Cognitive Behaviorists and Big Pharma Demonize Tranquilizers for PTSD

A medical society called the International Society for Traumatic Stress Studies (ISTSS) publishes a set of guidelines for treating those people suffering from post traumatic stress disorder (PTSD), such as soldiers returning from war zones or victims of natural disasters.

Treatments for PTSD generally involve both psychotherapy and psychiatric medications. No psychiatric medication controls two of the primary symptoms of post traumatic stress disorder:  re-experiencing the trauma as flashbacks, and becoming episodically numb or zoned out.  We do, however,  have a medicine that effectively controls the nightmares, believe it or not – an old blood pressure medication called prazocin. I will talk more about medication a little later in the post, but first let me discuss the psychotheray of PTSD. 

Many types of psychotherapy have been employed for PTSD, with widely varying results. 

In my clinical experience, many chronic PTSD patients have been given group therapy, in which they meet with other PTSD sufferers who have had similar experiences. I have found that this sort of treatment has been next to worthless for a significant percentage of such patients, particularly those patients who have been severely disabled by their disorder and who have been unable to work for years or even decades.

In patients with chronic PTSD (who do not also have severe personality disorders or majorly dysfunctional families), it is generally believed that the most effective type of psychotherapy is something called prolonged exposure therapy (PE), which is an intense form of what cognitive behavioral therapists (CBT) refer to as systematic  desensitization.  

It is a difficult process in which - and I am grossly simplifying it in order to be brief (and since I do not do this sort of work myself) -  the traumatic experiences suffered by the patient are relived under controlled conditions so that the anxiety and other symptoms generated by the memories can gradually be extinguished.  I have read that doctors have even experimented with recreating the traumatic events using virtual reality through computers, projected images, and earphones, to enhance the desensitization process.

In a PTSD treatment facility I know of, I was told that if a patient were taking a benzodiazepine tranquilizer like Klonopin or Xanax, then they would not be a candidate for PE and would therefore be referred to the aforementioned group therapy.  I was told this was the case because, CBT folks believed, that tranquilizers somehow affect the learning process so that the PE therapy was not effective if the patient were on the meds.  I had heard this idea before from other CBT therapists. 

However, since people who take benzodiazepines are almost never intoxicated, I had always thought this idea a bit strange. So I asked the head of the clinic for a reference. He did not know of one.  Interesting, I thought.  So I did my own literature search. 

Well guess what?  I found exactly one study that showed that benzodiazepines might affect learning in rats.  But in people?  All of the studies showed they had absolutely no effect whatsoever. 

Yet another urban CBT psychotherapy myth.

But then things got even stranger. I was also told that I should check out the treatment guidelines from ISSTS, which said that benzo’s were not indicated for the treatment of PTSD, and that  this clinic followed ISSTS guidelines.  On advice from the clinic leader, I looked up said treatment guidelines, which turned out to be pretty amazing.

Here’s what they said:

 “Although [benzos] are effective anxiolytics [anti-anxiety] and anti-panic agents, they are contraindicated [italics mine] for PTSD treatment.  They don’t reduce re-experiencing or avoiding/numbing behavior.  They should not be prescribed in patients with past or present alcohol/drug abuse or dependence.  Finally, they may produce psychomotor slowing or exacerbate depression. [Benzo’s] do not have any advantage over other classes of medications; therefore they cannot be recommended as monotherapy[again, my italics] in PTSD at this time.”

Being the cynical critic that I am, I should not have been shocked how a supposedly scientific document could be filled with so many half truths. (I’ll enumerate them shortly). But I was. And then I remembered that the pharmaceutical companies had been demonizing benzo’s ever since they all went generic and therefore became far less profitable for the companies (See my earlier post). 

The Cognitive Behavioral Mafia folks also has a vested interest in demonizing benzodiazepines, it seems to me, since the drugs are so effective for some symptoms. This leads to a situation in which  patients would rather just take drugs than go to a CBT therapist to go through systematic desensitization, which can be a long, involved process that is sometimes itself quite traumatic in the short run. 

