Do SSRI's Even Work? And if so, How?

Just in case you feel like reading Sunday's New York Times Magazine before it come out, over on "Post-Prozac Nation: The Science and History of Depression," Siddhartha Mukherjee will be writing about the history and efficacy of antidepressants.  Dr. Mukherjee writes:


Fast forward to 2012 and the same antidepressants that inspired such enthusiasm have become the new villains of modern psychopharmacology — overhyped, overprescribed chemicals, symptomatic of a pill-happy culture searching for quick fixes for complex mental problems. In “The Emperor’s New Drugs,” the psychologist Irving Kirsch asserted that antidepressants work no better than sugar pills and that the clinical effectiveness of the drugs is, largely, a myth. If the lodestone book of the 1990s was Peter Kramer’s near-ecstatic testimonial, “Listening to Prozac,” then the book of the 2000s is David Healy’s “Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression.”


He talks about depressed people in the 1950's being cured as a side effect of their treatment for tuberculosis (isoniazid was one of the first medicines to elevate mood in the depressed) and hyptertensive patients becoming depressed on Raudixin.


Mukherjee goes on:

In 2011, Hen and his colleagues repeated these studies with depressed primates. In monkeys, chronic stress produces a syndrome with symptoms remarkably similar to some forms of human depression. Even more strikingly than mice, stressed monkeys lose interest in pleasure and become lethargic. When Hen measured neuron birth in the hippocampi in depressed monkeys, it was low. When he gave the monkeys antidepressants, the depressed symptoms abated and neuron birth resumed. Blocking the growth of nerve cells made Prozac ineffective.

Hen’s experiments have profound implications for psychiatry and psychology. Antidepressants like Prozac and Zoloft, Hen suggested, may transiently increase serotonin in the brain, but their effect is seen only when new neurons are born. Might depression be precipitated by the death of neurons in certain parts of the brain?


He finishes off with the ideas:

The differences in responses to these drugs could also be due to variations in biological pathways. In some people, neurotransmitters other than serotonin may be involved; in yet others, there may be alterations in the brain caused by biological factors that are not neurotransmitters; in yet others, there may be no identifiable chemical or biological factors at all. The depression associated with Parkinson’s disease, for instance, seems to have little to do with serotonin. Postpartum depression is such a distinct syndrome that it is hard to imagine that neurotransmitters or hippocampal neurogenesis play a primary role in it. 

Nor does the theory explain why “talk therapies” work in some patients and not in others, and why the combination of talk and antidepressants seems to work consistently better than either alone. It is very unlikely that we can “talk” our brains into growing cells. But perhaps talking alters the way that nerve death is registered by the conscious parts of the brain. Or talking could release other chemicals, opening up parallel pathways of nerve-cell growth. 

But the most profound implications have to do with how to understand the link between the growth of neurons, the changes in mood and the alteration of behavior. Perhaps antidepressants like Prozac and Paxil primarily alter behavioral circuits in the brain — particularly the circuits deep in the hippocampus where memories and learned behaviors are stored and organized — and consequently change mood.

Ketamine, Special K, and Depression

I just wrote a post over on Clinical Psychiatry News about the experimental use of ketamine (aka, rave drug "Special K") for instant relief of depression and suicidal ideation.

Please go over there to read it (link above), and feel free to comment there (sorry, registration is required but it's free) or here. I'd like to hear about providers who have used ketamine for their patients and from people who themselves have used it for depression.

Edit: find a list of clinical trials using ketamine for depression on clinicaltrials.gov.

No Better Than a Sugar Pill?

We're only a few minutes in to "today" but here's a link to an article in the New York Times by Peter Kramer-- In Defense of Antidepressants.  Kramer writes:


Could this be true? Could drugs that are ingested by one in 10 Americans each year, drugs that have changed the way that mental illness is treated, really be a hoax, a mistake or a concept gone wrong?
This supposition is worrisome. Antidepressants work — ordinarily well, on a par with other medications doctors prescribe. Yes, certain researchers have questioned their efficacy in particular areas — sometimes, I believe, on the basis of shaky data. And yet, the notion that they aren’t effective in general is influencing treatment. 

