Archive for the ‘Treatments’ category

One More Question

December 20th, 2010

More than one senior colleague has advised me to include a family member as often as possible when interviewing a depressed patient. Often I’ve heard patients complain of sleeplessness or anhedonia, only to have a relative or friend present a very different picture. Such disparities should profoundly affect our diagnostic impressions and treatment decisions.

Yesterday there was only the resident and me in a room with a patient referred from a primary-care doctor for evaluation of depressive symptoms. The resident asked about low mood and anhedonia, both of which the man endorsed. But as I listened quietly, I thought I caught a spark of animation when the patient described some of his extracurricular interests. When it was my turn to ask a few questions, I inquired about what had given him pleasure over the past few days. Nothing, came the reply. There was no loved one to give collateral information, so I pursued an alternate tack. I asked the man about a few of his hobbies. As he described a team he played on and favorite spectator sports, he came alive, was engaged, passionate, and animated. His face lit up, and he smiled.  Our diagnosis and treatment recommendations shifted.

I enjoy the challenges of solving diagnostic puzzles. It’s one of the joys of medicine and psychiatry—and a reason ultra-brief visits can be costly in more ways than one.

- Alan J. Gelenberg, M.D.
Editor,
Biological Therapies in Psychiatry
Professor and Chair, Psychiatry, Penn State University
Editor-in-Chief,
Journal of Clinical Psychiatry

When mechanism matters

December 13th, 2010

Maprotiline (Ludiomil) is a tetracyclic antidepressant introduced in the early 1980s. It is a norepinephrine reuptake inhibitor, which is believed to be its primary mechanism of antidepressant action. It had a particularly high incidence of seizures, which the manufacturer initially minimized. Today maprotiline is seldom prescribed.

Initial advertising for maprotiline featured the headline, “When Mechanism Matters.” Perhaps the people who wrote the ad copy were banking on the Emperor’s-New-Clothes phenomenon: doctors would be too embarrassed to admit we didn’t know when mechanism mattered in selecting an antidepressant for a depressed patient. We still don’t.

We make assumptions. SSRIs work by enhancing serotonin. SNRIs work via both serotonin and norepinephrine. MAOIs work by inhibiting MAO. Perhaps these theories are valid; perhaps not. In theory, a patient who fails to respond to one SSRI should do better with a drug with a different mechanism of action, rather than a different SSRI. But the data say otherwise.

I am convinced that, ultimately, mechanism matters. And psychiatric patients are different one from the other. Someday we will understand the unique pathophysiology that underlies abnormal thinking, feeling, and behavior. Someday we will elucidate the various etiologies that distort normal brain function in these ways. And when that time comes, we will tailor treatments to the abnormalities: targeted treatments; personalized medicine.

But until that time, let’s not become gullible to those who peddle expensive new products with thinly veiled promises that understanding the receptor or other properties of a compound translates into real-life advantages. And remember that sales people are not only the companies’ marketers and representatives, but also some of our colleagues who write and lecture. A professor of mine admonished his students to be “therapeutic skeptics—but not nihilists.” Amen.

- Alan J. Gelenberg, M.D.
Editor,
Biological Therapies in Psychiatry
Professor and Chair, Psychiatry, Penn State University
Editor-in-Chief,
Journal of Clinical Psychiatry

ACNP Musings

December 8th, 2010

Attending the annual meeting of the American College of Neuropsychopharmacology is always a heady experience. The membership and guests are among the most brilliant humans anywhere, and I am invigorated that so many devote their lives to explicating the brain’s mysteries.

Here in a chilly South Florida, there is much about which to be optimistic. Presenters are young scientists, insuring a continuing pipeline of talent to the labors of cracking the code of brain diseases. And the science and its promise are rich and exhilarating.

But there is fodder for the pessimists and worriers too. Whither healthcare reform, with its promise of extending and rationalizing health care, of stopping discrimination against the mentally ill? And what will happen to the NIH budget, which nourishes the science and scientists on whom we vest our hopes for a better future? Big pharmaceutical companies are pulling back from psychiatric research and products. Where will that leave us over the decades to come?

There is cause for hope. And worry.

- Alan J. Gelenberg, M.D.
Editor,
Biological Therapies in Psychiatry
Professor and Chair, Psychiatry, Penn State University
Editor-in-Chief,
Journal of Clinical Psychiatry

Strong Medicine

October 25th, 2010

From time to time, a patient or family member asks about a treatment I have recommended and am about to prescribe, “Doctor, is this a strong medicine?” Sometimes the person talks about a previous doctor who just prescribed something “mild” for perhaps minor symptoms.

