A Reevaluation of the Relationship between Psychiatric Diagnosis and Chemical Imbalances

by Simon Sobo, M.D.

____________________________________________________________________________________________________________________

Over the last 10-20 years a particularly appealing way of presenting mental illness has been found. Axis I disorders are boldly portrayed as “chemical imbalances” in patient brochures, news articles, and other educational materials. While it is acknowledged that DSM-IV, the officially designated diagnostic manual used in the United States, is currently not based on etiology, it is, for now, an operationally defined diagnostic system based on the clustering of symptoms. The implicit premise of the chemical imbalance perspective is that this will be temporary. The working assumption of many researchers using the “chemical imbalance” model is that certain DSM-IV defined “disorders” are deficient in a particular neurotransmitter in a particular part of the brain that is causally related to the disorder. In the gray area are expansions of the basic illness with so-called spectrum disorders. Presumably, in this case, differences in symptoms are more apparent than real. A genetic or biological link explains the usefulness of certain medications across the entire spectrum of the related disorders.

The attractiveness of this model to patients is undeniable. By removing psychiatric illness from the realm of psychology, it removes blame, especially pejorative implications that weakness of character, poor upbringing, or lack of will are issues in bringing on the illness or combating the symptoms. It places psychiatry firmly under the umbrella of science and modern medicine. This is a crucial element in convincing patients to seek treatment and to be compliant with the treatment plan. In the United States, the chemical imbalance argument has proven to be important in winning legislative support for improved insurance coverage that gives psychiatry parity with other medical conditions. One other byproduct of the chemical imbalance model: its simplicity has led to a great deal of comfort, on the part of physicians other than psychiatrists, to dispense psychotropic medications. Believing that they are operating within the logic of cause and effect, they merely have to focus on the improvement of the symptoms of the disorder in question and watch for side effects from the medication. A majority of psychiatrists also work within these parameters. They typically see patients for med checks and that is all.

There are fundamental crucial problems with this perspective that need to be aired. First and foremost is that, while some day we may accumulate the knowledge to demonstrate the particulars of the chemical imbalance model, no such imbalances have been unequivocally demonstrated for any disorder. We are offered interesting conjectures, educated guesses that are forever shifting as the latest data is accumulated. The continual construction of new hypotheses is how science should proceed. But good science is normally modest. It clearly distinguishes between soft knowledge and what is known. It does not trumpet a few pieces of a jigsaw puzzle that have been brilliantly put in place, as the solution to the entire puzzle. The public (including practitioners) and the media are being misinformed about the state of our knowledge.

It isn’t that researchers are unaware of the difficulties of integrating current knowledge with theory. Frustration with the “chemical imbalance” neurotransmitter model has, for instance, led certain authors (e.g. Duman, Henninger, Nestler (1997)) to propose an intracellular hypothesis to explain the effectiveness of various medications. Even more to the point, despite the widespread respectability of the chemical imbalance hypothesis it has all along been met with skepticism in some very important places. Thus, the 1992 edition of The Pharmacological Basis of Therapeutics states flatly regarding the “neurotransmitter hypothesis of mood disorder” that “the data are inconclusive and have not been consistently useful either diagnostically or therapeutically.”

I will try to show later in this article that despite the ad nauseam use of the term “expert” to refer to treatment protocols and the like, (which in itself should arouse suspicions that we are dealing with a “Wizard of Oz” phenomenon) adherence to this model in what has become standard psychiatric practice, the once-a-month, 15-minute med check, is not only not “expert” care, but is grossly inadequate care. And, if this is the case, even if one shares a distaste for the hype and psychobabble, “the therapy cures all” excesses that once characterized the worst of psychiatry, the current cursory lip service given in training programs to the role of psychological and social factors in mental illness, is producing psychiatrists unequipped to properly treat patients. That is true even when medications are justifiably the main treatment strategy. Moreover, despite insistence on empirical data, and infatuation with the toys of science, the technological wonders available in modern laboratories, there has not been enough of the most crucial hallmark of “science,” rigorous critical thinking about the basic model. What are the most glaring difficulties with the chemical imbalance model?

1) Medications such as the Selective Serotonin Reuptake Inhibitors (SSRIs) are finding usefulness in so many Axis I and Axis II disorders (e.g. OC Disorder, Depression, Panic Disorder, Eating Disorders, phobias of many varieties, Borderline Personality, PTSD, Body Dysmorphic Disorder, Fibromyalgia, in selected cases Intermittent Explosive Disorder, Pathological Gambling, Kleptomania, not to mention OC Personality, Avoidant Personality, Dependent Personality) that to consider all of these forms of misery part of the same biological spectrum is stretching credulity. Occam’s razor demands a more parsimonious approach.

2) Medications that work in completely different ways are effective for the same disorder. For example, antidepressants such as desipramine and bupoprion have little serotonin effect yet are just as effective agents for depression as SSRIs. To keep the chemical imbalance hypothesis alive speculations are offered to explain the effectiveness of noradrenergic and dopamine enhancing agents as ultimately influencing serotonin receptors downstream. This is not impossible but it is only a guess. A completely different hypothesis is offered by Petty (1995) who argues that GABAnergic drugs are fundamentally related to mood.

