Robert Post on Depression, Bipolar Disorder

Robert Post, M.D., is an expert on bipolar disorder and a Dana Alliance for Brain Initiatives member. He completed his psychiatry residency at Massachusetts General Hospital, the National Institute of Mental Health (NIMH), and George Washington University. At NIMH, Post worked his way up to chief of the Biological Psychiatry Branch, a position he held for many of his 36 years there. He now leads the Bipolar Collaborative Network.

Bipolar disorder affects approximately 5.7 million American adults, or about 2.6 percent of the U.S. population age 18 and older in a given year, according to the NIMH. In the interview below, edited for clarity, Dr. Post talks about the disorder, including potential treatments.

There is a lot of buzz about the use of ketamine for bipolar disorder. What can you tell us about that?

The I.V. ketamine data are very interesting. They’ve been replicated by multiple groups for treatment-refractory, unipolar, and bipolar depressed patients. The interesting thing with this intravenous ketamine is that it seems to have positive effects within two hours, which is almost unheard of. The problem is it only lasts for three to five days. Everybody is scrambling trying to figure out how to sustain the therapeutic effects.
Robert post

The two clinical and theoretical points of interests are (1) that it works that fast and (2) that it implicates glutamate in the rapid-onset actions, because ketamine is a potent blocker of glutamate receptors. There is one subtype of glutamate receptors, NMDA, that it blocks pretty potently. And now some pharmaceutical companies are trying to develop other blockers of subunits of the NMDA glutamate receptors so that they could get the same quick onset antidepressant effects without the ketamine side effects. Ketamine is used as a dissociative anesthetic for operations especially in animals. In high doses it can be psychomimetic [produce effects that mimic the symptoms of psychosis]. In the doses used for depression the dissociative side effects are minor and transient, however.

Have you seen any changes in the way bipolar disorder is diagnosed or treated given the upcoming release of the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-V)?

It has evoked a lot of controversy and I’m afraid it’s not going to be terribly helpful. It brings a new diagnosis for childhood onset illness that’s not quite bipolar, but a lot of irritability. The problem is they haven’t demonstrated what treatments work for it. I think it’s a bit up in the air to how useful it may be.

Have you noticed a destigmatization over the last few years in regards to how mental health disorders are viewed by the public?

Yes, but it’s nowhere near enough. The news media often is not very helpful in providing people with accurate information these days about the seriousness of depression. They keep repeating data that the acute antidepressant effects of these drugs don’t always beat placebo. What they neglect to tell people is that the preventative effects of the antidepressants are astronomically huge. If you’ve had a couple of prior depressions and you stay on your antidepressants, the reduction in depressive recurrences is bigger than anything in cardiology or most of medicine; 70 percent reduction in depressive recurrences. That kind of thing doesn’t really get through to people. It’s often like cholesterol and blood pressure; they really need to stay on their meds to keep recurrent depressions away. The depressions are not only something that give you terrible amounts of suffering and dysfunction, they increase the lethality of almost any other medical illness. You’re twice as likely to have a heart attack if you’re depressed than if you’re not. Many illnesses are tougher to treat if you’re depressed. The news media is stuck on this issue of acute efficacy beating placebo; they’re forgetting to inform people about the need to treat this illness in the long term.

Is there anything else you’d like to add?

We need to try to recognize these illnesses and treat them early. The more depression you have, the more dysfunction can occur. If you have more than four depressions in your lifetime, it doubles your rate of getting a diagnosis of dementia in old age. Depression is a major risk factor for mild cognitive impairment converting to dementia. In terms of the dysfunction, the suffering, the disability, the medical problems, the cognitive problems, it really needs more attention for concerted long-term treatment.

Patients would be happy to know that if they stay on their antidepressants more of the time, they don’t get hippocampal atrophy with aging. Yvette Sheline, M.D., at Washington University in St. Louis did a study that showed on fMRI that lithium increases hippocampal volume. Some antidepressants increase neuroprotective factors, and in this case they actually prevent the hippocampal volume from decreasing. So it’s not just side effects associated with some of these agents, there are some positive effects too.

– Andrew Kahn

One response

  1. Antidepressants, more of the time, prevent hippocampal atrophy with aging. That IS a positive side effect. Also, that staying on your medication helps prevent recurrance of depression a whopping 70%. That’s huge. We should shout that from the rooftops. Thanks for this interview.

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