Bipolar Disorder

The articles in this Special Report reflect the growing recognition of the importance of the problem of treatment-resistant psychiatric disorders.

This statistic is as familiar as it is startling. According to the National Comorbidity Survey-Replication (NCS-R), the peak age of onset for any disease involving mental health is 14 years. True for bipolar disorder. True for anxiety. True for schizophrenia and substance abuse and eating disorders. The data suggest that most mental health challenges emerge during adolescence. If true, this brings to mind an important developmental question:

There is currently a small but impressive evidence base that shows that psychological and interpersonal factors play a pivotal role in pharmacological treatment responsiveness.

The chances for full recovery from major depressive disorder diminish the longer a patient remains depressed-a fact that lends a sense of urgency for appropriate therapy.

Since the inclusion of the borderline personality disorder (BPD) diagnosis in DSM, there have been multiple efforts to recast the disorder as part of an Axis I illness category. While the initial focus was on the schizophrenia spectrum, more recent authors have attempted to link BPD to mood disorders.

Rages are part of a syndrome of severe mood dysregulation, which is defined by markedly increased and frequent reactivity to negative emotional stimuli.

I have the highest respect and affection for Will Carpenter, MD, who wrote a recent response ("Criticism vs Fact: A Response To A Warning Sign on the Road to DSM-V by Allen Frances, MD," Psychiatric Times, July 7, 2009) to my earlier commentary, but we do differ sharply on the following points.

As we begin this brief review of the neurobiology of major depressive disorder (MDD), we face these fundamental questions

Findings of a recent large population survey suggest that 1 in 3 adults in this country (approximately 72 million people) uses 1 or more complementary and alternative medicine (CAM) modalities during any given year.1 Many CAMs are widely regarded as safe on the basis of their established uses in traditional systems of medicine over centuries or longer and their current widespread use in the United States and other Western countries. Unfortunately, there is limited reliable information on potential risks associated with the majority of these approaches.

Four recent studies have shed light on the effects of early childhood mood and behavioral problems on adulthood.

Allen Frances, an old friend, writes critically about the DSM-V project. I will address some key issues where his criticisms do not relate to reality as experienced from within the process. I chair the Psychoses Work Group and am a member of the DSM-V Task Force.

Alarmed by the rising suicide rate among soldiers returning from Iraq and Afghanistan and “wanting to help,” Matthew “Matt” Houseal, MD, a psychiatrist with the Texas Panhandle Mental Health Mental Retardation Center (TPMHMR), reenlisted as an Army Reservist and volunteered to serve in Iraq.

If I closed my eyes, it would have been easy to imagine that I was visiting a peaceful city park. The sounds of birdsong and children’s laughter rang in the air, and the odor of freshly cut grass filled my nostrils. But the sweet smells and soothing sounds belied the horror of the place where I actually stood-inside the wrought iron gates of Auschwitz-Birkenau, the Holocaust’s most infamous concentration camp. Today the camp is a museum, and there is an eerie dissonance between the tranquility of its sprawling grounds and the mass murders that were carried out here almost 70 years ago. Like many visitors to Auschwitz, I experienced powerful emotions-a mixture of revulsion, anger, and a deep empathy for the millions of souls who suffered and perished there. I also felt a discomfiting sense of doubt about the goodness of humanity, including my own.

We should begin with full disclosure. As head of the DSM-IV Task Force, I established strict guidelines to ensure that changes from DSM-III-R to DSM-IV would be few and well supported by empirical data. Please keep this history in mind as you read my numerous criticisms of the current DSM-V process. It is reasonable for you to wonder whether I have an inherently conservative bias or am protecting my own DSM-IV baby. I feel sure that I am identifying grave problems in the DSM-V goals, methods, and products, but it is for the reader to judge my objectivity.

In “Changes in Psychiatric Diagnosis” (Psychiatric Times, November 2008, page 14) Michael First relates the sad fact that the reorganization of DSM is still without formal guidelines and continues to be subject to the vicissitudes of groupthink and vocal constituencies. He relates that he and Allen Frances envisioned the application of biologically based diagnostic criteria when summarizing the work of DSM-IV, but complains that no criteria are forthcoming as yet.

I first met 22-year-old “Linda” when she was brought to the emergency department (ED) after a drug overdose. Although the drug Linda had ingested-clonazepam-was a CNS depressant, she did not appear groggy or sedated. In fact, her speech was rapid and pressured; she showed marked psychomotor agitation, which was demonstrated by her twitching feet and the incessant twisting of her hair. This presentation suggested a paradoxical response to her medication. Her chief concern was, “I feel as if I am going to come out of my skin.” I was puzzled.

