Simon Sobo, MD

The  paradigm for modern psychiatry is evidence-based medicine (EBM)-it represents  proven treatments for defined diagnoses. But there are major problems with this  position, starting with the fact that while they are superior to placebo,  evidence-based treatments too often are ineffective. Even with treatment  compliance, many patients do not return to their premorbid selves. Their  ailment may last for years. A given percentage is not helped at all. Typically,  30% to 50% of depressed patients will not respond, and among nonresponders only  23.5% to 28% are helped by a second medication.

 The relatively  common failure of evidence-based treatments to achieve remission is not unique  to depression. Similar results are found throughout the full spectrum of DSM-IV  disorders, which frustrates both doctors and patients.

This  is not surprising. The science of psychiatry is still young, its conclusions  necessarily preliminary. Psychiatry has not found its penicillin, a drug that  will succeed 99% of the time in eliminating strep throat, because it kills the  germ causing the illness. DSM-IV diagnoses are operational definitions, the  best attempt by committees of experts to group manifestations of  psychopathology into “disorders.” This cataloguing is not the same thing as  understanding cause and effect. We haven’t yet discovered the etiology of any  DSM-IV diagnosis.

It  cannot be assumed that doing a better job classifying psychopathology  diagnostically is the best way to move forward. Established diagnostic entities  are as much wish as reality. The convening of experts to create DSM-5 diagnoses  will probably not help researchers find new discoveries. The authors of  DSM-III, DSM-III-R, and DSM-IV had it right. They also made committee  decisions, but they emphasized that their conclusions were tentative: “. . .  there is no assumption that each category of mental disorder is a completely  discrete entity with absolute boundaries dividing it from other mental  disorders or from no mental disorder . . . [and] boundary cases will be  difficult to diagnose in any but a probabilistic fashion.”

Robert  Spitzer, MD, former Chair of the DSM-III Work Group, has rightfully condemned  the confidentiality agreements required of DSM-5 committee participants.

  He wants detailed minutes of DSM-5 Task Force deliberations, a no-brainer for  those who understand the necessary tentativeness of scientific information, but  problematic for those who want to provide an illusion of consensual certainty  about diagnostic categories. “EBM” is being touted for its scientific prestige,  precisely as the process has forsaken the true spirit of science. Considering  how much we still don’t understand, our steps forward should be exploratory,  investigative, and not closed off by the chilling effects of authority

There  are those who only respect the exactness of numbers and who believe only  statistics can determine what is factual and what is not. This is a given for  researchers, but it is not as relevant for clinicians who may need answers for  their patients that cannot be organized into questions answered with numbers.  Obviously, given the choice between what is understood and proven through  scientific method and what is, in essence, opinion or formulation, science  should command absolute loyalty. But that doesn’t mean that using a scientific  format, or waving its banner, adds validity to those who speak as “scientists.”  Its virtues can act as a smokescreen. The language, the prestige, and the  trappings of science can be so distracting that science’s core value is  overshadowed, absolute clarity about what is known and not known.


 There  is also a more fundamental issue, not answerable to the vote of even the most  “expert” committee. For instance, we can operationally define oppositional  defiant disorder, binge eating disorder, or all sorts of problematic behaviors.  We can classify and subdivide them and epidemiologically count numbers that can  be assigned to subcategories-but for what purpose? Does every diagnosis in  DSM-IV represent an actual “real” illness, in the sense that polio, cancer, or  a strept throat actually exist? Or are we reifying ephemeral qualities? We all  know of children who have been diagnosed with one condition after another when  behavior does not conform with defined criteria. Parents hope for that  moment-“Ah-hah, your child ‘really’ has ADHD [or bipolar disorder or an anxiety  disorder]. Now that we know what it is, we can treat it.”

Unfortunately,  the search for the “real” diagnosis in psychiatry is often unfruitful  therapeutically. The results won’t be the same as when a medical clinician  discovers, for instance, a thyroid tumor or diabetes that presented atypically.  In that case, elucidating the hard-to-discern illness has a purpose. We are not  discovering what is really wrong. Simply finding a label; then another label;  and another. (It mostly resembles the kind of diagnostic and treatment chaos  that accompanies illnesses such as chronic fatigue syndrome.) I cannot help but  add that, too frequently in clinical practice, providing a diagnosis isn’t even  driven by the wish to follow a consensus treatment plan (itself a polling of  “expert” opinions rather than one that is scientifically based). There may be  no doubt the patient has pathology, but the clinician needs to indicate 

 on the insurance form that  justifies medical attention.

Most  experts and the FDA (and perhaps insurance companies in the future) argue that  EBM should monopolize clinical approaches. But at this stage, the proper  question is 

 should we exclusively use treatments that have proven  superior to placebo? It 

 what is the best way to formulate treatment  strategies when now, and in the foreseeable future, science can’t offer answers  that we need? Sensible approaches, based on what we know about a particular  patient, not limited to statistically validated treatments, are often more fruitful.  Out of necessity, reasonable conjectures may play a significant role. Given  mediocre treatment results, we need all the help we can get, the art of  psychiatry as well as the science.


 EBM  eschews the anecdotal in the name of generalized conclusions, based on the odds  that the patient’s ailments are typical for their group, patients who can be  diagnosed with the same illness. This is not a ridiculous consideration, but it  can miss important particulars brought by the patient. Knowing a patient well  can be the difference between effective and ineffective treatment. It is not  unusual for patients to have psychopathology that is central to their condition  and treatment, but is ignored by a diagnostic approach that exclusively focuses  on symptoms described by DSM-IV. Premorbid defenses, character style, the  nature of the patients’ stressors, their 

 can guide clinicians to a particular treatment including medication. And, it  can influence dosage.

 While EBM has a place, especially when low  cost is a consideration, cookbook psychiatry cannot lay claim to being optimal  treatment. It is especially detrimental if this perspective acts like blinders,  obscuring relevant psychopathology more than it clarifies the clinical picture.

 in his “Nosological Tunnel Vision in Biological Psychiatry, A  Plea for a Functional Psychopathology” argued that pharmacological agents can  be viewed as inducing particular psychological states that, although not  specifically related to diagnosis, are nonetheless the basis for their  usefulness. I would like to suggest a perspective about how SSRIs affect  individuals, and why they are so clinically useful for so many psychiatric  conditions. SSRIs can be effective 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 

 affect 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 affect individuals in ways  that are not specific to diagnosis. What is that effect?

The  most frequent description that I have heard from my patients is “Don’t sweat the small stuff,” or “What’s the big deal?” It is this  calm that I believe is a unique blessing of SSRIs. 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 

, actually want to do the proverbial modern mantra, stop and  smell the roses.

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, 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 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. 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.

Let  me describe an unusual use of meds. A patient with PTSD for over 10 years  presented on high doses of Adderall that had been given to him for what his family  physician diagnosed as adult ADHD. (He had reported difficulty concentrating.)  His physician then became uncomfortable administering stimulants and sent him  to me. He didn’t have ADHD. But he reported that on the Adderall his PTSD was  the best it had been in over a decade. The explanation appeared to be found in  his history. He and his fianc had been trainees at a state police academy. His  fianc committed suicide, blowing her brains out. My patient found her. He  couldn’t clear his mind of the scene. During the day, during his dreams, it  remained vivid. Even with SSRIs and benzodiazepines, his PTSD not infrequently  took control of his mind. This no longer happened with the addition of  Adderall.

