Cymbalta: Good For Whatever Ails You

I don't have time to write much on the topic, suffice to say that John Russell of the Indianapolis Star raises some good questions about Cymbalta, Eli Lilly's antidepressant/antianxiety/analgesic/good for whatever ails you pill.  He calls it a Swiss Army Knife, which is ironic given that Lilly gave out Swiss Army Knives as part of its Viva Zyprexa campaign, likely as a reminder that Zyprexa (much like Cymbalta) was a broad spectrum psychotropic that could be used to treat, um, a lot of things.  Despite Cymbalta being touted as a cure for both depression and all sorts of different types of physical pain, once again it appears that the science has failed to live up to the marketing, at least for treating pain in depressed patients. Russell's article asks whether it is reasonable to expect that one drug could really work for so many different conditions.  It's well worth a read.

Hat Tip: Furious Seasons and an anonymous reader.

Conflicts, Bad Science, and Corlux: Part Two

The blogosphere has been abuzz with discussion of psychiatrist Alan Schatzberg's dual roles as a tycoon and an allegedly "objective scientist."  But wait... there's more.  Schatzberg is deeply involved with Corcept Therapeutics, a company that has repeatedly found that mifepristone (Corlux/RU-486) is a dud for psychotic depression.  Yet Corcept has continually attempted to spin the results as positive, in a manner that should be obvious to anyone who passed an introductory research methods or statistics course.  Schatzberg has millions of dollars in Corcept shares and should Corcept actually turn out to possess even minimal efficacy for psychotic depression, Schatzberg stands to profit quite handsomely.  

Bernard Carroll has the next chapter in this interesting saga, dealing particularly with Stanford University's claim that Schatzberg was not involved in "managing or conducting any human subjects research" using Corlux.  Such a claim is essentially saying that because of his financial connections with Corcept, Schatzberg avoided tight involvement with the studies of the drug so that he could avoid a conflict of interest.  Dr. Carroll, however, notes that it seems very likely Schatzberg was indeed involved in Corlux research.

There is reason to believe that Dr. Schatzberg had a key role in Stanford’s clinical trials of Corcept’s drug reported in 2001, 2002, and 2006. He was a co-author on all three publications, and there was no disclaimer about his role until 2006. This disclaimer is hardly credible. As Principal Investigator on the NIH grants, Dr. Schatzberg was expected to supervise the junior faculty and research staff at Stanford who recruited, assessed, and treated patients in the studies of RU 486. He was responsible for the choice of outcome measures, about which questions have been raised. He was responsible for the quality of the reported data analyses, which were, frankly, inexpert, when they were provided at all. Above all, he was responsible for the tone of the NIH-supported Stanford publications that claimed Corcept’s drug is effective.

That's just a tidbit -- there is much more to the story, and it should be read immediately at Health Care Renewal.  Keep in mind that Schatzberg is the president of the American Psychiatric Association.  You may then choose to giggle or cry -- your choice.  

Conflicts, Bad Science, and Corlux

Recently, the watchful eyes of Charles Grassley have been peering into the bank accounts of big name psychiatrists. Melissa DelBello and Joe Biederman (1, 2) from the Wonderful World of Child Bipolar were first, and now Alan Schatzberg has been hit. Schatzberg is the Chair of Psychiatry at Stanford University. He is also the President of the American Psychiatric Association. In other words, he's kind of a big deal.

Pharmalot hits the details, but the gist is that Schatzberg is deeply involved at Corcept Therapeutics, a company for which he is chair of the scientific advisory board and holds a large amount of stock. According to Grassley, he did not disclose some of his stock sale profits or the magnitude of his multimillion dollar stock holdings in the company. Additionally, Schatzberg allegedly underreported income received from other drug companies. It appears that Schatzberg was not really required to disclose some of this information, so according to my brief review of the information, it is quite possible that he has broken no rules. Now, whether the rules need to be changed is a different story. No offense to Grassley, but I was well ahead of him on part of this story, noting in April 2007 that Schatzberg had a mega-conflict of interest going with Corcept. I also noted previously that Schatzberg was on the Zyprexa bandwagon, helping to "educate" fellow physicians about the Lilly wonder drug.

