When Anecdotal Evidence is Sufficient Proof

Printed by Publish Any Damn Thing or Perish Press. Research funded by the Keep Unimaginative Academics Employed Foundation.

As I did on my posts of November 30, 2011,  October 2, 2012, September 17, 2013, June 3, 2014, and February 24, 2015, it’s time once again to look over the highlights of the latest issue of one of my two favorite psychiatry journals, Duh! and No Sh*t, Sherlock. We'll take a look at the unsurprising findings published in the latest issue of Duh! My comments in bronze.

As I pointed out in those earlier posts, research dollars are very limited and therefore precious. Why waste good money trying to study new, cutting edge or controversial ideas that might turn out to be wrong, when we can study things that that are already known to be true but have yet to be "proven"? Such an approach increases the success rate of studies almost astronomically. And studies with positive results are far more likely to be published than those that come up negative.

May 7, 2105. Study: Bisexual And Gay Children More Likely To Be Bullied As They Grow Up

The AP (5/7, Stobbe) reports that a research letter published May 7 in the New England Journal of Medicine suggests that bisexual and gay children “are more likely to be bullied as they’re growing up – even at an early age.” Researchers found that “many of the nearly 4,300 students surveyed said they were bullied, especially at younger ages,” but 13 percent of the 630 bisexual and gay youngsters reported being bullied “on a weekly basis,” compared to just eight percent of the other children.

        HealthDay (5/7, Haelle) reports that “consequences of bullying can include physical injury, anxiety, low self-esteem, depression, suicidal thoughts, post-traumatic stress and negative school performance...said” the study’s lead author. 

This is just more propaganda from people advancing the gay agenda.

6/15/15. Small Study: Lisdexamfetamine May Improve Memory, Concentration Problems Associated With Menopause.

HealthDay (6/13, Haelle) reported that the stimulant medication lisdexamfetamine, which is “marketed for attention-deficit/hyperactivity disorder, might improve memory and concentration problems associated with menopause,” according to a study of 32 menopausal women published online June 11 in Psychopharmacology. The study, which received support from the NIH and Shire, the maker of lisdexamfetamine, revealed that “brain activities such as memory, reasoning, multitasking, planning and problem-solving,” improved while women were taking the medicine.

Hate to break this to the Pharma shills, but stimulants will do that for ANYBODY.

8/4/15. Pediatric brain injuries may be associated with attention issues

The Washington Post (8/4, Cha) “To Your Health” blog reports that youngsters who suffer a brain injury, even one considered minor, may be “more likely to experience attention issues,” according to a study published online Aug. 3 in Pediatrics. For the study, investigators included “113 children, ages six to 13, who suffered from traumatic brain injuries (TBIs) ranging from a concussion that gave them a headache or caused them to vomit, to losing consciousness for more than 30 minutes, and compared them with a group of 53 children who experienced a trauma that was not head-related.” HealthDay (8/4, Doheny) reports that the study found that “attention lapses” suffered by the kids with TBIs “led to lower behavior and intelligence ratings by their parents and teachers.” What’s more, the “loss of focus was apparent even when scans showed no obvious brain damage, the researchers said.”

Because injuries to the brain always improve its performance.

8/18/15. Family Problems Early In Life May Raise Boys’ Risk Of Depression, Anxiety.

HealthDay (8/18, Preidt) reports, “Family problems early in life might raise boys’ risk of depression and anxiety, which is also tied to altered brain structure in their late teens and” into early adulthood, according to a study published online Aug. 17 in JAMA Pediatrics. The study, which “included nearly 500 males, ages 18 to 21,” found that “those boys who faced family problems during” the years from birth to age six “were more likely to have depression and anxiety at ages seven, 10 and 13.” Such boys “were more likely to have lower volume of...’gray matter’ in the brain by the time they reached ages 18 to 21.”

What was Freud even THINKING?

8/31/15. Risky Behaviors May Be Signs Of High Suicide Risk In People With Depression.