My  guess was that the Adderall brought back his premorbid, state policeman  defensive structure. Instead of experiencing his trauma again and again as a  helpless passive victim, the essence of the psychological position occupied by  those suffering from PTSD, on the Adderall he had returned to being a  take-charge kind of guy. Coincidentally I was also seeing another patient with  PTSD. She was a drug rep who had been a workout nut. She spoke in short  staccato sentences. Boom boom, bam bam, not a trace of sentimentality in her,  not a soft syllable in her repertoire. She had been in a car accident and  broken her collarbone, right arm, and one of her legs. She couldn’t work out.  She kept re-experiencing her helplessness in the accident. She was on SSRIs  which were helpful but not curative. The addition of Adderall worked like a  charm.

This  is not an endorsement of Adderall for PTSD. It is an endorsement, when  formulating a treatment, to think about a patient’s defenses, personality  structure, and the like, and how their symptoms may be helped by the  psychological consequences of a medication. Diagnosis per se may not be  critical in this process. Let me add another example.
 A  patient presented to me on Wellbutrin for his panic disorder. It is one of the  few antidepressants that is not recommended for this condition-it may give an  edginess that sets off further attacks. So I took him off it. He got worse. It  turned out that he was a procrastinator and his panic attacks were precipitated  when something was about to hit the fan, when the passive aggressive mess he  invariably made, was on the verge of being discovered.

As a  dopaminergic agent, the Wellbutrin was a motivator, an energizer. It helped the  patient get things done. I have since discovered that while dopaminergic agents  can make anxiety worse, they can have the opposite effect when a patient’s  anxiety is specifically driven by the pressure of undone work hanging over  their heads. The drug energizes them, helps them to initiate and complete their  chores. Thus, with certain generalized anxiety disorder patients, it is an effective  treatment.

For  what it is worth, let me also mention a seemingly bizarre clinical vignette. I  saw a patient with severe obsessive-compulsive disorder (supposedly a serotonin-based illness) whose symptoms completely disappeared when he joined the Jehovah’s  Witnesses. He gained a sense of innocence, of safety, of the world and his  personal experience making sense, of being directed by a benign and helping  force in the universe, a parent watching over him and loving him. He felt it  deeply. And that did it. No symptoms. Three months later, when disillusionment  began, the symptoms came marching back, some of them as religious compulsive  rituals. But still, what is the clinical meaning of his initial cure?

There  is one other perspective worth noting for the purpose of illustrating what DSM-IV represents. Let us consider congestive heart failure as a model. It can be  described in terms of observable symptoms that respond to specific  treatments-evidence-based treatments. But congestive heart failure has many different  causes. For argument’s sake, let us say our knowledge base remained at the turn  of the 20th century and hypothyroidism was causing the heart failure of a given  patient. Thyroid extract would fail miserably when tested in a larger  population of patients whose disorder had been defined as congestive heart  failure. It might worsen, in particular, the illness of those patients whose  congestive heart failure was, for instance, caused, or exacerbated, by atrial  fibrillation as a result of hyperthyroidism.

From the perspective of the  heart failure diagnosis, the few patients it might help may be described in  individual case studies, but would probably be rightly dismissed as anecdotal,  if proponents argued that it should be used as a general treatment for congestive  heart failure. The fact remains that it is precisely the correct treatment for  congestive heart failure as a result of hypothyroidism. My point is obvious. As  reasonable as evidence-based treatment protocols for symptom-defined disorders  might seem to be in psychiatry, they are, in fact, pathetic compared with what  will be possible when a true understanding of etiology can be used to provide  rational care.

There  are many other examples of treatments that are not evidence based. Clinicians  may confirm or not confirm the strategies I have illustrated here. The  important issue, however, is the 

 of approaching patients in the ways I have described. The journals should be  full of similar clinical vignettes and unique perspectives from other authors.  The exclusive respectability of scientific psychiatry, based on diagnosis  alone, should be ended, until, at least, that perspective has provided us with  what only science can provide, proven cause and effect. I don’t believe it is  going to come from diagnostic psychiatry and evidence-based treatments, but  time will tell.


 In  the meantime, we need to end the tyranny of the paradigm that EBM and  diagnostic psychiatry has had on the medical literature and legitimize the many  good ideas we can share with each other. It means editors and readers will have  to use their judgment about the quality of the presented ideas, rather than  exclusively rely on statistical validation. (It might also mean that the FDA  allow pharmaceutical salesmen to refer to these articles rather than consider  it a crime.) Presumably some of the ideas will work. This beats committees and  doctrines and all the certainties of approaches that aren’t getting the job  done.

Clinicians  need all the help they can get. They can begin by getting to know the  particulars of their patients better. Residency training programs might also  help this process by teaching greater psychotherapy skills rather than only  giving it lip service.

 Ruh HG, Huyser J, Swinkels  JA, Schene AH. Switching antidepressants after a first selective serotonin  reuptake inhibitor in major depressive disorder: a systematic review. 

 Nierenberg AA, Keefe BR,  Leslie VC, et al. Residual symptoms in depressed patients who respond acutely  to fluoxetine. 

 Baghai TC, Moller HJ,  Rupprecht R. Recent progress in pharmacological and non-pharmacological  treatment options of major depression. 

 Papakostas GI, Fava M, Thase  ME. Treatment of SSRI-resistant depression: a Meta-analysis comparing within-  versus across-class switches. 

 American Psychiatric  Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV.  Introduction.
  

 Sobo S. The strengths  and weaknesses of DSM IV: How  it clarifies, how it blinds psychiatrists to  issues in need of  investigation.

 http://simonsobo.com/the-strengths-and-weaknesses-of-dsm-iv

 Van Praag HM, Asnis GM, Kahn  RS, et al. Nosological tunnel vision in biological psychiatry. A plea for a  functional psychopathology. 

Articles

The paradigm for modern psychiatry is evidence-based medicine (EBM)-it represents proven treatments for defined diagnoses. But there are major problems with this position, starting with the fact that while they are superior to placebo, evidence-based treatments too often are ineffective. 

Does Evidence-Based Medicine Discourage Richer Assessment of Psychopathology and Treatment?

I was asked to see "Bob," a 16-year-old prep school student, who a month and a half earlier had been placed on a selective serotonin reuptake inhibitor by his family physician. The medication had been somewhat effective. He had been dysphoric periodically, and he still could get down, sometimes feeling very isolated. But overall, he was now OK when "doing things" with his friends. When Bob was alone for a few hours, he tended to have morbid thoughts about death. He felt the authorities at school had totally overreacted when the nurse misinterpreted some remarks he had made about death two months before he saw me. They immediately sent him home, insisting that he be put on medication, and did not let him return until his therapist, whom he had been seeing for a year, agreed Bob had never been suicidal.

Meeting Bob for the first time, I was struck by a false jocularity, an awkward quality he shared with his father, whom I briefly met in the waiting room. Both spoke slightly too loud and did not really give me a chance to be infected with their cheerfulness. Their eye contact and body language did not agree with this cheerful demeanor. They were on automatic pilot. Both looked a little frightened, which is not unusual when meeting a stranger, especially a psychiatrist. It was the cheerfulness that seemed off.

Bob's therapist suggested that he seemed to almost enjoy the darker side of things, especially conversations about death. The therapist wanted him to think more positively and gave him homework assignments to accomplish this. His negativity had tended to isolate him at his prep school, where conversation tended to the lighter side.