The Real Problem: But amidst all this discussion of conflicts of interest, I am afraid that we are getting a bit diverted from the main problem, that of shoddy science. It is admittedly interesting noting that Schatzberg is somehow supposed to be an independent, disinterested scientist while standing to make an absolute truckload of money if his sponsored product succeeds. But it runs deeper. While Schatzberg is a bigwig at Corcept, let's review how Corcept's main product mifepristone (RU-486; yes, the abortion pill) has done.

Mifepristone (aka Corlux) is intended to work as a treatment for psychotic depression. One main problem: It doesn't relieve depressive symptoms. In multiple trials, it has failed to demonstrate antidepressant properties. The CEO of Corcept and another member of their scientific advisory board have previously tried to spin away such inconvenient data by painting negative results as positive. To give Corcept credit, their scientists are consistent spinmeisters, seemingly always able to dredge a positive from obviously negative findings. Schatzberg has been an author on a couple Corlux-related papers that were shredded by independent analysts, who found statistical problems and overly optimistic interpretations of the study results. As the senior member of the Scientific Advisory Board, I assume that Schatzberg had some input on the other study reports that also overstated the efficacy of Corlux.

Could his millions of dollars in Corcept holdings bias Schatzberg, either subconsciously or overtly? You be the judge. But remember that this is not just about conflicts of interest -- this is about science. There is hard evidence that the research on Corlux, which is tightly linked to Schatzberg, has been misinterpreted for the sake of marketing. Conflicts of interest sometimes lead to bad science, but rather than focus just on conflicts of interest, we need to dig a layer deeper and see the poor science -- the shoddy evidence that is used as the foundation for "evidence based medicine" in many cases.

Note also that David Healy has written an interesting piece on the topic of conflicts of interest and bad science, pointing out that a larger problem is lack of access to company-owned data. Think Paxil and suicide. He concludes:

If I were employed in a company marketing department I would much prefer to have the field think that all that is wrong is that a few corrupt academics fail to declare competing interests than to have the field think that company practices that restrict access to data while still claiming the moral high ground of science are the real source of the problem.

I'd love to know what American Psychiatric Association members think about this. The news had already broken about Schatzberg overstating the efficacy of Corlux before he was elected APA president. Do APA members not care that their president has a documented record of putting product promotion before scientific evidence?

More Than Filling My Shoes

I'll be on hiatus for a while. Too many things to do in too little time. Fortunately, material that is right in the sweet spot for readers of this site can be found at:

• Carlat Psychiatry Blog. His takedown of Medscape is much needed, as is further digging into ye olde coverup of industry cash by child psychiatry key opinion leaders.
• PsychCentral. Who cares about St. John's Wort for ADHD? JAMA seriously published a small trial of SJW versus placebo. I thought JAMA was for higher importance issues -- and so did John Grohol at Psych Central.
• Furious Seasons. Overdiagnosis of ADHD? Not a new complaint, but interesting perspective is provided by a Canadian psychologist who thinks the ADHD label is being passed about unnecessarily in Canada.

I hope to return soon.

Say It Ain't So Joe

It appears that Joe Biederman, King of Child Bipolar, has been caught with his hands in the cookie jar. More specifically, the New York Times and Bloomberg have noted that Biederman has received a great deal of pharma cash (like at least $1.6 million dollars from 2000-2007) and has not been very forthcoming about such funds. How was such undercover money revealed? Courtesy of Charles Grassley, the Iowa Republican Senator whose prior investigation unearthed a similar situation impacting another Bipolar Child Key Opinion Leader, Melissa DelBello from the University of Cincinnati.

Here's one example, from Gardiner Harris and Benedict Carey at the New York Times:

In one example, Dr. Biederman reported no income from Johnson & Johnson for 2001 in a disclosure report filed with the university. When asked to check again, he said he received $3,500. But Johnson & Johnson told Mr. Grassley that it paid him $58,169 in 2001, Mr. Grassley found.

So Biederman is supposed to report outside income to the university, but he didn't. Then, his amended reports were in some instances a wild underestimate of his outside income. So how well is the "honor system" working out for conflicts of interest, anyway? To be fair, Biederman is not alone -- two other Harvard psychiatrists (Timothy Wilens and Thomas Spencer) had similar reporting problems. Indeed, there is nothing to say that Biederman's conflicts of interest are any more noteworthy than those of other "stars" in the academic psychiatry universe.