I’ve been a doctor for so long that such questions often take me aback. They are phrased in a foreign tongue. I think in terms of potency, efficacy, and safety. I weigh numbers needed to treat and harm, risks versus benefits. Scientific stuff.

Naïve questions prompt me to re-engage my empathy, to metaphorically put myself in the consumer’s seat. Occasionally I recommend something mild: mint tea for a little nausea, or walking for tension or easy exercise. They are pretty safe and unlikely to cause discomfort. But most of our treatments are in fact powerful. They can cause harm. It’s important to ask what a patient or family member means when a phrase is ambiguous. (“What do you mean by ‘strong?’”) But often the meaning is simply, “Will it hurt or harm?” And that’s a good place to start the process of building a partnership for treatment.

Press Reactions to the MDD Treatment Guideline

October 6th, 2010

The 3rd APA Treatment Guideline for Major Depressive Disorder is about to be published. Press releases went out late last week. I’m the only person who participated in the writing of all three iterations, and I chaired the work group that wrote the most recent one.

We began in 2006. I was then in Tucson and have since migrated to Madison, WI, and then to Central Pennsylvania and Penn State. It’s been a long four years. First came the scholarship, sifting through myriad papers, studies, and data. Many, many calls and emails. Then came over a thousand comments from colleagues in practice, scientists, and medical directors of companies that made depression treatments. All had to be responded to in multiple drafts and what felt like endless rewriting. Finally, the complex APA hierarchy had to read, discuss, consider, and vote. We’re finally done.

I was surprised  by some of the press reaction. ECT was a small part of a very long document, which details a growing panoply of options for treating depressed people: from diet and exercise through therapy and medication and on to various ways to stimulate the brain electrically or magnetically. But ECT, with its echoes of “Cuckoo’s Nest,” evokes emotion and, I suppose, captures readers’ attention.

A blogger for a major news weekly turned the Guideline into a battle between psychiatrists and psychologists. I learned that we hate each other. (Really?)

When Marty Keller and others looked at depression treatment in the early 1980s, they learned that only 20% to 25% of depressed people get minimally adequate treatment. NIMH and various advocacy groups launched campaigns to educate doctors and the public. Managed care was graded by accrediting agencies on how well they diagnosed and treated depression. Now, 30 years later, the percentage of depressed people who receive minimally adequate treatment remains more or less the same.

But what titillates the press is that “shock treatment” remains among our treatments. And that sometimes psychiatrists and psychologists disagree or have guild arguments. To me that’s sad. We need better press agents for improving mental health access and care.

Bad, bad Benzos?

September 27th, 2010

Six or seven years ago, a patient of mine was moving to a nearby state. Through the local university’s psychiatry department, I arranged for her care to be delivered by a recent graduate from their residency. We spoke by phone about the transfer. She sounded competent and nice.

My patient was taking an SSRI daily and a prn benzodiazepine—diazepam, I seem to recall. My younger colleague was appalled. She repeatedly questioned me with an anxious tone about the need and justification for this dangerous drug. I sought to clarify and reassure her.

Used appropriately and cautiously, benzodiazepines can do good. They can offer immediate relief of anxiety and insomnia, and they certainly feel different than an antidepressant. They work fast. They are good during the first few weeks of antidepressant treatment of depression or many anxiety syndromes. Benzodiazepines are also good for prn use during a “rough patch.”

Downsides? They have many. They should be prescribed with great caution, if at all, to patients with a history of dependency. Sudden withdrawal (even an abrupt reduction in dose) can be lethal. And they cause the full range of sedative-hypnotic side effects—like sedation, amnesia, confusion, and ataxia. Add alcohol or another sedative-hypnotic, and these effects can mushroom.

I caution patients strongly to be careful about driving or anything that can be hazardous—like climbing a ladder. If a patient takes a benzo at bedtime, I advise the patient to look for hazards between bed and bathroom. It’s so easy to trip in the dark if one is unsteady. With older patients, this problem is magnified.

Which benzo to choose? It depends. Know the pharmacokinetics. Duration of action is terminated by distribution with single use, so a lipophilic agent like diazepam is quick in/quick out. With repeated use, half-life determines how long the drug works. The one benzo I really dislike is alprazolam. Alprazolam’s kinetics and dynamics make it troublingly addictive and hard to stop.