In Obsessive Compulsive Disorder (OCD) similar problems emerge. Originally, the fact that serotonin enhancing drugs were uniquely effective led to a belief that there was a causal connection, but as early as 1991 there was confounding evidence. Thirty mg. of dextroamphetamine was found to ameliorate OCD symptoms (Joffe 1991). Moreover, while I am not advocating this as treatment, I have had patients report to me that intoxicants such as marijuana, alcohol, and cocaine have given them temporary relief from OCD symptoms. Indeed, a recent study has shown that oral morphine is reasonably effective (Franz, 2001). Once again it is possible to speculate that there is a downstream effect on serotonin, but if we use this argument we have come full circle in a tautological trap. The original reason for the serotonin-OCD chemical imbalance model was that serotonergic agents were believed to be unique in their effectiveness.

With so called “mood stabilizers” we are faced with similar difficulties in integrating theory with the facts. There is a murkiness in reasoning which can only be explained by the attractiveness of the idea that somehow a chemical imbalance is being corrected, and hence bipolar disorder is being treated on a fundamental, etiological level. However, the various “mood stabilizers” work through different chemical mechanisms. Thus, valproic acid and gabapentin have been hypothesized to work on GABAdenergic receptors, whereas (for example) the proposed mechanism of action for carbamazepine and lamotrigine is voltage dependent inhibition of Na⁺ currents. The latest speculations about lithium is that it is affecting G proteins, that it exerts a push/pull effect on the neurotransmitter glutamate. (Dixon And Hokin, 1998: Lenox et al., 1998), or that it alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines. (Physician Desk Reference, 1999). Even the definition of what constitutes a mood stabilizer is controversial. (Sobo, 1999). Originally, the idea was that a mood stabilizer had both anti-depressant and anti-manic qualities. When it has so far been difficult to demonstrate anti-depressant effectiveness for the anti-seizure medicines, Sachs (1996) replaced this concept with a new definition, an agent which will “decrease vulnerability to subsequent episodes of mania or depression” and not exacerbate the current episode or maintenance phase of treatment. So gripping is the appeal of the original mood stabilizer concept that despite the lack of double blind evidence for the effectiveness of any anti-seizure medication for bipolar depression (other than Lamictal), they are, nevertheless, recommended in the APA’s expert consensus protocol as a first line treatment for bipolar depression. Indeed, as soon as an agent has been shown to have antimanic properties it is invariably labeled as a “mood stabilizer.”

3) With all that is unknown about the chemistry of mental illness, using the chemical imbalance model, researchers are not shy about concluding that a given disorder is “really” something else on the basis of the effectiveness of a medication. Thus Donovan, SJ (as reported by Sherman, C) 1998 proposed that a new diagnosis, “Explosive Mood Disorder” be created and replace Conduct Disorder and Oppositional Defiant Disorder, for “children with irritable mood swings” because Depakote helped his cohort of inner city, out of control, kids. Similarly all kinds of problems with impulse control (called compulsions by laymen) such as overeating, gambling, paraphilias, various patterns of alcohol and drug abuse, and so forth have been labeled Obsessive Compulsive spectrum disorders because SSRIs are sometimes effective. The reason these “compulsions’ were originally excluded from OCD was that they revolved around giving in to temptation, over indulgence of a forbidden pleasurable activity. The fact that SSRIs can be useful here should change nothing regarding etiology or nosology.

4) The chemical imbalance model is not an important part of the basic (animal) research being done to test new potential anxiolytics and anti-depressant agents. The chemical imbalance model might or might not stimulate a search for agents that effect given neurotransmitters, but while there is some research on genetically predisposed strains of mice and guinea pigs, who may be wired differently, or chemically different, most research is done on ordinary animals that are environmentally stressed and then relieved of this stress by potentially useful chemical agents. For example, the FST (forced swimming test) tests the ability of drugs to postpone hopelessness in animals forced to swim and swim and swim to remain alive. SSRIs do this. So do noradrenergic agents (which interestingly enough, are more likely to cause the rats to try to climb out of their test environment (Detke 1995)). More pointedly, for the purposes of my argument, rat pups that are isolated from their mother and litter mates produce “ultrasonic sounds” that are indicative of stress. SSRIs reduce these sounds. (Oliver, 1994) Recently, there was excitement that substance P antagonists may be useful psychotropic agents because they were shown to reduce “stress induced vocalizations” in guinea pig pups (once again separated from their moms). A drug successfully screened in this manner will certainly not be presented to patients as a drug that is so good at shutting off distress that it even works to subdue what might be considered the prototypical model of terror, a helpless infant separated from its mother. A patient told he is being given a drug that will kill his reaction to what has been upsetting him will approach that treatment very differently than a patient given a different spin, one told that his medication is treating the chemical imbalance that is causing his ailment. Similarly, primary care physicians and psychiatrists will be far more enamored with the thought that an agent has been tested (and even better, FDA approved) for a specific DSM-IV disorder if the mindset is that the effectiveness is due to fixing faulty synapses, rather than that the patient is being drugged out of his suffering.

5) Slightly off the topic, but very relevant,  the mindset behind chemical imbalances causing a definite disease (one meticulously defined by DSM IV) is not coming from a good place.   A good number of the disorders are the product of a mutibillion dollar industry which can be described as medications in search of a diagnosis. The bias caused by this push is not subtle.  For example, there has been an absurd stretching of  what constitutes an illness.  This is not just my opinion.  Recently, the chairman of the committee that created DSM IV, Dr. Frances, warned the committees working on DSM V, to be careful not to fall into the same trap.  He blamed DSM IV for false epidemics of ADHD, Bipolar Disorder, and Autism.  This topic is expanded upon in more recent articles on this site.