 

HealthDay (8/30, Preidt) reported, “Risky behaviors such as reckless driving or sudden promiscuity, or nervous behaviors such as agitation, hand-wringing or pacing, can be signs that suicide risk may be high in depressed people,” research presented at the European College of Neuropsychopharmacology’s Congress suggests. The study, which involved some 2,800 people with depression, also revealed that “other warning signs may include doing things on impulse with little thought about the consequences.” People with depression “with any of these symptoms are at least 50 percent more likely to attempt suicide, the new study found.” 

This is just silly. We all know that people who are keen to die are risk averse.

10/7/15. Small Study: Older Adults Appear To Recover More Slowly From Concussion Than Younger Patients.

HealthDay (10/7, Preidt) reports that “older adults recover more slowly from concussion than younger patients,” according to a study published online Oct. 6 in the journal Radiology. Included in the study were “13 older adults, aged 51 to 68, and 13 young adults, aged 21 to 30.” All participants were evaluated at the four-week and 10-week mark following their concussions. While “a significant decline in concussion symptoms – such as problems with working memory – was seen among young patients between the first and second assessment,” researchers found “no such decrease in symptoms...in older patients.”

Aw come on. The body always improves with advanced age.

10/14/15.  Psychological Distress May Be Highly Prevalent In Caregivers Of Patients With Advanced Cancer.

Medscape (10/14, O'Rourke) reports that “psychological distress is highly prevalent in caregivers of patients with advanced cancer and is associated with both caregiver and patient factors, researchers said...at the Palliative Care in Oncology Symposium (PCOS) 2015.” Lead study author Ryan David Nipp, MD, said, “Caregiver characteristics that were significantly associated with caregiver depression were being female and having anxiety.” Dr. Nipp added, “Patient factors that were associated with caregiver depression included patients reporting depression, that the goal of their care was to cure their cancer, and using emotional support coping.”

The impending death of loved ones is always such a high!

10/21/15. Parental Involvement May Optimize Therapy For Kids With Disruptive Behavior Disorders.

Reuters (10/21, Rapaport) reports that having parents participate in therapy for youngsters with disruptive behavior disorders may help the children respond optimally to that treatment, according to a meta-analysis of 66 studies published online Oct. 19 in the journal Pediatrics.

Nonsense. We all know that being rude is genetic.

10/28/15. Cancer diagnosis may lead to loss of income, study indicates

The Washington Post (10/28, Blakemore) “To Your Health” blog reports that research indicates that cancer “can take a heavy toll on patients’ pocketbooks, even long after they recover.” The Los Angeles Times (10/28, Kaplan) reports in “Science Now” that researchers found that “in the second year after being diagnosed with cancer, survivors were earning up to 40% less than they had been before they became sick, on average.” The data indicated that “even in the fifth year after diagnosis, annual earnings still had not recovered to their precancer levels.”The findings were published in Cancer.

Because, thanks to the demise of unions, fewer and fewer folks get paid sick days from their job any more. (I'm not being funny).

11/10/15.  Study Supports Raising SSRI Doses in Patients Who Do Not Respond to Low-Dose Treatment

Using a higher dose of selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder appears to be associated with an increased likelihood of response, according to a meta-analysis published today in AJP in Advance. This benefit, which is somewhat offset by decreased tolerability of SSRIs at high doses, appears to plateau at about 50 mg of fluoxetine (250 mg imipramine-equivalent dose). A team of researchers in the United States and London searched PubMed for randomized, placebo-controlled trials that examined the efficacy of SSRIs for treating adults with major depressive disorder and assessed improvement in depression severity at multiple time points.
       

Er- the first lesson in psychopharmacology 101, I believe.

11/20/15.  Opioid Addiction In Women May Often Start With Physician-Prescribed Medications.

Medscape (11/20, Brooks) reports that new research suggests that the upsurge in the number of women with opioid addiction may be attributed to prescription medicines. Researchers evaluated “sex differences in substance use, health, and social functioning among 266 men and 226 women receiving methadone treatment for opioid use disorder in Ontario.” The researchers found that over half of women (52%) and a third of men (38%) “reported physician-prescribed opioids as their first contact with the” medications. The findings were published online Nov. 9 in the journal of Biology of Sex Differences.

