EXPERT ANALYSIS AT THE NPA PSYCHOPHARMACOLOGY UPDATE

LAS VEGAS (FRONTLINE MEDICAL NEWS) – If a published study ever challenged the way Dr. Joseph R. Calabrese thinks about mental and substance use disorders, it was the Global Burden of Disease Study 2010, which evaluated 291 illnesses in 187 countries worldwide from 1990-2010.

It found that mental and substance use disorders are the most disabling disorders worldwide, ranking No. 1 in years lost because of disability, No. 5 in disability-adjusted life years, and No. 9 in years of life lost ( Lancet. 2013 Nov;382:1757-86 ). “The take-home message from this study is, don’t wait until illness becomes syndromal,” Dr. Calabrese said at the annual psychopharmacology update held by the Nevada Psychiatric Association. “Early intervention is not only appropriate in all of medicine, but it’s appropriate for us.”

Dr. Calabrese, director of the Mood Disorders Program at Case Western Reserve University, Cleveland, said the findings support other work that reconceptualizes mental and substance use disorders as neurodevelopmental disorders. Pathophysiological changes begin during fetal and/or early postnatal life, followed by delayed onset of symptoms. In fact, “50% of people have the onset of illness by age 15, and 75% by age 25,” he said. “This is really important, because as a field, I don’t think we’ve been that aggressive in treating prodromal presentations or subsyndromal presentations.”

A key finding from the Global Burden of Disease Study 2010, which he characterized as “groundbreaking,” is that the burden associated with depression and anxiety rises abruptly in childhood (ages 1-10), and then peaks during adolescence and young adulthood (ages 10-29). “This is a big deal,” said Dr. Calabrese, who is also the Bipolar Disorders Research Chair and professor of psychiatry at the university. “Maybe from the perspective of our discipline, this isn’t something that’s actionable, but mothers know this. They usually say, ‘I could have told you so.’ We have to be more aggressive, and we have to intervene earlier, especially in the presence of family history.”

Prior to the Global Burden of Disease Study 2010, he continued, researchers had never evaluated the trajectories of morbidity and mortality of mental and substance use disorders. The study found that depression emerges first, and quickly worsens during childhood and adolescence. “It’s incumbent upon us to diagnose and treat depression in childhood, because it worsens quickly, and it peaks robustly around the mid-20s,” he said. Anxiety confers “about half as much morbidity” as depression, “but it still peaks in childhood, and the severity is less than half that of depression,” he said. “Clinically, this rings true to me. Parents will typically say that their child has been anxious since birth.”

According to the Global Burden of Disease Study 2010, bipolar disorder and schizophrenia emerge during adolescence and young adulthood, and reach peak severity during ages 30-40. Worldwide morbidity from bipolar disorder and schizophrenia is not as severe as that from depression. The study also found that mood and anxiety disorders precede drug and alcohol dependence by about 10 years. “To me, as a clinician, this is extremely important,” Dr. Calabrese said. “We should not only recognize and treat depression and anxiety, because they’re bad illnesses, but if we don’t intervene early, [they] lead to drug dependence and alcohol dependence. Drug dependence is worse than alcohol dependence, and it peaks earlier.”

Dr. Calabrese went on to note that major depressive disorder (MDD) continues to be the most common misdiagnosis in bipolar disorder, an issue that “has huge ramifications.” One study found that about half of properly diagnosed hospitalized patients with MDD convert to bipolar depression over 20 years, at a constant rate of 0.5% and 1% per year for bipolar I and bipolar II, respectively ( J Affect Disord. 2005 Feb; 84[2-3]:149-57 ). “The big question that has intrigued a lot of people is, how do you distinguish bipolar disorder from MDD?” he asked. “There is no one place where MDD stops and bipolar disorder begins. Most patients have most symptoms of both illnesses. In our nomenclature, we’re supposed to say, ‘mania with mixed features,’ or ‘depression with mixed features,’ but it doesn’t work that way. From a clinical perspective, it means anything goes when it comes to treating people in the middle. The thing to do is look for symptoms of the other phase of the illness. The more symptoms you see at the other phase of the illness, treat that patient as if they had the other illness.”

Patients with bipolar disorder live the majority of their symptomatic lives in the depressed phase of the illness, he continued. In fact, one study estimated that the ratio of time spent depressed to hypomanic symptoms is 39:1 in bipolar II and 3:1 in bipolar I ( Arch Gen Psychiatry. 2003 Mar; 60[3]:261-9 ). Patients with bipolar I disorder “are not that hard to diagnose, but digging out hypomania in somebody who has spent a large portion of their time depressed is really difficult to do,” Dr. Calabrese said. “It’s just not possible, unless we meet with the family at the same time. Patients either don’t remember the symptoms they had when they were manic or mixed, or they don’t want to talk about it.”

He concluded his remarks by revisiting the Global Burden of Disease study, which found that patients with mental and substance use face a lifespan that’s shortened by an average of 10 years. Some 67% of this premature mortality is tied to the earlier onset of chronic conditions such as cardiovascular disease, diabetes mellitus, and chronic obstructive pulmonary disease, while suicide only accounted for 17.5% of early deaths. “Therefore, when treating bipolar disorder, look for co-occurring medical illness, signs of metabolic burden, and unhealthy lifestyle behaviors, such as obesity, smoking, physical inactivity, and poor diet,” he said. Other emerging data suggest that in patients with bipolar disorder, premature death tied to cardiovascular disease exceeds that tied to suicide ( Ann Clin Psychiatry. 2011 Feb;23[1]:40-7 ). “It’s almost as if we need a nurse seeing our patients before or after we see them, to counsel them about healthy living and how, over time, lifespan is shortened if you don’t get this illness treated,” he said.

Dr. Calabrese reported having numerous financial ties to the pharmaceutical industry.

dbrunk@frontlinemedcom.com

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