I would like to suggest a different approach to explaining how SSRIs affect individuals, and why they are so clinically useful for so many psychiatric conditions. A case can be made that SSRIs are efficacious in conditions as disparate as borderline character, depression, obsessive compulsive disorder, anorexia nervosa, panic disorder, social phobias, and so forth because increasing serotonin has a psychological impact that is nonspecific to the disorders in question. Alcohol will produce inebriation in a person with schizophrenia, obsessive compulsive disorder, depression, or someone with no psychiatric diagnosis. Analogously, SSRIs typically impact individuals in ways that are not specific to diagnosis. What is that effect?

The most frequent description of the effects of SSRIs that I have heard from my patients are “It doesn’t matter.” or “Don’t sweat the small stuff.” or “What’s the big deal?” It is this “Don’t sweat the small stuff” perspective that I believe is SSRIs unique blessing and curse. It means relief from worry, relief from the feeling that something is missing, something needs to be done, something needs to be fixed, “my makeup isn’t right, the sky is falling, I won’t be able to pay my bills, I’m not smart enough, I won’t be able to tolerate the loneliness if I leave my lover” (even if he/she is abusive).

SSRIs supply, if not always happiness, a nice contented feeling that all is well and will be well. They can allow parents to be able to play with their children more, fret less over the details, appreciate what is, actually want to do the proverbial modern mantra, stop and smell the roses. They are the answer to existential angst. Perhaps Sisyphus, if he had only been born in the 90’s, could have left that rock alone and had a nice snooze.

On the other side of the equation, I have a psychiatrist colleague who took Prozac to relax and enjoy his vacation. It worked very well. He told me that he tried it at home when he returned. He quickly stopped it when he found himself thinking, “Who cares?” when his patients described their problems.

According to this theory it is the “well whatever” feeling, emotional blunting, that is so useful in the great variety of different syndromes. Thus, for a person with anorexia nervosa to react with “well whatever” after they have gained a pound or two is to get at the heart of the problem. The same can be said for body dysmorphic disorder, a condition in which a person’s life is completely distorted by imagined or slight body defects (such as thinning hair, a big nose, and the like). In obsessive-compulsive disorder the ability to treat compulsions and obsessional thoughts in this manner is a godsend. Similarly, a depressed person’s preoccupation with the hopelessness of their situation, the gravity of their errors and defects, the inadequacy of their decisions, and so forth will be enormously relieved to regain a less “negative” perspective. In panic disorder, a condition characterized by exquisite sensitivity to body sensations, and a catastrophizing of consequences, (I once had a patient who described a horrible attack of panic because she feared something was going wrong with her vision. Only later, when she removed her glasses did she realize that her dirty eyeglasses had set her off) SSRIs have been found to be effective because the sense of catastrophe leaves. For similar reasons social phobias and bridge phobias and flying phobias often become manageable on SSRIs, as do intermittent explosive disorder which may improve because it is harder to press the patient’s button. Alcoholism, pathological gambling, overeating and the like may respond if a sense of frustration has significantly contributed to the pathological behavior. (They may worsen these conditions if a heroic disciplined battle is being waged against temptation, which is then weakened by a “well whatever” letting down of the guard.) SSRIs can help perfectionists (“obsessive compulsive personalities”) give themselves a little (or a lot of) slack. They can allow borderline personality disorder patients to cool their heels, to not be tortured, like a wounded lover, when the person, upon whom they have passionately centered their survival, is not reciprocally involved with them. And so we can apply this perspective about SSRIs down a long list of DSM-IV defined disorders that have been empirically found to be treatable by a change in brain chemistry.

This perspective also suggests itself as useful in psychological circumstances where a specific DSM-IV diagnosis is not at issue. Thus, for instance, a not uncommon treatment scenario is teenagers who are having a very rough go of it with their classmates, kids who are picked on precisely because of their vulnerability. The popular students are the ones who are cool; that is, they don’t blush easily, are bold with the opposite sex, and so forth. Adolescents often turn to illicit drugs (analogous to adults at cocktail parties), to get rid of their social anxiety. But teenagers are often extremely up front about these issues, meaning they out and out torture the nerds. It is not unusual for adolescents to come to therapy because they feel like misfits and to put it bluntly, the use of SSRIs may be very helpful here to magically assist them in having a thicker skin, which is exactly the quality they needed all along to not get picked on and possibly even have the “cool” to be “popular.” How does that differ from drugging oneself out of problems rather than “learning critical skills during the formative years?” Isn’t discomfort often a stimulant of growth, (the stutterer who becomes the grand public speaker, the short guy who becomes Napoleonic)? I’m not sure it is different, but that discussion will have to await a different article. The fact is however, that SSRIs are used exactly in this way and a myriad of other analogous ways by clinicians to the tune, according to one estimate, of 65 million people in the United States since their introduction. Right now, when they are found effective, the chemical imbalance perspective leads to the conclusion that the patient must have “really” been depressed, or had a subclinical version of an illness or had a spectrum disorder. I am suggesting we can spare ourselves this pseudo logic and address the more important question raised above. Should we or should we not drug people into subjectively improved states when an officially designated “illness” is not at issue?

On a still more fundamental level the use being made of the DSM-III and IV model of illness is at issue. DSM-II, perhaps out of respect for the underlying psychodynamics believed to be behind patient’s symptoms, tended to be loose about how to label patients. What was going on inside was more important. Beginning with DSM-III the decision to cluster symptoms into operational definitions that were consensually agreed upon seemed to be a proper step in trying to use scientific models. We were asked to buy into the principle, that regardless of theories about causality, there would be an agreed upon name for the collection of observed symptoms. But it has all too often deteriorated into a Platonic essence model, that is, a belief that there is a “real” version of the illness and actual illnesses are imperfect derivatives. If we truly understood etiology and pathogenesis this approach would be wonderful. It would mean we had arrived at the promised land. But short of this, DSM-IV can actually hinder therapeutic perspectives and treatment approaches.