This can't be right. Addiction can only be caused by that evil weed gateway drug, marijuana. Or was that beer?

Double Standards for Brand Named vs. Generic Drugs in Literature Reviews: Use of Medication in Borderline Personality Disorder

In the free psychiatric "journal" Psychiatric Annals (Psychiatric Anals?) of August 15, 2015 - no doubt financed by PhARMA - one article correctly points out that studies on medications used for symptoms of Borderline Personality Disorder have been very small, extremely infrequent, very short-term, poorly controlled, and of limited usefulness. (And done without ANY consideration for comorbid disorders like panic disorder, which is seen in about 40% of subjects, I might add).

It also points out, again correctly, that there are no medications for the disorder itself, and that psychotherapy is the treatment of choice for that. Nonetheless, most of these patients do take medications for certain symptoms of the disorder: most usually the mood instability, irritability, and impulsivity that lead to such other problems such as self-injurious behaviors like cutting.

The review of the studies that have been done is fairly complete, although I notice that they left out an extremely important article on the use of Prozac for the symptom of "impulsive aggression" by Coccaro and Kavoussi from 1997.

During its rather limited review of studies of the use of antidepressants in the disorder, it says things like, "The authors found a reduction in anger among the fluoxetine (Prozac) recipients," "Fluvoxamine (Luvox) improved rapid mood shifts," "Sertraline (Zoloft) was more effective in decreasing symptoms of depression, hypersensitivity in interpersonal relationships, and obsession," and "superior efficacy for phenelzine (Nardil, and MAO inhibitor) on measures of depression, borderline psychopathologic symptoms, and anxiety."

In the summary of this part of the review, it nonetheless says, "No statistically significant effects were observed for the selective serotonin reuptake inhibitors (SSRIs) or phenelzine." So what on earth were those that they had just listed?

Yet, after discussing similar weak data for mood stabilizers, it makes the following summary: "RCT's (randomized controlled studies) involving the mood stabilizers were limited by low statistical power. Divalproex sodium (Depakote) shows an effect for anger and interpersonal sensitivity. Topiramate (Topamax) and lamotrigine (Lamictal) were found to have an effect on anger."

And for atypical antipsychotics, after reviewing even weaker evidence, the summary says: "Olanzapine (Zyprexa) has the most supporting data of the antipsychotics; studies have shown its use can lead to reductions in anger, paranoia, anxiety, and interpersonal sensitivity. Effects were found for aripiprazole (Abilify) on impulsivity, anger, anxiety, psychosis, and interpersonal problems."

Misleading double standard for summarizing the effect of brand-named versus drugs available as generics, ya think?

Randomized Controlled Studies vs. Widespread Clinical Experience: the Case of Lamictal

There has been an increasing debate about whether doctors are using "evidence-based medicine" or instead are merely going by conventional wisdom or listening to pharmaceutical company sales pitches. Often, as I have discussed several times, the so-called "evidence base" consists of randomized controlled studies (RCT's), while clinical experience is written off as "anecdotal." 

An anecdote is a report of a single, or at most a few, specific incidents, such as a patients' seeming to get better after taking a medication, along with the interpretation of the event by an allegedly biased observer. Besides the fact that one or two cases may not be representative of a psychiatric condition, and that other causes for the observed effect have not been ruled out, the description provided by the source of the anecdote may be incomplete or incorrect. And his or her conclusion may be logical, or it may be fallacious in any of a variety of different ways.

Widespread clinical experience — or the clinical experiences of a wide variety of practitioners who are known to do careful diagnostic work-ups and to follow patients closely — is somehow also written off as "anecdotal," but this is just nonsense. 

First of all, as I discussed in a previous post, in psychiatry there are almost no objective diagnostic blood tests or direct measurements of brain function that can tease out the difference between neuropathology and normal neural plasticity in response to environmental factors. Therefore, conclusions drawn in RCT's are based entirely on the self-report data from subjects or by the potentially biased observations of the experimenters. They are just as much anecdotal as widespread clinical experience in that sense. 

