second this one. You'll get better round-the-clock coverage of anxiety from Klonopin because it has a much longer half-life. So taking 1mg before bedtime may accomplish what you're getting out of the 0.5mg Xanax around noon during the day with less of a chance of building a tolerance. And if you do build a tolerance, it may take longer.

On 3/14/2018 at 5:18 PM, dtac said:

Since you're on an SNRI, your choices are adding a mood stabilizer like Lamictal or an antipsychotic, like perhaps Abilify or Rexulti. Both of the latter drugs are approved as adjuncts for MDD (not saying it's your diagnosis) and can be stimulating. I think if you're already depressed and sleeping a ton and having problems getting out of bed, adding an AD that is sedating is just going to compound the problem (speaking from experience.) You could go the TCA or MAOI route, but I would put those as secondary choices due to the prevalence of side effects (not that APs are great drugs, but the newest ones are much better.)

I found Abilify extremely activating -- to the point that I couldn't sleep at doses above 2mg, but I'm an extreme case. I've been on Rexulti for almost 2 years now, and it has killed 90% of my depression --- better than any other single med -- and has practically zero side effects for me. 

Agree 100% with @dtac, if you can get Rexulti to take with your Effexor, go for it.

Another thing to consider would be to switch the Effexor out for Pristiq at like 100mg.

[dtac]

26 minutes ago, browri said:

Abilify will definitely be activating, although for some that starts to smooth out after getting to 10-15mg. I personally never made it past 7.5mg. I found it to be too agitating. Rexulti, however, has been awesome. Don't let anyone tell you that Rexulti is pharmaceutical evergreening and that it's just "the new Abilify". While it was fully intended to replace Abilify, it is definitely a different medication. I actually find it to be more sedating, and I take it at night, but it doesn't make me feel tired during the day and I think it provides a little bit of extra stimulation to the Vyvanse. Since starting Rexulti, I've gone from taking Xanax 2-3 times a week to taking it once a month or less. And it has a very strong antidepressant effect. Works really well with the Trintellix.

I just added Trintellix three weeks ago, and I'm noticing the same combo effect. I'm taking waaaay less Xanax too, although some of mine could be related to Klonopin QHS (but not BID, only QHS). I'm on the flip dosing of the drugs as you (heavy on the Rexulti/light on the Trintellix) but there is definitely something to the combo. I was taking 1mg of Xanax probably 4-5 times a week, and if I stay at 0.5-1mg of Klonopin, I generally don't need any Xanax. If I cut back to 0.25mg Klonopin, I may need 0.5mg Xanax 1-2 days a week.

Comparatively, my last trial of Klonopin was 1mg BID, and it didn't do anything for my anxiety, so the Rexulti/Trintellix combo is definitely doing something to lower my anxiety and curb my depression. Rexulti has been 90% effective alone at stopping it, and I'm hoping Trintellix can knock out that last 10%. I'm seeing very positive benefits from the combo, with negligible side effects -- highly recommended for depression and anxiety as a primary mix! Add a PRN benzo for breakthrough anxiety (or Klonopin for maintenance) and it's a winner.

Sorry for the derailment, but I think Rexulti + Trintellix is a combo worth further investigating.

[browri]

15 minutes ago, dtac said:

I just added Trintellix three weeks ago, and I'm noticing the same combo effect. I'm taking waaaay less Xanax too, although some of mine could be related to Klonopin QHS (but not BID, only QHS). I'm on the flip dosing of the drugs as you (heavy on the Rexulti/light on the Trintellix) but there is definitely something to the combo. I was taking 1mg of Xanax probably 4-5 times a week, and if I stay at 0.5-1mg of Klonopin, I generally don't need any Xanax. If I cut back to 0.25mg Klonopin, I may need 0.5mg Xanax 1-2 days a week.

Comparatively, my last trial of Klonopin was 1mg BID, and it didn't do anything for my anxiety, so the Rexulti/Trintellix combo is definitely doing something to lower my anxiety and curb my depression. Rexulti has been 90% effective alone at stopping it, and I'm hoping Trintellix can knock out that last 10%. I'm seeing very positive benefits from the combo, with negligible side effects -- highly recommended for depression and anxiety as a primary mix! Add a PRN benzo for breakthrough anxiety (or Klonopin for maintenance) and it's a winner.

Sorry for the derailment, but I think Rexulti + Trintellix is a combo worth further investigating.

Agree with you 100% on this, @dtac. I'm not sure that Trintellix really did anything for my anxiety. It wasn't until I added the Rexulti that things started to get better. I've done a lot of research on Trintellix and anxiety and found a couple things that may be of interest:

Vortioxetine (2.5mg, 5mg, and 10mg) has been tested in placebo-controlled studies with duloxetine (Cymbalta) 60mg as an active reference. While vortioxetine was inferior to duloxetine on anxiety rating scales, duloxetine was associated with more people leaving the study prematurely due to side effects; and vortioxetine, unlike duloxetine wasn't associated with treatment-emergent sexual dysfunction:

https://www.ncbi.nlm.nih.gov/pubmed/24341301

One critique that others have given to this study, post-hoc, is that the 15mg and 20mg doses were never used, and those doses were associated with a far greater rate of remission than <= 10mg in depression trials.

Based on my own reading of other people's subjective experiences with vortioxetine and anxiety, 50% of the time it helps, and 50% of the time it does nothing or makes your anxiety worse. What's interesting is that one of vortioxetine's primary effects is antagonism of 5HT₃. Unlike most of the serotonin receptors, which are G-coupled receptors, the 5HT₃ receptors are ion channel receptors and are located on GABA interneurons. Vortioxetine's activity there actually reduces GABA firing and increases the release of glutamate, which for people with anxiety, not always but oftentimes is not a good thing. I've felt that for me, Depakote has played an important role here because valproate inhibits the breakdown of GABA and increases its synthesis to ensure this activity by vortioxetine doesn't get out of control.

I'm not entirely sure where this is going to go yet, but a review has determined that pre-treatment function is a major determining factor of whether or not vortioxetine will work for anxiety. See this article:

https://www.psychiatryadvisor.com/anxiety/vortioxetine-generalized-anxiety-disorder-tx-pre-treatment-functioning/article/737747/

Of course the Trintellix+Rexulti combo has been great for my depression and my anxiety. But it's insufficient to keep my hypomania and mixed episodes under control. The Depakote is really the backbone in that regard. And after those three are put together my ADHD symptoms are most pronounced, which is what the Vyvanse is for. And I do feel that aside from helping with my ADHD, the Vyvanse does augment the Trintellix and the Rexulti.

Keep in mind that most of what Trintellix does actually causes dopamine release unlike most of your run-of-the-mill SSRIs, which actually end up inhibiting dopamine release without the serotonin antagonist actions. The increased dopamine release combined with Rexulti's dopamine partial agonism really helps to control Trintellix's "outflow" if you want to call it that. A truly modulating combo.

Another thing that changes from Rexulti when you add Trintellix is that Rexulti is a partial agonist of 5HT_1A, whereas Trintellix has a lower affinity but MUCH higher intrinsic activity at that receptor making it mostly a full agonist, a modification of Rexulti's pharmacology, essentially.