Break the cycle of chronic pain and depression with Milnacipran / Ixel

Taking Milnacipran for depression is becoming an increasingly popular choice for sufferers of low mood and persistent, long lasting pain. It’s a chronic pain treatment that’s also one of the most effective fibromyalgia treatments on the market today. The key to Milnacipran (also known as Ixel) lies in its ability to sidestep the side effects traditionally associated with Selective Serotonin Re-uptake Inhibitors (SSRIs). Milnacipran can also help with other debilitating conditions, including Lupus.

Using Milnacipran for depression works by strongly inhibiting the re-uptake of both serotonin and noradrenaline levels in a balanced and calculated way. Helping to substantially increase levels of wellbeing, as well as deliver chronic pain treatment, Milnacipran also provides Lupus and fibromyalgia treatments. A drug to improve quality of life by alleviating pain, Milnacipran is fast gaining a reputation as a breakthrough treatment. It’s one of the few Selective Serotonin Re-uptake Inhibitors without many of the side effects associated with other well know treatments, such as Prozac or Effexor and tricyclic anti-depressants (TCAs).

How does Milnacipran avoid the side effects of well known treatments?

The most common Selective Serotonin Re-uptake Inhibitors (SSRIs) are drugs like Prozac. Similarly, drugs like Efexor are Selective Norepinephrine Re-uptake Inhibitors (SNRIs), which tend to just affect serotonin.

Milnacipran works quite differently to both Efexor and Prozac. By influencing the two neurotransmitters norepinephrine and serotonin almost equally (in a 3:1 ratio to be precise), well known and unpleasant side effects such as erectile dysfunction and loss of libido (sex drive), are avoided.

Some evidence suggests that drugs to increase either serotonin or norepinephrine are equally effective in treating depression. However, norepinephrine is also deemed very important in the treatment of pain. Until recently, the most effective way to increase both norepinephrine and serotonin was through administering tricyclic anti-depressants (TCAs).

TCAs bring the risk of even more side effects and, with this, the potential for a downward spiral of treatment to counteract the effects of treatment! Side effects with TCAs can include a dry mouth, weight gain, drowsiness, fatigue, confusion, disorientation and cardiac abnormalities - all of which can lead to more discomfort and depression.

Milnacipran research

In tests involving more than a thousand patients, Milnacipran was found to have antidepressant efficacy similar to that of fellow antidepressant, Imipramine, and significantly superior efficacy in treating depression compared with SSRIs.

Treating Fibromyalgia and Lupus

Affecting 2 to 4 % of the general population, Fibromyalgia Syndrome (FMS) is a chronic pain syndrome. Symptoms are notoriously debilitating, and are characterised by chronic and widespread pain throughout the body, often accompanied by severe fatigue and inability to sleep.

What’s surprising for such a common condition is that treatment options are limited. As yet, there are no drugs specifically approved by the U.S. Food and Drug Administration for the treatment of FMS.

In tests, Milnacipran-treated patients showed significant improvements in pain management, fatigue and general mood compared to those who received a placebo.

Milnacipran has also shown promise in the treatment of Systemic Lupus Erythematosus (Lupus for short) - a condition described as like the body ‘turning on itself’. In a Lupus sufferer, antibodies can attack over 116 different types of their own proteins - as if they were foreign bodies, dangerous viruses or invading bacteria. Trials using Milnacipran, however, provide hope. They appear to demonstrate a large degree of pain relief amongst sufferers, coupled with a substantial boost to well-being.

The therapeutic option for depression and chronic fatigue

Adding the evidence of Milnicipran’s everyday effectiveness, analysis of over 3300 patients revealed that both general and cardiovascular tolerance of Milnacipran were superior to those of TCAs, with fewer side effects.

This is just one of the reasons why Milnacipran has been hailed as a new therapeutic option for depression.

Taken to treat depression, dosages are typically in the order of 25mg to 50mg daily (maximum 100mg).

With high levels of tolerability and few side effects, it’s no surprise that Milnacipran has become the treatment of choice for depression and fatigue, and to ease the chronic pain associated with Fibromyalgia and Lupus.


Frequently Asked Questions About Milnacipran

Disclaimer: Please note that only your own physician can determine your precise needs, but in order to give you some information these answers are based upon the ‘average person’ and clinical / published results.

With respect to IXEL, I have one reservation: it is not to be used in conjunction with selective Monoamine Oxidase B inhibitors [Selegiline, L-Deprenyl]. This is a problem for many of my patients who are on Selegiline for cognitive enhancement and neuro-protection. What are the pharmacology and the reason for this contraindication?

Regarding Ixel®, I have also noted the manufacturer's warning of combining Ixel with MAO inhibitors, including MAO-B inhibitors such as selegiline, although there is scant little of this in the literature. What we do know about Ixel's pharmacokinetics are here:

We know that it is not metabolized through the P450 system, that it raises 3 parts noradrenaline to 1 part serotonin and has no affinity for neurotransmitter receptors. As I am sure you know it is being touted as a safe and relatively fast acting anti-depressant with significant improvement to fibromyalgia fatigue syndromes and lupus pain flares etc. (I expect you may have been following nutritionist Karen Kaufman's progress with Milnacipran in the Antiaging Magazine).

The manufacturer's insert suggests that Ixel interferes with other anti-depressants, and the normal proviso is to be weaned off one, whilst slowly increasing the dose of the other. However, the physicians Karen and I have spoken to who have found themselves in this situation with patients, appear not to be too concerned about this, as they see little negative interaction, and many of them have continued their patients on drugs such as Wellbutrin along with Ixel (albeit at lower doses).

So I wondered why Ixel may be contraindicated with Selegiline, my first thoughts were dopamine and dopamine pathways, but I found this trial that used a combination of Ixel (milnacipran) with Cabergoline, a D2 agonist similar to Bromocriptine, and it was most favorable.

Then I discovered that in some animal trials that Ixel has some MAO inhibiting effects. It was difficult to ascertain the potency of this affect, but I find little reference to it in the human literature, so I presume it is mild.

As the manufacturers also warn against possible contraindications with agents that enhance noradrenaline and serotonin (i.e. Sumatriptan), my presumption is that Ixel is not recommended for use with Seligiline on the basis of MAO inhibition x2.


Dosages for depression are usually in the order of 25mg to 50mg daily (maximum 100mg).


Like most anti-depressants there are contraindications with other anti-depressants and MAO inhibiting drugs, including Gerovital-H3, Deprenyl and Manerix, therefore combined use is not advised unless under the guidance of a physician. Furthermore, we do not advise combination with other Serotonin or Noradrenaline enhancing agents such as Adrafinil, Modafinil, Paxil, Prozac®, Yohimbine and Zoloft unless you are under the guidance of a physician.


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What our customers say

I wish to give a gracious 'thank you' to "International Antiaging." You've been providing me with an antidepressant, Milnacipran, a drug that is not yet available in the United States. It works for me in 2 hours! I do normally respond to antidepressants very quickly (one to three days), but never this quickly. I took the drug in the afternoon and 2 hours later I looked bright and cheerful after a period of sadness that lasted for several years. It is an unbelievable drug. In addition it has no side effects for me.

Dan E

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