Worry not, Biederman is still interested in saving lives. He is recruiting 4 to 6 year olds with "bipolar disorder" for a Seroquel trial.

For some reason, I thought Biederman's prior comments were worth repeating here. From the Boston Globe:

Biederman dismisses most critics, saying that they cannot match his scientific credentials as co author of 30 scientific papers a year and director of a major research program at the psychiatry department that is top-ranked in the "US News & World Report" ratings.

"The critics 'are not on the same level. We are not debating as to whether [a critic] likes brownies and I like hot dogs. In medicine and science, not all opinions are created equal,' said Biederman, a native of Czechoslovakia who came to Mass. General in 1979 after medical training in Argentina and Israel. He now lives in Brookline.

You tell 'em, Joe! I suppose those who dare critique his conflicts of interest are "not on the same level" as him. Some say that we shouldn't be concerned about conflicts of interest, that we should just look at the quality of a person's work, regardless of financial conflicts. Well, Biederman is the undisputed King of Bipolar in kids, and I'm still awaiting any impressive outcome dataon the "bipolar" kids being treated with antipsychotics. Especially the young kids. 4 year olds on Seroquel -- I'm glad I'm not on Joe's level. Are we better off now that the diagnosis of bipolar has run rampant in kids?

Also see and Furious Seasons and Pharmalot.

Update: Also read the Carlat Psychiatry Blog post on the topic.

Antipsychotics: Global Buckets of Money

Antipsychotics were the sixth best selling class of medications globally in 2007, according to IMS Health. They raked in a cool $20.7 billion, an increase of 10.7% from 2006. Thank God we are doing a better job of overrecognizing, er, appropriately treating bipolar disorder. Antidepressants were #7, at $19.7 billion, down nearly seven percent. This does not appear to be due to declining prescriptions. Blame generics, not decreased prescriptions for the lower numbers. With Cymbalta, Lilly has shown that new antidepressants don't have to be anything special, so it would behoove other companies to release other run of the mill antidepressants, attach a comical, er, highly educational marketing campaign such as Depression Hurts, then watch the money roll in. Just some free advice.

How about the top 10 drugs? Three of them were antipsychotics. No, I'm not kidding. Most surprisingly, Zyprexa had the best figures worldwide, which was interesting given the flat U.S. sales in 2007. Seroquel outsold Zyprexa in the U.S., but Zyprexa had a better run globally. Who knows what tricks are being used to sell Zyprexa internationally? Never mind, it's not like Lilly would do anything sly to market Zyprexa.

The new era of antipsychotics for everything appears to be in full swing.

BOLDER Update: Lilly Started It

Some of my longstanding readers probably remember that I long ago wrote about a statistical issue in the Seroquel trials for bipolar depression (known by the corny acronym BOLDER). It was just a minor issue, you know, the kind that would make a drug look about 50% more effective than a placebo depending on which type of analysis you chose to use. No biggie.

Lilly Started It: It just so happens that Philip Dawdy (who has apparently been christened as Dr. Dawdy) at Furious Seasons recently had a letter published in the Journal of Clinical Psychopharmacology on this issue of statistics. Dawdy noted that the authors' use of a statistical method known as mixed models repeated measures (MMRM) rather than the more conventional last observation carried forward (LOCF) resulted in a major inflation in effect size. As I mentioned earlier, the choice of methods to calculate the effect size (the magnitude of difference between drug and placebo) had a big impact. Dawdy aptly noted that the authors should have reported the effect sizes calculated by both methods so that readers could note how one method made Seroquel look better than did the other method. To quote Dawdy, "...the authors should also have reported the LOCF effect sizes so that the readers would have been aware of how the method impacted the findings." I was flattered to see that my blog was cited in Dawdy's letter. I heard through the grapevine that another author attempted to cite my blog in a letter to the editor, but that the journal struck the citation to my site in the final version of the published letter. If some of y'all researchers who read this blog wanna cite my site, go ahead.