Let me develop this last point. DSM-IV allows researchers to gather together a group of patients who meet the described criteria for the disorder, try different treatments, and compare the results. Thus, a given percentage of patients with social phobia might be helped by placebo, and if a greater number will be helped by Paxil, or Neurontin, or cognitive behavioral therapy or whatever the treatment in the research design might be, than these treatments can be designated effective if statistical significance is reached. At first blush this seems to be a good thing. Evidence-based treatment appeals to the FDA and, more importantly, appeals to common sense. Empirical data is usually far more valuable than theories and controversy that cannot be backed up by a test of the facts.

The main problem with this is that it can lead to conclusions that make no sense whatsoever, when viewed in light of later understanding of what is truly occurring. For the purpose of illustration let us consider heart failure as a model. An important aspect of treatment is to focus on a manifest symptom such as edema, especially pulmonary edema and pleural effusions. The strain on the heart from excessive fluid demands the use of diuretics (which, of course, do not act on the heart at all but on the kidneys). Unencumbered by fluid in the lungs shortness of breath and orthopnea will improve. The treatment addresses pathophysiology without taking etiology into account. The actual diseases that brought about the heart failure are once removed from the focus of treatment. Heart failure might be due to muscle damage from an MI or a viral cardiomyopathy. There might be valvular damage from rheumatic fever, or subacute bacterial endocarditis and so forth. A clinician focusing on presenting symptoms is proceeding rationally because regardless of etiology, when the heart doesn’t do its job, when it is not pumping blood efficiently, the final common pathway manifested by the accumulated fluid may be of more immediate concern than the underlying cause of the illness. One hundred years ago congestive heart failure could be described without an understanding of its many causes and that description remains therapeutically relevant today even after we can now better understand underlying causality.

But there is a problem with congestive heart failure as a diagnosis. For argument’s sake let us say our knowledge base remained at the turn of the 20^th century and atrial fibrillation was causing the heart failure of a given patient. A treatment aimed specifically at the fibrillation would fail miserably when tested in a larger population of patients whose “disorder” had been defined as “congestive heart failure.” For example a beta blocker could, in those cases with atrial fibrillation, be the proper treatment for cases of heart failure caused by atrial fibrillation but otherwise this drug might worsen the illness of the other patients in a larger test group of heart failure patients. Viewed from the perspective of the heart failure diagnosis (“disorder”), the few patients it might help might then be described in individual case studies but would probably be dismissed as anecdotal if proponents argued that it should be used as a general treatment for congestive heart failure. Indeed it would be seen as harmful to the treatment of congestive heart failure, even though it was the proper treatment for the subgroup whose heart failure was due to the fibrillation. And let us say the fibrillation were due to hyperthyroidism. Then what? My point is obvious: As reasonable as evidence-based treatment protocols for symptom defined “disorders” might seem to be, they are, in fact, pathetic compared to what is possible when a true understanding of etiology and pathogenesis can be used to provide rational care. There is a pseudo “scientific” conclusion presented because an exact number can be tabulated about effectiveness.  But that number is nonsense. It starts with a very inexact description (the diagnosis) and collects statistics using  that.  Giving clusters of symptoms a name  (a diagnosis) may seem reasonable but consider this.

Penicillin works with  syphilis, strep throat, pneumococcal pneumonia, gonorrhea  even though the cluster of symptoms surrounding each diagnosis is totally different. How come? Since we understand what is happening we have absolutely no difficulty with that finding. Our understanding of the etiologies of these diseases and how penicillin works makes it entirely logical that these differences in symptom clusters could be treated by the same medicine. All are caused by bacteria. Penicillin kills bacteria by destroying its cell wall. We are not mystified because we understand what is going on. But if this were a psychiatric phenomenon it would seem paradoxical. Clusters that are so different treated by the identical medicine? Most of the time we don’t have a clue that resembles our understanding of bacterial diseases. We don’t know the etiology and we don’t know how our medicines work. But instead of fully understanding the implications of our knowledge gap we leap forward into categorizing treatments as evidence based and useful or worthless whenever the numbers don’t  jive.

Given that DSM-IV does not represent an advanced understanding of the actual causes and pathogenesis of the disorders in question my focus on the psychology of these disorders and the psychology of psychopharmacological agents should have remained and still be a focus of study. Van Praag (1990) in his “Nosological Tunnel Vision in Biological Psychiatry, A Plea for a Functional Psychopathology” made this point a decade ago. His description of the psychological effects of serotonergic and noradrenergic agents may not exactly correspond to my own, but the model is similar. Most psychotropics ameliorate component psychological functions that are misfunctioning rather than “cure” specific syndromes at the etiological level. As noted we use diuretics for congestive heart failure, and, sometimes edema due to liver and kidney disease, not because they are all part of the same disease or “spectrum disorder”, but because we are addressing an aspect of the pathophysiology. There is no mystery in the fact that a drug that affects the kidney helps a failing heart. A feel for what the various psychiatric drugs do psychologically is often far more effective for the skillful clinician.

