Posted by LouisianaSportsman on May 12, 2012, at 19:03:06
In reply to Re: Suggestions for meds augmentation? (BP2, GAD, MDD), posted by LouisianaSportsman on May 12, 2012, at 18:41:02
I forgot to mention, I was considering Symbyax. I am dubious about it now since I'm not sure about Zyprexa and how strong it is and the side effects. I made a Microsoft Word document that contains graphs to give to my PDOC to encourage him to write me Symbyax.
It is a lot to read and I don't expect anyone to read the whole thing; regardless, I will post the plain text here. I am sorry that it does not reference the studies. Remember, this is a case I was making to my PDOC about prescribing me Symbyax.
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I would like to try Symbyax for Bipolar Depression/Anxiety and, also, as a way to possibly reduce clonazepam treatment. This front page explains my reasons and the subsequent pages are my evidence to back up my idea.
Symbyax allows the ability the concomitant efficiency of an antidepressant that is indicated for anxiety with the addition of Zyprexa, with similar effects as Seroquel XR, to protect against a manic episode. I would rather be on long-term Prozac (and low dose olanzapine) than long-term high-dose Seroquel. Zyprexa alone is not effective as a monotherapy like Seroquel XR; however, I believe the augmentation and synergistic effects of the Zyprexa and Prozac combination are superior to Seroquel XR in one convenient, name-brand, pill for easy titration. Dosing control is one problem; however, since we are aiming for below threshold antipsychotic effects (3mg.), the issue of dosage increase can be satisfied by augmentation of generic fluoxetine or an increase to a higher dose of Symbyax, I really like the synergistic feel of the one pill. 2.5mg. Xyprexa is not a high enough dose to function as an antipsychotic with D2 occupation similar to Seroquel XR 300mg. 2.5 mg. Zyprexa (due to lower H2 shown below) is proven to have less sedation than that dose of Seroquel with the same 5-HT2 occupancy even at such a low dose. 5mg Zyprexa = 50mg Seroquel = 3mg Risperdal.
I think Symbyax would be very effective for my Bipolar Depression/Anxiety. If not:
I can tell the effects of Zyprexa apart from Prozac; thus, continuation of fluoxetine treatment is a possibility with olanzapine discontinuation and if an adequate response from fluoxetine is not obtained, augmentation with Abilify, indicated for Bipolar, may be effective because I believe that AD + Abilify therapy is more effective and less sedating than 300mg. Seroquel XR.The use of Symbyax would be faster than a possible Seroquel XR failed attempt; especially due to similarities between the two, I can hedge my bets on the Symbyax or AD alone or AD + Abilify being more effective than Seroquel XR first-line; additionally, Symbrayx allows for less sedation and effects similar to Seroquel XR and on-label SSRI treatment for anxiety with prior positive response to Zoloft; which may reduce the need for clonazepam treatment.
Therefore, the properties of 3mg. Zyprexa are similar to the effects of Seroquel XR target dose, but a low dose of 3mg. Zyprexa might achieve these same effects with less sedation.(and not time released, although it does have a longer half-life)
1.The addition of Zyprexa 3mg. which has similar antidepressant properties as Seroquel XR to a proven antidepressant should reduce any side effects of mania.
2.Zyprexa might be less sedating that Seroquel XR 300mg and the 3mg. Zyprexa also carries a lower risk for TD. I would rather take low-dose olanzapine and Prozac over Seroquel.
3.The Seroquel-esque and anti-manic effects of Zyprexa augmented with a proven antidepressant should be more effective than Seroquel XR alone for Bipolar Depression.
4.Prozac is on-label for anxiety and may reduce the need for Klonopin.
The antidepressant effects are likely derived from effects at 5HT2c, 5HT1a agonism, and NRI effects.Olanzapine shares 5HT2C blocking properties with quetiapine. It is missing NRI and the partial 5HT1a agonism since it is a full agonist as one study points out; furthermore, the addition of fluoxetine adds the NRI effects of norquietapine via:
Study:
Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex.Quietapine Affinities on Left; Olanazapine on the right. (I do realize it is missing the norquietapine metabolite)
D142831
D262611
5-HT1A1040?
5-HT2A 38 4
α1B 14.646.4
α2 6171290
H1 4.417
M1 108626
NET >10000>10000Zyprexa is less sedating than Seroquel due to (slightly) less H1 activity.
Olanzapine is full agonist at D2, HT-1A, and 5-HT2C. Although the affinity of quetiapine is lower than olanzapine for the 5-HT2C receptors in general, previous literature is quite consistent that quetiapine has similar structural properties to olanzapine and clozapine. A dose of 3mg. olanzapine would be around 40% of D2 receptor occupation with nearly all of the 5-HT2 occupation. It would take a dose of ~150mg. Seroquel to reach the same level of occupation. At 6mg., olanzapine would reach the antipsychotic threshold, thus possibly making amphetamine less effective for ADHD; however, this is not true for 3mg. olanzapine.Study:
Experience has shown olanzapine (Zyprexa) to be very effective against agitation and anxiety in patients with bipolar disorder.Study:
Prozac worked 76% of the time to reduce depression clinically below placebo for Bipolar patients who did not discontinue treatment.Study:
Fluoxetine monotherapy produced minimal improvement on various scales that rate severity of depression. The benefits of olanzapine
monotherapy were modest. Olanzapine plus fluoxetine produced significantly greater
improvement than either monotherapy on one measure and significantly greater improvement than olanzapine monotherapy on the other measures after 1 week. There were no significant differences between treatment groups on extrapyramidal
measures nor significant adverse drug interactions. CONCLUSIONS: Olanzapine plus
fluoxetine demonstrated superior efficacy for treating resistant depression compared
to either agent alone.Study:
Therefore, the large, sustained increase of [DA](ex), [NE](ex), and [5-HT](ex) in PFC after
olanzapine-fluoxetine treatment was unique and may contribute to the profound
antidepressive effect of the olanzapine and fluoxetine therapy in TRD.Study:
The uniqueness of the Prozac-Olanzapine combination is better than the combination of SSRI/SNRI + Abilify in the treatment of patients with TRD.Study:
"[Symbyax]-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale ..."
In conclusion, fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate. Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder.Article:
Fluoxetine appears superior to lithium in preventing recurrence of major depressive episodes in patients with bipolar type II, according to new research.Study:
Patients taking lithium were at risk of suffering a relapse much sooner than those on fluoxetine (Prozac), according to a study published online April 1st in the American Journal of Psychiatry. Moreover, the researchers found no significant difference in hypomanic symptoms between the two drugs.
poster:LouisianaSportsman
thread:1017746
URL: http://www.dr-bob.org/babble/20120508/msgs/1017792.html