This preference is unfortunately common even though it is probably better to treat chronic anxiety with psychotherapy than with medication alone, because when the therapy is successful, the patient might be  more or less cured. Not so with the medication.  If you stop them, the symptoms often return.  (And no, not because the medications cause the symptoms, but because they stop but do not cure the symptoms).

Of course, it is also a perfectly good idea to treat anxiety issues with medicine for the quick relief andtherapy for the eventual cure. You might then be able to stop the drugs after therapy is completed.  Remember, there is no evidence that medications interfere with systematic desensitization. Still, the CBT folks (and many psychiatrists as well) seem to think of drugs versus therapy as some sort of competition or zero sum game, so their prejudices just happen to coincide with the interests of drug companies: demonizing benzodiazepines. 

It is well documented by several news organizations that drug companies have insinuated themselves into scientific committees that draw up treatment  guidelines to make sure that their interest in making higher profits from their brand-named medication is advanced.  I do not have any proof, of course, but might this have been what happened with the ISSTS treatment guidelines for PTSD?

So let us return to the subject of the half truths in the ISSTS guidelines.  Most of the misleading ideas in the paragraph reproduced above have to do with the misconception implied in the guidelines that PTSD generally exists in some sort of psychiatric vacuum in which PTSD patients show no other symptoms of any other psychiatric disorders as well (Comorbid conditions). In fact, comorbidity is the rule rather than the exception.

For patients suffering from PTSD, I find clinically that the most important common co-morbid condition is panic disorder. In this disorder, sufferers experience severe anxiety attacks with physical symptoms that mimic those of a heart attack.  People who have been traumatized are especially vulnerable to developing panic attacks. 

I found it difficult to find information about exactly what percentage of chronic PTSD sufferers also have panic attacks, but in one study it was 35% and in those patients who sought treatment, 49%! (Cougle et. al., Anxiety Disorders 24(2), p. 183, 2010.)  In another study  (Falsetti & Resnick, Journal of Traumatic Stress 10, p. 683, 1997) the percentage was 69%. More than two thirds!

Yet another study (MacFarlane and Papay, Journal of Nervous and Mental Disorders 180 (8)p.498, 1992) showed that comorbid panic disorder is an important predictor of PTSD turning in to a chronic disorder.

People who have panic disorder also often develop agoraphobia - the fear of being out in crowded places.  Agorophobia is particularly likely to develop in combat veterans who have comorbid PTSD and panic disorder because of another symptom of PTSD: hyper-vigilence. It is as if these veterans have to remain constantly on guard for enemy soldiers, rocket propelled grenades, and improvised explosive devices – even though they are now back home in a safe environment. Being hyperalert in a crowd will often bring on panic attacks. 

This is probably one reason why patients with chronic PTSD and panic disorder may do not do well in group therapy. They are deathly afraid of groups.

Supposedly the first line treatment for panic disorder is an SSRI antidepressants like Paxil or Zoloft, but in my clinical experience benzodiazepines tend to be far more effective. The SSRI’s often only decrease the frequency and severity of panic attacks, but do not stop them completely as certain benzo’s often do. In fact, many victims of PTSD are already on SSRI’s when I first see them, and their panic symptoms and agoraphobia are not under any semblance of control whatsoever. 

So I add a benzo. The combination of an SSRI and a benzo is probably the most effective pharmacologic treatment of panic attacks of all, but you will never find a study that shows that.  In fact, you will never find a study using them in combination for the treatment of any disorder. The drug companies won’t fund such studies, because they don’t want doctors to think that benzo’s are good drugs.

Interestingly, the clinic I have been discussing allows patients who are on SSRI’s to get PE, whereas not so for those on benzo’s or the combination.

Back to the ISSTS guidelines.  They correctly point out that benzo’s do not help the PTSD symptoms of flashbacks and numbing - but no one has said that they do.  I agree that they should not be used as monotherapy for PTSD, as the guidelines say, for that very reason. But why would they be contraindicated (which means they should never ever be used under any condition)? The guidelines themselves start out by admitting that they are very effective for panic disorder, which as I have shown is highly comorbid with PTSD.

Well, maybe it’s because, “They should not be prescribed in patients with past or present alcohol/drug abuse or dependence. Finally, they may produce psychomotor slowing or exacerbate depression.” 

