How Antidepressants Should be Prescribed

 

As psychiatrists are pressured by various business interests to see more and more patients in less and less time, more and more shortcuts have come into practice. Not a good thing. Especially when it comes to anti-depressant prescribing practices. The drugs have become way over-prescribed, and antipsychotic medications are added to them for "augmentation" far more often than necessary. I’ve spoken about the use of symptom checklists, which are screening tests and not diagnostic tests, being used to make diagnoses.

Another recent development has been companies that offer various “genetic testing” to try to predict which medications might work best in a given patient, or what side effects they are likely to get. For example, GeneSight Psychotropic offers a “pharmacogenomic” test which means that it analyzes how your genes may affect medication outcomes. They say: “The GeneSight test analyzes clinically important genetic variations in your DNA. Results can inform your healthcare provider about how you may break down or respond to certain medications commonly prescribed to treat depression, anxiety, ADHD, and other psychiatric conditions.”  

The problem with these tests is that their predictive validity is actually quite poor – even the company admits that “It is important to note that not all patients who received a GeneSight Psychotropic test experienced improved outcomes.”  According to two docs at the NYU School of Medicine, "The tools were developed using small sample sizes, focusing on specific patient populations...and were not tested in real world settings different from the one in which they were developed."

The tests are IMO a waste of money.

Because people are so complicated biologically, psychologically, and socially, I think a far better way for docs to decide which meds to use is to use pattern recognition: Doing a wide-ranging diagnostic evaluation and looking at what factors suggest certain courses of action.

Let’s start with the diagnosis of major depressive disorder. That diagnosis has to be based on a variety of considerations. Symptoms must be pervasive (almost all day every single day, even if you suddenly win the lottery. I exaggerate, but only slightly) and persistent (at least two straight weeks), and the patient’s functioning and stress responses must be significantly different that their norm. (Antidepressants do not work on chronic unhappiness). All symptoms must take place at the same time – having no appetite on Monday and poor sleep on Thursday does not cut it.

If it’s a patient’s first episode, another big issue is that there is no way for the doc to be absolutely certain that it is not a first episode of bipolar disorder rather than a unipolar depression. This is important because if the doc prescribes an antidepressant to a bipolar patient, it can trigger a manic episode – with disastrous consequences. So what is a doctor to do to make sure that doesn’t happen?

Family history is important, since bipolar disorder usually runs in families. If a patient has a family history, the doctor has to be more careful. The problem is of course that the patient might not know if he or she even has a relative who had a manic episode. So what does a good doctor do? In addition to asking about family history, the doc should carefully review the patient’s history for any symptoms suggestive of the disorder. These symptoms should not have occurred only when the patient was high on cocaine, or during a rage reaction upon having found out that the their spouse and best friend were having an affair!

Next, the doc warns the patient about the bipolar issue, and informs patients that in the event of suddenly feeling revved up, they need to STOP the antidepressant and call the office immediately. This instruction can be given at the same time as the doctor describes all possible major side effects with instructions on what to do should they occur. Then, the doctor needs to have the patient comeback for a scheduled follow up visit, preferably within two weeks.

Now, about picking an antidepressant with which to initiate treatment. As I mention, genetic testing is not particularly valuable. It’s always a bit of a crap shoot because a patient’s presentation may be somewhat atypical, but if the doc takes a complete history, it can suggest which agent to try first. If the patient has some obsessive-compulsive qualities, an SSRI like fluoxetine  or escitalopram is a good first choice. If in addition to that there is a lot of anxiety, the SSRI paroxetine is usually the best choice. If the patient has chronic pain, then duloxetine is usually a good starting point. If sexual side effects are a big concern, buproprion is usually the place to start.

Next, the doctor raises the dose of the medication every three to four weeks until there is a response, or it reaches the maximum dose, or until side effects become too big a problem. At this juncture, the doctor should NOT add another, different class of medicine to “augment” the antidepressant, as is suggested by a lot of Pharma commercials. If there has not been a good response to the first drug, the anti-depressant should be stopped, and a trial of a second antidepressant should come next. And again, if no response, a third one. There are diminishing returns here but eventually most patients will have a decent response. If they do not, then than and only then should an augmentation strategy be instituted. Or the diagnosis may need to be re-evaluated.

Close follow up. Close follow up. Close follow up.

The Conflation of Chronic Sadness With Major Depression

When I bring up with many other professionals the idea that major depression is now over-diagnosed by relabeling what used to be called dysthymia as "mild' major depression, a lot of them seem to disagree. Or they just tune out. “That’s just your opinion,” I might hear. Well, luckily the DSM-V now provides evidence that I am on the right track. In the DSM-V, the term “dysthymia” has been replaced! It is now called Persistent Depressive Disorder. 

As I have discussed in many previous posts, my opinion about major depressive disorder is that it is more of a brain disorder than mere unhappiness. The word depression itself is a symptom, not a disorder. It is in the interest of drug companies to conflate chronic psychological unhappiness with major depression so they can sell more antidepressant drugs to people who will not actually benefit from them.  Now,  it is also possible to have both, which is called double depression.

