Major Depression (Unipolar) vs. Bipolar Depression

Dr. Philip Grossi
Wednesday, 17 July 2019
A common clinical presentation of a patient in my practice is one of chronic depression starting in early teenage years or even younger and manifesting a pattern of frequent recurrences. Often these people have had forty or even fifty dpisodes of depression over twenty or more years. They have usually been treated with many antidepressants with erratic or downright poor rexsults. Are these individuals suffering from treatment resistant depression (TRD) or bipolar disorder? How can a psychiatrist differentiate the two conditions and why does misdiagnosis occur so frequently with such tragic and ruinous consequences. There was one study that found that there was a gap of nine and a half years between first presentation in the office and correct diagnosis. Part of the problem, in my view, is overly restrictive diagnostic criteria set out in DSM-IV and its succesor DSM-5. For example DSM-5 requires a hypomanic state to last at least four days and be "present most of the day every day." In my experience most hypomanic states last less than two days and sometimes just six or eight hours. Furthermore DSM-5 sets out severity criteria which many patients fail to meet. Those include grandiosity, decreased need for sleep, racing thoughts, and excess involvement in activities with painful consequences such as buying spres, sexual indescretions, or foolish business decisions. In contrast, many patients characterize these periods as being normal with more activity, productivity, socialization, and motivation. If the psychiatrist misunderstands the significance of these states, it may well lead to a diagnosis of major depression rather that bipolar disorder. Remember, the core pathology in depression is depression but the core pathology in bipolar disordewr is mood gyrations. Complicating the assessment is the patient's propensity to seal over these brief hypomanic states because they are viewed as irrelevant to their psychiatric problems. It is incumbant on the examiner to ask about these states directly both from the patient, family, friend, and spouse. What are some of the other factors I take imto account in distinguishing unipolar depression from bipolar disorder? 1) Age of onset. Bipolar disorder typically starts before twenty years of age, often in childhood, and with mood swings. I always ask the patient's age when he/she experienced their first depression. 2) Bipolar depressions are frequently brief, develop in a short period of time, have a high recurrence rate, and often have a seasonal pattern. 3) Postpartum onset is common. 4) Response to antidepressants are unpredictable. Sometimes there is no response, other times the response in incredably rapid, sometimes the patiend gets more depressed, sometimes there is a dysphoric response with agitation and insomnia. Medications frequently lose effectiveness quickly in bipolar patients. 5) Family history of bipolar disorder. 6) Bipolar patients often have histories of self-harm, such as cutting which is experienced as relief from tension. 7) High frequency of substance abuse, usually over 50%. 8) ADHD is co-morbid in about 50% of cases. 9) Bipolar depression is atypical,i.e.,oversleeping, tremendous loss of energy, weight gain, and interpeersonal sensitivity. Usually there is also trouble getting up in the morning and pronounced daytime sleepiness. In contrast, unipolar depression is characterized by insomnia, weight loss, agitiation, and typically no complaint of daytime sleepiness. 10) Bipolar patients frequently have vocational problems, romantic problems, fiscal extravagances, multiple marriages, and episodes of promiscuity. To review, unipolar depression is suggested by later age of onset (after 25), minimal history of mood swings in childhood and adolescence, depressions developing over many months, middle of night awakenings and early morning awakening, usually no complaints of daytime sleepiness, diurnal variation, i.e., worse in AM and improvement during the day or the reverse pattern, depressive pattern is typical, i.e., insomnia, weight loss, and agitation. Treatment of mood disorder patients includes psychotherapy and pharmacotherapy. There are many types of psychotherapy but the most important point is that forming a relationship characterized by empathy and strong rapport is the most important aspect because it helps the patient listen to the therapist and incorporate him/her into their psychological operations. Mood stabilizers are the foundational pharmacological treatment of bipolar disorders. The six mood stabilizers are lithium, divalproex, carbamazepine, oxcarbazepine, lamogrigine, and zonisamide. In my opinion lithium's side effect burden is greatly overnblown in the literature much of which dates from a time when higher doses were commonly used. It is effective for about 33% of bipolar patients and for them it is the closest thing to a miracle drug available in psychiatry. Divalproex can cause birth defects and weight gain. Carbamazepine has a multitude of drug interactions and lamotrigine must be ramped up slowly because of the possibility of a serious drug rash. It is an alergic phenomena and so must happen at initiation. Once you are on lamotrigine for a few months, you can forget about the rash. Zonisamide should be ramped up slowly at bedtime to avoid side effects. For some reason it seems to work best in adolescents. Second generation antipsychotics (SGA) have mood stabilizing properties as well as antidepressant, anti-manic and antipsychotic properties. They can be helpful in mananging bipolar patients with or without psychosis. They tend to produce weight gain and various metabolic problems.