Actually, widespread clinical experience is better than most RCT's in determining the efficacy of drugs. It employs a sample size far larger than all the RCT's on a treatment put together. Also, there are several important  limitations with RCT's.

In a paper by G. Parker and S. McCraw (Acta Psychiatrica Scandinavia, 2015: 1-10) about the drug Lamictal (lamotragine), they discuss the disconnect between the reported efficacy of a new psychotropic medication as quantified in RCTs and its actual effectiveness as observed in the 'real world' of psychiatric practice:

"Most commonly any such disconnect is one of degree, with the medication being progressively clinically judged as less or more effective. Less commonly, the medication may be judged to have a different therapeutic 'signal' than for its formal indication. Two examples of the latter are the selective serotonin reuptake inhibitors (SSRI's) which seemingly modulate emotional dysregulation as much as they have antidepressant propensities, and some atypical antipsychotic drugs having utility in augmenting antidepressant medications and in having mood stabilizing propensities rather than being confined to the management of psychotic conditions.

Any such disconnect can reflect multiple factors, as considered now in relation to antidepressant medications. An antidepressant's 'efficacy' is evaluated from RCTs with the 'control' treatment being either a placebo or a comparator drug. In such trials, the duration is often limited to several weeks, the sample constrained by inclusion and exclusion criteria (e.g. non-suicidal, no substantive co-morbid conditions) that do not hold in clinical practice, and which may, depending on recruitment strategies, be weighted to those with potentially spontaneously remitting and/or less severe conditions. 

RCT-evaluated efficacy may he overestimated using a lower-than-usual dose of any comparator medication, or underestimated if the antidepressant is prescribed at what might be later determined to be a suboptimal dose. Biases may emerge if the sponsoring developers provide data only on trials generating superior findings. "

Richard Horton, editor of the medical journal The Lancet, recently observed, “The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness.”

In studies used to evaluate medications for treatment of various mood disorders, there is another glaring problem: the use of inadequate and incomplete diagnostic evaluations of the subjects. I have written several posts about the nonsensical expansion of the diagnosis of bipolar disorder, in which researchers lump together Bipolar I with the bogus disorder Bipolar II. 

Readers of this blog know my attitude about the latter: In my practice since I started training, I have seen four patients who actually met the DSM criteria for this supposed disorder when they were interviewed carefully and followed closely, and all four responded to lithium, suggesting that they were just milder cases of Bipolar I. And most patients who were given that diagnosis by previous psychiatrists did not have bipolar disorder at all but had the mood instability characteristic of certain personality disorders. Some studies have shown this to be true.

Worse yet, some studies include patients diagnosed with unspecified bipolar disorder and "bipolar spectrum disorder."  Neither is defined clearly nor is there any agreement on exactly with what criteria these diagnoses are to be made. So the RCTS's are basically comparing apples to oranges.

This particular problem is not discussed clearly in the Parker and McCraw article. In fact, they conclude that the anticonvulsant drug Lamictal (lamotrigine) is probably not effective in bipolar I disorder, but probably is effective in bipolar II disorder - which probably means it may help the affective instability of patients with personality disorders. This puts this drug as a possible alternative to SSRI's, which the authors themselves note "... seemingly modulate emotional dysregulation."  Emotional dysregulation and affect or mood instability are basically the same thing.

(Combining SSRI's and a long acting benzodiazepine such as clonazepam is even more effective in "raising the bar" on the strength of environmental stimuli required to set off an episode of affect dysregulation, as well as in decreasing self-injurious behaviors like cutting. There are no RCT's on this combination for these symptoms; the drug companies won't do them because most of these drugs are generic and the drug companies probably know that it is effective but do not want docs to know this. However, widespread clinical experience by those doctors who know the difference between bipolar disorder and borderline personality disorder backs me up on this).

The history of the FDA approval for the drug Lamictal for bipolar disorder is bizarre. Its manufacturer first touted it as a treatment for the depressive episodes in bipolar disorder, although later studies showed it to be ineffective in the acute phase of bipolar depression. Then, when it got the FDA approval for psychiatric use, rather than being given the indication for prophylaxis for (prevention of) episodes of bipolar depression, it was given a general indication for bipolar disorder as a whole. This, even though there was zero evidence that it prevented episodes of mania, or that it was useful in acute mania.