While many of the criteria are the same for the new diagnosis as the previous criteria for dysthymia, there are subtle differences that obscure the difference between that disorder and major depressive disorder. In a percentage of people with the latter disorder, it may become chronic. This is seen in the new definition of the disorder, which reads “This disorder represents a consolidation of DSM-IV-defined chronic major depressive disorder and dysthymic disorder. These disorders should not be consolidated.

There is one additional change which is telling. The only specific criteria for the disorder that has been changed has gone from “The disturbance is not better accounted for by MDD or MDD in partial remission” to “Criteria for Major Depressive Disorder (MDD) may be continuously present for 2 years, in which case patients should be given comorbid diagnoses of persistent depressive disorder and MDD."  Double depression has nothing to do with the length of the major depressive episode.

Drug companies have enlisted academic psychiatrists to become “key opinion leaders” in order to push this idea, and have even advocated the use self report surveys designed to screen for major depression (therefore having a lot of people test positive who don’t really have the disorder  – false positives) as diagnostic instruments.

This has led to a host of articles in the popular press that seem to indicate that antidepressants are nothing more than placebos. Nothing could be further from the truth, but a lot of psychiatry critics like Robert Whitaker have seized on “research” articles (which do a crappy job of making the correct diagnosis) that seem to show this to be the case.  After all, since most anti-depressants are generic,  it's better for drug companies' bottom line if instead of those drugs, expensive new anti-psychotic drugs can be recommended instead.

The critics also use the fact that we don’t know exactly what causes major depression to dismiss the whole diagnosis. The incorrect hypothesis that the condition is due to a “chemical imbalance,” which is sometimes advanced by clinicians, must mean that it is not a real disease. Dumb. Clinicians have often used this oversimplified idea to convince resistant patients to take the medications. Researchers rarely if ever actually said that a chemical imbalance was the cause of the disorder.

Of course, it’s not always easy for clinicians to tell the difference between dysthymia and major depression in a given patient, but in most cases it’s fairly straightforward.  There is nothing that stops anyone from being chronically unhappy when they are not having an episode(the euthymic state) of major depression. And major depression is episodic with normal-for-them baseline mood periods in between episodes.

A good clinician will define a response to antidepressants as good if the patient returns to their baseline. They don’t have to be in a good mood to have had a good response, but may just need psychotherapy like any other dysthymic patient. Nonetheless, many of these patients who have double depression are mislabeled in the literature as “treatment resistant,” which means that docs are encouraged to add still more drugs to antidepressants to “augment” them. There are of course patients who actually are treatment resistant and need this augmentation, but in my 45 years of practice this was a relatively small contingent.

Briefly and in an oversimplified manner, distinguishing the two disorders has to do with the “three P’s” – persistence, pervasiveness, and pathological. (You can tell if a study employs the correct definitions by seeing how the diagnosis was made with their subjects. The P’s are emphasized in an excellent diagnostic interview called the SCID). Persistent: this is the duration criteria. An episode has to last at least two weeks. Admittedly, the two-week criteria is arbitrary, but is put in so clinicians don’t make the diagnosis after too short a period.  The “everything is bipolar” crowd routinely poo poo's the duration criteria.

Pervasive: the symptoms have to be present nearly all day every day no matter what goes on in a patient’s life. This means that if a patient were to win the lottery, it wouldn’t cheer him up all that much.  Pathological: this means that the ways that the patient reacts to any stress is different from the way they might react if they were not in an episode. See the lottery statement. Also, if a lover were to, say, break their heart, this would not always make a whole lot of difference in how bad they feel.

These issues are not seen with good doctors, who not only know how to take a complete bio-psycho-social history but actually still do them.

Treatment of Bipolar Disorder Goes Psychotic

 

Ever since I did my psychiatric residency training way back in 1974-1977, bipolar disorder (then called manic-depressive illness) was the easiest of the major psychiatric disorders to treat medically. There was (and is) absolutely no evidence the craziness of the patient during a manic episode or a bipolar depressive episode is amenable to any psychotherapy technique, although therapy might be important when the patient is euthymic (that is, not in a manic or depressive episode – which is most of the time) to deal with the aftermath of their having been psychotic or for other co-morbid psychological problems. Euthymic bipolar patients can have co-occurring personality disorders and anxiety disorders and anything else just like anyone. Since, when euthymic, they are in fact just like everyone else.

If you want to see what a manic patient looks like, look at this video of Charlie Sheen (https://www.youtube.com/watch?v=pipTwjwrQYQ). He actually took a show on the road but had no act. Now, cocaine can mimic mania, but he’d taken cocaine before and he never acted like this. See videos of him when he was back to his usual self to see the difference. Sheen denies he was manic, but I’m not sure I believe that.

Anyway, about 80% of these patients could tolerate and were responsive to lithium for prevention of manic episodes. The longer they took it, the more likely it would be to also prevent depressive episodes as well. If the patient got depressed while taking lithium, antidepressants worked just great. Journal articles saying they do not were full of crap – the most important of these is discussed in this post.  Most of my patients on lithium were basically symptom free for decades, no matter if I saw them in a public clinic, an academic clinic, or a private practice environment.

