Advertising Works

On the Maryland Psychiatric Society's listserv I recently heard about a newly available (in the US) SNRI, Savella (milnacipran). It came out for fibromyalgia earlier this year but is used for depression in other countries. First I heard it was available. Who knew?

Then, I pick up the June issue of the Psychiatric Times. I usually let this languish in a pile, still wrapped in plastic, for a few months, and then summarily discard it, unread, once it breaks my "3 months rule". (If a throw-away mag/journal is more than 3 months old, toss it.)

I flip through it and discover -- only because of the advertisements -- several other new drugs I am unaware of. Where have I been that I've not been clued in? Twitter #fail!

So here are the other things.

• Fanapt (iloperidone) was approved, for treating schizophrenia. Vanda makes it.
• You can get 225mg of Effexor XR in a *single tablet*! But it's not "Effexor," it's actually a generic brand called Venlafaxine Extended Release (yes, that is the actual brand name). And it's a tablet, not a capsule. Made be Upstate Pharma. Who knew?
• There's also a new brand of bupropion (aka Wellbutrin) out there that puts an extended release formulation of the maximum dose (450mg) all in one pill. I heard about that one in an email from Sanofi, about this new formulation called Azplenzin (though you have to order 522mg to get 450mg). This one's so new, a Google search turns up only 3 hits.

So, I'm just saying that the marketing works to get something new noticed. The more important part is doing the research to determine if it is something that may help you or your patient.

The SSRI Horse Race-- Take Our (Meaningless) Polls

This is not science, I'm just playing here, nothing random, nothing controlled, just questions for our readers.

I just read Peter Kramer's Psychology Today blog post called Lexapro and Zoloft in a Cloud of Dust. Dr. Kramer talks about the relative efficacy of SSRI's, their market share, and if the drug company's influence docs to prescribe in a way that isn't in sync with research. Lexapro, the most expensive SSRI, apparently has the biggest market with 13% of the market share. He writes:
Now comes news of a large-scale analysis of research on antidepressant efficacy. Published in The Lancet, it finds a hierarchy, with Remeron, Zoloft, Effexor, and, yes, Lexapro, leading the pack, Cymbalta and Prozac in the middle, and Luvox, Paxil, and (especially) reboxetine, which is marketed outside the US, bringing up the rear. Celexa and Wellbutrin gave statistically fuzzy efficacy results; the two drugs appeared to be about average for the group. In terms of tolerability, Zoloft, Lexapro, Celexa, and Wellbutrin led the pack. So the results give a special place to Zoloft and Lexapro.

Do read the original post.

So I thought I'd put up two polls, and again, this isn't science, it's just curiosity. Pretend you didn't read the paragraph above, and I'd like you to answer two questions: What do you think is the most Effective SSRI, and Which SSRI do you think causes the most side effects. I don't care if you're the patient or the doctor, or a non-MD therapist who's simply just heard patients talk about the meds. It's a question of perception, with the awareness that maybe you haven't seen all the horses race. Efficacy: Which med works the best (If you've only been on Prozac and that worked great, it's fine to answer that!). Side Effects: Which med makes people feel the yuckiest (now there's a scientific term).

How A Shrink Picks An Anti-Depressant

[Part Two of this post is here]

Midwife With A Knife wants to know how a psychiatrist chooses a medication for an SSRI-naive patient. Wow, I'd already started that post when she asked.

So a patient comes for treatment. His symptoms meet criteria for Major Depression, no question here, and he wants medication to help his condition. This is his first visit to see me.

Prozac Paxil Zoloft Lexapro Celexa Luvox Effexor Cymbalta Lamictal
Wellbutrin Remeron Serzone Pamelor Elavil Nardil Parnate Emsam Trazodone

I probably missed a few.

So how does a shrink decide what medicine to begin?

1) Past history of response. If the patient says, Oh, yeah, six years ago I felt this way, I took Paxil for six months and that helped a lot and I didn't have any side effects, then Paxil it is.
The path changes if the story is that the medication didn't work or had side effects.

2) Family history of response. This is the patient's first episode, but mom swears by Wellbutrin, it's helped her when nothing else would. This would be a good first choice.

3) Patient preference. He's here because his best friend took Celexa and became a new and wonderful person. I have no idea what friend's diagnosis is or why Celexa was chosen for friend, but if there isn't a contra-indication, then I might as well honor a patient's wishes and there's some power to believing something will help. Similarly, if patient reports that Celexa caused best friend to commit outrageous acts of horror and he wants anything but Celexa, I pick something else.

4) Other Medical Issues. I don't start with meds that interact with what the patient's already on. I don't pick meds that might exacerbate an existing medical condition. Wellbutrin is contra-indicated in patients with seizure disorders, eating disorders, or a history of CNS lesions, so I don't start with it in these patients. I save the risky stuff for after we've been at it a while, and then only with a fair amount of discussion about possible risks compared to possible benefits.

5) My Best Guess at What Will Help the Target Symptoms. Patient is tired and unmotivated...Wellbutrin is reportedly a bit energizing, so maybe that's what I use. Patient also has a lot of OCD symptoms, I might go with an SSRI. If someone has a concurrent pain syndrome, Cymbalta or a TCA might be my first choice.

6) My Best Guess at the Side Effect Profile, for better or for worse. Really, this is a guess. I actually hate this issue because patients often worry about side effects they never get, but okay, if someone is agitated, I might start something I think of as being more calming. If someone says they'll die if they gain a single pound, I pick something more weight neutral.

7) The Patient's Financial Concerns and What I have Samples of. This is only a consideration if the patient is uninsured and paying cash for the meds, but this is not a trivial thing. After that, I move to What's Cheapest that will work and won't cause intolerable side effects. If the patient has been on something and had good success, then loses their insurance, I might try something cheaper in the same class of meds, but I wouldn't recommend a switch from say a working SSRI to a cheap Tricylic-- it's not worth the risk.