When Bob settled down and told me his story, the happy face dissipated, and we began to connect. Bob had been raised by his grandparents. He had never met his biological father and did not know who he was, and his mother was a drug abuser who had given him to his grandparents for adoption at infancy. He had met his biological mother a few times but preferred "not to think about her." However, he did think about his (grand)parents a lot. His (grand)mother had died two years before in her mid-70s after several strokes. He thought this was a good thing because she had suffered greatly in her later years. His (grand)father was 79 years old and also was not healthy. In my waiting room, he labored to catch a breath. My assumption was that he had emphysema. He sat in the chair with a broad-based posture, like he might fall off. There were not a lot of good years left. Bob told me that many of his parents' friends had died in recent years, as well as two of his aunts. He might soon be an orphan, and this got him down. It should be noted that his visit to the school nurse occurred shortly before Thanksgiving. He had been thinking about the holidays without his (grand)mother.

The issue for us is whether positive thinking is relevant in this kind of situation. Would it help him, or would it create more problems than it would solve? True, finding a positive outlook is helpful in any set of circumstances. If he could relax and let life's bountiful pleasures and rewards reach him; if he could turn off bad death thoughts and replace them with optimistic ways of thinking about life's mysteries -- who knows? Hope is always crucial. If only he were religious, that could put a positive spin on everything. Meaning and purpose would be restored. However, he wasn't religious and neither was his counselor. So he was left with homework assignments, which he diligently attended to. His counselor felt that his need to think about death was not only causing his depression but that his morbid thoughts were "obsessive" in nature. Given that Bob was trying not to be so negative, the negative thoughts were "intrusive."

It reminded me of another patient I saw whose husband left her after a 35-year marriage. She still could not get him off her mind eight months after his intentions about their future were made clear and four months after she began doing cognitive-behavioral homework assignments to clear her thinking of obsessive morbidity. In her case, the futility of this became clear at one of our medication visits. She told me how she had overreacted to playing terribly at her tennis game. She was not simply down about her poor play; she was down on herself for being down. As with Bob's case, her therapist seemed to imply that she liked being negative. I told this patient to be kinder to herself. If she needed to be down, it was perfectly fine. Anyone in her circumstances would not be enjoying a wonderful state of mind. It would take a little while -- maybe more than a little while -- until she would get back to her old self. Trying to be positive was unnecessary, certainly not as a standard to hold for herself. In the meantime, I told her we could probably medicate her into a state of relative comfort.

Obviously, Bob's need to talk about death was based on a real ongoing stressor in the here and now. It was going to have social consequences. Bob was going to be heavy-hearted, and those looking for a good time would most likely be able to identify his state with a glance. It would not matter if he talked about death or did not talk about death. True, if he could become a very funny guy, his popularity might improve. And for teen-agers, being acceptable to peers, getting asked to parties and having someone to sit with in the cafeteria are all important parts of gaining self-esteem. But even if his (grand)mother had not died and she was a healthy 75-year-old, it is unlikely that Bob's joke-telling abilities would have been greatly improved. He is not that kind of guy. Nor is his (grand)father. Their cheerfulness in social situations comes across as being "off." As for coming across with a relaxed persona, that is always helpful in dealing with people, and fluoxetine (Prozac) might do wonders for him in this regard, but, important as it is to teen-agers, I would like to drop this whole subject of how to seem positive to others and get to the real point of this article.

What if Bob were negative and enjoyed being negative and wanted to pull others into his negativity because he wanted company in that part of his experience? What if "misery loves company"? I would argue that Bob has a right to his morbidity. He needs to work through his experiences, and having someone, maybe more than one person, go there with him and understand, rather than react to his negativity like he is being a creep, is crucial to the formation of a solid identity and his later capacity for intimacy. True, many, perhaps most, of his friends cannot and, probably, do not want to go there. They do not really want to understand, which is certainly understandable. It would be futile for Bob to force the issue on others, and it might just be that there will be limitations on how close he can get to certain people. Maybe many people. It is very possible, however, that he might find a companion who can dig the "blues," and this could form a solid starting point for a relationship. I think of the character Mel Gibson played in the movie "The Man Without a Face," his calm guiding strength shaped out of suffering, able to help the teen-ager transform life's hardship into tolerable proportions with his dignity and vision.

That used to approximate the ideal in therapy. That was a "positive" outcome. Oh, none of us were ever as cool as Mel Gibson. But sometimes we were. All this focus on chemical imbalances and negative thinking! The old kind of therapy does not loan itself very well to short-term efficacy studies. The new scientific therapy loans itself all too well to short-term results. We live in a world of short-term corporate profits; a "Have a nice day" sensibility about our well-being.



 provided a scientific discipline with its clearly defined syndromes, based on clearly defined symptoms. From there, the next logical step was empirically based treatments, based on the defined disorder. But the downside of 

 is that it has tempted clinicians to force a diagnosis so that they can use a proven treatment (Sobo, 1999). Apparently, some clinicians feel that if a 

 category cannot be assigned, there is no illness and therefore no justifiable treatment. Certainly, this is the position of HMOs, and at this point, treating 

 symptoms has become the only thing that some psychiatrists will do. Everything else is not illness but problems in living. Bob qualifies for a diagnosis of depression not otherwise specified. Cognitive-behavioral therapy has been shown to work for depression. The issues I am raising in his treatment have nothing to do with 

, yet they are most certainly vitally connected to his treatment.

The point of 

 was not to ignore clinical phenomena that are not categorized by 

. It was not to toss out decades of observations, thoughts, discussions and theories about the developmental and emotional needs of patients should their unhappiness not fit easily into modern categories. We are far too young in our science, far too ignorant of etiology to limit our field in this way. Ultimately, even our science will suffer if heuristic pathways are dismissed as not a part of our field. But, more to the point, our patients now, as much as ever, still turn to us for understanding, not cookie-cutter, one size fits all treatments. Is it sound clinical judgment to bypass hard efficacy data for a softer but, I believe, more relevant perspective? Or is this a bit of nostalgia that interferes with the work at hand? To me the answer is clear.



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

The issue for us is whether positive thinking is relevant in certain situations. Would it help, or would it create more problems than it would solve?

On the Banality of Positive Thinking

Mood-stabilizing drugs slipped into the vocabulary of psychiatrists during the last 15 years without a proper discussion of their definition. Consequently, these medications have been used in ways that have no empirical justification. The original idea behind the term

was the apparent ability of lithium to offer antimanic qualities as well as some measure of antidepressant action. 

The American Psychiatric Association's Practice Guideline for Treatment of Patients With Bipolar Disorder 

 (1994) defines mood stabilizers as "medications with both antimanic and antidepressive actions." From time to time, research has been contradictory about the efficacy of lithium as an antidepressant (Keck and McElroy, 1996). However, the concept was clear. This is not the case with the various anticonvulsant medications that have been labeled

 Despite widespread use, it is not obvious what is meant by a mood stabilizer and how anticonvulsants fit that description.

There is little if any clear-cut evidence that valproate (Depakote, Depakene), carbamazepine (Tegretol) (Kalin, 1996-1997) or gabapentin (Neurontin) are effective antidepressant agents. Yet as soon as they were shown to have efficacy in acute mania, they were quickly labeled mood stabilizers rather than antimanic agents.

