Remeron + Effexor

[flash]

I'm a PGY1.

So I asked about this "California (or Kentucky) rocket fuel" (after reading Stahl and random internet posts) and my attending encouraged me to get comfortable with trying new treatment regimens in the inpatient setting, particularly given this guy's long standing treatment resistant depression. I know little, but giving it a shot. So we shall see over the next few days/week, but if anyone has experience, I'm interested in hearing about it. E.g, he has mild generalized anxiety in addition to severe, non-situational depression; seclusive to room, sleeping alot, quick to state "nothing works"...how to think about wrt potential of worsening anxiety? Any experience is appreciated. Good deal of patient posts online, hoping for clinician experience. Effexor 75mg to start, on a base of Remeron 15mg QHS. Plan to move up on Effexor quickly assuming tolerating.

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[whopper]

While pharmacologically it makes sense, both are higher up on the side effect risks. I'd only recommend this if several other treatment regimens failed.

 

[nitemagi]

Are you at least using Effexor XR?

 

[billypilgrim37]

This seems like a pretty common regimen. Is there something special about this I don't know?

 

[nitemagi]

This seems like a pretty common regimen. Is there something special about this I don't know?

Depends on if you buy into Stahl's rational polypharmacy argument.

 

[billypilgrim37]

Depends on if you buy into Stahl's rational polypharmacy argument.

I believe in the "augment everything with Remeron" theory

I've established myself as the "we don't use enough mirtazepine and bupropion" guy on the forum, I think.

Btw, I wouldn't think you could call something a treatment resistant depression if he hasn't had a trial of an SNRI yet. Maybe technically, but that's still pretty standard issue stuff. 8 weeks of 300mg and 45mg and a decent therapist, then I'd buy it.

 

[jettavr6]

Hypertension, weight gain, and sedation?

 

[whopper]

Wellbutrin I don' t think is utilized enough. Anyone with a non-anxiety related depression with low energy, poor sex drive, and someone wishing to stop smoking should be considered.

 

[OldPsychDoc]

Effexor & Remeron sounds fine to me, wouldn't expect much increase in anxiety. Remeron's not my first choice for a guy who is sleeping all day though. More dopamine, baby.

"Longstanding treatment resistant depression" ==>> ECT.

 

[zenman]

Wellbutrin I don' t think is utilized enough. Anyone with a non-anxiety related depression with low energy, poor sex drive, and someone wishing to stop smoking should be considered.

Some think Wellbutrin is ok for anxiety also. What's your experience?

 

[BobA]

See this:
http://ajp.psychiatryonline.org/cgi/content/abstract/appi.ajp.2009.09020186v1

Combination of Antidepressant Medications From Treatment Initiation for Major Depressive Disorder: A Double-Blind Randomized Study

Pierre Blier, M.D., Ph.D., Herbert E. Ward, M.D., Philippe Tremblay, M.D., Louise Laberge, M.D., Chantal Hébert, R.N., and Richard Bergeron, M.D., Ph.D.
OBJECTIVE: Various classes of antidepressant medications generally induce remission of major depressive disorder in only about one-third of patients. In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation, the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone. In this double-blind study, the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation. METHOD: Patients (N=105) meeting DSM-IV criteria for major depressive disorder were randomly assigned to receive, from treatment initiation, either fluoxetine monotherapy (20 mg/day) or mirtazapine (30 mg/day) in combination with fluoxetine (20 mg/day), venlafaxine (225 mg/day titrated in 14 days), or bupropion (150 mg/day) for 6 weeks. The primary outcome measure was the Hamilton Depression Rating Scale (HAM-D) score. RESULTS: The overall dropout rate was 15%, without notable differences among the four groups. Compared with fluoxetine monotherapy, all three combination groups had significantly greater improvements on the HAM-D. Remission rates (defined as a HAM-D score of 7 or less) were 25% for fluoxetine, 52% for mirtazapine plus fluoxetine, 58% for mirtazapine plus venlafaxine, and 46% for mirtazapine plus bupropion. Among patients who had a marked response, double-blind discontinuation of one agent produced a relapse in about 40% of cases. CONCLUSIONS: The combination treatments were as well tolerated as fluoxetine monotherapy and more clinically effective. The study results, which add to a growing body of evidence, suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication.