 

When patients first got manic, we used antipsychotic medications to bring them down, usually in inpatient settings, because lithium takes a couple of weeks to kick in. Once lithium was on board, we discontinued the antipsychotic medication because they didn’t need it any more. The only other time we used antipsychotic medication in bipolar patients was during depressive episodes in which the patient also had delusions and hallucinations (psychotic depression). Again, the antipsychotic meds could often be discontinued after the episode was over.

 

When a patient couldn’t tolerate or was not responsive to lithium, we would then use antipsychotic medications as the only alternative back then, but always had to worry about them causing a neurological disorder (tardive dyskinesia [TD]). Until it was found that the anticonvulsants Tegretol and Depakote were good for mood stabilization – so then they became the second line drugs.

 

When the new, “second generation” antipsychotics came out, which can cause huge weight gain and diabetes in addition to TD, the drug companies started to push them. The use of lithium started to plummet. After it was found that some of them had some antidepressant effects – although usually only to augment an antidepressant – Pharma started to push them even more. Despite the major risks, use of them increased from 12% of cases to 53% of cases between 1997 and 2008.

 

Not only that, but the number of patients diagnosed with bipolar disorder inflated by more than double since 2000. Everybody and their brother who had any mood symptoms at all were misdiagnosed with it, most due to the insane idea known as “bipolar spectrum,” or as I call it, B.S. Another study in the Journal of Clinical Psychiatry that I wrote about previously  showed that 40% of patients in their sample who met clear DSM criteria for borderline personality and not for bipolar had been misdiagnosed as bipolar by a prior mental health professional, as well as 10% of all of the other patients.

Caveat emptor, which in this case means, let the patient beware!

Another Pharma Trick for Overstating the Effectiveness of their Drugs: The Will Rogers Phenomenon

Will Rogers

Big Pharma has a number of ways, many of which have been described in this blog, of making their drugs look a lot better than they actually are. And some psychotherapy researchers use the techniques to push their favored school of thought. I recently came across another one of which I wasn’t aware. 

It is easiest to see with drugs used for cancer chemotherapy, but can be applied in other cases.

It is called the Will Rogers phenomenon (and is also called Stage Migration). It is an apparent epidemiological paradox. The Rogers reference comes from a remark made by the famed humorist Will Rogers about migration during the American economic depression of the 1930's: "When the Okies left Oklahoma and moved to California, they raised the average intelligence level in both states."

With cancer drugs, it comes from changes over time in the way the severity of the disease is assigned to patients - how the various stages of a disease are determined in each case. (Stage I is when the cancer is smallest, has not spread, and is usually the most easily treated. Stage IV is the most advanced with metastases). The issue comes about because the technology for staging a cancer in a given patient has improved significantly. This can produce spurious improvements in stage-specific prognosis, even though the outcome of individual patients has not changed.

New imaging tools have allowed detection of cancer metastases before they became evident clinically. As a result, more patients are classified into the more severe metastatic disease stage from the less severe single tumor stage. Such a 'stage migration' resulted in an improved survival of patients in both the less and the more severe disease stages. (Multiple sclerosis is another disease where this sort of thing has taken place).

Some studies compare a new treatment to the treatment of so-called historical controls who had received other treatments. This is usually done because carrying out placebo-controlled studies in potentially dying patients is unethical. The Will Rogers phenomenon is recognized as one of the most important biases limiting the use of historical controls groups in experimental treatment trials. 

Essentially, the use of different diagnostic criteria may generate spurious improvements in the medium-term prognosis which then may be wrongly interpreted as treatment effects.

In psychiatry and psychology, placebo controlled studies can be done ethically, but a variation of the Will Rogers phenomenon can still take place because of how rigorously DSM diagnostic processes are applied to patients. When I first started training, the criteria for major depression and mania were rigorously applied in treatment studies; now they are often applied sloppily – on purpose. 

Chronic unhappiness, which may respond very well to cognitive behavioral psychotherapy, is often now misdiagnosed as the more serious major depressive disorder. If you have a bunch of those folks in your psychotherapy outcome study, CBT can be “shown” to be effective in major depression by including people in your study who really don’t have major depression.

The more serious depressions respond better to antidepressant medications. Since most antidepressants are now generic, drug companies who want doctors to use other, more profitable drugs like Latuda can do the same thing to “show” that antidepressants are actually less effective than they actually are. Placebo response rates in antidepressant studies have gone up about 10% every decade, and this is what I believe to be the reason.

Depression is a Symptom, Not a Psychiatric Disorder

Lately there have been a slew of articles about "depression" that seem to go out of their way to avoid discussing any specific psychiatric diagnosis listed in the DSM - instead strongly implying that "depression" is itself a disorder. These articles appear in the popular press, but, frighteningly, also in newsletters and newspapers for psychiatrists and psychologists. They explore such questions as "Do antidepressants work?" and "What is better for depression, drugs or cognitive behavioral therapy?"

These types of questions are completely meaningless. Depression is discussed as if it were a single phenomenon that, at best, exists on a continuum from "mild" to "moderate" to "severe." This type of wording is in fact completely ignorant, but does not necessarily reflect real ignorance. In many cases, different entities such as big Pharma have a vested interest in conflating several different psychiatric conditions.

