О новом фармсредстве. Антидепрессант и лекарство от фибромиалгии

Не стоит на месте доблестная Фармацевтическая Промышленность!!! Вот, очередной препарат - http://scienceblogs.com/corpuscallosum/2009/01/milnacipran_savella_approved_f.php
Milnacipran (Savella™) Approved for Fibromyalgia

Category: Neuroscience • Science News
Posted on: January 26, 2009 8:25 AM, by Joseph j7uy5
Milnacipran (Savella™)On 14 January, 2008, the US FDA approved milnacipran for use in treatment of fibromyalgia. It is ( or soon will be) available in tablets of 12.5, 25, 50, and 100mg. It has been marketed as an antidepressant in Europe for years, but has not been available in the USA until now.

Milnacipran is a drug that inhibits reuptake of serotonin and norepinephrine. The effect on norepinephrine is stronger than the effect on serotonin. It can be thought of as an SNRI, is the same family as venlafaxine (Effexor), duloxetine (Cymbalta) and desvenlafaxine (Pristiq).

From the Savella package insert (PDF), I've copied the dosing guidelines below. Note that the initial dosing guidelines often are not quite right; it takes experience in a larger population to figure out the best dosing. The titration schedule, as proposed, has the potential to be troublesome. It is likely that they will distribute dose-packs to make the titration easier to follow.

• Administer Savella in two divided doses per day
• Begin dosing at 12.5 mg on the first day and increase to 100 mg/day over a 1-week period (2.1): Day 1: 12.5 mg once Days 2-3: 25 mg/day (12.5 mg twice daily) Days 4-7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily)
• Recommended dose is 100 mg/day
• May be increased to 200 mg/day based on individual patient response

For milnacipran, the kinetics are as follows: oral bioavailability is 85-90%; the extent of absorption is not affected by food; half-life is 6-8 hours; 55% percent is excreted unchanged in the urine. Note that the active enantiomer, d-milnacipran, has a longer elimination half-life (8-10 hours) than the l-enantiomer (4-6 hours). Small percentages of the parent drug are metabolized by desethylation (N-desethyl milnacipran, 8%) and glucuronidation (d- and l-milnacipran carbamoyl-O-glucuronide, 2% and 17%, respectively). Plasma protein binding is 13%. No dosage adjustment is needed for mild renal impairment, or for mild to moderate hepatic impairment. Cmax and area-under-the-curve are 30% higher for persons over 65, and 20% higher for women, but no dosage adjustment is necessary. Milnacipran did not inhibit or induce any of the cytochrome P450 enzymes listed in the PI.

Savella carries a black-box warning about suicidality, based upon its similarity to other SNRI. This is addressed in this Medication Guide (PDF).

What role will milnacipran have in the armamentarium of available treatments? As it happens, a meta-analysis was published in JAMA a couple of weeks ago: Treatment of Fibromyalgia Syndrome With Antidepressants: A Meta-analysis (JAMA. 2009;301(2):198-209) Only the abstract is openly accessible. There's a summary available on Medscape (free registration) that contains more detail than the abstract:

The researchers found that amitriptyline had a large effect on reducing pain, fatigue, and sleep disturbances, a small effect on HRQOL, and no significant effect on mood.

In addition, they found that the SSRIs fluoxetine and paroxetine had a small effect on reducing pain and improving HRQOL but had no effect on fatigue or sleep.

SNRIs duloxetine and milnacipran had a small effect on reducing pain and sleep disturbances, and duloxetine had a small effect on improving mood and HRQOL, but no effect on fatigue.

The MAOIs moclobemide and pirlindole had a small effect on pain reduction. Moclobemide had no effect on sleep or fatigue, and pirlindole did not affect depressed mood.


HRQOL=health-related quality of life.

Only one study of milnacipran was included in the analysis, so there is a lot of information that was not included. Plus, the meta-analysis isn't ideally suited to compare one drug against the others. The bottom line, though, is that amitriptyline appeared to have the biggest effect. Unfortunately, amitriptyline is more likely than the others to have burdensome adverse effects. Amitriptyline is inexpensive, $4/month in some places. I don't know what milnacipran will cost, but it will be a lot more than $4/month.

Some additional perspective can be gained from this interview with a fibromyalgia expert, Daniel J. Clauw, MD:

Q: Do you have a standardized treatment protocol for your FM patients?

Dr. Clauw: I use a combination of low-impact aerobic exercise, symptom-based pharmacologic therapy, and cognitive behavioral therapy. Not all patients need all three.

I usually begin by prescribing medications to target the two or three most prominent symptoms that a patient has. In most cases pain is one, but poor sleep, fatigue, memory problems, or other symptoms sometimes interfere more with function than pain.

I only use one treatment at a time, and see if it works before deciding whether to continue with the treatment, or discard it. One of the biggest problems I see in practice is that doctors and patients try too many things at once, and then they have limited ability to tell if something is working, or whether a new symptom is a side effect of a treatment.

After I find the correct one or two medications to reasonably control many of the symptoms, then I will add aerobic exercise, and sometimes cognitive behavioral therapy (CBT). Both exercise and CBT can either be done simply (with simple instructions for exercise or a workbook or Arthritis Foundation course for CBT) or with more professional guidance (e.g., with a physical therapist, personal trainer, social worker, or psychologist).

These treatments take many months to work (in contrast to medications, which usually work within a month or so if they are going to work at all), but the benefits are more durable than the benefits obtained from medications.


Clauw goes on to discuss specific drugs, but milnacipran is not included, since the interview is from 2007.

The main points from the interview: patients often have to try several different medications or combinations, and the medication is only part of the overall treatment. There is no single treatment that stands out as clearly superior, and there is no single treatment that eliminates the need for multimodal intervention. In such a situation, it is always nice to have another option. In my view, milnacipran is exactly that: another option. Probably it will be a great thing for some people, pretty good for others, so-so for some, and worthless for others.