This is not a matter of small significance, since it is not unusual for bipolar patients with a predominantly depressive history to be exclusively put on mood stabilizers with the expectation that the depression will be treated, and that rapid cycling due to the use of traditional antidepressants will be avoided. I'm not referring to the prophylactic use of mood-stabilizing agents when it is expected that antidepressants will later be necessary so that protection against a potential manic episode seems judicious. Frequently, mood stabilizers are used as the sole antidepressant. Indeed, an expert consensus treatment protocol recommends mood stabilizers alone as a first-line approach in treating milder major depressive episodes in bipolar I disorder and as a second-line approach in bipolar II disorder (Frances et al., 1996).

Some experts such as Bowden (1996) and Keck and McElroy (1996) are so concerned about the possibility of rapid cycling that they go still further, considering the use of antidepressants as a last resort in treating bipolar depression only after multiple mood stabilizers have been tried first. While the concern about antidepressants causing rapid cycling is based on an indisputable clinical possibility, these experts have no illusions about the effectiveness (or indisputable evidence for the effectiveness) of anticonvulsant medications as treatment for acute bipolar depression. Both valproate and carbamazepine did little better than placebo in the studies they cited, but if I understand them correctly, they considered bringing relief from the torment of depression as quickly as possible a less important priority than not iatrogenically causing mood instability.

According to Gary S. Sachs, M.D., the definition of the term 

does not require antidepressant or antimanic efficacy, per se, merely that the medication "decrease vulnerability to subsequent episodes of mania or depression" and not exacerbate the current episode or maintenance phase of treatment (1996). The use of anticonvulsant medicines as mood stabilizers has become even more relevant since the expansion of the bipolar disorder (BD) diagnosis to include bipolar II patients (American Psychiatric Association, 1994). Bipolar II is a reasonable addition to the nosology of mood disorders, sometimes allowing earlier recognition and an appropriate alertness to the softer signs of the illness. However, it also has contributed to an excessive looseness in diagnosing BD. On more than one occasion, I have had patients hospitalized for severe depression and, after a three- or four-day stay, they have returned on a mood-stabilizing agent and nothing else. They have been told that they have bipolar disorder and that their anticonvulsant medication treats the basic problem.

Ariel, a 16-year-old girl, had a history of repeated severe suicidal depressions punctuated by periods of a few hours, sometimes a day or two (definitely not four days as specified in the 

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition

 for hypomania), in which she felt a bit giddy as well as more social, energetic and creative. There was no family history of manic-depressive illness. She did not feel that her "up" times were a problem. Indeed, she was able to perform at a high level academically and felt more connected to her friends and parents. There was no pressured speech, flight of ideas or a sense that her mind was racing. There was no distractibility; impulsivity; irresponsible spending, driving or sexual behavior; or loss of judgment. Insomnia was not present, and there was no history of a decreased need for sleep. Although there was an improvement in self-esteem, it was not inflated or grandiose. Ariel's parents and friends, as well as Ariel herself, considered her good moods entirely normal and delighted in them.

The arguments for and against using a loose definition of BD hinge on the risk/benefit ratio of active treatment. On the benefit side, at least theoretically, is the kindling model for bipolar disorder. It is hoped that the prevention of frequent manic episodes may prevent rapid cycling that often develops later in the illness. But this is theory, not fact. Even when the diagnosis is clearly bipolar, there's no empirical documentation and no longitudinal studies that demonstrate long-term administration of medications will prevent rapid cycling later in the illness. Despite this lack of proof, when a bipolar diagnosis is unequivocal, treatment is a no-brainer. We treat vigorously with the hope there will be this eventual benefit because good acute control is desirable anyway.

When the diagnosis is based on looser criteria, it is a more complicated issue. There are at least two prospective studies demonstrating that patients with major depressive disorder and a definite family history of BD have a very high risk for transformation to bipolar I disorder (Akiskal et al., 1983; Strober and Carlson, 1982). Clearly in this situation, it is advisable to monitor patients with serious depression closely for early signs, even more so when there are soft signs of hypomania. But if there is no family history, a case can be made to hold back on treating the patient's not diagnostically definable highs.

From this vantage point, if a patient such as Ariel does not have symptoms that she, her family and friends, or any layperson, would consider symptoms, what are we treating? If we believe that we are somehow correcting a fundamental chemical imbalance, there would be a rationale. But we don't know what the chemical imbalance(s) is (are) in bipolar disorder. We don't really know what mood stabilizers do for the illness. Even our guesses hint at diverse possibilities. Thus, valproate seems to have an effect on ?-aminobutyric acid (GABA) receptors, and gabapentin may increase brain levels of GABA. In contrast, the proposed mechanism of action for carbamazepine and lamotrigine (Lamictal) is voltage-dependent inhibition of sodium currents. The latest speculations about lithium are 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

Diverse research hypotheses are a good thing, but they are not the same as hard knowledge. How can we argue that we are treating at a fundamental, etiological level of the illness when we don't know what the chemical problem is, when our best guesses about how various mood stabilizers work are that they work differently from each other, and when we don't know how these proposed mechanisms might or might not be related? Moreover, we don't have clear proof that we will prevent the eventual development of the 

 illness, we don't yet know if we are altering its long-term course. All we do know is that we have good-not great-medications that help control symptoms.

Hagop S. Akiskal, MD, makes the strongest argument for a liberal view of a very broad bipolar spectrum of abnormalities. He believes 

 is far too limiting and would include a bipolar III and a variety of conditions under the bipolar umbrella (Akiskal, 1996; Akiskal and Mallya, 1987). This position is not absurd in the sense that when we eventually understand the genetics and biology of manic-depressive illness, we may discover fundamental relationships. However, 

 is not a true collection of illnesses defined by etiologies. It is a collection of disorders about which committees decide certain symptoms should be clustered with the hope that someday, true etiological understanding will correlate with these clusters or future clusters as the evidence indicates. The issue here is using medications that may only be working on symptoms (and possibly or probably not etiology or pathogenesis) in patients who do not have symptoms as defined by themselves or reasonable laypeople. In Ariel's case, she was suffering from depression and was given a treatment that has not been shown to be effective for depression.

On the risk side of the equation, the danger of unnecessary medication is obvious with carbamazepine because of the possibility of aplastic anemia and agranulocytosis. While this is rare (six patients per 1 million population per year for agranulocytosis and two patients per 1 million population per year for aplastic anemia), if carbamazepine is used by enough psychiatrists over enough years for unjustifiable purposes, there will be deaths that might not have occurred. In the case of valproate, hair loss, weight gain, fatigue and, most recently, the threat of polycystic ovaries, favors caution in a patient such as Ariel. Tiredness and, sometimes, hypersomnia are not uncommon even at therapeutic levels and contribute to treatment noncompliance. A huge number of patients whom I have followed after inpatient stays with an equivocal diagnosis are sleeping 14 hours a day. Of course, it does not help that locally the standard regimen resulting from these hospitalizations seems to also include Zyprexa (olanzapine).

Ariel did have "mood swings." She would be in a perfectly good mood and then suddenly, with relatively minor provocation, switch to sadness, irritability or an outburst of anger. This was the other major justification for placement on a "mood stabilizer." There's only one problem with this. The use of the term 

in bipolar disorder has usually referred not to labile affect, but to relatively long stretches of depression or mania lasting weeks or months-although occasionally days-which would then swing to the opposite.

While it is true that mixed episodes are not rare and may be characterized by very rapid shifts in mood over the course of a day, mixed episodes may also consist of a vague blending of both euphoric and dysphoric themes. In any case, until recently, the term, 

Apparently, however, without a discussion in the literature of this changed definition, mood swings have come to mean labile affect. Similarly, rapid cycling-defined in the 

 as four or more switches in a year-not infrequently appears in clinical summaries when what is being described are labile moods.