 

[nitemagi]

See this:
http://ajp.psychiatryonline.org/cgi/content/abstract/appi.ajp.2009.09020186v1

Combination of Antidepressant Medications From Treatment Initiation for Major Depressive Disorder: A Double-Blind Randomized Study

Pierre Blier, M.D., Ph.D., Herbert E. Ward, M.D., Philippe Tremblay, M.D., Louise Laberge, M.D., Chantal Hébert, R.N., and Richard Bergeron, M.D., Ph.D.
OBJECTIVE: Various classes of antidepressant medications generally induce remission of major depressive disorder in only about one-third of patients. In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation, the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone. In this double-blind study, the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation. METHOD: Patients (N=105) meeting DSM-IV criteria for major depressive disorder were randomly assigned to receive, from treatment initiation, either fluoxetine monotherapy (20 mg/day) or mirtazapine (30 mg/day) in combination with fluoxetine (20 mg/day), venlafaxine (225 mg/day titrated in 14 days), or bupropion (150 mg/day) for 6 weeks. The primary outcome measure was the Hamilton Depression Rating Scale (HAM-D) score. RESULTS: The overall dropout rate was 15%, without notable differences among the four groups. Compared with fluoxetine monotherapy, all three combination groups had significantly greater improvements on the HAM-D. Remission rates (defined as a HAM-D score of 7 or less) were 25% for fluoxetine, 52% for mirtazapine plus fluoxetine, 58% for mirtazapine plus venlafaxine, and 46% for mirtazapine plus bupropion. Among patients who had a marked response, double-blind discontinuation of one agent produced a relapse in about 40% of cases. CONCLUSIONS: The combination treatments were as well tolerated as fluoxetine monotherapy and more clinically effective. The study results, which add to a growing body of evidence, suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication.

105 pt's into 4 treatment arms = 26 pt's or so per treatment arm. 16 pt's dropped out. So while it's encouraging, has it been replicated with greater numbers?

Funded by Organon.

 

[flash]

Thanks...I appreciate everyone's perspectives and the link, BobA. It's hard to make sense of the decisions I see being made everyday as a PGY1, just 3 months on inpatient unit now. But working hard to do so, coming to accept limits of 'science' and pitfalls of 'art', appreciating biases and developing some semblance of a teachable, professional identity. Patient is doing well...will elaborate when have a few more minutes on call tomorrow.

 

[BobA]

105 pt's into 4 treatment arms = 26 pt's or so per treatment arm. 16 pt's dropped out. So while it's encouraging, has it been replicated with greater numbers?

Funded by Organon.

The size is small, but reasonable for this type of study. The drop out rate of 15% is average as well, and not different between groups. You could combine the three combination-therapy arms and say that there were 75 people in the combo-group and all had about double response rates. However, somewhere I read a more recent meta-analysis that contradicted this study's findings - but I forget where I read it.

And I'm not saying I agree with starting two antidepressants - I don't. I always would start with psychotherapy +/- 1 antidepressant. But the OP was asking specifically about California Rocket Fuel, and there's at least some evidence to say that it's more effective than monotherapy.

Also, if someone is extremely depressed and failed two monotherapy medication trials I would go for ECT.

FWIW, I've also had very few patients actually tolerate mirtazapine. I've probably used it 20 times and only 5 people responded well without significant weight gain or next day sedation. And note that you need higher doses of mirtazapine to get serotonergic and noradrenergic effects.

 

[whopper]

Some think Wellbutrin is ok for anxiety also. What's your experience?

I haven't seen much evidenced-based data to back it up.

I've only seen this in private practice because there's a psychologist there that does TOVA testing for me. I've had a subset of patients present with their chief complaint as anxiety. Okay, sounds like an anxiety disorder right? Wrong. These people never got better on an SSRI. After several of them didn't improve on 3 trials of SSRIs with augmentation with buspirone, and me grasping for straws, I had them do a TOVA test that suggested they had ADHD.