In fact, most of the studies in bipolar disorder with the drug were based on a rather flawed outcome measure. The drug was found to delay, but not to prevent, the emergence of another bipolar episode. Whether the episode was a depressive episode or a manic episode was not specified in the majority of these studies!  

Furthermore, lithium — the standard prophylactic treatment—when used at the dosages which lead to the correct blood levels of the drug in patients who respond to and can tolerate it (about 80% of bipolar I patients) completely prevents the re-emergence of manic episodes. In those cases, the measurement "time until the next manic episode" would essentially be the patient's entire lifetime. 

Delaying episodes of bipolar disorder is better than having them more frequently, but why would you use a drug to do that when there is another drug that can prevent them from happening completely?

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 psychotherapy 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 and therapy 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).

Is Marketing Drugs for Non-FDA Approved Uses Free Speech?

A recent ruling by a three-judge panel of the Court of Appeals for the Second Circuit in Manhattan threatens to legalize the marketing of snake oil without any restrictions. It maintains that the marketing  of pharmaceuticals by drug companies for conditions for which the FDA has not approved them is free speech!

Considering the ruling of the Supreme Court in the Citizens United case, many of us are highly concerned that if the lower court ruling is appealed and ends up there, that the current court will concur, and this will become the law of the land.

U.S. Supreme Court

As my colleague Ken Harvey says, only in America.

I have posted here several times about the huge fines levied against big Pharma drug companies for marketing psychiatric and other medical drugs for uses in conditions for which the FDA has not approved them as safe and effective. For a summary, see my last post on the subject.

Once a medication is FDA-approved for any indication, doctors are absolutely free to prescribed it for any other condition they see fit, but pharmaceutical companies are not allowed to market the drugs for these other conditions. This is important because pharmaceutical companies can run poorly-constructed studies that show that a drug might help this or that condition, and if there were no law against it, use their various marketing techniques and financial inducements to get doctors to prescribe the drug to larger and larger populations of patients.

Many of these powerful marketing techniques have been described by me in a series of previous posts (the last one being my post of August 7, 2012). The profits to be gained by so-called off-label marketing are enormous, and completely dwarf even the billion dollar plus fines levied by the U.S. Department of Justice. The fines are considered to be just a cost of doing business by Big Pharma.

This situation has also led to an explosion of disease mongering, in which the definitions of disorders like bipolar disorder for which certain drugs are FDA-approved are expanded beyond all reason (see my posts of 10/20/12 and 8/13/11).

The damage to patients, especially in the field of psychiatry, has been particularly horrendous. People with family and behavioral problems who are in desperate need of psychotherapy are instead given only drugs, many with potentially toxic side effects.  Patients unfortunately are all to eager to buy in to the proposition that their emotional problems or those of their children are merely the result of some brain dysfunction rather than their own behavioral difficulties.

(Disclaimer for the anti-medication lot: of course some psychiatric conditions do indeed result from brain dysfunction, and for those medication is the primary and most effective treatment, and psychotherapy is next to worthless. Which ones are those?  Read this blog! Also, medications can control anxiety and emotional reactivity so that psychotherapy becomes even more effective).

Just as an aside, readers may wonder if I think it should be illegal for doctors to prescribe medications for non-FDA approved indications. This is a complicated question, because of the crazy way the FDA in the U.S. works. For example, we know that if one SSRI antidepressant (Prozac, Paxil, Zoloft, Lexapro, Luvox, Viibrid) works for, say obsessive compulsive disorder, then they all do.

However, once one drug company does the studies that result in their getting an approval from the FDA for their product for this indication, the other drug companies have no financial incentives for doing studies with their own product. Doing the studies is expensive, and they know doctors know about the if one-then all idea, so they will use the other me-too drugs off label. I don't see anything wrong with doctors doing so in properly diagnosed patients (which, BTW, is unfortunately a big "if" nowadays).