At first, I thought the problem was our local inpatient unit and a mistaken reading of

 by one doctor in particular. If that were the case, there would be no reason for this article. It soon became apparent that similar diagnoses were being made at three other inpatient units that I have contact with, including two prominent academic centers. I have questioned several nurses on these wards and learned that most misbehaving, impulsive teen-agers (once characterized as rebellious) are now being diagnosed as bipolar. At an outpatient alcohol rehabilitation center, a counselor told me the same thing was happening there. Erratic moods and behavior were being called 

 and thus had become bipolar symptoms. Moreover, the new use of the term

 had been embraced by the other psychiatrists in town who were doing strictly outpatient work. Social workers and psychologists were asking, as never before, for medication evaluations for bipolar disorder on the basis of mood swings, and many patients were self-referring themselves for mood swings, having read about them on the Internet.

The typical story I heard when I questioned a patient with mood swings was something like the following: "I'd be in a perfectly good mood at a party but then would feel like going home. When my boyfriend gave me a hard time, I'd let him have it." Or, "I would be doing fine shopping at the supermarket. Suddenly, someone would cut in front of me in line, and I'd go ballistic." Or, "I'd be getting along with my parents at home. Then my father would say something, and I'd go stomping off to my room." Sometimes, there would be no external event at all, but the patient would notice a dramatic shift in mood from when they woke up feeling fine to later in the day when they were feeling down.

Generally, in all of these cases the patients had almost no introspective capacity. They had never attempted on their own, or been encouraged by their psychiatrist, to make sense of the personal meaning of their father's comment, or why their boyfriend made them so angry by refusing to come home from the party and so forth. As far as they were concerned, their behavior was totally incomprehensible and beyond their control. They were relieved to hear that the explanation for their difficulty was a chemical imbalance because, not only would it no longer be their fault, but just as importantly, it could now be fixed.

Undoubtedly, over time, some of the impulsive and/or moody adolescents now being diagnosed bipolar II on the basis of their mood swings will later prove to be suffering from manic-depressive illness. This may turn out to be true of Ariel.

Kramlinger and Post (1996) described clear-cut bipolar patients who were followed on a ward and rated for mood every two hours during the course of a day. They found a group of five patients who went up and down throughout the day and wondered whether these represented "ultra-ultra rapid cycles or ultradian cycling." However, this interesting observation is a far cry from the routine labeling of volatile patients as bipolar.

There is another contributing issue to what I believe is the overdiagnosis of BD. In addition to "mood swings" being used as the basis for diagnosis, irritability has gained new status. It has always been appreciated that irritability, rather than euphoria, can be part of a manic episode. But one would assume that irritability by itself would not be the basis for diagnosing bipolar disorder in an unhappy teen-ager or depressed individual, especially since irritability is found much more commonly in depression than in mania. However, I am discovering that many psychiatrists are using this criterion quite freely, especially with patients who have labile affect, and are basically making the diagnosis on a hunch.

Although the considerations above regarding risk/benefit ratio still apply, ordinarily I would have no difficulty with a clinician following a clinical intuition and diagnosing atypical BD now and again when full criteria were not met. The problem is, if my observation of local practice patterns hold elsewhere, such hunches have become routine, especially in the rapid-turnover inpatient wards that now characterize our mental health system. It has become the diagnosis du jour. Observing practice patterns in Penn Valley, Pa., psychiatrist David Behar, MD, in a letter to

 (1998) described bipolar disorder as being absurdly overdiagnosed. "Any overreacting patient now gets the label and a mood stabilizer," he said.

If this is the case nationally and not just in the Northeast, it is reasonable to look for an explanation. We also must include the pressure on outpatient psychiatrists from referring therapists who themselves are under pressure from health maintenance organizations and mass media articles that foster patient expectations of rapid results. The psychiatrist is placed in a situation not dissimilar to some family doctors who would prescribe antibiotics for the common cold so the patient would feel the doctor "did something." Pressure also comes from the occasional therapist who doesn't like their diagnostic acumen questioned and will refer elsewhere if the patient doesn't receive medication for mood swings. This can be likened to schoolteachers who want their unruly students labeled as having attention-deficit/hyperactivity disorder and Ritalin (methylphenidate) prescribed.

Ultimately, the problem may be language itself. Even when a bipolar diagnosis, per se, is not considered, having a category of drugs called mood stabilizers lends itself quite well to a belief that it is a valid approach to moodiness. In this case, the issue is not whether anticonvulsant, antimanic medications deserve to be called 

 in bipolar disorder, but rather that the term

conveys the impression that they are a perfect fit for volatile, overemotional patients.

As noted, alcohol and drug abusers are now very often being diagnosed with bipolar disorder, once again because labile affect, a common finding in alcohol and drug abusers, is being called 

 One factor contributing to this is our better appreciation of how many bipolar patients abuse alcohol and drugs. However, in the absence of a clear-cut history, I don't know how a bipolar diagnosis can be made until the patient has been off intoxicants for a reasonable period of time. Rapid shifts in mood have always characterized the behavior of alcohol- and drug-abusing patients as well as those recovering from addiction. What is gained by the bipolar label? Some alcoholic patients like it because it "explains" their lack of control. Like genetic theories of alcoholism, it shifts blame and gives an external enemy to fight against. However, these should not be the reasons for us to make the diagnosis.

Mood lability is also an important component of borderline personality disorder (BPD) and here, too, an unusual number of patients are being diagnosed bipolar on the basis of their mood swings. Granted one can legitimately make a case, as Akiskal does, that borderline personality disorder is fundamentally an affective disorder and possibly a variant of bipolar disorder (1996). In the case of BPD, the ravages of this diagnosis are so extreme, and so many of our treatments are ineffective, that I see nothing wrong with trying one of the anticonvulsant medications on an empirical basis. However, in my experience, high doses of selective serotonin reuptake inhibitors seem to work far better for labile affect, probably because of their ability to alleviate frustration and dull passions rather than from an antidepressant action, per se.

To summarize, there are three important questions:
1) Are rapidly shifting moods (now mislabeled as mood swings) particularly diagnostic of bipolar disorder?
2) Are mood-stabilizing medications useful in patients with rapidly shifting moods whether or not they are truly bipolar?
3) What is the mechanism of action of the anticonvulsant medications that make them useful in psychiatric conditions?

Question 1: I do not know if rapidly shifting moods are a typical feature of manic-depressive illness. My clinical impression, after close to 30 years of practice, is that they are not uncommon, both before other symptoms have become manifest and afterward. But rapidly shifting moods are far more common in the instances already discussed: unhappy or rebellious adolescents, alcoholics and drug abusers, and those with borderline personality disorder. Whether the mood changes during the course of a day seen in mixed episodes of bipolar patients constitute ultradian cycling or are simply what typically constitutes mixed episodes has to be settled (Kramlinger and Post, 1996).

Regardless of the outcome of that issue, I think we have to address the separate issue of whether the presence of mood lability should raise our index of suspicion for manic-depressive illness in moody adolescents, borderlines, alcoholics and others with short fuses. (It should be emphasized that Kramlinger and Post's ultradian cycling referred to ratings of mood systematically made every two hours and not sudden mood shifts.)