Thus, it is no mystery that gabapentin or benzodiazepines might ameliorate both agitated depression and social phobia. Anxiety is an important component in both disorders, and targeting this is more relevant than research that exclusively correlates DSM-IV disorder with a given medication. It might be more productive, for example, to study the role of anxiety (or fear!) in schizophrenia, depression, alcoholism, borderline characters, social phobias and so forth and how the relief of anxiety improves symptoms in these illnesses. Interestingly, there was recent soft evidence that SSRIs administered to a group of “at risk” adolescents (for developing schizophrenia), may have had some efficacy in heading off the disease (Cornblatt, 2000). Sticking to the chemical model might lead to all kinds of elaborate chemical pathways to explain this strange finding. But if the model for explaining what leads to psychosis is a different one, if for instance a premorbid period of emotional isolation or intense forbidden conflicts, overwhelmingly intense (possibly “limbic”) level cognitively disruptive emotions, and factors such as these play a role in pushing a genetically primed vulnerable person over the edge into psychosis (never to return to normalcy again) then SSRIs would make perfect sense because of their powerful effect in calming (in my model) stormy emotions.

Similarly, using the model of SSRIs giving a “thicker skin,” I tried them with two delusional disorder patients (with paranoia) in addition to antipsychotic medications. They were very helpful. Once again my model was the psychological effects of the medications not concern with a particular neurotransmitter. I am confident that if others were using this model they would develop other useful applications for medications that might be helpful.

In this same vein, if drug manufacturers were doing research based on Van Praag’s model they might convince the FDA to sanction medications for broader usage rather than force studies verifying effective use for one diagnosis at a time. DSM-IV is doing a disservice if it distracts researchers, clinicians, and journal editors away from its originally carefully defined purposes and toward the chemical imbalance model as the exclusive etiology for psychiatric disorders. It is doing a disservice regarding potential uses of medications if there is practically no discussion of this approach in the literature and little if any discussion in training programs.

Other important implications for treatment

The specificity and empirical nature of the chemical imbalance perspective loans itself better to the brevity of scientific articles. Perhaps, this is part of the reason that it has gained a measure of legitimacy for psychiatry in the world of science. But I don’t know of any other way to present the data necessary to illustrate that it has led to poor therapeutics other than through a series of short case illustrations (with commentary) which emphasize the subtleties required to adequately deliver care. Unfortunately this approach is shamelessly “anecdotal”. It is in the language of the humanities, the arts, the very opposite of science, the very defect that has plagued psychiatric literature from the very beginning. But there is no other choice if the true acceptable goal, that we share, is trying to gain as accurate a glimpse of the nature of things as we can. If these case illustrations can be viewed by the critical reader as analogous to photographs and pictorial illustrations, than perhaps we can venture into less rigorous territory.

Pomerantz has reported a case of a patient on SSRIs who was completely indifferent to speeding tickets he had gathered while on SSRIs, a reaction that was completely out of character for him. Pomerantz attributed it to “overmedication” and indeed it reacted to a reduction in dosage. I’ve had patients, successfully treated on SSRIs, report many similar phenomenon. One woman, doing well with a phobia that had crippled her for over 40 years, was struck by her medicated lack of reaction to her only son’s diagnosis of testicular cancer. I’ve seen this same reaction do wonderful things for a patient in despair over her hopeless prognosis. She was able to gather her resources, and replace her terror with courage.

This case is noteworthy not only because his judgment was altered by the meds but because, at ten months, when we first tried stopping the meds, he would have illustrated the statistics often replicated in studies, of patients who have a recurrence without their meds, thus providing one more piece of evidence confirming the biological basis of his illness. But at 16 months, with the apparent cause of his depression eliminated (his critical supervisor), he did just fine without an SSRI. This doesn’t diminish the almost miraculous effectiveness of his original meds, or even that Prozac may very well have helped him gain the initiative to find a new job. However, it does highlight the kind of questions that clinicians should ask themselves about the particulars involved in a specific patient’s illness, as opposed to exclusively focusing on the operative factors in a specific diagnosed illness. This perspective is in contrast to the clinical practice guideline issues by the U.S. Department of Health and Human Services which flatly states that where there has been a prior episode(s) of major depression “maintenance of antidepressant medication treatment should be for at least one year”

The fact that on follow up recurrences are found so frequently in unmedicated, as opposed to medicated, patients does not automatically prove biological origin. Generally speaking the issues involved in a depression are deeply woven into a patient’s character or the fabric of his life. Miraculous transformations are the stuff of melodrama not reality. One would not expect a change in the original factors that led to depression eight months or nine months into treatment, or even years later unless the patient or his circumstances changed. Hence depression is going to recur off of meds. But it is not impossible for there to be a dramatic change in circumstances. If a patient has gone into a deep depression because of financial hardship after he/she has been fired from a job, chances are that finding a new terrific job will very effectively keep depression from recurring. Winning the lottery works even better. The same can be said for a person who does not have a neurotic pattern of relationships, who has gone into a depression after being rejected by a spouse or lover. Finding a new mate works wonders whether it is three months or two years after medication was begun.

I’ll put the issue in a nutshell. What if the Prozac worked like a charm and completely rid him of his depression? What if Prozac returned bounce to his life and now he found he could, after all, live happily with the status quo? What if 25 years from now, Mr. T. were to wake up and suddenly realize he had wasted his life? He really had wanted children and a family all along. What if he wouldn’t allow a doubling of his Prozac dose at that point? A drug had deceived him, cheating him of what had been meant to be. Would Mr. T. have had major depression if he weren’t biologically predisposed? We don’t know. (Nor do we know with others.) But even if he would not have gotten as depressed without having a biological predisposition, it is wrong to dismiss his marital situation as merely a precipitant. In this case, the depression was an alarm signal. It told the patient that the life he was living would not do.