Also, sometimes there is widespread clinical experience that shows that a given drug is effective for a certain indication for which studies have not led to FDA approval for that indication. For instance, many of us have successfully used SSRI antidepressants in patients with borderline personality disorder to decrease their emotional reactivity (neuroticism). The drugs do not stop the hyper-responsiveness that these patients show to problematic interactions, but they do raise the bar. It takes a higher level of stress to get them into a state of dysregulation than it would in an unmedicated state.  Hardly a cure, but still very useful.

There have been many studies to show that SSRI's do this, some performed by Emil Cocarro, a highly respected researcher. But so far, no drug company has, for a variety of reasons, made a petition to the FDA for this indication.

Dr. Emil F. Cocarro

I would be very much opposed to any action that would limit my ability to help my patients in this way. Unfortunately, many of my colleagues listen to drug company propaganda and use drugs in ways that are very inappropriate. I'm not sure what the solution to this quandary is, but of one thing I am certain: allowing Big Pharma to market drugs for unapproved indications ain't it.

An Update of Some Earlier Blog Posts

There have been some new developments recently concerning some of the issues and stories I have discussed previously on this blog, so I thought I would write a new post that updates some of my previous ones.

First, apropos my post of May 25, Pro-death Florida Legislators Run Amok, about a recently-enacted Florida law prohibiting health care practitioners from even discussing health care concerns about gun ownership with their patents: it was temporarily blocked by Federal U.S. District Court Judge Marcia Cooke. The state plans to appeal the injunction blocking enforcement of the law.

Second, concerning the debate about SSRI antidepressants and whether they are better than placebos:  A Commentary in the December 2011 edition of the American Journal of Psychiatry pointed out that placebo response rates to antidepressants in studies have increased as much as 7% per decade since 1980. 

Not coincidentally, this bizarre inflation of placebo response rates correlates very well with the timing of the rise of the so-called contract research organization, or CRO (http://opp.morningstar.com/PDFs/MOI-EvoCRO.pdf).  These organizations are usually doctors in private practice who are hired by drug companies to do their randomized controlled studies of medications.  These doctors get paid - quite handsomely - for each subject that they successfully recruit for the study. 

The subjects are, in turn, recruited through offers to pay them for their participation. ABC News recently did a story about stay-at-home moms who turn themselves into guinea pigs to earn extra cash. The use of paid subjects has led to the phenomenon of the "professional research subject" who participates in multiple drug trials.

Under these circumstances, both the doctors and the patients are being given cash incentives for exaggerating their symptoms in the initial evaluation so they can qualify for the study!  Once they are picked, no one then has a financial incentive to exaggerate symptoms on follow-up exams.

No wonder placebo response rates have skyrocketed.

CRO Newspaper ad clues in potential research subjects who wish to get paid as to what symptoms to complain about



Last, there are two developments concerning schizophrenia and its treatment with antipsychotic drugs. 

First, as the states have been cutting back on funding for community mental health centers due to the economic downturn, we are seeing a lot of what is described in the following news article:

http://www.freep.com/article/20111127/OPINION02/111270434/After-closing-psychiatric-hospitals-Michigan-incarcerates-mentally-ill-?odyssey=tab%7Ctopnews%7Ctext%7COpinion

After closing psychiatric hospitals, Michigan incarcerates mentally ill

"Wayne County Sheriff Benny Napoleon spoke for most sheriffs when he said, during a community meeting earlier this year, that his jail had become his county's largest mental health care institution.
Over the last two decades, changes in state policy and big cuts in funding for community mental health care have pushed hundreds of thousands of mentally ill people into county jails and state prisons...

"'We closed too many (hospitals), too quickly,' Mark Reinstein, president of the Mental Health Association in Michigan, told me this month. "It wasn't done in a planned, rational way."
Community mental health agencies -- which were supposed to take up the slack but never received the resources to do so -- face continuing budget cuts. The state has resumed warehousing its mentally ill -- this time behind bars...