Questions 2 and 3: Ironically, despite the unfocused use of the term

 described earlier in this article, I think clinicians may have found a legitimate use for anticonvulsant medications in psychiatric practice. The literature includes theories that GABAergic mechanisms may play a role in depression (Petty, 1995; Petty et al., 1996). From time to time, various benzodiazepines have been claimed to have antidepressant efficacy. This might be due to the hypothesized fundamental chemical relationship between GABA and mood. Or, it might be an indirect result of their tranquilizing function. After all, patients with panic disorder often develop depression secondary to their lost sense of control and have an improvement in mood once benzodiazepines have put out the fires. Similarly, some patients with agitated depressions experience anxiety as the most distressing part of their syndrome and find their mood improves, even before antidepressants kick in, when benzodiazepines have provided relief from their anxiety.

If there is a fundamental relationship between GABAergic mechanisms and mood, then the use of valproate and gabapentin might eventually be empirically shown to have antidepressant action, and my earlier denigration of the term 

 would be misplaced. The term would legitimately apply to these anticonvulsant medications in its traditional sense. However, since carbamazepine and lamotrigine are not believed to work through GABAergic mechanisms, and they are mentioned in the same breath with the other mood stabilizers, my best guess is that the quality that anticonvulsant medications have in common is that they are calming agents or tranquilizers. They may represent the long-sought effective, nonaddicting tranquilizers. (There is some support for valproate's anxiolytic-like function in animal research [Dalvi and Rodgers, 1996; de Angelis, 1995].)

On an intuitive level, it makes sense that anticonvulsant medicines, whatever their mechanism of action, are calming. Indeed, if we picture seizures as "a massive discharge of neurons," it is not much of a stretch to think of the various psychiatric conditions where anticonvulsant mechanisms are finding particular usefulness-explosive disorder, mania, panic disorder, borderline personality disorder-as conditions that may possibly have analogous massive discharges of nerve impulses. And one step down from that, one could imagine that

 as the term is being used today for those with fiery temperaments, or those caught in the storms of adolescent turmoil, might be attenuated by calming agents, with or without a bipolar diagnosis. In other words, 

 as the terms are being misused today. Eliminate calling the patients bipolar and not that much harm is done. Valproate may deserve its widespread usage.

We are still left with the question of whether anticonvulsant medications' calming action is necessarily working directly on mood. This question is of some relevance because of the kind of backward reasoning that seems to accompany the effective use of anticonvulsant medications. For example, Stephen J. Donovan, M.D., has proposed that a new diagnosis-explosive mood disorder (EMD)-be created and replace the diagnoses of conduct disorder or oppositional defiant disorder in one subset of patients-children with irritable mood swings-"because these are sociological not psychological constructs. They do not identify what is 'disordered,' suggest etiology or guide treatment" (Sherman, 1998). And what was Donovan's basis for suggesting that the primary difficulty is mood? Adolescents meeting the EMD criteria improved on the mood stabilizer divalproex.

Similarly, because such agents as valproate and carbamazepine have been found useful in recovering alcoholics does not necessarily support a view that these patients are probably bipolar. Rather, the patients' improvement might be the result of these agents' tranquilizing function. This kind of thinking is entirely separate from whether or not anticonvulsant medications have an antidepressant action.

Going out on a limb, I would argue that even in bipolar disorder, the various anticonvulsant medications being used to control mania may not be directly treating the elevated mood, per se, but rather treating the intensity of mania, the exuberance of energy, racing thoughts and the like. Just as patients with panic disorder often feel less dysphoric when they regain control through the use of benzodiazepines, it is possible that mood stabilizers could, with chronic administration, be demonstrated to have an indirect antidepressant action by returning a measure of self-control, rather than through a direct antidepressant action. Certainly, many patients with BD rue the foolishness of their mania, not to mention the broken marriages, lost friendships and jobs, depleted bank accounts, and sheer havoc left in the wake of their exuberance. Over a period of time, less havoc would serve as one less stressor to precipitate dysphoria and depressive episodes.

Also, I have treated several bipolar I (mixed) patients who resembled agitated depressives in their level of anxiety. Although admittedly a small anecdotal sample, my personal impression is that these are the only patients who have shown an antidepressant effect from divalproex. My guess would be that it is the calming effect of the divalproex that was helpful here rather than the antidepressant effect. Otherwise, from pure chance, I would have seen more cases in which the divalproex worked as an antidepressant. Moreover, considering the amount of research done, one would expect by now to see good double-blind evidence of divalproex antidepressant action (rather than the usual "soon to be published" impression) if the effect were a robust one. I am also curious if, within the studies showing that anticonvulsants have an acute antidepressant action (in the range of 30% to 40%), there are data that could be teased out regarding agitation. Did the responding patients have greater amounts of agitation than other depressed patients?

Finally, before we get too excited about "better living through chemistry," a word about mood swings of the adolescent variety. Classic psychoanalytic concepts are more relevant than ever. The vicissitudes of self-esteem regulation in many adolescents are closely linked to the loss of an idealized authority figure (and accompanying culture) from whom they can feel protection and confirmation. As they leave the cocoon of their own family's world and values, they must replace it with a stark and uncertain court governed by peer approval. It is a faddish, unforgiving universe of shifting gurus and uncertain alliances that plays havoc with mood until, with maturity, a more stable identity can be established. This is not to mention the effect of changing hormones, astonishing physical growth and emergence of sexual passion. Medication may have a role to play during this transitional period. But I would hope that psychiatrists have the wisdom to guide parents and children appropriately through this difficult time, and not confuse matters with scary diagnoses such as bipolar disorder and the use of chemicals that work in ways that are poorly understood.

A Psychodynamic Perspective on Treatment-Refractory Mood Disorders 

Female Gender, Mood Disorders Are Historically Related 

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Mood-stabilizing drugs slipped into the vocabulary of psychiatrists during the last 15 years without a proper discussion of their definition. Consequently, these medications have been used in ways that have no empirical justification.

Mood Stabilizers and Mood Swings: In Search of a Definition

It is now customary psychiatric practice to think of a patient's illness as primarily biological in origin-so much so that, for many illnesses, published practice guidelines almost exclusively describe medication strategies. Psychotherapy, when it is mentioned, is usually in the form of patient education about the nature of the particular illness and supportive work aimed at helping the patient cope with its symptoms.

Clearly, there has been a paradigm shift in American psychiatry during the last 25 years that is no less remarkable for its unanimity of focus than the previous chorus of apparent agreement about the wonders of talk therapy. While cognitive behavioral therapy is granted a certain legitimacy, it is similar to pharmacotherapy in that it focuses on the outer manifestations of the illness or the symptoms per se and avoids at all costs any hint of the dynamic psychiatry that once filled the halls of academia.

The nature versus nurture controversy is not new and the controversy is far from over, but supporters of the nature viewpoint have found a particularly appealing way to present mental illness. Axis I disorders are boldly portrayed as " chemical imbalances" in patient brochures, news articles and other educational materials.

The problem with this portrayal is that, while some day we may accumulate the knowledge to demonstrate the particulars of this perspective, no such chemical imbalances have been unequivocally demonstrated for any disorder. We are offered interesting conjectures, educated guesses that are forever shifting as the latest data are 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 brilliantly placed pieces of a jigsaw puzzle as the solution to the entire puzzle.

