Current psychiatric drugs are only marginally effective

The scientific journal Nature ran an editorial recently with a rather ominous headline: “Psychopharmacology in Crisis.” What exactly is this “crisis” they speak of?  Is it the fact that our current psychiatric drugs are only marginally effective for many patients?  Is it the fact that they can often cause side effects that some patients complain are worse than the original disease?  No, the “crisis” is that the future of psychopharmacology is in jeopardy, as pharmaceutical companies, university labs, and government funding agencies devote fewer resources to research and development in psychopharmacology.  Whether this represents a true crisis, however, is entirely in the eye of the beholder.

In 2010, the pharmaceutical powerhouses Glaxo SmithKline (GSK) and AstraZeneca closed down R&D units for a variety of CNS disorders, a story that received much attention.  They suspended their research programs because of the high cost of bringing psychiatric drugs to market, the potential for lawsuits related to adverse events, and the heavy regulatory burdens faced by drug companies in the US and Europe.  In response, organizations like the European College of Neuropsychopharmacology (ECNP) and the Institute of Medicine in the US have convened summits to determine how to address this problem.

The “problem,” of course, for pharmaceutical companies is the potential absence of a predictable revenue stream.  Over the last several years, big pharma has found it to be more profitable not to develop novel drugs, but new niches for existing agents—a decision driven by MBAs instead of MDs and PhDs.  As Steve Hyman, NIMH director, told Science magazine last June,  “It’s hardly a rich pipeline.  It suggests a sad dearth of ideas and … lots of attempts at patent extensions and new indications for old drugs.”

Indeed, when I look back at the drug approvals of the last three or four years, there really hasn’t been much to get excited about:  antidepressants (Lexapro, Pristiq, Cymbalta) that are similar in mechanism to other drugs we’ve been using for years; new antipsychotics (Saphris, Fanapt, Latuda) that are essentially me-too drugs which don’t dramatically improve upon older treatments; existing drugs (Abilify, Seroquel XR) that have received new indications for “add-on” treatment; existing drugs (Silenor, Nuedexta, Kapvay) that have been tweaked and reformulated for new indications; and new drugs (Invega, Oleptro, Invega Sustenna) whose major attraction is a fancy, novel delivery system.

Testing and approval of the above compounds undoubtedly cost billions of dollars (investments which, by the way, are being recovered in the form of higher health care costs to you and me), but the benefit to patients as a whole has been only marginal.

The true crisis, in my mind, is that with each new drug we psychiatrists are led to believe that we’re witnessing the birth of a blockbuster.  Not to mention the fact that patients expect the same, especially with the glut of persuasive direct-to-consumer advertising (“Ask your doctor if Pristiq is right for you!”).  Most third-party payers, too, are more willing to pay for medication treatment than anything else (although—thankfully—coverage of newer agents often requires the doctor to justify his or her decision), even though many turn out to be a dud.

In the meantime, this focus on drugs neglects the person behind the illness.  Not every person who walks into my office with a complaint of “depression” is a candidate for Viibryd or Seroquel XR.  Or even a candidate for antidepressants at all.  But the overwhelming bias is that another drug trial might work.  “Who knows—maybe the next drug is the ‘right’ one for this patient!”

Recently, I’ve joked with colleagues that I’d like to see a moratorium on psychiatric drug development.  Not because our current medications meet all of our needs, or that we can get by without any further research.  Not at all.  But if we had, say, five years with NO new drugs, we might be able to catch our collective breaths, figure out exactly what we’re treating after all (maybe even have a more fruitful and unbiased discussion about what to put in the new DSM-5), and, perhaps, devote resources to nonpharmacological treatments, without getting caught up in the ongoing psychopharmacology arms race that, for many patients, focuses our attention where it doesn’t belong.

So it looks like my wish might come true.  Maybe we can use the upcoming slowdown to determine where the real needs are in psychiatry.  Maybe if we devote resources to community mental health services, to drug and alcohol treatment, pay more attention to our patients’ personality traits, lifestyle issues, co-occurring medical illnesses, and respond to their goals for treatment rather than AstraZeneca’s or Pfizer’s, we can improve the care we provide and figure out where new drugs might truly pay off.  Along the way, we can spend some time following the guidelines discussed in a recent report in the Archives of Internal Medicine, and practice “conservative prescribing”—i.e., making sensible decisions about what we prescribe and why.

Sometimes, it is true that less is more.  When Big Pharma backs out of drug development, it’s not necessarily a bad thing.  In fact, it may be precisely what the doctor ordered.

