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April 15, 2010

Relieving the burden of mood disorders


Ellen Frank

Ellen Frank traces her atypical path

to becoming a Distinguished Professor at Pitt

Ellen Frank admits she followed an atypical path on her way to being named a Distinguished Professor of Psychiatry.

She earned a bachelor’s degree in drama at Vassar, then a master’s in English at Carnegie Mellon before earning master’s and PhD degrees in psychology at Pitt and moving through the academic ranks as a faculty member in the University’s psychiatry department.

Now an internationally known expert in mood disorders, Frank developed interpersonal social rhythm therapy for the treatment of bipolar disorder.

She directs the psychiatry department’s depression and manic depression prevention program and is co-director of the UPMC Bipolar Institute.

In recognition of her designation as Distinguished Professor, Frank received a medallion from Provost James V. Maher. She delivered her inaugural lecture, “Relieving the Burden of Mood Disorders: A Three-Decade Journey,” April 6 in the Frick Fine Arts auditorium.

“When I graduated from Vassar College in 1966 with a bachelor’s in drama, this is the last place I thought I’d ever be,” Frank said.

Noting that of four As on her undergraduate transcript, three were in psychology, she said, “It never would have crossed my mind that actually constituted a profession or one that I would follow.”

Her career began when, in 1973, David Kupfer and Thomas Detre came from Yale to found Pitt’s psychiatry department in the School of Medicine. They had to leave behind their research assistant “who happened to be about 5 feet tall, had brown hair, brown eyes, and had a talk show on the radio on women’s issues. So, arriving in Pittsburgh they found this 5-foot-tall woman with brown hair, brown eyes, who had a talk show on television on women’s issues.

“So they assumed I’d be their perfect research assistant,” Frank said with a laugh.

“Eventually they convinced me that there was, in fact, a science of psychiatry and that it might be interesting to work in this area. I spent most of my time going to the library for them, looking things up and rewriting their Hungarian English.”

Her curiosity led her to ask questions repeatedly about reanalyzing the data they had gathered. Eventually, they handed her data they brought from New Haven, paired her up with a statistician and said, “See what you can do with this.” That work led to her first presentation at the American Psychological Association meeting and one of her first peer-reviewed papers.

Soon after, the National Institute of Mental Health (NIMH) sought proposals for the study of rape victims. At Detre’s suggestion, Frank wrote a grant proposal and received funding for two treatment approaches for women in the aftermath of rape.

Post-traumatic stress disorder was unknown at the time, she said, but what was known as rape trauma syndrome included a mix of anxiety and depressive symptoms.

“In the literature at the time all of the emphasis was on anxiety but when we looked more carefully at women we were studying, one of the first things we noticed was that a very substantial portion of them also had depressive symptoms and many met full criteria for major depression,” she said.

Early intervention, either with behavioral or a more cognitive behavioral type of therapy, reduced both the depression and the anxiety experienced by these women, Frank said, adding that without intervention, depression and anxiety tended to persist. “But if we instituted intervention six months, eight months, 10 months after the assault, we were equally successful at reducing the depression and anxiety that these women were experiencing.”

Other research at Pitt at the time involved treatments for patients with bipolar and unipolar disorders, including research into improving the long-term outcomes for patients with depression.

In one such study, researchers compared how patients fared with different maintenance approaches after being treated for an episode of depression. Participants were divided into groups that received interpersonal psychotherapy (IPT), medication, IPT plus medication, or a placebo.

Researchers found “maintaining a full dose of antidepressant treatment was a really good idea. Monthly IPT did not add to the benefits of medication, but there was very little room to add to the excellent outcomes we saw with the medication,” Frank said. “But IPT did provide some protection and this was especially true for those who could remain highly focused on the interpersonal themes.”

Frank said visits to the clinical research center by Nobel laureate Julius Axelrod contributed to her departure from following the research “opportunities of the moment.”

She noted that when Axelrod visited, he would examine the results of the prior day’s experiments in his lab, discuss them with his post docs and design another experiment. “The post docs would go into the lab, carry it out, usually that night, and return to the lab again the next morning, usually with the results,” she said.