I'm not saying that Seroquel was a dud, but that it did get a boost from the analysis used in the study. When the authors are playing by a new rule when it comes to calculating the differences between drug and placebo, it would make sense to report the results using both the old rules and new rules. In his response, Michael Thase of the BOLDER team responded that "It is my understanding that mixed model repeated measurement (MMRM) analysis was chosen to compute effect sizes in the BOLDER studies because it would permit direct comparison with the results of the study of the only other treatment approved for bipolar depression, the combination of olanzapine and fluoxetine (OFC). Thus, in plain and simple terms, we were attempting to facilitate an apples to apples comparison between quetiapine monotherapy and OFC." So because Lilly did it, we did it. Um, OK. But is there some kind of law against reporting the results from both the newfangled MMRM analysis and the old-fashioned LOCF analysis? Just wondering. And if Lilly started saying it was okay to market Zyprexa off-label for various conditions, would that mean all antipsychotics could be marketed off-label for all sorts of issues? (Hypothetically speaking, of course.)

Stats: Thase goes on to note that there is some research suggesting that MMRM does not overinflate effect sizes; rather, LOCF underestimates them. I know a bit about stats, but I'm not a statistician. Basically, the differences between the methods boil down to how data is handled for persons who dropped out of a study. The best solution is to try to track down study dropouts and assess how they are functioning, rather than having a statistical model guess at their sense of mental well-being, but this requires extra effort and time, and is sometimes not possible. Basically, the LOCF model makes some assumptions that are quirky at best, while MMRM seems to handle missing data better in many situations. All that being said, in many trials where a drug beats placebo, MMRM appears to generate effect sizes that are higher than LOCF, which then leads us to a question "Geez, have we been underestimating the effects of drugs by 50%?" -- um, that seems a little hard to swallow. I'm not quite ready to buy into that.

Smoke and SHHHHHHHHHHHH!

Alan Finder at the New York Times  has, pardon the bad pun, a smokin' good story about entangled relationships, cigarettes, secrecy and Virginia Commonwealth University (VCU).  To what do I refer?  VCU signed a contract with Philip Morris to conduct research, but the catch is that there is a mega-gag order.  Professors aren't allowed to discuss or publish their results without the permission of (guess...) Philip Morris.  If someone (say, a journalist) asks someone at the university about this agreement, university officials are required to decline comment.  The inquiry is then passed along to the company.  Apparently intellectual property rights emerging from any discoveries from such research belong to Philip Morris, not the university researchers.  Until this story broke, it appears that the vast majority of faculty and students were unaware of this contract, maybe due to its potential for negative public relations.

What does VCU have to say?

“There is restrictive language in here,” said Francis L. Macrina, Virginia Commonwealth’s vice president for research, who acknowledged that many of the provisions violated the university’s guidelines for industry-sponsored research. “In the end, it was language we thought we could agree to. It’s a balancing act.”

Oh, that's okay then.  Just because you are Philip Morris's hush-hush scientific whore, it's not a big deal.  It's a "balancing act," which roughly translates to "We'll do anything for a buck."  

But then...

Rick Solana, the senior vice president for research and technology, said university scientists were studying how to identify early warning signs of pulmonary disease, and how to reduce nitrogen and phosphorus drained into rivers from processing tobacco leaves. Dr. Solana also said the contract represented a new focus on developing tobacco products with reduced risks, a shift in strategy in underwriting university research that requires more confidentiality to protect the corporation’s intellectual property rights. And he said Philip Morris had similar arrangements with other universities — although he declined to say how many or which ones.

Imagine that, other universities taking money from tobacco.  All in the name of good science, naturally.  The contract forbids faculty from publishing results without PM's permission, which is a direct violation of VCU's guidelines for industry-faculty collaboration.  But, again, when taking in buckets o' money, all is fair game.  Hey, keep cutting public funding for universities and see if we can make researchers yet more dependent on pharma, tobacco, and whomever else waves the dolla dolla bill.  

Much more analysis available here.

The Bipolar Child Strikes Again

Newsweek has a lengthy story on bipolar children. Well, really, it's about one child and his family. After reading it, there is no doubt that something is very much wrong with the child (Max) profiled in the story. The story is interesting in how it portrays bipolar disorder in kids. A few things I noticed follow.

1. Max's problems are described by the journalist as "incurable" and as "a life sentence." It is true that the kid is likely in for a life of trouble. But stating that such difficulties are a certainty for the rest of his life? That's a little too certain and it's not based on any evidence. Show me one study that indicates that 100% of children like Max will always have a high level of psychological difficulties and essentially be unable to function independently.