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 authors to propose an intracellular hypothesis to explain the effectiveness of various medications (Duman et al., 1997). I would like to suggest a different approach.

 is not a nosology based on etiology, the implicit premise of the chemical imbalance perspective is that certain 

 -defined " disorders" are lacking a given neurotransmitter in a particular part of the brain that is somehow related to the disorder. In the gray area are expansions of the basic illness with so-called spectrum disorders. Presumably, there is a genetic or biological link that explains the usefulness of certain medications across the entire spectrum of the related disorders. The weakness of this formulation is that medications such as the selective serotonin reuptake inhibitors (SSRIs) are proving efficacious in so many Axis I and Axis II disorders that to consider all of these forms of misery as part of the same biological spectrum is stretching credulity. Occam's razor demands a more parsimonious approach.

I would argue that there are certain psychological effects of medications that make them useful in a variety of 

 -defined disorders not because they are necessarily correcting a chemical imbalance, but because the psychological effect is useful. Rat pups that are isolated from their mother and littermates produce ultrasonic sounds that are indicative of stress. SSRIs reduce these sounds (Oliver, 1994). Is a chemical imbalance being corrected? I doubt it.

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 or depression, as well as in someone with no psychiatric diagnosis. Analogously, SSRIs typically impact individuals in ways that are not specific to diagnosis.

I will go one step further. Understanding the psychological effects of medications such as the SSRIs can lead to productive uses of the medication even when a specific 

What is that effect? The most frequent description that I have heard from my patients of the effects of SSRIs is an attitude of " it doesn't matter" or " don't sweat the small stuff" or " what's the big deal?" This don't-sweat-the-small-stuff perspective, I believe, is the SSRIs' unique blessing and curse. It means relief from worry, relief from the feeling that something is missing, needs to be done or needs to be fixed. Thoughts such as " my makeup isn't right," " the sky is falling," " I won't be able to pay my bills," " I'm not smart enough" -the chatter that occupies the unsettled mind-are endless and particular. The emotion is more basic.

SSRIs supply, if not always happiness, a nice contented feeling that all is well and will be well. They can allow parents to play with their children more, fret less over the details, appreciate what is, and actually want to do the proverbial modern mantra-stop and smell the roses. SSRIs are the answer to existential angst. Perhaps if Sisyphus had been born in the 1990s, he 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 (fluoxetine) to relax and enjoy his vacation. It worked very well. He told me that he continued it at home when he returned. He quickly stopped it when he found himself thinking, " Who cares?" when his patients described their problems.

Mrs. L. had originally required 40 mg of Paxil (paroxetine) per day to recover from a postpartum depression. After 12 months on the medication, an incident happened that disturbed her. During her lunchtime, she was visiting her 1-year-old son at his day care center when one of the workers began screaming at another infant instead of picking her up. The next day Mrs. L. went shopping during her lunch break. Later that week a co-worker became tearful during the course of a conversation with Mrs. L. regarding her own child's day care center. Only then did Mrs. L. wonder about her decision to go shopping the day after she had witnessed the day care worker's inappropriate reaction. She wondered if her Paxil had made her indifferent when ordinarily she would have reacted and worried about such a thing.

We decided to taper the dose of medicine to 20 mg. Sure enough, on less medicine there was a dramatic change in her perspective about many things. For the first time I learned about the pressures she had been under at the time of her original hospitalization. Mrs. L. had tried to find time to be the same powerhouse worker at her job that had brought her so many promotions in the past, an ideal mother for her newborn infant and responsive to her husband's very exacting standards about her housekeeping. Suddenly, without the higher doses of Paxil, her fury poured out. She described, in detail, episode after episode in which her husband stood to the side and endlessly critiqued her adequacy as a mother. The higher doses of medication had muted her responsiveness and allowed his criticism to go in one ear and out the other, but now there would have to be change " or else." Mrs. L. also acknowledged that she had not been doing her job as carefully as in the past and eventually the company would discover her drug-induced " what the hell" attitude. At home, she had bounced several checks, which she never did before being on the medication.

Therapy now turned to how her life would have to change. She seriously considered quitting her job. She loved being a mother and didn't want to miss out on her son's crucial early years. She demanded changes in her husband (with the threat of divorce). Her new assertiveness rapidly put him on good behavior even before marriage counseling started. Occasionally she became tearful about her dilemmas. Although we discussed the possibility of returning to higher doses of medication, she was not eager to do this. She felt her tears were about real things and did not consider herself depressed. She felt neither hopeless nor helpless. Her sleep was not as restful; she sometimes tossed and turned. But she was OK. We joked that we might go up on the Paxil temporarily if and when she needed a vacation from her stresses. In fact, throughout, I was concerned that her greater emotionality might be a prelude to the return of her original symptoms. But our perspective was quite different than an automatic increase of medicine at the first sign of tears. As it happens, she did not need to return to higher doses. She did quite well, eventually deciding to work part time. Three months after making that decision, she was the happiest she had been in years.

It is noteworthy that when she was reduced to 10 mg (at her urging), there was another change. She again noticed dust on her furniture and the haphazard placement of pictures on her table. She arranged them more aesthetically. She did not feel driven to fix these things. She took pride in her newly regained attention to detail.

She also regained a degree of empathy for her husband. There was the danger that she was returning to a dynamic of taking care of everyone and everything, of offending no one, a role that she had assigned herself from early on in childhood. This pattern may have played a part in her original postpartum depression as she tried to juggle her responsibilities and became overwhelmed, consequently generating forbidden anger at her newborn.

Mrs. L.'s case illustrates the potential downside of too much of a good thing, too much of the " well, whatever" feeling. From a 

 perspective, her 40 mg emotional blunting would not be identified as a problem. Only by viewing the patient's needs and her clinical presentation in terms of a psychological narrative could the treatment properly focus on what once would have been, and obviously still is, deservedly a high priority-to help the patient in her struggle to come to terms with her psychological makeup, and to do the best she can in reconciling her dynamics and values and the reality of her situation.

Medication may, or may not, play an important role in reaching a desirable acute and/or chronic equilibrium in these matters, but the issue cannot even be approached if 

 " symptoms" are used as the sole guideline. Nor, it must be added, would these issues have been addressed in what has become standard psychiatric practice-the once-a-month 15-minute med check.

Viewing SSRIs as " well, whatever" medications, I believe, best accounts for their usefulness in so many disorders. It is precisely this feeling that is so helpful in obsessive-compulsive disorder. Similarly, the ability of patients with anorexia nervosa to not freak out after they have put on a pound or two is helped by a dose of that attitude. The same can be said for body dysmorphic disorder. In panic disorder, the loss of patients' exquisite sensitivity to their body sensations is extremely helpful, as is the dulling of their sense of danger. Ditto for phobias of all varieties, including social phobias. Many a patient with a short fuse has been helped by SSRIs. While the fury of intermittent explosive disorder patients, once provocation has occurred, may not be helped by SSRIs, the medication often makes it harder to push their buttons. When effective, perceived insults go in one ear and out the other.

As I implied above, the perspective I am presenting, if correct, leads to clinical distinctions that may not be related to diagnosis. For example, I saw a 15-year-old boy who had broken his father's heart by quitting the basketball team and by not producing his usual good grades. The question was whether he was depressed. There was a hint of rebelliousness in this teen-ager but no obvious dysphoria. He could still have a great time with his friends, including playing basketball for fun. He wanted to take it easy, to coast for awhile.