I had a patient who was having an affair with a married man who was on Prozac. Every time he came off his medications he couldn’t stand his marriage for a moment longer and he intended to marry my patient. As soon as he was back on meds his concern switched to his teen-age daughter who needed him to stay. I’ve had patients find the courage to ignore their fear of loneliness and leave an unsuitable marriage with the help of SSRIs, others find the courage on meds to have what proved to be an unwise affair. I’ve seen a medicated patient quit his 9-5 job, use his inheritance and “go for it” as a singer. Was this realistic? I suppose it depended on his talent, connections, luck. He had previously been cautious about his inheritance, recognizing that it was a one-time thing and was his only hope for financial security. Only after he also decided he was going to use this money to develop a solar car did I become concerned. He was not manic or hypomanic, but he was definitely feeling better than he had ever felt. When told he would have to stop the Prozac, so that he could review his choices unmedicated, he stopped therapy and went to a different doctor.

I successfully treated a woman for depression with Prozac. Three years later she was again depressed and I suggested Prozac. “Are you kidding?” She answered. While on Prozac she put all of her misgivings aside and married a man she knew was unsuitable.  When she was off of it she realized what a horrible decision she had made.

It is particularly in the realm of decision making that the illness model being used becomes crucial. If we use the chemical imbalance model than the medicated view is presumably the “real” view of a normal person now fixed. Certainly, with severe depression, where a person may be completely crippled by his symptoms, one can view the undepressed person as improved in his decision-making capacity. But even in that case it doesn’t mean the medicated person’s judgment represents the “real and true” view of the patient. If the meds are seen as agents that reduce a sense of consequence, than even a person feeling “better than ever” is not necessarily thinking the way he should be thinking. When the feared consequence is obviously neurotic and distorted than the reduced fear can be seen as useful. But I am arguing that the medication works across the board. It reduces the terror of guinea pig pups separated from their mothers. It reduces neurotic over reactions to perceived fears. It also reduces fears that should not be reduced. It can make a mole hill out of a mountain. I am not saying it necessarily creates a drunken sense of abandon, the intoxicated person finally telling off his boss, only to find himself unemployed the next morning. But it works in the same direction. The point is that what is good about the drug is also what is bad about the drug. They are one and the same thing. What might be wonderful for a salesman who has to make cold calls, might not be best for someone in a job  that demands exacting standards such as an engineer  designing a bridge. In Pomerantz’ case and some of the case presented here a reduction in medication may lessen the patient’s reduced sense of consequences, and therefore be clinically appropriate, but as noted, it does not follow that these “side effects” necessarily indicate “overmedication” These effects may be intrinsically linked to what is working well for other symptoms. The chemical imbalance model assumes the medicine fixes what is wrong and returns complete normalcy when the right dosage is found. I agree the meds can do away with most, and sometimes all of the DSM-IV symptoms, but not because basic causality has been eliminated.

Dr. Peter Kramer, in his thoughtful book, “Listening to Prozac”, describes the discomfort many psychiatrists have felt using this drug. As he notes, we often are in the position of reassuring patients that “medication merely combats illness….If the pills work, they will restore you to your former self….Medication does not transform, it heals”. However, Prozac, in a substantial minority of patients does transform. Prozac causes many people to become hyperthymic, that is “optimistic, decisive, quick of thought, charismatic, energetic and confident.” Dr. Kramer described many patients whose newfound confidence did wonders for them. But what if becoming more confident, less self critical, more outgoing, does not improve performance? Here is a quote from James Wolcott, TV critic for the New Yorker that appeared several years ago:

I watched Paula Poundstone with appalled fascination, dumbfounded that such earnest dither occupied an hour of prime-time television. The people at ABC must have been equally agape, because they dropped the cloth on her cage after only two episodes, even though they had committed themselves to thirteen…. The embarrassing rubout of the “Paula Poundstone Show” has been compared with Chevy Chase’s quick flop. Both were comics who through ego or bad advice let themselves get caught unprepared. But there’s one difference. Chevy Chase’s eyes knew fear. They flinched, as if pleading “please make it stop, please make it stop.” Poundstone, on the other hand, was unfazed. She galumphed around on-stage nattering about nothing, her face a blank slate. She was like a pod person, Prozac in a flesh colored shell. She seemed to screen out any signals that didn’t conform to her alpha state.

As noted above, especially among certain adolescents, being “cool” is the whole point of their existence. Their seeming indifference to stressful challenges defines their sense of mastery. On a less glamorous level it can be said that they are avoiding whatever is unpleasant. In a sense they develop “mini-phobias”. I suppose it isn’t very different than the narrowing of experience that goes on for all of us when we find activities that invoke anxiety rather than pleasure.

I’ve had athletes report to me that on meds they could deal with their coach better, but they had lost their fire, their competitive edge. A Los Angeles psychiatrist wrote in the Psychiatric Times that his actor patients refuse SSRIs because it dulls their emotions. Writers have complained that they have lost their pain but at the price of their creativity. Interestingly, the public seems better informed than psychiatrists about this phenomenon. Here is an ad for a T-shirt that recently appeared:

I was listening to a talk radio show when the guest got quite excited about a subject. The host shot back. “You better up your Prozac.” Why does the public know more than professionals? The answer is obvious. How could psychiatrists observe these things if patients are seen very briefly and all of the questions are directed to DSM-IV symptoms and side effects from the meds?