Well first of all, the first statement is not at all true for all patients, particularly those patients who have been sober for a significant period of time. Two different studies have shown that ex-alcoholics do not abuse benzo’s at a higher rate than anyone else. Also, some alcoholics are drinking only because they are, in fact, medicating themselves with alcohol for their panic attacks. They often STOP drinking when put on a benzo.

And even if a chronic PTSD sufferer becomes dependent on benzo’s, so what?  Is that somehow worse that being nearly housebound and completely disabled from work because of panic disorder with agoraphobia?  I think not. And the drugs have almost no side effects. The worst thing about being addicted to a benzo is that you are addicted to a benzo.

Ironically, a lot of the PTSD patients I see are never taken off SSRI’s. Essentially, they are dependent on them. But somehow that’s different. How?  Beats me.

What about benzo’s causing depression?  They sometimes do.  Rarely. The studies that led to FDA approval of the various benzo’s show that this happens in the range of 2-6% of cases. Not much different than placebo!  Sometimes one benzo will have this side effect on a given patient, while another will not. And if they all do in a given patient, they can be discontinued. Or an SSRI can be added for the very effective combination therapy, which prevents this side effect as well as the panic attacks.

The treatment guidelines do not say that SSRI’s are contraindicated because some people might develop side effects, so why should benzo’s be? This is particularly nonsensical in light of the fact that one common side effect of SSRI medication is increased agitation. PTSD is an anxiety disorder!!  (This side effect can also be treated with – you guessed it – a benzo).

For Big Pharma Charity Begins at Home and at Taxpayer Expense

Martin Shkreli

According to an article in the British Medical Journal, from 2011 to 2014 drug companies have increased the prices of four of the top 10 drugs sold in the United States by more than 100%, and the prices of the remaining six by more than 50%. 

Most people are familiar with the story of Martin Shkreli, former chief executive of Turing Pharmaceuticals. In August 2015, he purchased a generic drug called Daraprim that treats toxoplasmosis—a life-threatening parasitic infection that many AIDS patients contract—and immediately raised its price by more than 5,000 percent. He has not been alone. The price of many generic as well as brand-named drugs has skyrocketed. In psychiatry, an old antidepressant named Parnate, available since the early 1960's, can cost over $250 per month. It probably ought to be one of those five dollar generics.

What a lot of people may not know is that these price increases are part of what seems to be a scam to bleed tax dollars from Medicare. According to a recent article in Bloomberg News, within days of increasing the cost of Darapin, Turing contacted Patient Services Inc., or PSI - a charity that helps people pay for the insurance copayments on costly drugs. Turing wanted PSI to create a fund for patients who had the AIDS complication that could be treated with Daraprim.

PSI, as it turns out, is one of seven patient-assistance charitable organizations commonly known as a copay charities. There are also many smaller ones. They offer assistance to some of the 40 million Americans covered through the government-funded Medicare Part D drug program.

Having just made Daraprim much more costly, Turing was now seemingly offering to make it more affordable. But that is hardly the whole story. It is also a story about how U.S. taxpayers support a billion-dollar system in which charitable giving is, in effect, a very profitable form of investment for drug companies—one that may also be tax-deductible!

Drug companies know that, all other things being equal, the more expensive they make a drug, the fewer people will purchase it. However, if insurance pays for the drug, then this is is no longer much of an issue. The kicker is that when the Part D Medicare drug law was passed, it included a provision that Medicare, with its leverage on negotiating drug prices created by the size of its insured population, cannot bargain with drug companies for lower prices. If the insurance company uses a "charity" which covers patient co-pays and the so-called donut hole, patients will fill their prescriptions and taxpayers end up paying the huge price increases.

As the Bloomberg article points out, "A million-dollar contribution from a pharmaceutical company to a copay charity can keep hundreds of patients from abandoning a newly pricey drug, enabling the donor to collect many millions from Medicare. The contributions also provide public-relations cover for drug companies when they face criticism for price hikes."

The article added, "Fueled almost entirely by drugmakers’ contributions, the seven biggest copay charities, which cover scores of diseases, had combined contributions of $1.1 billion in 2014. That is more than twice the figure in 2010, mirroring the surge in drug prices. For that $1 billion in aid, drug companies get many billions back.