So those people I tried on Wellbutrin and in some of them the anxiety went away. If a trial of two non-stimulants didn't work, I did eventually try a stimulant in some, and it ended up relieving anxiety. Remember, none of these people ever wanted a stimulant in the first place when they saw me. They only wanted me to get rid of their anxiety.

It made sense to me only after I thought about it long and hard. Everyone has symptoms of ADHD. Everyone. Everyone's been in a situation where they didn't want to do their homework, walk out of a class, etc. That doesn't mean they have ADHD.

That TOVA test has been the only good indicator so far in my experience if a person actually has ADHD or not because it doesn't rely on self-report. IT has a symptom exaggeration scale to weed out malingerers.

And let's assume a guy truly has ADHD? After years of it not being treated, wouldn't you expect the person to feel anxious?

How many of these patients have I encountered? I haven't done a hard study of the numbers but off-hand it's been about 5-10% of those that came to the office complaining of anxiety.

So my current theory is if Wellbutrin is relieving anxiety, it's because the person has ADHD, or it's simply the NRI component doing the benefit.

 

[firedoor]

Tranylcypromineversus venlafaxine plus mirtazapine following three failed antidepressantmedication trials for depression: a STAR*D report.

McGrath PJ, Stewart JW, Fava M, Trivedi MH, Wisniewski SR, Nierenberg AA, Thase ME, Davis L, Biggs MM, Shores-Wilson K, Luther JF, Niederehe G, Warden D, Rush AJ.
Source

Depression Evaluation Service, New York State Psychiatric Institute, 1051Riverside Dr., New York, NY 10032, USA. [email protected]

Abstract

OBJECTIVE:

The purpose of this study was to compare the effectiveness and tolerability oftranylcypromine and combination treatment with extended-release venlafaxine andmirtazapine in patients with treatment-resistant major depression whose currentdepressive episode had not responded adequately to treatment in three priorprospective medication trials.
METHOD:

Adult outpatients with nonpsychotic major depressive disorder who had notachieved remission or had withdrawn from treatment because of intolerance inthree previous prospective medication trials were randomly assigned to receiveopen-label treatment with either tranylcypromine (N=58) or extended-releasevenlafaxine plus mirtazapine (N=51). The primary outcome measure was whetherpatients achieved remission, which was defined as a score < or =7 at exit onthe 17-item Hamilton Depression Rating Scale (HAM-D). The HAM-D wasadministered by telephone by raters to whom treatment was masked.
RESULTS:

Remission rates were not significantly different between the two treatmentgroups (6.9% for the tranylcypromine group and 13.7% for the venlafaxine plusmirtazapine group). The mean daily dose at exit for tranylcypromine was 36.9 mg(SD=18.5); for venlafaxine, 210.3 mg (SD=95.2); and for mirtazapine, 35.7 mg(SD=17.6). Tranylcypromine was associated with significantly less symptomreduction and greater attrition due to intolerance.
CONCLUSIONS:

Remission rates were modest for both the tranylcypromine group and theextended-release venlafaxine plus mirtazapine group, and the rates were notstatistically different between groups. The lower side effect burden, lack ofdietary restrictions, and ease of use of venlafaxine and mirtazapine suggestthat this combination may be preferred over tranylcypromine for patients with highlytreatment-resistant depression who have not benefited adequately from severalprior treatments.


[FONT=OceanSansMM_648_800_]http://ajp.psychiatryonline.org/cgi/reprint/163/9/1531.pdf.

 

[OldPsychDoc]

Some think Wellbutrin is ok for anxiety also. What's your experience?

Always ask "What do you mean by 'anxiety'?"

If anxiety is worry tinged with depression, hopelessness, and ineffectiveness, or if its dominant component is of social insecurity, I've found Wellbutrin to be quite well tolerated without agitating the patient or inducing panic.

If the anxiety is spontaneous, unprovoked panic attacks however, I'd avoid it.

 

[firedoor]

Effexor & Remeron sounds fine to me, wouldn't expect much increase in anxiety. Remeron's not my first choice for a guy who is sleeping all day though. More dopamine, baby.

"Longstanding treatment resistant depression" ==>> ECT.

Yes, more dopamine and ECT!

Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of &#945;2-adrenergic and serotonin2C receptors: a comparison with citalopram

Abstract

Mirtazapine displayed marked affinity for cloned, human &#945;2A-adrenergic (AR) receptors at which it blocked noradrenaline (NA)-induced stimulation of guanosine-5&#8242;-O-(3-[35S]thio)-triphosphate ([35S]-GTP&#947;S) binding. Similarly, mirtazapine showed high affinity for cloned, human serotonin (5-HT)2C receptors at which it abolished 5-HT-induced phosphoinositide generation. Alpha2-AR antagonist properties were revealed in vivo by blockade of UK-14,304-induced antinociception, while antagonist actions at 5-HT2C receptors were demonstrated by blockade of Ro 60 0175-induced penile erections and discriminative stimulus properties. Mirtazapine showed negligible affinity for 5-HT reuptake sites, in contrast to the selective 5-HT reuptake inhibitor, citalopram. In freely moving rats, in the dorsal hippocampus, frontal cortex (FCX), nucleus accumbens and striatum, citalopram increased dialysate levels of 5-HT, but not dopamine (DA) and NA. On the contrary, mirtazapine markedly elevated dialysate levels of NA and, in FCX, DA, whereas 5-HT was not affected. Citalopram inhibited the firing rate of serotonergic neurons in dorsal raphe nucleus, but not of dopaminergic neurons in the ventral tegmental area, nor adrenergic neurons in the locus coeruleus. Mirtazapine, in contrast, enhanced the firing rate of dopaminergic and adrenergic, but not serotonergic, neurons. Following 2 weeks administration, the facilitatory influence of mirtazapine upon dialysate levels of DA and NA versus 5-HT in FCX was maintained, and the influence of citalopram upon FCX levels of 5-HT versus DA and NA was also unchanged. Moreover, citalopram still inhibited, and mirtazapine still failed to influence, dorsal raphe serotonergic neurons. In conclusion, in contrast to citalopram, mirtazapine reinforces frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission. These actions reflect antagonist properties at &#945;2A-AR and 5-HT2C receptors.

 

[kugel]

When it comes to choosing an antidepressant, first-line, second-line, or combination, I work hard to learn what has/hasn't worked in the past, and why.
If that doesn't give me clear indications on what to do, I
Ask The Patient.

I lay out a table that shows pros/cons for each group of medications (plus psychotherapy, herbals, ECT), then explain that there is little evidence to suggest which choice will ultimately be right for this patient. So I need help choosing what The Patient thinks will be of the most help, and cause the least harm.

If the pt is psychotic, then I will suggest a choice and give a brief explanation of my reasoning - but make it clear I am open to other suggestions or changes down the road. If the pt is paralyzed by helplessness, I still ask them a few times if they can help me decide. Then I offer to let them off the hook and allow me to make an initial decision over which they have full veto. And that I would love to have them question my decision later, because it means they are getting better (whether that's because of the medication or not.)

When it comes to combo tx, I explain that there have been some studies showing that it can help a little more or a little faster, but that we then run the risk of SE's from each drug, and (rarely) additional ones from the combo itself. However, none of those are terrible, and if they did arise they are manageable, and we can Always back off to just one medication if SE's became a problem.
Plus, "You're not alone in this. If you have problems or questions, Don't Wait for your next appt. You can ALWAYS come back and ask questions, make suggestions, or just yell at us if you decide we were idiots. Who can resist that?"

"Now let's talk about all the other things you can be doing to help yourself..."
Sleep hygiene, diet, socialization, being active in a worship group, exercise, support groups, crisis hotline, therapeutic workbook, avoiding drugs/ETOH.

Personally, I think getting the pt involved in the decision, feeling a part of the treatment team (thus more likely to TAKE the medicine) is all more important that which medicine or combo is chosen. Plus, the process of choosing by discussion often reveals new information that is important. Like, "I used to be 100 lbs overweight, so I can't risk having a medication cause that again," or "Oh, yeah. I forgot until I saw this. My mother and brother both had terrible side effects to that one," or "Is that safe to take with my Imitrex and my Demerol? From the look on your face, doc, I guess I forgot to mention those."

Okay, that's my rant for today.
Thank you for pretending to listen.