Are benzodiazepines good? Or bad? They are drugs—double-edged swords. We can prescribe them wisely.

I want happy.

September 13th, 2010

She was 20 and bedeviled by episodic bouts of depression, anxiety, and irritability. I saw her for an initial visit with an excellent fourth-year psychiatry resident. She asked to be joined by her 21-year-old live-in boyfriend to hear our impressions and recommendations.

After a thorough and comprehensive evaluation, the resident explained that the patient was wrestling with a host of developmental issues: establishing independence from her parents, confronting her mother’s mental illness and its meaning for her, choosing a job and career, working out a meaningful relationship with her boyfriend (if, in fact, that’s what she wanted). He recommended psychotherapy. She belittled therapy. (“If I want to talk, I can just call a friend.”)  And she balked at the time and money it would cost. No go.

The boyfriend also had no use for talk therapy. He wanted her to be more energetic and available to him at the end of her work day, to be less irritable. He wanted her medicated. We were willing to consider an SSRI, but she balked at meds.

She wanted to be happy. He wanted her to be the girlfriend and roommate he felt he deserved. The resident and I described the scope, nature, and limits of modern psychiatric interventions—for that matter, all medical treatments. That line of reasoning went nowhere.  I asked each what he/she hoped to come away with. We were back (slowly) to square one.

Two unhappy “customers” left our facility. It’s too bad. But we have our limits.

The Whole Truth

September 3rd, 2010

It’s been some years since I last gave—or attended—a promotional talk. Or been “detailed” by a pharmaceutical rep.

Yesterday, I walked into a meeting of colleagues. It was noon, and a pharma rep had brought sandwiches and was giving a “spiel,” backed up by two colleagues (at least one presumably monitoring her performance—and the doctors’ responses).

Her company had just come out with a new compound. One of the most popular competitor drugs is about to come off patent, making inexpensive generics available. She enthusiastically pitched her medicine and distributed a reprint of a recent study—featuring her drug, the competitor, and placebo.

Her drug does not cause some of the side effects associated with the competitor as often as the competitor does.  That’s true. To be provocative, I asked in front of the group if that meant more patients completed treatment with her drug, or that there were fewer drop-outs due to adverse reactions. “I’m sorry,” she said. “I don’t have that information. But I can get it and send it to you.” Her companions remained mute.

As she went on extolling the wonders of the new drug, I flipped through the reprint. In fact, the competitor showed a larger effect size, more patients completing the protocol, and fewer drop-outs due to side effects.

She had not lied. Everything she said was true. But she had not told the whole truth. Caveat emptor.

Learn when to bend

August 30th, 2010

Earlier this week I interviewed a patient in front of our residents and medical students. A woman in her early 50s, she had been hospitalized following a serious suicide attempt.

The patient had borderline personality features, including cutting, that had begun in early adolescence. She also carried diagnoses of MDD eating disorder, and substance abuse.

What struck me on meeting her was how composed she was. She was calm and rational. She had it all together. She could see the path forward, understood the error of her ways, was intent on living healthy. It was an easy interview. I was terrified.

She was the last person to speak to her dad before he took his own life. She was 13. She retained considerable guilt about his death and had never completed grieving it. I feared she would follow his path.

In my own life, and observing friends, patients, and loved ones, I have come to value toughness, discipline, and resolve. But I have also learned to appreciate the roles that softness, flexibility, patience, acceptance, and humility must play in keeping us strong and resilient.  I told the patient that palm trees survive hurricanes by bending. I hope it helps.

Personalized Medicine: when will it come to psychiatry?

August 23rd, 2010

I recently wrote a piece on personalized medicine, which appears in the September issue of BTP. I thought of it following a meeting with pharmacology faculty members from Penn State Hershey’s cancer center.

As I mention in the newsletter, personalized medicine is gradually becoming a reality in cancer treatment, as genetic understanding points the way to specific diagnoses and tailored treatments. Now scientists are extending understanding slowly to brain diseases and psychiatric therapies.

My colleagues are working with in vitro preparations to identify drug-metabolizing enzymes and the genetic variants that control them. Based on new research, we hope to figure out which patients may be at greater risk of specific medication toxicities, and conversely, who may take our drugs with relative impunity. Soon, I hope, this new knowledge will affect the treatment of major psychiatric diagnoses.

Much research remains to be done—in laboratories, hospitals, and clinics—before these new approaches will be ready for “prime time.” But I anticipate that this “brave new world” will soon be upon us.