 "In 1999, a Department of Community Health study -- conducted by Wayne State University -- of jails in Wayne, Kent and Clinton Counties found that more than half their populations were mentally ill and one-third were seriously afflicted, suffering from schizophrenia, bipolar and other psychotic disorders... Since 2008, the state has slashed $50 million from community mental health agencies, with Wayne County absorbing more than half of the cuts.

"Treating one client in a community program costs about $10,000 a year, compared with $35,000 a year to house one prisoner.  Statewide, more than 200,000 people a year use community mental health services, but experts say at least twice that many need them."

To really understand what happens when funding to community mental health centers is cut significantly, one has to realize that fewer patients with schizophrenia will get treated with anti-psychotic medication. Such medication is all the treatment that community mental health centers are providing nowadays.  In addition, those patient with schizophrenia who are seen will be seen much less frequently.  We know from multiple sources that lack of close follow-up highly exacerbates the issue of people not taking prescribed medications (non-compliance).

Off their meds, psychotic patients still end up being incarcerated, but as this story indicates, in jail, not in a hospital. Paradoxically, psychotic inmates are usually then prescribed anti-psychotic medications in prison - at a much higher cost.

One wonders how author Robert Whitaker (Anatomy of an Epidemic), who believes that antipsychotic medications make psychotic people worse, explains away how people with schizophrenia somehow become far more likely to end up in jail when they do not take antipsychotic medication.  Or perhaps he thinks that this development is the result of a malicious government plot .

The question of whether schizophrenia is in fact a real brain disease, and why it has been so hard to pin down the actual pathology, was recently addressed in a newspaper column by neuroscientist  par excellence John J. Medina. 

John J. Medina

An excerpt:

"... a biological explanation for the disease seems heartbreakingly just out of reach. Schizophrenia has a powerful genetic component (heritability percentage is in the low 80s), something I’ve known for years, something that could make it low-hanging research fruit. There is also a large clinical base on which to do studies: schizophrenia afflicts millions of people (the estimated prevalence rate is about 1% of the global population). Despite these seeming advantages, a molecular mechanism capable of describing all aspects of schizophrenia has almost completely eluded researchers.

"There’s a simple reason for this. A deep understanding of schizophrenia at such an intimate level has been hampered by a single technical bottleneck: the lack of a robust in vitro [in the lab as opposed to in the body] disease model.

"That may all be about to change. The results from a study that used cells derived from a deceased patient’s skin tissue has recently been published. Findings from the study may provide just such a model. It is not yet full-fledged schizophrenia-in-a-dish, but the findings portend a powerful future for the field."

Medina then goes on to explain a new technology - a way to produce something called Pluripotent stem cells (iPSC's) which I will not go into here.  Basically, they are re-programmed stem cells.  He then goes on to say:

"With these technologies in mind, I now have the tools needed to understand how to create a dish-bound model of schizophrenia. It involves answering some simple questions: What if you took the skin cells from patients who had schizophrenia and turned them into neurons? Would they exhibit behaviors of typical, healthy cells? Or would they exhibit behaviors reminiscent of previously determined properties of neurons in patients with schizophrenia? If the latter were observed, would you have a robust cellular model of schizophrenia, the missing link in this line of work? A consortium of researchers decided to to find out."

Skin cells from diseased patients made iPSCs that were similar to cells that were obtained from unaffected people.

"The most interesting result came from what happened next. Even though the reprogrammed cells were clearly neural tissue, they did not behave like typically functioning neurons. Several observed differences were eerily similar to previous findings other researchers had seen in tissue samples from patients with schizophrenia."

Despite what you may hear from mental illness deniers, neurons (brain cells) derived from patients with previously diagnosed schizophrenia "exhibit specific, aberrant properties."  I do not wish to get into highly technical neuroscience on this blog, but anyone interested might want to look up definitions for the following terms, and learn about how brain cells from people with schizophrenia differ from those who do not show symptoms of the disorder:

Dendritic arborization,  neuregulin expression, and Global gene expression changes.

After pointing out that this technology does have some problematic aspects to be resolved, Medina concludes: "Having a dish filled with cells that carry many characteristics of a human disease is a lot like having a flashlight in a dark cave. The greatest utility is in the ability to illuminate molecular mechanisms that might go undetected without such a model. It can go a long way toward relieving the frustration often associated with this line of work. Give it enough time and it might even—someday—illuminate a cure."

