Posted by andrewb on November 10, 2014, at 10:38:25
In reply to CRP levels predict which AD someone responds to., posted by SLS on September 16, 2014, at 8:07:04
Hi Scott and others. I've been involved with helping someone with related issues on an ongoing basis, so I have some input.
Broadly speaking insulin resistance causes inflammation (but this is also bi-directional) as measured by CRP and IL-6. IL-6 can be predictive of depression.
Concerning Lexapro being ineffective or pooping out if insulin resistance is suspected: insulin resistance interferes with tryptophan availability for conversion to serotonin. Furthermore, citalopram, of which Lexapro of the left-sided enantiomer decreases the synthesis of 5-hydroxytryptamine (5-HT) in the mouse brain and also seems to require endogenous 5-HT for its full effect (see Pharmacological characterization of the decrease in 5-HT synthesis in the mouse brain evoked by the selective serotonin re-uptake inhibitor citalopram.) Note this effect may not apply to Lexapro (the right-side enantiomer of citalopram), as citalopram has already been found to antagonize escitalopram in other ways.
A recent large study looked at whether 5-HTP and relevant co-factors could reverse citalopram poop-out. They claimed dramatic results. They also state that Seratonin Syndrome is not possible with this add-on at the dose of 300mg/day. Also, insulin resistance interferes with tryptophan availability for conversion to serotonin.
Source: Monoamine depletion by reuptake inhibitors, (FullText, 11), http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237392/. Notes: This study is was done by a clinic that is under FDA order to stop selling the amino acid formula it is promoting as being able to treat various conditions. Reason: unproven claims.
Notes: If taking 5-HTP, take these cofactors: vitamin C 1000 mg, calcium citrate 220 mg, vitamin B6 75 mg. Also, start with just 100mg of 5-HTP and stay at that dose for (3) days before stepping up to 200, etc. Be aware of the symptoms of too much 5-HTP (e.g. grogginess). 100mg may be plenty. Also be aware of the symptoms of serotonin syndrome. There is controversy here, but some, especially older sources, state the serotonin syndrome is poss. with the combo. of an SSRI and 5-HTP.NOW!!....what I really want to talk about: insulin resistance, inflammation, and depression, and how to identify and treat.
There is evidence that when IL-6 inflammation caused insulin resistance is present, an insulin sensitizer such as pioglitazone can be effective.
Evidence: 1) PPAR-y agonism as a modulator of mood: proof-of-concept for pioglitazone in bipolar depression. Abstract, 14, http://www.ncbi.nlm.nih.gov/pubmed/24715548. In this study, pioglitazone decreased depression and anxiety in treatment resistant bipolars with metabolic syndrome/insulin resistance, and the degree of response was associated with a) a higher initial IL-6 score and b) the amount the IL-6 was reduced. Reduction in inflammation may represent a novel mechanism by which pioglitazone modulates mood.
Evidence: 2) Does pioglitazone improve depression through insulin-sensitization? Results of a randomized double-blind metformin-controlled trial in patients with polycystic ovarian syndrome and comorbid depression. Ab.s, 12, http://www.ncbi.nlm.nih.gov/pubmed/22999261. In this study they found pioglitazone, but not metformin, to be effective for depression in those with PCOS. Metformin isn't effective for insulin resistance. PCOS is a genetic disorder where insulin resistance is inherent and the depression prevalence is as high as 40%. Furthermore, obese (BMI > or = 27 Kg/m(2)) PCOS women have significantly higher IL-6 and other inflammatory markers than matched controls. BMI and HOMA (a test of insulin resistance) were predictors of IL-6 levels. While BMI alone predicted CRP.
ALL THIS IS TO SAY...if you suspect you have insulin resistance or metabolic syndrome, get tested.
When you or yourdoctor should suspect insulin resistance (even though glucose tolerance test is normal)?. These are some warning signs: high BMI, high waist to hip ratio, high triglycerides, elevated CRP, diagnosed with PCOS, and taking antipsychotics (e.g. Zyprexa!). But the list goes on, it is really quite common nowadays, after a certain age anyway.
TESTING.... Insulin resistance is measured with the HOMA-IR test or the QUICKI test. Should be covered by insurance. If the test comes back showing insulin resist. I suggest spending, if you can spare it, about $150 for an IL-6 test.
From there you can proceed to discussing treatment with your doctor (e.g. pioglitazone). Perhaps specialists in Metabolism and Endocrinology have the most relevant expertise in this area. They would also tell you that how and what you eat is very important when insulin resistance is involved and perhaps give specific advice.
poster:andrewb
thread:1071203
URL: http://www.dr-bob.org/babble/20141017/msgs/1073320.html