In truth, "depression" is just a mood state, and as a symptom, it can be part of many different psychiatric disorders that are, despite some overlap in symptomatology, as different as night and day when it comes to their clinical presentations as well as their response to various treatments.

To name but a few actual diagnoses, there is major depression (both as part of unipolar and bipolar disorder), dysthymia, adjustment disorder with depression, depression due to a medical condition, and depression due to a substance. Medical conditions that can lead to depressive symptoms include hypothyroidism and some strokes. Substances that can do that include some steroids like prednisone and the "crash" that results when an acute cocaine high wears off.

Furthermore, "depression" as discussed in every day conversation can be a normal mood that is part of chronic unhappiness, or that occurs in response to grief at someone's death or due to any other loss or misfortune.

The most important diagnostic distinction for this discussion is between major or clinical depression and dysthymia. Although we don't know enough about the brain to know the exact causes of either one, and there is some overlap in symptomatology, they appear for the most part with very distinct clinical presentations, especially in their classic forms.

Dysthymia appears to be more of a psychological reaction, while major depression probably involves the more primitive part of the brain called the limbic system. The latter, unlike the former, is accompanied by a whole array of chronic, persistent (lasting all day every day for at least two weeks), and pervasive (coloring all aspects of the patient's mental life) physical symptoms - all at the same time - involving sleep, appetite, ability to experience pleasure, energy level and motivation, and concentration. Sufferers may have an unrelenting and constant sense of foreboding accompanied by inexplicable hopelessness and helplessness. We used to refer to these types of symptoms as vegetative symptoms.

Furthermore, someone in a major depressive disorder episode reacts completely differently to life's every day ups and downs than they do when they are not in the middle of such an episode. It's almost Jeckyl and Hyde territory.

These people stay depressed no matter what life events occur around them. They could literally win the lottery and would not really feel a whole lot better for more than a few minutes.

The most severe form of major depression is called melancholic depression. Most people who have never worked in a mental hospital have never seen a case, but the anti-psychiatry types who have not seen it blather on about depression incessantly as if they knew what they were talking about.

People with melancholic depression exhibit something called psychomotor retardation. People with this symptom move and think at a snail's pace.  It takes them longer to respond to any verbal interactions. They can even appear to have significantly impaired memory, although it is actually a more severe form of concentration impairment. That clinical picture is sometimes referred to as pseudodementia. 

You cannot spend more than an hour with such people without realizing that this condition has next to nothing in common with the type of "depression" people see in their everyday interactions with others, and that there is something seriously wrong with their brain functioning.

In severe major depression, doing any kind of psychotherapy (short of telling them, "take these pills") is a complete and utter waste of time. Sufferers literally do not have the mental wherewithal to deal with any kind of problem solving or other interactions with a therapist. And I say that as a major advocate of psychotherapy.

The symptom of depression in dysthymic disorder, on the other hand, rarely responds to antidepressant medication at all (although the drugs can be useful for other symptoms seen in patients with dysthymia such as panic attacks, obsessive ruminations, and the affective instability characteristic of borderline personality disorder). For these folks, psychotherapy is essential.

In my experience a very high percentage of the people who do drug and psychotherapy outcome studies, at least in adults, make almost no meaningful effort to differentiate dysthymia from major depression by: 1) Not spending any time making certain that patients understand the pervasiveness and persistence criteria that differentiate the symptoms of the two disorders; and by 2) Not taking a complete biopsychosocial history to distinguish psychological from limbic system factors.

All of the fancy biological research is not being complemented by good old fashioned clinical typing.

Furthermore, with the private Contract Research Organizations that do a lot of the studies, experimenters get paid only if they recruit a subject, and subjects get paid only if they get recruited - giving a financial incentive for everyone to exaggerate symptoms in order to qualify.

And people with suicidal ideation, comorbid (other, co-occurring) conditions, and significant personality pathology are excluded from studies. Those "exclusions" eliminate the vast major of subjects that have any of the psychiatric disorders in which depression is a symptom.

Garbage in, garbage out.

By the way, you can also have something called double depression. Such people are generally dysthymic but every so often can have a superimposed episode of major depression. So they have both conditions.

Once a major depressive episode starts to occur, it takes on a life of its own. However, being chronically unhappy, anxious, or stressed out may be risk factors for triggering a major depressive episode to begin with.  If you are genetically vulnerable to an episode of major depression, being chronically unhappy might make an episode more likely.

This is another reason why the question, "Should you treat these people with medications or therapy" is a really stupid question. It's a bit like asking, "Which treatment should people who have extensive, severe, cardiovascular disease get, bypass surgery or high blood pressure medication?" 

These treatments address completely different aspects of the disorder. In major depressive disorder, drugs should be used during the acute disorder, but psychotherapy should be given later to address personality  and relationship risk factors - in order to reduce the likelihood of subsequent episodes.

Adventures in the Veterans' Hospital Mental Health Clinic - Part III

Not everyone, apparently

This post continues on from my post of 4/14/15 about the practice of psychiatry in the outpatient mental health clinic at the Veterans' Affairs Hospital in Memphis. I retired from my part-time position a few months ago. While the bureaucracy and some of their requirements on physicians were annoying, they were also amusing, if not entertaining, in a perverse sort of way.