Eastern philosophy and religion have always had what the philosopher Hajime Nakamura2 called “a preference for the negative.” This stands in stark contrast to our Western penchant for the positive, and our proclivity for defining and intervening is most pronounced in the overactivist mode of modern American medicine."

Anger is an emotion that is familiar to everyone. An episode of anger may dissipate quickly and harmlessly or evolve into a murderous rage. Between the benign and malignant end points in this spectrum, a seething, chronic anger may come to dominate a person’s thinking, feeling, and behavior.

To improve validity, we proposed extending the current MDD bereavement exclusion-which excludes “uncomplicated” (relatively brief, lacking certain severe symptoms) depressive bereavement from diagnosis-to also exclude uncomplicated reactions to other major stressors, such as romantic breakups, job loss, and serious medical diagnoses.

For many antidepressants, the issue of brand-name versus generic has no practical significance. Elavil was first marketed almost a half century ago, and its patent has long expired. It lives on, however, but as generic amitriptyline. Today, only a few antidepressants are still fully protected by patents, namely, Cymbalta (2010), Lexapro (2012), and Pristiq (2022) for major depressive disorder (MDD); and Seroquel (2011) and Symbyax (2017) for bipolar depression.

Several classes of hypnotic medication are available: the older barbiturates and their derivatives; benzodiazepines; chemically distinct “z-compounds”; antihistamines and antihistaminic antidepressants; and melatoninergic compounds. The use of hypnotic medications continues at a high rate. However, some switching to the shorter-acting benzodiazepines has occurred. The z-compounds-eszopiclone, zolpidem, and zaleplon-have become popular; they seem to have fewer residual effects than the benzodiazepines. Even so, care is needed in prescribing such hypnotics for the elderly.

This Special Report presents an important set of articles that considers controversial issues relevant to the practice of psychiatry. These articles demonstrate that what we do as practitio­ners is often based on incomplete evidence and/or reliance on experience and the art of psychopharmacology. There are considerable limitations to “evidence-based medicine” as applied to the issues considered and also to what can be said officially about “off-label” uses of medications. All that said, these articles represent a very interesting set of perspectives on important and, to date, unresolved problems for which our science falls quite short of giving us definitive answers.

For Allen, that film was the measure of Bergman’s genius, and it reached aesthetic heights that he conceded his own films would never attain. Bergman, like his Knight, Allen observed, could not put off the ultimate checkmate nor would his great art secure for him a personal afterlife as intellectuals wanted to believe. Allen was sure that Bergman would barter each great film he had made for another year of life so he could go on making films.

Psychotropic treatment can often prevent the relapse of psychotic and mood symptoms. However, many patients take medication intermittently or not at all; or the symptoms may be only partially responsive to medication. Therefore, there is a need for interventions that can supplement the effect of medication and improve treatment outcomes.

The assessment and treatment of psychiatric symptoms in persons with cognitive dysfunction are becoming increasingly important. Prevalence estimates of dementia in the United States range from 5% in those aged 71 to 79 years to 25% to 50% in those 90 or older.

Autism spectrum disorders (ASDs) are a group of 5 neuro developmental conditions (autism, Asperger syndrome, pervasive developmental disorder not otherwise specified [PDD-NOS], Rett syndrome, and disintegrative childhood disorder).1 Once thought to be rare, the incidence of these disorders is now estimated to be 1 in 150 children in the general population.2 Furthermore, the number of recognized cases has increased markedly in recent years.

Optimal management of bipolar disorder (BD) includes the careful selection and regular ingestion of appropriate medication to stabilize mood. Unfortunately, between 40% and 50% of patients with BD in routine clinical settings take breaks or forget to take their medication or even discontinue the drug altogether.1-3 Treatment nonadherence is associated with mood relapse, hospitalization, and suicide.4,5

What exactly is a “mental disorder”? For that matter, what criteria should determine whether any condition is a “disease” or a “disorder”?

Medications cannot be marketed in the United States without an FDA determination that they are safe and effective for their intended use. To obtain such certification, pharmaceutical companies submit their products to rigorous scrutiny (eg, in vitro studies, animal studies, human clinical trials) and present the subsequent data to the FDA, which determines whether the medication in question is safe and effective for a specific purpose.

Patients with bipolar depression who exhibit even minimal manic symptoms are at heightened risk for switching into mania if they receive antidepressant medication, according to a new report from the Bipolar Collaborative Network.