Undoubtedly, mental illness deniers will find something wrong with any evidence that schizophrenia is a brain disease.  It's in their nature.

The False Theory That Refuses to Die

"The great tragedy of Science — the slaying of a beautiful hypothesis by an ugly fact."  ~ Thomas Huxley

The presence in the brain of a "chemical imbalance" is one theory about the cause of certain mental illnesses. Specifically, the basic concept is that neurotransmitters -  the different chemicals that are released from the ends of brain cells into the space between two neurons (synapses) and are the means by which two neurons communicate - are out of balance within the brains of patients suffering with clinical depression or schizophrenia. Therefore, medication which helps these conditions must surely correct these "imbalances."

In the case of clinical depression, two neurotransmitters are thought to be the primary culprits. Because antidepressants increase the amount of serotonin and norepinephrine in synapses, these monoamines or catecholamines - different name for the class of chemicals in which they are classified - this was presumed to be the mechanism of action through which the drugs helped depressive symptoms.


Zoloft Ad



Research into other mental illnesses such as schizophrenia also found that too much activity of certain neurotransmitters such as dopamine was correlated with these disorders.  The basic problem with this theory is that it is wrong. There is no evidence that a "chemical imbalance" is behind serious clinical depression. 

A few problems with this idea: 

First, the effect of antidepressants on serotonin and norepinephrine in the brain is immediate, but the therapeutic effects do not begin to appear until after about a week and a half pass by, and the full effect takes 3-6 weeks.

Second, all of the drugs affect the monoamine neurotransmitters, but some people respond to one but not another, while others do not respond to the first but do to the second.

For a third point, I quote neuroscientist John J. Medina, author of the wonderful Molecules of the Mind column in the Psychiatric Times.   From his April column: 

"When we consider the molecular mechanisms of SSRI interactions, it is easy to resort to commonly taught ideas about interactions that involve a single synapse.  Nothing could be further from the truth. 

The most comprehensive neurological view of SSRI actions must take into account the participation of thousands of individual neurons strung together in coordinated, complex neural networks.

And not just serotonergic neurons.  The cells are in contact with many other central nervous denizens, from adjacent glial cells to the extracelular matarix into which the cells are embedded."

And yet, the monoamine theory refuses to die!  "Biological" psychiatrists have become obsessed with monoamine neurotranmitters and the parts of the neurons which snap them up and react to them - the neurotransmitter receptors. I think that horse has been beaten to death.  Studying receptor physiology will, I predict, not lead to any new drugs with a different mechanism of action from the ones we have now.



The propaganda coming from Big Pharma continues to push the importance of the neurotransmitters and their receptors, even when the significance of many findings of receptor differences is completely unknown.  A recent ad that does this is discussed in Dan Carlat's blog.

For one thing, these monoamines make up only about 5% of all neurotransmitters in the brain.  For another, all the other ones, most notably glutamate and GABA, all regulate each other in a cascade of two-directional influences among thousands or even millions of cells. Last, all neurotransmitters are widespread throughout the entire brain.

Now do not get me wrong.  Just because one theory about how antidepressants work is wrong, this does not mean that the drugs do not work.  Clinically, in properly diagnosed patients, they work fabulously.  I have personally witnessed their dramatic positive effects in literally thousands of patients.

There are other reasons why recent studies seem to show that antidepressants do not work in moderate to mild depression (NO honest study says they do not work in severe depression). Not the least of these reasons is that the drugs have mostly gone generic and Big PhARMA has a vested interest in seeing other, less effective drugs being used.  See my 8/31/10 post, SSRI Tales.  The drug company marketing departments are so sophisticated that they use the anti-psychiatry zealots to help them sell more (and more dangerous) brand named drugs!

To those that think antidepressants never work, I have one word for you:  Bullsh*t!

For ages, we did not know how aspirin works.  I am not sure that we really do now.  But it relieves an awful lot of headaches for sure.