Human foibles have always interested me, so I managed to put up with practicing there for several years. I was only working part time - just 30%. This limited time made the craziness tolerable for quite a while. I had been planning to stay there until the end of 2015, but I did not make it that long.

Why? There were two developments that made my continuing to work there problematic, and I found myself counting the weeks until I could escape. Then I received a warning letter for my having made comments in some of my patients' electronic medical records (EMR) about the negative effects of some of the VA policies on the well being of the veterans I was treating. 

I knew very well that one is not supposed to do that and I would probably hear about it sooner or later, but complaints at staff meetings went absolutely nowhere - even though many of the other VA psychiatrists agreed with me - and I felt I had to protect myself from being held responsible for negative outcomes over which I had absolutely no control.

The expected write-up, when it finally came, was insulting. It was obvious that the VA was far more concerned about the way I had documented serious problems adversely affecting patients than they were about the serious problems themselves. And they had the nerve to offer me psychological help if I needed it, as if my valid complaints about the mistreatment of our fighting men and women were a symptom of an anger management problem on my part!

In discussing the letter with me, one of my bosses mentioned in passing that if I was unhappy with the practice environment at the VA, I didn't have to work there. I knew she meant that it would be better for her and everyone else if I did not conspicuously challenge VA policy, even though I had kept my complaints in-house. (Going public while still working at the VA was an act of professional suicide). But after she said it, I thought to myself, "You know, she's right!  I don't have to work here." Soon thereafter I gave two months notice of my intent to retire from my VA practice.

Neither of the two problems most responsible for my leaving was actually the subject of my letter of reprimand. The first big issue was briefly mentioned at the end of Part II of this post - a psychiatrist there who seemed to me to have been using almost all the worst practicess of bad psychiatrists that I have been describing in this blog. I'll call this doctor Dr. X. Dr. X had a large caseload. Upon Dr. X leaving the VA after practicing there for several years, I started getting some of Dr. X's patients re-assigned to me.

Dr. X's notes in the electronic medical record (EMR) were next to worthless:  No documentation of diagnostic criteria for the diagnoses that were made. No descriptions of why certain medications were chosen - some of which were not indicated for the diagnoses on the chart. 

Diagnoses were often written as just "depression," which is a symptom and not a diagnosis at all. The notes never discussed psychosocial issues, or if the patient might need psychotherapy, and rarely mentioned any of the patients' personality issues, which were plentiful.

The notes also never mentioned which medication side effects the patients might have complained about. Dr. X would increase the dose or change medications without saying why. If the patients were on antipsychotic medications notorious for sometimes causing increases in a patients' blood sugar and/or cholesterol, no blood test monitoring for this was done.

Worse yet, Dr. X would start someone on a new antidepressant, and then not schedule a follow-up appointment for three months or more. 

Antidepressants, when they work, take 2-3 weeks to start kicking in, and up to six weeks to get the full effect. Often the dose must be increased if the first dose of drug does not work. Different patients may respond to one drug but not another, and to which antidepressant a patient may best respond is unpredictable. Furthermore, certain agents may have serious side effects in a given patient, necessitating a switch to a different one. 

Thus, several changes in medication must often be made for some patients. Each time a change is made, the clock for the long 2-6 week kick-in period starts running from the very start all over again.

Therefore, patients started on these drugs need to be followed up within 3-5 weeks at the longest. Dr. X's patients who did not respond to this doctor's initial prescriptions or who had problematic side effects, on the other hand, had to wait months for a follow-up appointment. At that rate, they would often experience no improvement in debilitating depressive symptoms - unnecessarily - for months and months.

Then there was another issue with an SSRI antidepressant named citalopram (brand name Celexa). The FDA suddenly came out with a warning about the use of higher doses - doses that had previously been recommended - because of some minor EKG (heart rhythm) changes that may occur in some patients, which sometimes but rarely cause serious problems.  

Of course, the VA immediately mandated that dosages above the new recommendations be reduced poste haste with no exceptions, even if the patient had been stable both medically and psychiatrically on that dose for quite some time!

When patients were on the higher dose because they had not responded to the lower dose, Dr. X then unceremoniously reduced the patient's dose to the previously ineffective one, and then said see-ya-later for three to four more months. The patients of course relapsed because the lower dose had never worked for them in the first place. There were other SSRI's to choose from that Dr. X might have considered switching to, since the relapses in these cases were completely predictable. 

Although I occasionally had seen one of this doctor's completely worthless "progress notes" before I inherited some of these patients, I did not of course know about Dr. X's typical practice pattern until after this doctor left and I started treating them. However, Dr. X had been there for years. Because Dr. X kept a very low profile, apparently the powers-that-be played a game of "see no evil."

My getting these patients created two major problems for me. For one, I was getting potential cases of malpractice dumped in my lap.

Second, I started getting a lot of these patients. To understand the problem this created for me, first some background: Before I had taken the job at the VA, I was told that I would have a full hour to see any patient who was "new." Being aware of managed care tricks, I specifically asked: new to me, or new to the clinic? (I insist on not just taking the word of a previous doc but doing my own independent evaluation, although I do take the opinion of the other doc into account). I was told I would get a full hour for any patient who was new to me.