“Although I couldn’t understand any of the content, I surely understood the process: and that was that each result is really a hypothesis generator and that what we really want to be doing if we’re trying to relieve the burden of mood disorders is not only publish our results but take those results to ask the next question.”

That realization prompted her to derive questions from the earlier studies: “If it’s true that IPT has some power to protect against new episodes of depression, who would want, given the excellent outcomes of medication, to be treated with psychotherapy alone?” she pondered. “Not surprisingly, the answer I came up with was women in their childbearing years,” Frank said, noting that most women and their doctors would prefer they not take medication during pregnancy.

She designed a maintenance trial to study different frequencies of IPT treatment to determine whether women who had had an episode of depression could be kept in remission for a period of two or two-and-a-half years without the use of medication — the time needed to conceive, carry and nurse a child.

She found that IPT worked for a substantial subset of the group. “Among those women, even monthly sessions of IPT seemed to be effective in preventing new episodes of depression,” Frank said, adding that several women — at least three of whom had previous severe postpartum depression — did become pregnant and give birth during the study. “We felt very good about that,” she said.

Frank still was interested in earlier research into patients with bipolar disorder. “The belief system in psychiatry at that time was that bipolar disorder was very much a problem solved. We had lithium. It was a great treatment, we didn’t need to worry about these patients.” However, she said, “There was mounting evidence from both controlled and naturalistic studies that this was far from a problem solved.”

Frank was among a network of mood disorder researchers who developed a theory about how biology and life events might interact to produce new episodes of illness.

“What we said was life events not only have the power to precipitate new episodes through their meaning, through the stressfulness of these events, but that they also have the capacity to change social prompts — the routines in our lives,” Frank said.

Such changes can destabilize daily routines, impacting social rhythms, which in turn can lead to a change in the stability of biological rhythms, she said, citing the effects of jet lag or the transition from standard time to daylight saving time as examples that produce physical symptoms.

Most people easily can regain their equilibrium, but in those vulnerable to mood disorders, the disruptions can trigger episodes of mania or depression.

Using data in which researchers rated life events not only for their stressfulness but also for the extent to which they disrupted patients’ daily routines, Frank said they found rhythm-disrupting events were much more potent than events traditionally thought of as stressful.

That discovery prompted thought about what sort of therapy might be helpful.

“Therapy that combines interpersonal psychotherapy and a focus on regularizing social routines could lead to an increased stability of social rhythms,” Frank said. “That could in turn lead to increased stability of biological rhythms and increased ability to manage current interpersonal stresses, and that in turn would lead to decreased mood symptoms and eventually to increased ability to manage disruptive life events.”

Known as interpersonal and social rhythm therapy (IPSRT), the treatment was found to help a substantial subset of patients with bipolar disorder, leading to significantly longer periods without a major episode of illness, regardless of whether the therapy was continued after the acute phase of treatment.

Although she initially was surprised, Frank said, she realized the therapy is an educative treatment. “If patients were able to learn the new lifestyle … it seems we don’t need to continue to reinforce that because in fact it’s kind of self-reinforcing,” she said. “Indeed, when they lived lives that were characterized by much more regular routines, they felt a lot better, and so the behavior change tended to persist.”

Research is continuing into further identifying those who are likely to have better outcomes with medication compared to those who can be treated with psychotherapy.

One study randomly assigned individuals with an acute episode of unipolar depression to receive either medication or IPT. “If they responded, we continued that treatment. If they stabilized they went on into a six-month continuation phase. If they didn’t stabilize, we added the other treatment,” she said.

In addition to gaining insight into which subsets of patients were likely to respond, researchers found the method to be very effective. “I don’t know too many areas in psychiatry where treatments get remission to 75, 85, 87 percent levels,” she said. “What this suggests to me is this strategy of starting monotherapy and then moving to combined treatment is really a very good strategy for treatment of depression.”

Frank is continuing research into the impact of IPSRT on patients with bipolar disorder. She is seeking NIMH funding to compare patients treated with IPSRT with those who receive a standard pharmacotherapy approach with respect to the alignment with their circadian rhythms and sleep rhythms “and whether IPSRT really does in fact change circadian alignment,” she said.

—Kimberly K. Barlow

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