Psychiatric Appraisal, The Way Forward

Dr. Philip Grossi
Thursday, 31 March 2016

In recent days I began to redesign the initial evaluation form used in the office for new patients entering the practice. As I began this project a friend of mine became gravely ill and is about to die. This sparked my thinking about the similarities between the methods used by the psychiatrist and those used by the historian. We both use the case history method in which the psychiatrist relies on the patient's report of his/her past whereas the historian relies on documents of various sorts to draw conclusions about either the psychological makeup of an alive patient or a dead historical figure. There are strengths and weaknesses with each approach.

For the purpose of the current psychiatric evaluation I am thinking in categorical terms mostly but some dimensional ones as well. What then are the pieces of evidence I seek to support the conclusions I reach and the treatment recommendations I make. First there are symptoms, sometimes referred to as complaints., These are often non-specific and this suggestive of certain disorders but nowhere hear definitive. Then there is the course of illness whose diagnostic importance is unappreciated by most mental health professionals. It generates many questions. What was the age of onset? Are the symptoms constant or episodic? Is the central problem over time one of mood? Is the central problem over time one of distorted thinking? Do thinking and mood problems co-occur at times? etc. etc. etc. Then there is the genetic window to peer through. Psychiatric problems tend to run in families and I often observe more assortative mating than I would expect in the families I see. Schizophrenia and bipolar disorder are highly heritable disorders. Unipolar depression is less heritable and the environment is a greater participant in producing the clinical presentation. The fourth area of evidence is drawn from treatment response. This area is more difficult to appraise because some people never seek treatment and others receive treatment which is inadequate thus making it problematic to draw a reasonably accurate and firm conclusion. Yet, there are circumstances when a startlingly effective and rapid response to treatment can clearly point to a diagnosis. We are looking at the drug or other intervention as a probe. In the case of medications, where this is easiest to see, we know how a drug works. When I see certain responses from drugs, I can reason backward to a condition because I usually know what the drug effects. For example, when using an antidepressant I might produce a phenomena known as switching, i.e., converting a depressed patient into a hypomanic or manic one. This would directly support a diagnosis of bipolar disorder and would help to clarify the distinction between unipolar depression and bipolar disorder or bipolar depression. In the case where some social engineering is involved, for example, in urging a patient to leave an unhealthy relationship, I might observe a reduced reliance on medication over time as well as greater happiness and productivity. The use of this framework allows for the making of a psychiatric diagnosis in keeping with the categorical schema set out in DSM5.

This case method and categorical diagnosis will gradually be giving way to diagnosis based on a constellation of symptoms PLUS various laboratory findings which could include blood values, genetic study findings, brain scanning and other brain study results etc. Indeed in the current DSM5 the B 2 and 3 criteria for narcolepsy cites hypocretin deficiency and nocturnal sleep study showing REM sleep latency of less than or equal to 15 minutes as diagnostic criteria. These are the first citations of laboratory values in the DSM series.