2. The biology of child bipolar disorder is discussed as if we have a very firm grasp on the concept, then one major limitation is noted quite briefly.

Scientists now know that bipolar children have too much activity in a part of the brain called the amygdala, which regulates emotions, and not enough in the prefrontal cortex, the seat of rational thought. "They get so emotional that they can't think," says Mani Pavuluri, a child psychiatrist at the University of Illinois at Chicago. More than the rest of us, a bipolar child perceives the world as a dramatic and dangerous place. If he is shown a picture of a neutral face, he may see it as angry. Show him one that really is angry, and his prefrontal cortex will shut down while his amygdala lights up like a firecracker. The typical result: a fury that feeds on itself. Neurological research has its limits, though, and bipolar disorder still cannot be identified based on brain scans.

So dedicate space to how far science has progressed then quickly note that, by the way, these biological findings are useless in making a diagnosis. That's a rather important limitation.

3. How are all of the medications working out for Max?

By 7½, Max was on so many different drugs that Frazier and his parents could no longer tell if they were helping or hurting him. He was suffering from tics, blinking his eyes, clearing his throat and "pulling his clothes like he wanted to get out of his skin," says Richie. In February 2005, under Frazier's supervision, the Blakes took Max off all his meds. With the chemicals out of his system, Max was not the same child he had been at 2. He was worse. Bipolar disorder often gets more serious with age. The brain also reacts to some drugs by remodeling itself, and its dopamine receptors end up naked and sensitive. When the drugs are removed, it's a shock. Off his meds, Max became delusional and paranoid. He imagined Amy was poisoning him and refused to eat anything she cooked. He talked about death constantly and slept little more than two hours a night. Within a month Frazier had put him back on medication, but with a caveat: she wanted to place him in a short-term bed in a child psych ward.

But wait, there's more...

At 10, he has been on 38 different psychoactive drugs. The meds have serious side effects. They have made Max gain weight, and because he's still growing, they frequently need to be changed. The Blakes are aware that many people think their child—any child—should not be on so many drugs. They aren't always happy about it either. But to some degree, they have made their peace with medication.

Yes, you read that correctly -- he's been on thirty-eight psychiatric meds and he's 10 years old. Gee, I wonder if such a heavy regimen of medication is healthy for the developing brain?

4. More on "the bipolar brain"

The bipolar brain tries to compensate for its weak prefrontal cortex by roping in other areas to help; these areas may now become dysfunctional, too. Child psychiatrists thus face an enormous practical challenge: they often can't treat one disorder without affecting another one. "It's like a balloon where you push on one side and the other side pops out," says Wozniak, the MGH psychiatrist who helped define childhood bipolar disorder. With kids like Max, she adds, parents often have to settle for "just having one part of the symptoms reduced."

Um, okay. The bipolar brain "ropes in" other, unspecified brain areas to help the weakling prefrontal cortex and then these areas become dysfunctional too. I'm not a neuroscientist, but I think this explanation is strange at best.

5. Get ready for MANIA

During a recent appointment at Frazier's office, he went into full-fledged mania. Laughing wildly, he rolled on the floor, then crawled over to his parents and grabbed an empty medication bottle, yelling, "Drugs! I've got drugs! It's child safety!" Richie grabbed it back, Max screamed, Richie threw the bottle across the room, as if playing fetch. Max squealed and dove for it, then began to sing into the neck of the bottle: "Booorn to be wiiiiild …" Amy rolled her eyes: "Two kids." And then: "It's hard not to laugh."

It was. And it was hard to look at Max, who has borne so much, and remember that the grin on his face was not a sign of childish goofiness but a symptom of an illness.

Laughing, yelling, rolling on the floor -- it's definitely a manic episode. They probably should have given him a fat injection of Risperdal Consta to calm him down. Oh, and smiling is a symptom of mania as well. Gosh, I am learning sooooooooooo much about bipolar disorder from this article. I can't wait until the DSM-V comes out, at which point we'll discover that we're all bipolar.

Sarcasm aside for a moment, I am not making light of the situation faced by Max and his family. I can understand the sense of desperation felt by the parents and, to some extent, by the treating physicians. The story just rubbed me the wrong way a few times. The story's author was able to find some psychiatrists who were on the bipolar bandwagon, but she was somehow just not quite able to track down the unnamed critics of the bipolar child paradigm that she briefly mentioned in her story. So the bipolar advocates are given names and are quoted, while the nameless critics are essentially a footnote in her story.