Can I say a word about Weight Gain as a side effect? Some patients refuse any medication that's been associated with this. But clearly, and I'm probably repeating myself at this point, there are people who don't gain weight on medicines that are said to cause weight gain, just like there are people who don't get better with anti-anythings. People respond to meds differently. My suggestion to those who are concerned they'll gain weight-- if there's some reason to believe a medicine might help, it may be worth a try. Buy a scale. Get weighed before starting the medication. Get weighed every 2-3 days after starting it. If you gain 5 pounds (1 or 2 or 3 can be variations in fluid retention or scale flakiness), Then it's worth worrying about weight gain and addressing whether it makes sense to continue.

We've been at this blog so long, I've lost track of what I've said already, what I've thought about saying, what I want to say.

FDA Drugs: February 2007

2007: Mar | Feb | Jan . . . 2006: Dec | Nov | Oct | Sep

---

FDA Drugs: February 2007

• Warning Letter: Signature Genetics. Seryx is the company that markets an excellent (but expensive) pharmacogenetics program which will take your blood or cheek cells and analyze your DNA for various genotypes which affect how your body metabolizes certain drugs, many of which are psychotropic drugs. This information may be used to help a prescriber make decisions about starting dosages or drugs or combinations of drugs to use or avoid. This topic is a whole 'nother post I could do, but this type of testing can be used inappropriately (2002 Quackwatch page), as well. Anyway, this computer program is considered by the FDA to be a "device", and it has not applied for FDA approval, so the FDA is telling it to stop until approval is obtained.
• Wellbutrin (bupropion) Medication Guides updated: PDF versions of Medication Guides for Wellbutrin and Wellbutrin SR were updated.
• Generic Focalin (dexmethylphenidate) approved.
• Only 22 New Drugs Approved in 2006: Merrill Goozner comments on his blog, GoozNews, about the lowering of innovation in the pharma industry.
• FDA Starts Podcasts: The FDA Commissioner, Dr. Andy von Eschenbach, has started a series of drug safety-oriented podcasts. The first one just announces the series. Go to the XML feed to subscribe.
• ADHD Drug Warnings: The FDA is requiring all manufacturers of drugs used to treat ADHD, including Adderall, Concerta, Ritalin, and Strattera, to develop Medication Guides to warn patients about the risks of cardiovascular (sudden death, stroke, heart attack, blood pressure) and psychiatric (mania, psychosis, aggression) side effects.
• Vyvanse releases Medication Guide: Shire's Vyvanse (lisdexamfetamine dimesylate) was listed last month (before the name was changed from Vynase) as a new ADHD drug. It is a prodrug, meaning it is metabolized into an active drug by the body. Advantages are said to be that it is once-daily and that it is less likely to be abused (ie, 4 out of 5 drug abusers prefer other stimulants to this one). It now has full approval as a Schedule II drug (for full prescribing info, see link to Label Info here.)
• Changes in Nardil (phenelzine) Prescribing Info: added severe renal impairment or renal disease to list of contraindications; added cautions about use in diabetes; and added warning about drug interaction with guanethidine (Ismelin).
• Changes in Cymbalta (duloxetine) Prescribing Info: a number of changes were made, though I cannot tell how substantive these were. Lilly did receive a new indication for the treatment of GAD (Generalized Anxiety Disorder) with Cymbalta.
• Changes in Effexor XR (venlafaxine) Prescribing Info: the following was added under the Precautions section: "Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine therapy have been rarely reported. The possibility of these adverse events should be considered in venlafaxine-treated patients who present with progressive dyspnea, cough, or chest discomfort. Such patients should undergo a prompt medical evaluation and discontinuation of venlafaxine therapy should be considered."
• Zimulti or Acomplia (rimonabant) review extended: This cannibinoid receptor antagonist, which is being reviewed as a weight loss drug (you guessed it... it blocks the munchies, even if you are not smoking pot), was to have a final decision on approval status on April 26. The review period has been extended to July 27. (I reported in November's update that this drug was approved in Mexico.) The latest proposed brand name is Zimulti. The hearing for this drug will be held on June 13, 2007, before the Metabolic & Endocrinologic Drugs Advisory Committee. When the background resource documents are ready, they will be found here.
• Warning Letter: Provigil (modafinil). Cephalon got slapped for promoting its wakefulness-promoting drug (indicated for use in narcolepsy, obstructive sleep apnea, and Shift Work Sleep Disorder) by distributing a document by Dr. Kerasidis which states the drug is effective in multiple sclerosis, Parkinson's, depression, ADD, and chronic fatigue syndrome. Interesting, in that this document was provided as testimony to the Maryland Dept of Health and Mental Hygiene's Committee which is responsible for making decisions about which drugs will be placed on the Medicaid formulary list.
  

FDA Drugs: Sept 2006

2007: Mar | Feb | Jan . . . 2006: Dec | Nov | Oct | Sep

---

Just a quick list of relevant FDA and related notices...

Lamictal & Pregnancy: cleft lip in first trimester... see also Neurology abstract reviewing risk of fetal abnormalities in 4 anticonvulsants (note: take numbers with grain of salt... the N for each drug exposure is kinda low)

Generic Topamax released

Effexor label revised: mentions risk of serotonin syndrome with triptans

Abilify 7.5mg injectable: approved for agitation associated with schizophrenia and bipolar disorder

Contrave advances: New obesity drug... combines Wellbutin/bupropion and Revia/naltrexone to cause weight loss... 6-month trial in 250 people results in 7.5% wt loss (vs 1% for placebo). [see also Orexigen site]