As it turned out, an hour was not the usual allotted time for visits at the VA for those patients who had been seen previously by any of the staff psychiatrists. Any patient who had been seen by another doctor was instead scheduled for the usual 30 minute follow-up. When I insisted on an hour for any patient new to me, and made the people responsible for scheduling patients change appointments which did not have the correct duration, the powers-that-be begrudgingly accepted my demand. This worked fine for quite a few years.

I was officially slated to see two patients that were brand new to the clinic every week, which is fine for someone working 30% time. I could usually get such new patients in for a follow-up appointment in a reasonable period of time. However, when Dr. You-know-who left, I was suddenly seeing 4 or 5 patients who were new to me every single week. And essentially starting from scratch with each of them. The VA, unlike me, did not count Dr. X's  patients as being "new," so according to them, my caseload of new patients had not increased - when in fact, it had more than doubled!

Soon all of my follow-up appointment times started to fill up. I was no longer able to get these patients scheduled in for follow-up within an appropriate time period.

This was made even crazier because the VA does not penalize patients who do not show up for multiple appointments - even if they miss several in a row. Therefore, some of my appointment times for follow up patients were being wasted on patients who had missed three or four appointments, and were therefore not likely to show up.  Of course, if I double booked patients, and everyone did happen to showed up, there would be no way I could see everyone on the schedule.

I knew we were short staffed, but I was not going to enable the system by short-changing the patients whom I was already seeing, which was what seemed to be expected of me.

The issue of being short staffed relates to the second issue that caused me to abruptly curtail my expected period of employment with the VA. That will be the subject of part IV of this series of posts.

Latuda and Bipolar Depression

Have you seen them? The brand new, direct to consumer (DTC), ads touting the drug Latuda for bipolar depression? The drug company just received the indication for this purpose from the FDA a very short time ago, but the drug company, Sunovion Pharmaceuticals Inc., was ready to roll.

Latuda is a dopamine blocking drug, which makes it an antipsychotic medication and not an antidepressant.  We have known since the 1950’s that all antipsychotic medications have some effectiveness in bipolar disorder, although primarily for the prevention of the manic phase of the illness. We have known that they also may augment an antidepressant for those who only get a partial response to the antidepressant in both unipolar and bipolar depression. A colleague of mine routinely used the antipsychotic Navane to augment the old tricyclic antidepressants in the 1970's.

Only two other antipsychotic medications have official FDA indications for bipolar depression, probably because the other drug companies did not spend the money to get it.  If doctors know one member of a class works, they’ll know that the others probably will too, so why bother?  One of these two drugs that has the bipolar indication is actually a combination drug containing an antipsychotic medication (Olanzepine [Zyprexa]) AND the antidepressant Prozac. The other is Quetiapine [Seroquel].

The main problem with using an antipsychotic instead of an antidepressant in this condition – aside from the unequivocal fact that antidepressants are way more effective – is that antipsychotics have much more potential toxicity. Latuda is probably one of the safer ones in this regard, having a low incidence of the two biggest concerns, metabolic syndrome (weight gain, higher cholesterol, diabetes - horrible and very common problems with Zyprexa and Seroquel) and the long-term neurological side effect, tardive dyskinesia.  Interestingly, the FDA won’t let Sunovion make that claim despite the fact that it’s true!  Go figure.

Almost simultaneously with the start of Latuda's DTC ad campaign, two research studies of the drug’s use in bipolar depression were published in the February 2014 issue of the flagship psychiatry journal, the American Journal of Psychiatry (AJP). The studies showed that the drug was effective by itself for the disorder, and also effective as an adjunct treatment when combined with either of the two major anti-manic drugs, lithium and valproate.  Weirdly, the  “effect size” of the improvement in patients, a measure of how much better patients got, was less (0.34) with combination therapy than it was in the case of the drug by itself (0.51). Both of these effect sizes are moderate at best, btw.

That difference is particularly odd in the case of valproate, since there is zero evidence that it is effective for the depressed stage of bipolar disorder (lithium sometimes is, but not usually). Does valproate somehow make Latuda less effective than it would be otherwise?

There is a big issue here:  the question of whether antidepressants alone are the better choice for treatment of bipolar depression.

The last author of the first AJP Latuda  study is Gary Sachs, someone I have discussed previously in this blog [ 10/31/11].  He is the author of a major study that claimed to show that antidepressants were completely ineffective – worse than placebo – in the treatment of the depressed phase of bipolar disorder.  

He conveniently neglected to point out in the earlier paper that the sample of patients he used in this study had already proved to be resistant to antidepressant medication in the first place, and continued to dissemble about this omission when I had the opportunity to confront him about it. Some subjects of his had even failed a trial of a combined antidepressant and antipsychotic. The conclusion of the study as presented in the study was bogus as hell.

A defender of Dr. Sachs made this point: Dr Sachs and colleagues in the abstract did not say that they had proven that antidepressants were ineffective in bipolar depression. They reported their finding and immediately called for additional long-term well designed studies - what I have called plausible deniability.