Interestingly, what I have been describing has been mentioned (although not prominently) in the literature. Thus Pies (1999) referred to certain patients feeling emotionally “flat” or “blah.” His speculation was that it might “involve decreased dopaminergic functions in the brain that mediate pleasure or reward.” His solution to this “side effect”(?)–treatment with psychostimulants (amphetamines and the like).

I view Wellbutrin as a “kick ass” drug which seems to bring energy, initiative, clear mindedness, increased ability to experience pleasure, qualities that are associated with stimulants and cocaine. In this patient’s case, the panic attacks seemed to be related to his tendency to procrastinate, and related to that, terrifying feelings that judgment day was near, and his frequent feelings that the “s-t was about to hit the fan.” He kept up with his work far better when he was on Wellbutrin than when he was off of it. Hence there were fewer feelings of impending doom on the meds.

I’m not sure if my explanation of what was happening in this patient is correct. Nevertheless, I am suggesting that a fruitful area to consider in the literature might be that the “personality” or as I am calling it the”psychological” effects of a given drug might be a deciding factor in choosing a particular drug for a particular patient even if evidence based protocols argue against it(using exactly the same logic used earlier in the article in the example of beta blockers being helpful in congestive heart failure caused by atrial fibrillation but harmful in the other cases of heart failure). Of course there is a complete absence of this kind of discussion in the literature because what I am presenting is totally out of the loop.

The argument I am presenting is not denying the importance of biology in mental illness. Unquestionably, there are strong genetic factors in many (perhaps all) cases of schizophrenia, bipolar disorder, and more than likely, many forms of depression. Biological differences could predispose certain people to have a full-blown depression rather than what would be a touch of wistfulness in those not predisposed. Although, there is good evidence in panic disorder that childhood trauma is a key factor (e.g. 20% of patients have experienced the death of a parent as children, a certain percentage have been found to have been sexually abused) it is not impossible that some patients are genetically built so what would have set off anxiety in one patient becomes panic in another. Differences in temperament have been well documented in infants.

But there is little doubt in my mind that psychopharmacologists will eventually reinvent the wheel and come back to psychodynamic formulations or something akin to them in explaining complex behavioral patterns. Cognitive behavioral therapists have been forced (if they want to be effective therapists) to acknowledge the importance of transference, and there is simply no way that a syndrome as complicated, for example, as obsessive compulsive disorder can be “caused” by genetics alone, or a neurotransmitter. An understanding of the particulars of this disorder will have to include psychic conflict. As I noted earlier one can treat strep throat and syphilis with penicillin because, without knowing the particulars of each illness, the medicine is so effective that the particulars of the pathogenesis of each condition becomes academic. Penicillin will work beautifully and all that matters is that each germ has a cell wall that penicillin destroys. But behavior is different. Clearly, like penicillin, SSRIs treat a factor (for simplicity we will call it “emotional reactivity”) that is common to very many psychopathological conditions. And it is, therefore, useful, but at the same time it may dull “signal anxiety,” an extremely important part of normal motivation, and negatively effect a mature judgment of consequences. The classical psychoanalytic wariness regarding medications still holds regarding their appropriateness in therapy. While it is true that some patients become more accessible, less guarded, more able to tolerate upsetting material when they are on medication, and that seriously ill patients require medication if they are to function, drugs often dull affect and lessen the significance of material. More importantly they may lower the motivation of patients to come to terms with their inner demons.

I can’t help observing that the paradigm shift from nurture to nature that has occurred in psychiatry is partly a sociological phenomenon between warring camps within our field, the pendulum revengefully swinging in the opposite direction of where it had been. Although in selected cases psychotherapy does wonders, frustration with psychotherapy as a primary treatment is understandable. It does not offer a solution to all of life’s mysteries and difficulties, it is expensive, and there are abundant examples of treatment that did little or nothing. But what has happened to the practice of psychiatry is not justified. A fair-minded approach to psychotherapy should have built upon the sophisticated thinking of psychodynamically oriented clinicians instead of driving them out of academia.

At the very least, psychiatrists should know their patients reasonably well if they are to prescribe medications wisely. This is true whether or not it will eventually be determined that the odds of a patient developing a disorder has been increased by biological factors. Prozac and the other SSRIs are too powerful, too far reaching in their effects, their influence too subtle in too many areas of a patient’s life, to be given by gynecologists, family practitioners, physicians assistants, and others who have brief contact with their patients. They are too powerful to be given by psychiatrists who see their patient for 15-minute med checks once a month and know close to nothing about their patient’s lives.

The Columbine tapes haunt us as well they should. It would be truly a disservice to patients, past, present, and future if they were frightened by still one more episode of a media feeding frenzy regarding the safety of SSRIs. These are wonderfully effective drugs that are usually very safe. It would be terrible if the fact that Eric Harris had taken Luvox turned into another lawsuit circus (which, as in war, truth is the first casualty). It would be terrible if parents were unwilling to let their children be treated for conditions that could be helped by SSRIs. I do not know if Luvox played a role in his indifference, if it shut off alarm signals that might have gone off. He felt he wanted to be off of it because, if anything, it diminished his anger. But nonetheless, many crimes, some very violent, have been committed by patients on SSRIs. True, drugs used by tens of millions of people are bound to have murderers among them, but still, I have been arguing that SSRIs diminish a sense of consequence, good or bad. It behooves us to ask these questions, or at the very least to challenge dispensing psychotropic medications without following the consequences more closely.