As I got to know him, what emerged from our talks was that an enormous amount of stress built up in situations where his father expected him to do well. Here was a guy who had developed a " well, whatever" attitude as a defense, a not uncommon phobic posture among teen-agers (and adults) who avoid situations when the going gets tough. With luck, therapy could help him understand and work through his difficulties with his father and help him approach competitive situations with greater equanimity. If I used medication, an important component of the decision would not be whether this patient was diagnosable as having a subclinical depression. My focus would be on his " well, whatever" attitude. Would it be worsened by an SSRI, or would the medication lessen his anxiety and fear sufficiently to take on challenges and not resort to avoidance?

Therapeutic decisions regarding forbidden impulses revolve around similar treatment dilemmas. If I sense that a person is gambling, drinking or eating excessively out of incessant frustration, SSRIs can be markedly effective. On the other hand, the " well, whatever" attitude extends to discipline and standards, including moral standards. Some patients, able to battle their temptation to drink, gamble, overeat and the like, find that they loosen the reins too much on SSRIs.

Increasing courage and lessening the fear of irrational consequences are very helpful in phobias, but that same decreased fear of consequences can apply to rational fears. Sometimes SSRI-induced decisiveness can lead to ill-advised risk taking. One significantly depressed patient whom I saw refused to be medicated because she reported that an earlier impetuous decision to go ahead with a marriage could only be explained by her medication. Off of SSRIs, she was normally extremely cautious, carefully considering all possibilities. On the SSRI, this changed to " What the heck...you only live once." I could not reject her observation out of hand.

SSRIs are extremely useful in anger management when a low frustration tolerance is leading to frequent eruptions. On the other hand, many patients have proudly related to me how they told someone off that they had been itching to tell off. Like alcoholics the morning after, some of the time their boldness was later regretted. Analogously, the misbehavior of many delinquents and those with conduct disorder is frequently driven by unending anger and unappeased needs. SSRIs can be helpful here. But it is also possible that an SSRI can contribute to the courage needed to do outrageous things, including crimes. These issues should be weighed by the clinician. I realize that the last issue has been sensationalized by the media and the " Prozac defense" rejected by the courts, but I do not think it is impossible.

Mr. T. was a 30-year-old man who was very unhappy in his marriage. He had always pictured a family life with two or three children. His wife, a beautiful woman whom he had originally been smitten by, had never wanted kids. Mr. T. had assumed she would change her mind. But now, six years into the marriage, he had realized that there would be no change of heart. She was to be the project of the marriage, her vulnerabilities, her needs, the vicissitudes of her emotions. It had gotten old for Mr. T. Over the years, he had noticed his impatience with her grow into indifference and then sarcasm. He came for help when he had become depressed.

I'll put the issue in a nutshell. What if 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, seeing it as a drug that had deceived him and cheated him of what had been meant to be?

There are times when removing the symptoms of depression might not be a valid choice, times when depression is serving a function. It can be an alarm signal that something is heartbreakingly wrong. Often people can learn to make do, learn to live with what is. When there is no choice, or life is not very good but is good enough, the individual's ability to justify or rationalize his existence is a stabilizing force. Sometimes, however, more powerful emotions occur. The individual feels stuck, at a dead end, defeated. A depressed person's self-questioning (and self-depreciation) can represent a search for a way out of the trap, a need for change or for setting off in a new direction. Depression may mean that internal change is taking place: they may be learning to reevaluate priorities, set goals less high, or finally take chances for things that really matter. For instance, depression may provide the impetus for a person to begin to appreciate the importance of loved ones rather than career or, conversely, to realize that taking care of family needs and stifling individual ambition no longer work.

Not infrequently, depression occurs at times of passage. Adjustments that worked 10 years earlier have worn out. Every truth eventually becomes a lie. A solution to a problem may eventually become the new problem. Marriage may have brought an end to feeling lost, lonely and directionless, but marital responsibilities may later become a prison. Being a bit of a rascal, being able to dance around and away from problems may have broken many a bad mood, but eventually comes the time to pay the piper. There are thousands of scenarios that culminate in depression.

Change is not always possible. A person dying or in wretched poverty doesn't need recognition that change is needed. That is obvious. However, even in the cases of those in such dire circumstances, we cannot escape the observation that there are those who die with relative ease and peace of mind, and others who go screaming into the abyss. Inescapable poverty is tolerated better by some and worse by others. What makes the difference? In some cases it is religion, spiritual values, a deep love, and sense of loyalty from and between those who matter.

Those who favor a biological perspective might further argue: What about individuals who are neither sick nor poor, but who get depressed? What about those who appear to have everything, the love of family members, good friends and career success, yet still get depressed? There are certainly individuals who have put on a big act, who have fooled even themselves, never dared to challenge their assumptions, pathways and dreams. When they get what they wanted, they realize it wasn't what they needed after all.

Undoubtedly true, but are there individuals who are biologically predisposed to depression? Are the examples of the scenarios I have described merely precipitants, stress factors that would not have caused serious difficulties unless biological factors were at work? Certainly we have long known that depression can result from hypothyroidism, pancreatic cancer and as a side effect of certain medications. There are depressions that run in families. We cannot dismiss genetic priming. But I would argue that even if many current biological assumptions will eventually be proven accurate, if we grant that certain people are biologically predisposed to depression, and the unhappy tale they tell is merely a precipitant of foreordained illness or, using a different model, the result of their negative thinking, it still behooves the clinician to consider that the precipitant is not meaningless. The timing of their misery holds crucial clues to the etiology and cure.

It is true that for certain severely depressed individuals, symptoms are so overwhelming and in need of mitigation, and their despair so palpable, that it would be cruel to not offer quick and effective relief. Moreover, a patient may be so much in the savage grip of his or her symptoms that addressing anything else would be irrelevant, not to mention useless.

However, this rule is not absolute. I once saw a patient, not with depression, but with anxiety bordering on panic, who wanted a tranquilizer. He worked in security at a jai alai facility and had discovered Mafia influence in the gambling activities. He was to testify the following week. A rock had been thrown through his window and written threats placed in his mailbox. He had sent his wife and children to her mother's house and sat alone in his house listening for every suspicious sound. He was terrified. He wasn't sure if he would go ahead and give testimony. I refused to give him medication. If he was going to be a hero and take a chance with his survival, the decision would have to come undrugged.

Analogously, it is in the best interest of patients on SSRIs to be warned that the medication could distort their judgement when it comes to decision-making, especially big decisions. We cannot automatically assume that their symptoms only represent pathology and that feeling good (or more ominously, as psychiatrist Peter Kramer put it, " better than well" ) represents normalcy. Therefore, decisions made when they feel confident and good are truly good decisions. The chemical imbalance perspective seems innocent enough when propagandists use it to convince patients that their symptoms are not signs of weakness, that they should get treatment because they have a medical disease. But clearly, we are not doing our patients a favor if they are not warned of the downside of this viewpoint.

Finally, we should address the traditional psychoanalytic view on medication, " No pain, no gain." There are valuable lessons to be learned in passing through the trials that life sometimes offers us (with or without symptoms). True, in therapy, we mean optimal anxiety, optimal dysphoria, optimal stress fosters growth. The spirit can be broken and distorted by too much of a bad thing. And certainly, many patients are so overwhelmed by their symptoms that they cannot learn anything during the meltdown of their ability to cope. Only after medication restores a firm underpinning can they begin to address their problems. As always, the skill and wisdom of the psychiatrist is called upon to weigh these factors and to help guide the patient to a reasonable course.

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


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

It is now customary psychiatric practice to think of a patient's illness as primarily biological in origin-so much so that, for many illnesses, published practice guidelines almost exclusively describe medication strategies. 

Author | Simon Sobo, MD

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