The more recent Latuda article which Sachs co-authored did in fact state the following: “There is limited evidence of the use of standard antidepressants for the treatment of bipolar depression.”  I guess that isn’t exactly the same as saying they don’t work, is it?  Might as well be, though! It's not what you say, it's what people hear.

Furthermore, I learned from the article that Dr. Sachs is a paid consultant for Sunovion pharmaceuticals!  

The article’s reference for the statement about antidepressants not being effective was one study that was a meta-analysis of existing studies of antidepressants in bipolar depression (a study which combines the statistics from several other studies). In an editorial in the same AJP issue publishing the Latuda studies, one R.H. Belmaker restates the opinion that “the evidence that antidepressants can be useful seems less and less convincing.”  

His reference for this statement? It is an editorial he himself wrote in the same journal as the original bogus Sachs article appeared [New England Journal of Medicine 356 (17), 4/26/07 (NEJM)]!  I went and got a copy of it.  These folks seem to all run in the same circles, as well as in the same circular reasoning.

In that editorial, he mentions the same meta-analysis that was mentioned in the AJP Sachs article.  But he also mentions that there are two other meta-analytic studies, both totally ignored in the AJP Latuda articles, that showed that antidepressants could be “highly beneficial” in bipolar depression.

There is fairly subtle obfuscation of the evidence going on here, since the other two meta-analyses never seem to be mentioned in articles touting antipsychotics for bipolar depression any more.  I wonder why that is?

In Belmaker’s original NEJM editorial, he opines that maybe the condition is heterogeneous and that subjects in studies outside of the United States may be different than they are here. The two positive metastudies were by authors from outside the USA.

Aside from the fact that there is absolutely no clinical evidence for that whatsoever, Belmaker neglects to mention that at least one of the two meta-analyses showing that antidepressants were effective did not limit itself to studies done overseas, but included studies done in the States! (I could not get a hold of the second, but this is probably also true of that one as well).

Of course, the issue of antidepressants causing bipolar patients to switch into mania is also brought up again and again ad nauseum all over the place, even though everyone agrees – even the original Sachs article in NEJM - that the anti-manic drugs like lithium and divalproate prevent this.  Since true bipolar patients should be on one of those drugs to begin with, this is a superfluous issue.

I also have my doubts that all of the subjects in the Latuda studies were even diagnosed correctly, since one of the diagnostic tools used was the Bipolarity Index, which includes the items, “Episodes with characteristic symptoms of hypomania, but symptoms, duration or intensity are subthreshold for hypomania or cyclothymia” and “baseline hyperthymic personality when not manic or depressed. " 

For a discussion of the significance of that nonsense, see my posts about treatment resistant depression and bipolar disease mongering.

These folks are doing nothing but trying to sell expensive and potentially toxic drugs to both doctors and the public when more effective and safer alternatives already exist.

Antidepressant Medication and Bipolar Disorder: The Lies and Confusion Continue

The continuing stoow-ry of psychiatric research that has gone to the dogs

In my last book, How Dysfunctional Families Spur Mental Disorders, I discussed my theory that the drug companies of Big Pharma seem to go out of their way to demonize entire classes of drugs once they are mostly available as generics, so that practitioners will use their new brand named drugs instead - regardless of whether or not they are as effective or more dangerous. This happened with benzodiazepines, which now seem to be referred to absurdly as the most addictive and dangerous substances on the planet and full of "side effects" - which don’t actually occur in the real world in the vast, vast majority of patients who take them.

(BTW. demonizing generics does not just occur in psychiatry. One patient told me that a relative was given an anticoagulant that was more dangerous than generic Coumadin because, according to the doctor, “That’s what the drug companies want us to do”).

I wrote that I suspected that the same strategy is now being applied to antidepressants. Most of them have gone generic. (The ones that haven’t yet are Viibryd, Cymbalta, and Prestique.  Although no more effective that the generics, it amazes me how many doctors seem to use them as first line drugs). All of sudden we are being deluged by both news and journal articles questioning whether the drugs are effective. I have written in previous posts on this blog that placebo response rates for antidepressants have gone up significantly every decade, indicating that the patient population being used in the studies is changing. 

Specifically, so-called contract research organizations are being given financial incentives for finding patients that they can diagnose with major depression, and potential patients are given financial incentives for exaggerating their symptoms so they can get paid for being research subjects. So the studies are using patients that don’t really have the diagnosis they are supposedly being treated for. No wonder they have a high placebo response rate. This higher rate makes the advantage of the drug over placebo in these studies seem highly questionable.

A similar process is happening in doctors’ offices all over the country. Diagnostic interviews are getting sloppier and more slipshod all the time. A new study published by Psychotherapy and Psychosomatics, according to the June 2013 issue of the newspaper Clinical Psychiatric News, seems to be highly consistent with this idea. The authors ascertained whether patients who were identified by their doctors as depressed actually met DSM criteria for major depressive disorder. Results with 5639 participants showed that only 38.4% of these patients actually met the criteria!

This phenomenon has led to a couple of ironic developments. First, the rabidly anti-psychiatry zealots point to the bad studies as “proof” that psychiatric meds are a hoax, while of course completely ignoring all the earlier studies that show that antidepressants are highly effective. The more severe the depression, the more likely a patient is to respond to them.