Steve Balt is a psychiatrist who blogs at Thought Broadcast.

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  • carolynthomas

    Hi Dr. Steve,

    I’m so glad to see your perspective on this here.

    When you write:  “Not every person who walks into my office with a complaint of depression is a candidate for … Seroquel XR”, you have unintentionally confirmed why the dearth of psychiatric drug R&D is not as tragic as some (in Big Pharma, anyway) might want us to believe.  Seroquel’s approved to treat schizophrenia and bipolar disorder, not depression.  A number of studies suggesting its off-label efficacy for depression and/or anxiety (presented at your American Psychiatric Association meetings, for example) have been funded by AstraZeneca, who of course are the makers of Seroquel. Quelle surprise…. 

    And those “Ask your doctor” Direct-To-Consumer drug ads are, interestingly, legal in only two countries on earth – New Zealand and the U.S.  We might well wonder what powerful industry lobby is responsible for that reality. More on this at: “Same Old Duet: Drug Companies and Psychiatry” – http://ethicalnag.org/2011/04/05/big-pharma-psychiatry-duet/

  • Anonymous

    Dr. Balt, hereare a few examples of the dozens of novel mechanism of action drugs whose development has been suspended in Phase II or III over the last 2 years. .

    AZD2624 Tachykinin antagonist for schizophrenia
    CP-101606 glutamate antagonist for MDD
    ONO-233Ms CRF antagnonist for MDD
    Geripone 5HT1A antagonist for MDD
    Vabicaserin 5HT2C antagonist for schizophrenia
    PF3654746 H3 agonist for schizophrenia
    RG3487 nicotinic agonist for schizophrenia
    JNJ18038683 5HT7 antagonist for MDD
    ACR325 dopamine stabilizer for bipolar disorder

    By focusing on the novelty of those new drugs that have successfully made it to market, your analysis confounds the relative effort put into new mechanism of action drugs with the success of those efforts.  A closer look reveals the true crisis in psychopharmacology, which is the inability to successfully identify novel mechanism of action drugs, not the lack of effort directed to doing so.
     

  • http://www.facebook.com/tniers Thomas Niers

    Dear collegue,
    I am a psychuatrist in the Netherlands. I am glad to hear your critical view on psyhiatric drugs but I’m also amazed that you write about the situation as if your a hostage of the industry! Off course, a lot of psychological symptoms are not to be cured by drugs, and it is our job to let our clients understand how he or she could understand his/her psychological symptom (except in case of severe mental disease without insight off course, but in the majority of cases on a outpatient clinic).
    Hope to hear your reaction or other’s.
    Kind regards,
    Thomas Niers

  • Anonymous

     It would be interesting to try with the information frequencial using magnetic fields, such as VR7-729. It uses frequencies from 0 to 15 Hrz.
    antonio ferrari

  • http://twitter.com/DoctorPullen Edward Pullen

    I recently looked at the manufacturer’s claims as to efficacy of Pristiq, and it had a 52% rate of 8 point HAM-D improvement at 8 weeks, vs. 42% with placebo.  Statistically significant, but clinically significant?  I wonder.  Certainly no big improvement over the expiring patent on venlafaxine that to no surprise this was to replace as a new superior drug.   Another shortcut by pharma to a new drug whose real role was to try to switch patients off a drug whose patent was about to expire. 

  • Anonymous

    Ed, nobody sets out to develop a new drug that is marginally better than existing ones.  You start out with a theory regarding a completely new or modified mechanism of action, and at the end of 8 – 10 years of clinical trials and hundreds of millions of dollars of spending, you get your data and find out whether you’ve accomplished anything.

    Its easy to slam the pharmaceutical industry for marketing  those products that prove to be very modest improvement over older drugs.  But one could just as easily moralize about psychiatrists taking home six figure incomes, when their ability to help most patients with depression, schizophrenia, and OCD is extraordinarily modest. 

    Most of us in the industry work hard, try to have an impact, and are as frustrated by our limited ability to help patients as most psychiatrists are (or should be).

  • http://www.fiveforce.co.uk Antonio Ferrari

    We are all right, but it may be that only the chemistry is not enough? The man is a electro-magnetic and therefore there are more elements needed for his recovery.

  • Dr Joe

    We have medicalized life so as to sell more drugs. In doing so we have reduced the human condition to “chemicals” which need to be balanced. It is time to reclaim some humanity in mental health and see peoples behavior in the context of their life and circumstances.