According to a recent article in USA Today, charity-run funds are now facing new scrutiny by prosecutors in two states and by The Department of Health and Human Services' office of the inspector general. But the focus is only on whether or not co-pay charities favor donor companies' drugs over those sold by other companies. No one is challenging the whole scheme.

Those who are concerned that the government spends too much money and that the national debt is too large should ask themselves why politicians prohibited Medicare from negotiating volume discounts with Pharma companies, thusly creating these lucrative opportunities for them at taxpayer expense.

Pharma Still Up to its Old Tricks

It looks as though big Pharma is still up to one of its most disturbing practices: not publishing or making public studies that show that its products might be ineffective. As described by my colleague Peter Parry later in this post, we had thought this problem was successfully addressed back in 2010.  

Apparently not.

And do not think this problem is unique to psychiatric medications. 

Of course, as I have pointed out several times in this blog, recruitment and assessment of subjects for many research studies these days has become so warped by financial incentives that many of the studies, published or not, are not worth the paper they are printed on to begin with. 

And some studies are purposely designed to mislead readers into believing that certain generic drugs, particularly antidepressants, are not effective when in fact, when used properly for the right patients, they are among the most effective drugs in all of medicine. But that's a 'hole 'nuther issue.

To get back to the issue at hand:

From Medscape, 10/29/13: 

An analysis of nearly 600 registered clinical trials published online October 29 in BMJ has shown that 29% remained unpublished 5 years after completion, that no results were available in ClinicalTrials.gov for three fourths of those unpublished trials, and that industry-funded trials were nearly twice as likely to go unreported as studies that had not received industry funding.

Previous studies have shownthat published trials contain less than half of the patient-outcomes data contained in company-controlled documents.

Dr. Jones and colleagues from the University of North Carolina, Chapel Hill, conducted a cross-sectional analysis of trials that had at least 500 participants and had been prospectively registered with Clinical Trials.gov and completed before January 2009. 

Their analysis included 585 registered trials, 171 of which (29%) remained unpublished. These unpublished studies included nearly 300,000 participants.

"By focusing our investigation on studies with at least 500 participants, we greatly limited the possibility that non-publication of trials in this cohort was due to rejection of manuscripts by journals or a lack of time or interest on the part of investigators or sponsors," the authors write.

The non-publication rate was 32% for industry-funded trials and 18% for those without industry funding (P = .003), and 78% of the unpublished trials also had no reported data in ClinicalTrials.gov.

From Peter Parry (on the webpage TheConversation.Edu.Au):

Dr. Peter Parry

A large proportion of drug trials, particularly those sponsored by pharmaceutical companies, never get published, skewing our picture of drugs' effectiveness and safety.

Research published in 2010 showed results unfavorable to sponsored drugs are less likely to be published, or selectively published to put a favorable spin on poor results.  And internal pharmaceutical industry documents released from court cases show concealment of data is a widespread practice.

A colleague and I assessed such documents about psychiatric medications from five pharmaceutical companies. The papers suggested widespread overstatement of benefits and understatement of adverse effects. Other researchers have found similar problemswith different drugs.

In response, some medical journals voluntarily agreed to publish only studies registered on a website of the US National Institutes of Health, ClinicalTrials.gov. At least studies with unfavorable results would not be buried by drug companies. But the BMJ article confirms that many registered studies still don’t get published.

The AllTrials initiative aims to make the (de-identified) results and methodology of drug trials available to independent researchers so journals can publish in-depth articles based on all of the full data.

In 11 months, the campaign’s petition has gathered over 59,000 individual signatories and over 400 medical and health-care organizations. These include many British medical colleges and learned academic medical science institutions, such as the Cochrane Collaboration and the British National Institute for Health and Clinical Excellence (NICE).

Although the campaign is progressing slower outside the United Kingdom, it is managing to get some traction internationally.

The World Association of Medical Editors (WAME), the South African Medical Research Council and the Canadian Agency for Drugs and Technology in Health have signed.

Maybe there is still hope this problem can be rectified.