Second, people both inside and outside of the psychiatric profession unfairly rail against the diagnostic manual, the DSM, for not having valid criteria, when the real problem is in many cases that many doctors are not applying the criteria to the patients in making "diagnoses!"

Then there is the matter of the use of antidepressants in the depressed phase of bipolar disorder.  Of course, as I have said many times, the duration and pervasiveness criteria for bipolar episodes, either manic or depressed, are more and more often ignored, which calls into question whether the diagnoses in studies are even correct.

Anyway, in my book I brought up a study by Sachs and others in the New England Journal of Medicine, the most prestigious journal in all of medicine, that purported to show that antidepressants work worse than placebo in this population. I showed how the authors of the study used a sample of patients that were especially treatment resistant, having already failed a trial of at least one previous antidepressant, but did not acknowledge this fact in the paper at all. I was even able to question the author through a third party, since my e-mails directly to Sachs were ignored, and he steadfastly refused to answer the question, “What percentage of your sample had failed a previous antidepressant?”

Now comes another bogus study that purports to show the same thing as the Sachs study. According to an article in Medscape on May 20, 2013, “Investigators at Brown University in Providence, Rhode Island, found there was no difference in hospital readmission rates among patients who received antidepressants and those who did not." Since the authors are strongly implying that the patients had to be readmitted because their antidepressant was not working, this is taken to mean that antidepressants don’t work in bipolar depression.

That antidepressants do not work in bipolar depression is a flat out lie. Psychiatrists like myself have been using antidepressants successfully in bipolar patients for thirty five years. Of course, true bipolar  patients need to be on a mood-stabilizer first, preferably lithium, so they don't switch from depression into mania.

So what’s wrong with this study? Well, just about everything. First of all, we do not know if these patients were correctly diagnosed for the reasons discussed above. Another huge problem: all over the country, hospitalized patients with borderline personality disorder are being misdiagnosed with bipolar disorder because of the “everything is bipolar" craze, coupled with the fact that insurance companies will often not pay for hospital stays if the patients are given the correct, "lesser" diagnosis! 

The subjects in this survey were undoubtedly a very mixed lot. The study did not address whether the patients even took their medication after they were discharged. Non-compliance rates for all medications are very high according to every available study that has looked at this issue. Also, we do not know what percentage of these patients may have fallen into the “treatment resistant” category described above. Most depressed patients are treated as outpatients, not inpatients, so the ones that are hospitalized have often failed a trial of outpatient medication.

Adding to this is the fact that antidepressants do not work for at least a couple of weeks, while managed care insurance companies will not pay for that length of stay. Therefore, patients on antidepressants are often discharged before the doctor knows whether a particular antidepressant even worked. Often patients do not respond to one antidepressant but do respond to a different one. 

Hence, discharge and re-hospitalization rates tell us pretty much nothing about the effectiveness of antidepressants in the depressed phase of bipolar disorder.

The International Society for Bipolar Disorders (ISBD) Task Force recently released its long-anticipated recommendations on antidepressant use in bipolar disorders. "The take-home message is that antidepressants have a questionable benefit-risk and should only be used in certain cases in bipolar disorder," said Dr. Eduard Vieta, who presented the recommendations on behalf of the ISBD Task Force, in an interview.

Eduard Vieta

"First, they shouldn't be used in mania or in mixed episodes, they should only be used in bipolar depression in patients with a history of a good response in the past to antidepressants and no history of rapid cycling or switches into mania right away," he said.

“Further, antidepressants should not be used in patients with bipolar disease with mixed features during a depressive episode or some manic symptoms during depression.” 

The recommendations said that antidepressants should not be used as monotherapy for bipolar depression, or in rapid cycling. 

I have a few reactions to this.  

1. Duh! We've known about the risks of using antidepressants alone in Bipolar I patients since the sixties. We've also known that they are perfectly safe and highly effective if a bipolar patient in a depressive episode is on an effective mood stabilizer, preferably Lithium.  

The way that the recommendation is made, however, is highly misleading. Antidepressants indeed should not be used as "monotherapy," but not because they are ineffective for depression. It may sound to some doctors that this is what is being said. The real reason is because patients need to be on a second drug to prevent switching into mania.

2. What are they defining as "rapid cycling?" A majority of patients who get this diagnosis nowadays are not bipolar at all, but have anxiety disorders, mixed anxiety and dysthymia, and/or personality disorders - otherwise known as 'crappy childhood syndrome." A lot of drugs can cause these folks more harm than good if improperly used!  Why single out antidepressants?

3.  How are we supposed to know if a patient will respond to an antidepressant in cases of patients who have never taken one, if we are not supposed to use them unless the patient already has a history of responding to them? That would be quite a trick! Additionally, a history of a switch into mania is not a contraindication for antidepressants unless this history took place when the patient had been adequately medicated with a mood stabilizer. If they switched when not taking one, that fact would be completely irrelevant. Even the Sachs study showed patients on a mood stabilizer don’t switch into mania with antidepressants.

4. As for so-called mixed episodes, they are in reality manic episodes, with the difference being that the patient feels really uncomfortable instead of the more typical euphoria. Since they are in a manic state and not a depressed one, of course antidepressants should not be used!