This isn’t to deny that there are patients who have very little interest in seeking anything other than medication dispensed by doctors who will see them briefly on occasion. The majority of health systems in the United States will not allow anything other than this form of care. This should not be the case, but unfortunately it is the case. I am not claiming that medications should never be dispensed in these circumstances. They have been and will be, and with luck are adequate, but I am strongly arguing that this is inferior care and should be labeled as such. It isn’t just HMOs. The chemical imbalance perspective loaned credibility to this kind of treatment, indeed as I noted “expert” consensus panels have made it appear that it is state of the art, but the model is wrong scientifically and wrong therapeutically. It is time for the word to get out.

References

Clinical Practice Guideline, Depression in Primary Care: Detection, Diagnosis and Treatment, US Department of Health and Human Services, Agency for Health Care Policy and Research, Washington DC, Quick Reference Guide for Clinicians Number 5, April 1993

Cornblatt B (2000) Early pharmacological intervention in the prodromal phase of schizophrenia: Is this a good idea? The Journal of Psychotic Disorders 4:2-15

Detke MJ, Rickels M, Lucki I (1995) Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants Psychoparmacology (Berl) Sept;121 (1):66-72

Dixon JF, Hokin (1998) LE Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. Proc Natl Acad Sci USA. 7;95(14):8363-8

Donovan, SJ (as reported by Sherman, C) (1998) ‘Explosive Mood Disorder Quelled by Divalproex’ Clinical Psychiatry News Nov, 26(11):29

Duman RS, Heninger GR, Nesler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54(7): 597-606

Franz,B (as reported by Sherman, C) (2001) ‘Adjunctive Oral Morphine Effective for Refractory OCD’ Clinical Psychiatry News July 29(7):4

Frances A, Docherty JP, Kahn DA (1996), The Expert Consensus Guideline Series: Treatment of bipolar disorder. J Clin Psychiatry 57(suppl 12A):S3-S88 The Pharmacological Basis of Therapeutics ed. Louis S. Goodman, Alfred Gilman et al. ninth edition (New York: Pergamon Press, 1992).

Joffe RT, Swinson RP, Levitt AJ Acute psychostimulant challenge in primary obsessive-compulsive disorder J Clin Psychopharmacology 1991; Aug 11(4): 237-241

Kramer, P Listening to Prozac (New York: Viking, 1993)

Lenox RH, McNamara RK, Papke RL, Manji HK (1998), Neurobiology of lithium: an update. J Clin Psychiatry. 59 (Suppl 6):37-47

Oliver B, Molewijk E, van Oorschot R, et al. (1994), New animal models of anxiety. Eur Neuropsycho-pharmacol 4(2):93-102

Petty F (1995) GABA and mood disorders: a brief review and hypothesis. J Affect Disord, 34(4):275-81

Pies, R (1999) The psychodynamics of drug side effects with newer agents. Psychiatric Times 16 (4):15

Physicians Desk Reference (1999) Montvale, N.J. Medical Economics Co.

Pomerantz, J Loss of Appropriate Anxiety: An SSRI Overmedication effect? http://pharmacotherapy.medscape.com/SCP/DBT/1999/V11.n10

Sachs GS (1996) Bipolar mood disorder: Practical strategies for acute and maintenance phase treatment J Clin Psychopharmacol 16(2 suppl 1):32s-47s

Sobo, S (1999) Psychotherapy perspectives in medication management; The inadequacy of 15-minute med checks as standard psychiatric practice. Psychiatric Times 16 (4) 23-25

Sobo, S (1999) Mood stabilizers and mood swings: In search of a definition. Psychiatric Times 16 (10):36-42

Sobo, S (1977) Narcissism as a Function of Culture The Psychoanalytic Study of the Child 32:155-172

Van Praag, HM. et al (1990) “Nosological tunnel vision in biological psychiatry. A plea for a functional psychopathology” Ann NY Acad Sci. 1990;600:501-10

Addendum 3/5/11:  Please see this article  Talk Doesn’t Pay, So Psychiatry Turns to Drug Therapy Unfortunately, this is an accurate and fair description of what’s become of my profession.  This, and other articles by me,  were an attempt to combat it and still remain true in that even medication therapy is done better when the psychiatrist knows the patient.  But one of the reasons these articles  have been ignored is that it means real sacrifice for  psychiatrists, which they can’t afford.  I don’t want to be a hypocrite.  In my semi-retirement, as I’ve cut my practice to 1 1/2 days  per week, I want to maximize what I can earn in that time.  So at this point,  I am no different  from what is described in this article.  Some of the principles can still be ascertained from relatively superficial contact, but many more are missed.

This internet article is an expansion of a presentation given as the invited speaker at Psychiatric Grand Rounds, November 15, 1999, at the University of Alabama Medical School. It has been rejected by every psychiatric journal that it has been sent to. The reader can draw his own conclusions about that. In any case this lack of openness in psychiatry to challenging ideas led to the decision to put it on the Web. For years it occupied a #1 position on google searches for a variety of topics (“chemical imbalances”, “psychiatric diagnosis” and so on. Fortunately this point of view is prevailing, so there are many similar article now avaiable. My regards to Professor Herman Van Praag, now in Amsterdam, for the originality of his thinking and his encouragement.

Here is a link to other articles by me not all psychiatric

 

Copyright 2001 by Simon Sobo, MD Updated 2009

e-mail: SS06470@yahoo.com