I've also written previously about the tangled web of child bipolar disorder.

Hat Tip: Furious Seasons.

Sexual Side Effects of SSRI's: Is the Blindfold Coming Off?

This is my 613th post. One of my most popular posts was called "Sexual Side Effects of SSRIs: Even More Troubling". Well, now there is more information on the topic, courtesy of Audrey Bahrick, a psychologist at the University of Iowa University Counseling Service. Dr. Bahrick has published an article in the Open Psychology Journal regarding the long-term sexual side effects of SSRIs. It is disturbing, important and one of the best articles I've read in quite some time. Quotes from the piece are interspersed with my commentary. [UPDATE: If the link to the article is not working, please scroll to the update at the bottom of the page and try the alternate link.]

Don't Ask, Don't Tell. Because they were often not assessed in clinical trials, sexual side effects were reported to be relatively rare occurrences. If you've followed this story much at all, this is not necessarily news, but it is certainly worth mentioning anyway.

Post market research has clearly established that the SSRIs and SNRIs can affect most every aspect of sexual functioning at rates significantly higher than the 2-16% rates reported in pre-market trials and currently listed in the drug insert literature. Large prospective studies in which baseline assessment excludes participants with pre-existing sexual dysfunction have found rates of treatment-emergent sexual dysfunctions such as decreased libido, delayed orgasm, anorgasmia, erectile dysfunction, and difficulties with arousal, of between 36 and 70%.

"Evidence-Based" Guidelines. Bahrick notes that the literature contains advice that sexual side effects are "medically benign" and "all data suggest return of sexual functioning to baseline once the medication is stopped." Which would be fine if such statements weren't wrong. A lot wrong. Bahrick cites research indicating that:

An estimated 5 to 10% of individuals may experience a diminution of the SSRI or SNRI emergent sexual side effects over time as they remain on the medication, but for the vast majority, the sexual side effects are intractable and will continue for at least as long as they take the medication.

Numb Genitals, Anyone? A variety of SSRI-induced sexual side effects have been reported. Bahrick goes into depth about some of those that are less commonly reported in the literature (maybe because nobody bothers to ask about such effects).

There are indications that some SSRI/SNRI sexual side effects thought to be rare are actually common. The most frequently documented sexual side effects are diminished libido, unspecified problems with arousal, and delayed orgasm or anorgasmia. Delayed ejaculation or orgasm, and anorgasmia have been those symptoms that the literature links most clearly and most frequently to SSRI treatment, vs. to depression itself. However the symptoms of genital anesthesia and pleasureless orgasm, outside the range of common experience and appearing to often occur together, are frequently reported among men and women in Internet communities, in an accumulating case reports literature, and in one research investigation.

Sounds like fun, no? Bahrick then briefly describes the cases of one man and one woman who clearly experienced treatment-induced genital anesthesia. Even after researchers belatedly began to examine the sexual side effects of SSRIs, their measures do not assess for the presence of genital anesthesia. Again, don't ask, don't tell. Only one measure (Rush Sexual Inventory) was reported to assess genital anesthesia, and here's what research found using this measure:

Ferguson did not report specific symptom results, and Zajecka et al. reported only partial results. Zajecka et al. found that among 42 depressed patients taking a variety of SSRIs, 28% of women reported treatment-emergent decreased genital sensitivity and 25% of men reported treatment-emergent decreased intensity of orgasm, suggesting the symptoms are not uncommon.

Zajecka et al. was a small study, to be sure, but this clearly indicates that more research needs to be done on the topic.

In the Long Term. Bahrick also went over some of the evidence she presented in an earlier paper, which I discussed months ago as follows...

According to Bahrick, there is only one study (Montejo et al., 1999) that has examined the emergence of sexual side effects after cessation of SSRI medication. In this study, patients who had experienced significant reductions in depressive symptoms in response to an SSRI were switched to amineptine (which impacts the dopaminergic system and noradrenergic systems to a much greater extent than it impacts serotonin) or to Paxil. A third group received amineptine only (they were not switched from an SSRI). Amineptine-only treatment resulted in 4% incidence of sexual dysfunction, whereas the switched-to-Paxil group had an 89% incidence of sexual dysfunction, and the switched-to-amineptine group decreased from a 100% to a 55% incidence of sexual side effects. Mind you, these treatments lasted for six months, so those who switched to amineptine, a drug that rarely induces sexual side effects, still had a high rate of sexual side effects six months after SSRI treatment discontinuation.