The Research Domain Criteria (RDoC) which I discussed in one of my earliest blogs, has as its goal building the linkage between symptom complexes and underlying pathological mechanisms. The RDoC will be attempting to link symptoms to more biological and less biologically restricted categorizations than is found in the DSM5. The RDoC framework includes dimensional concepts, e.g., negative valences,, positive valences, social processes, cognition and arousal that mesh psychological and biological phenomena. Several biological concepts in the RDoC include physiological and genetic concepts. The RDoC also includes psychological constructs and implicates the neural circuits that underlie them. This acts to narrow the focus of the DSM5 and therefore will allow better tracking of many clinical findings which vary throughout the population and become pathological only at the extremes of population distribution. The probable outcome of RDoC is a faster evolution than the DSM has produced thus far and a more robust generation of hypotheses linking genetics and observed findings to interacting brain domains in mapped brain areas  produced by modern neuroscience. This is likely to result in hybrid concepts linking biological mechanisms with psychological findings. Many psychiatrists and psychiatric researchers believe that psychiatric syndromes, DSM5 categories, are the result of dysfunctrional connectivity and not receptor malfunction. Therefore identifying specific circuit dysfunction and relating it to clinically observable phenomena is an important goal of RDoc and is likely the way forward from categorical diagnosis.

Learning to Eat Soup with a Knife

Dr. Philip Grossi
Wednesday, 13 January 2016

The title of this blog is the title of a book by John A. Nagle. I was reminded of the book, which I read many years ago, by the current news especially the unconventional conflict in Syria and with ISIS. The title clearly points to doing something that is unconventional. The book compares the British Army's response in Malaya to the American Army's response in Vietnam. The British adapted to the insurgency while the Americans continued a conventional war approach. The British won, the Americans lost.

I began to wonder whether the lessons of war could inform the skillful practice of psychiatry especially in a multicultural world. One of the first lessons of war is to understand the enemy, i.e., the enemy's values, beliefs, history, religious beliefs, economic organization, social structure, response to interventions, and their way of seeing the conflict. The understanding of these attributes of a human being is fundamental to good psychiatric practice. This understanding is usually referred to as empathy and involves listening to the patient and "climbing into their skin". This will inform the psychiatrist about their attitude toward treatment, medication, and interactions with other people and institutions as well as how these attitudes have developed and their consequent strength and constancy. This information is invaluable in developing an approach to a specific issue or problem that is effective and efficient. Simple reasoning to arrive at an approach is insufficient, empathic understanding is required to be successful . Contemporaneously, the military commander must be aware of current and past events that might be influencing his decision making in battle. Likewise, the psychiatrist must be aware of the impact of current and past events in his or her life that could be influencing the response to the patient. This is an active and dynamic process which often results in a response or feedback to a patient which should be framed in as many words as are necessary to convey the idea but not more.

In war there should be a proportionality between magnitude of the enemy's action and the response.  So too, when assessing the severity of the patient's problem, including social, financial, vocational, and other environmental component contributions, the formulation of the response should be proportional to the severity of the gestalt which should maximize efficiency. With regard to individuals with psychotic problems, it is crucial to make the best selection of agents at an appropriately scaled dose which is an example of proportionality. In these cases it is important to hit the bullseye because the consequences of missing it can be substantial and might include unpredictable and disturbed acts in the community with possible self-harm or harm to others. it also supports or fosters the idea in the patient that psychiatric intervention is ineffective.

In war it is important to get the data and to constantly reexamine your thinking especially if failing to achieve goals. In psychiatric practice I have learned to value what I am seeing in front of me more than any belief based on education or experience. When facing poor clinical response, I am always prepared to reexamine the reasoning that got me to that point and I am always prepared to change my mind. In war one should be suspicious of the common or standard response to a problem. The most uncommon responses are often the most successful. So too in psychiatric practice the most uncommon interventions are often the most successful. Above all when choosing an intervention or strategy, never say never. Keep your mind as open as possible because we are dealing with the human mind which is the most complex object in the universe.

I wondered whether the lessons of war could inform the practice of psychiatry. The answer is yes. However, the reverse is also true, i.e., the lessons drawn from psychiatric practice can also inform the decision making in war.