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Cases Show Complexity of Personalized Treatment in Major Depression


Changes under the DSM-5 mean that certain "mixed features" create a gray area of characteristics that could signal major depression or bipolar disorder, even if a patient has not exhibited hypomania.

Each year at the US Psychiatric and Mental Health Congress, Michael E. Thase, MD, offers a must-attend update on treating major depressive disorder. This year, in advance of the 30th meeting in New Orleans, Louisiana, Thase gave his format a twist: he sent out a call for questions about difficult cases—those involving judgment calls that are increasingly part of the landscape in treating depression.

Now a professor of psychiatry at the University of Pennsylvania’s Perelman School of Medicine and the Philadelphia Veterans’ Affairs Medical Center, Thase explained that diagnosing and treating depression is increasingly personal. Just as one would not treat hypertension by measuring blood pressure, depression cannot be treated without measurement. There are choices among the QIDS (Quick Inventory of Depressive Symptomatology), PHQ-9 (Patient Health Questionnaire), and other scales to fine tune where patients are. But it’s the gray areas that make treatment so challenging: is it depression, or bipolar disorder? Are comorbidities present?

“We are slowly becoming more personal. The very notion that the entity, major depressive disorder, would tell us exactly how to treat a person has left us a long time ago,” Thase said. “Our diagnoses are pervasively frameworks of ways of describing people that only start in motion a treatment plan, and that treatment plan must be personalized. Slowly but surely, we are gaining more tools to personalize a person’s care.”

The cases Thase selected highlighted the complexities under the Diagnostic and Statistical Manual of Mental Disorders, known as the DSM-5, which was published in 2013.

Grief or depression? Bereavement once stood apart from depression, but that is no longer the case. Thase presented the case of a widow who suffered major depressive episodes years ago, and who appears to have relapsed with the loss of her husband of 35 years. She’s reluctant to be treated, but Thase said a grief-focused intervention—with pharmacological treatment—would be warranted if clinical features are present: inability to feel pleasure, neurovegetative signs, diminished capacity, psychosis, or suicidal thoughts.

Major depression or bipolar disorder? Can a person have bipolar disorder without hypomania? Under the DSM-5, the “mixed features” would suggest so, especially if certain symptoms occur right before the onset of a major depressive episode. Specific rating scales for this purpose, interviews with a spouse, partner, or family member, and especially attention to overlapping features—insomnia, agitation, irritability, poor concentration/distractibility—can offer insight into the right diagnosis and course of treatment.

“The old distinction between unipolar and bipolar is so much grayer and not as well defined as we once thought it was,” Thase said.

One might ask, “How can somebody really have this if they don’t have a history of mania or hypomania? I have to give the least intellectually satisfying answer I can give: because it exists.”

It’s important, he said, for patients to be screened for the 4 overlapping mixed features of depression and bipolar disorder.

Is there a preferred scale for measurement? Thase said the VA uses PHQ-9, which has roots in primary care, while he likes QIDS. “Both are reliable, have clearly defined thresholds, and cost nothing to administer,” he said.

Newer antidepressants, and combinations. Thase reviewed features of newer antidepressants, including:

· Vilazodone, a combined selective serotonin reuptake inhibitor (SSRI) and a 5-HT(1A) receptor partial agonist, which Thase said may have lower incidence of sexual side effect than SSRIs.

· Levomilnacipran, which he said is a comparatively strong norepinephrine uptake inhibitor at lower doses,

· Vorttioxetine, which has multiple effects on pre- and postsynaptic 5-HT receptors and may help patients who have not responded to other drugs; it may reduce sexual side effects and improving effects on cognition.

More interesting, is the once unthinkable practice of using antidepressants in combination. Adjunctive therapy avoids the washout period. And there are the new questions of whether atypical antipsychotics, some of which are used as adjuncts, should be considered antidepressants based on their effects; 3 are used alone in bipolar depression.

Thase lamented that some new medications that work perfectly well are beyond the reach of patients because of where they are on the formulary. He’s even seen commercial payers that no longer let patients use coupons. “The sad reality is for a short moment in human history, there are some perfectly good medicines that could be considered first line that are functionally placed on a lower tier simply because they cost too much,” he said.

Side effects and lifestyle management. Side effects, especially sexual side effects, are a major reason patients skip doses or quit medications completely. Physicians need to be realistic about this and help patients, Thase said, especially in advising men what time of day to take medications. Audience members discussed how young soldiers with post-traumatic stress disorder who won’t take certain medications because of the sexual side effects, and Thase offered lists of alternatives.

Thase offered caution about letting patients gain weight. “Preventing weight gain is easier than facilitating weight loss,” he warned. Getting patients to boost their activity if they start certain atypical antipsychotics is crucial, and adding drugs like metformin, topiramate, or psychostimulants can thwart appetite or aid weight loss. Managing sleep is challenging, too, since insomnia is a characteristic of so many disorders, and many medications may add to the condition.

When it comes to depression, one size doesn’t fit all. “Although there are many effective treatments, all have limitations and many patients require a patient, sequential, and iterative approach to get it right,” Thase concluded.

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