Bahrick also noted that there is quite credible evidence from two trials that SSRIs can prolong ejaculatory latency after the discontinuation of treatment. For some individuals, this is a desired effect. For others, not so much. Likely because they are perceived as so benign, it was also noted that, among urologists, SSRIs are the most widely used treatment for premature ejaculation.

The Internet. Over 1500 individuals belong to one internet-based group whose main focus is the discussion of SSRI-related sexual side effects. Bahrick's review of their discussion indicated:

Sexual side effects are reported also to sometimes change over time: for example, there are indications that what was initially experienced as a positive ejaculation delay evolved over time into persistent post-medication low libido, impotence, leaking semen, and a precipitous decline in quality of orgasm and genital sensation.

Again, sounds like fun, right? Some naysayers may say that this is just a bunch of internet crazies who bonded together based on some bogus perceptions, who blamed treatment for their psychological problems. Alternatively, one might note that the small body of available evidence all converges on SSRIs causing sexual dysfunction in a relatively high percentage of people, so the concerns of this internet group are likely well-founded in reality.

And More. Bahrick also notes that there are four published case reports, totaling eight cases, where the symptoms described in the article have occurred in patients who had no history of sexual difficulties prior to starting SSRIs. On top of that, another report recently appeared in Primary Psychiatry, which noted, among other items...

Sexual side effects manifest in a variety of presentations and severities, but sexual functioning is assumed to return to normal once antidepressants are discontinued. In the recent peer-reviewed literature, three separate case reports have detailed sustained persistence of sexual dysfunction and genital anesthesia well after termination of SSRIs in the absence of residual psychopathology or another identifiable disorder. In each report, the annoying symptoms were absent prior to antidepressant therapy. Oddly, these case reports have not appeared in the psychiatric or psychopharmacology literature, but rather, two have been published in psychology journals and the third in a gynecology/women’s health journal.

Starting a Movement. I often get hits to my site based on Google searches for genital anesthesia combined with various SSRI drugs. These hits have come from across the world. There appears to be a real problem with long-lasting sexual side effects from SSRIs, but the "key opinion leaders" in psychiatry seem much more interested in lining their pockets with drug company money, badly misinterpreting research findings, and looking the other way. And this is what passes for evidence-based medicine?

Read Bahrick's article regarding long-term sexual side effects of SSRIs and ask your doctor about these effects. You are certain to receive an awkward glance. When that happens, feel free to pass along a copy of the article to your physician. If continuing medical education and drug reps aren't going to educate doctors on this issue, I suppose a grassroots effort is in order. Let me know how it goes.

Update. Thanks to an alert commenter for noting that the link to the article does not work. A less direct way to access the article is to follow this link then look for the article in Volume 1. The journal publisher has not yet mastered decent web design. The point of an open access journal is to allow easy access!

Bipolar Overawareness Week Starts With a Bang

As I mentioned last week, Bipolar Overawareness Week begins today.  There is a little bit of media coverage about the latest study from Zimmerman et al. which found that bipolar disorder was being rampantly overdiagnosed in at least one sample.  If you missed my discussion of the study and its implications, feel free to check it out.  

Furious Seasons noted that the Providence Journal has a story in which leading psychiatry researchers Michael Thase and Gary Sachs agreed that bipolar is indeed being overdiagnosed.  I was surprised that they so quickly jumped on the Bipolar Overawareness bandwagon. Welcome aboard, gents!  I have to admit I was shocked to see that Sachs gave the study any credibility given that he recently expressed uncertainty as to whether there was overdiagnosis of bipolar in children (where the rate of bipolar diagnosis has increased much faster than in adults) and has previously written about the underdiagnosis of bipolar disorder in adults.

National Public Radio also has a brief audio bit on the story.  

Philip Dawdy also chronicles his own experience of being diagnosed with bipolar disorder, a diagnosis that from his account seems questionable at best.  A very interesting story.