Kramer goes on to discuss issues in the research that may have biased studies that deem anti-depressants to be no better than placebo.  Do read it if you get the chance.

Podcast #58: I Need a New Drug and Happy Five Years of Shrink Rap and Still Blogging

(Belated) Happy Blogiversary to Us!

Five Years and Still Blogging

Shrink Rap quietly turned Five on April 21st. We chatter about this while we podcast. We kept it short again and talked about some new medications. Roy mentioned a new antidepressant, Viibryd that's a bit like a combo of an SSRI + buspirone. Dinah talked about a conference she went to on psychopharm update and she read some of the slides that were presented by Dr. Neil Sandson. This led us to talk about some other new medications, including long-acting antipsychotic medications that are administered by injection.

We then talked about Silenor, a sleep medication which is the re-packaging of an older medication, Doxepin, in a lower dose. A phone call to the pharmacy revealed some interesting information about the cost of these medications, but you'll have to listen, or call the pharmacy yourself, if you want the answer.

This all led us to a discussion of the combination medication for the treatment of obesity, Contrave, that did not get FDA approval, and Steve's post on his psychiatry blog, Thought Broadcast, on Contrave compared to Swiffer floor cleaning system. Huh? Oh, listen and maybe we make sense.


Thank you for listening.
We invite you to go to iTunes and write a review.

And our Shrink Rap book should be available in the next few weeks: our review copies have arrived. Our next line will be "Go To Amazon and write a review!"

****************************

This podcast is available on iTunes or as an RSS feed or Feedburner feed. You can also listen to or download the mp3 or the MPEG-4 file from mythreeshrinks.com. Thank you for listening. Send your questions and comments to: mythreeshrinks@gmail.com.

Is This Fish Happy or Toxic?

Thank you to Anon who sent us a clip to this interesting article in the Montreal Gazette about all the fish in the St. Lawrence River who are being exposed to anti-depressants though human waste.

William Marsden writes in "Antidepressants Found in Fish":

"It's very hard," Sauve said. "The question itself is quite interesting. You can't ask a fish whether it is happier or not. One of things they can do is use cameras to look at the male behaviour. Will it have the same behaviour in mating or feeding? Then you have to go back and look at its normal behaviour. It's quite tedious work and difficult."

Quebecers purchase about 555 million antidepressants a year. That works out to about one in four Quebecers taking one pill a day. That does not include the amount prescribed by psychiatric hospitals.

Hmm... I'm not sure what to say. Should we be more alarmed about what the meds are doing to the fish (and just how happy should a fish be?) or the idea that Quebecers average a one in four rate of taking anti-depressants?

Antidepressants on Kevin.MD

Dheeraj Raina is a healthy who has a blog post on KevinMD called "How an Antidepressant Can Hurt Your Patient."

The post is directed at primary care docs and talks about the danger and downside of prescribing anti-depressants. Too much use as 'feel good' drugs without careful consideration of the diagnosis, appropriate treatment with adjunctive psychotherapy, and the risk of manic induction and suicide.

It's probably not likely that every patient with anxiety and depression will end up seeing a healthy. Obviously, we at Shrink Rap don't think antidepressants should be doled out mindlessly--- if primary care docs are going to prescribe them, they should--

Know how to diagnose depression.
Know how to use the medications. This is not as easy as it might sound: Antidepressants take time to work and the dosing requires titration. Sometimes they need to be changed, increased, augmented. If the first try at a standard dose works, you can call it a day---but this is why the meds have the rap for being only as good as placebo. They don't work if you don't know how to use them and one size doesn't fit all.
There are risks, side effects, adverse reactions, and contraindications.
With psychotherapy, time, and support, there are people who won't need treatment with medications and those options get bypassed when a script gets written in a quick visit.

PS. I agree with Dr. Raina that this can't be done in a 15 minute office visit.