A Glut of Antidepressants

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    A Glut of Antidepressants

    August 12, 2013, 2:53 pm


     Over the past two decades, the use of antidepressants has skyrocketed. One in 10 Americans now takes an antidepressant medication; among women in their 40s and 50s, the figure is one in four.

    Experts have offered numerous reasons. Depression is common, and economic struggles have added to our stress and anxiety. Television ads promote antidepressants, and insurance plans usually cover them, even while limiting talk therapy. But a recent study suggests another explanation: that the condition is being overdiagnosed on a remarkable scale.

    The study, published in April in the journal Psychotherapy and Psychosomatics, found that nearly two-thirds of a sample of more than 5,000 patients who had been given a diagnosis of depression within the previous 12 months did not meet the criteria for major depressive episode as described by the psychiatrists’ bible, the Diagnostic and Statistical Manual of Mental Disorders (or D.S.M.).

    The study is not the first to find that patients frequently get “false positive” diagnoses for depression. Several earlier review studies have reported that diagnostic accuracy is low in general practice offices, in large part because serious depression is so rare in that setting.

    Elderly patients were most likely to be misdiagnosed, the latest study found. Six out of seven patients age 65 and older who had been given a diagnosis of depression did not fit the criteria. More educated patients and those in poor health were less likely to receive an inaccurate diagnosis.

    The vast majority of individuals diagnosed with depression, rightly or wrongly, were given medication, said the paper’s lead author, Dr. Ramin Mojtabai, an associate professor at the Johns Hopkins Bloomberg School of Public Health.

    Most people stay on the drugs, which can have a variety of side effects, for at least two years. Some take them for a decade or more.

    “It’s not only that physicians are prescribing more, the population is demanding more,” Dr. Mojtabai said. “Feelings of sadness, the stresses of daily life and relationship problems can all cause feelings of upset or sadness that may be passing and not last long. But Americans have become more and more willing to use medication to address them.”

    By contrast, the Dutch College of General Practitioners last year urged its members to prescribe antidepressants only in severe cases, and instead to offer psychological treatment and other support with daily life. Officials noted that depressive symptoms may be a normal, transient reaction to disappointment or loss.

    Ironically, while many patients in the United States are inappropriately diagnosed with depression, many who actually have it suffer without treatment. Dr. Mark Olfson, a professor of clinical psychiatry at Columbia University Medical Center, noted that from the time they develop major depression, it takes Americans eight years on average to seek care.

    Diagnosing depression is an inherently subjective task, said Dr. Jeffrey Lieberman, the president of the American Psychiatric Association.

    “It would be great if we could do a blood test or a lab test or do an EKG,” Dr. Lieberman said, noting that similar claims of overtreatment have been made about syndromes like attention deficit hyperactivity disorder. “A diagnosis is made by symptoms and history and observation.”

    The new study drew 5,639 individuals who had been diagnosed with depression from among a nationally representative sample of over 75,000 adults who took part in the National Survey of Drug Use and Health in 2009 and 2010. The subjects were then interviewed in person with questions based on the D.S.M.-4 criteria.

    Only 38.4 percent of the participants met these criteria for depression during the previous year, Dr. Mojtabai said.

    It’s possible some of the participants did not appear to be depressed because they had already been successfully treated, said Dr. Jeffrey Cain, the president of the Academy of Family Physicians. Their improved mood may also have colored the way they responded to questions about the past.

    “If I’m checking people who are being treated for high blood pressure and taking medication, I would expect it to be better when I’m checking them,” Dr. Cain said.

    According to the D.S.M., a diagnosis of major depressive episode is appropriate if the patient has been in a depressed mood and felt no interest in activities for at least two weeks, and also has at least five symptoms that impair functioning almost every day. These include unintentional weight gain or loss, problems sleeping, agitation or slowed reactions noticed by others, fatigue and low energy, feelings of excessive guilt or worthlessness, difficulty concentrating and recurrent thoughts of death.

    “We’re not just talking about somebody who’s having a bad day or got into an argument with their spouse,” Dr. Lieberman said. “We’re talking about something that is severe, meaning it’s disabling and distressing and is not transient.”

    Many doctors have long prescribed antidepressants soon after the death of a family member, even though the D.S.M. urges clinicians to differentiate between normal grief and pathological bereavement.

    One 50-year-old New York City woman said her doctor prescribed an antidepressant a few weeks after her husband died, even though she thought her feelings of shock and sadness were appropriate.

    “He told me, ‘You have to function, you have to keep your job, you have a daughter to raise,’ ” said the woman, who asked that her name be withheld because few friends or family members knew she was taking antidepressants.

    Most of the study participants were not receiving specialty mental health care, but Dr. Cain pointed out that it was not clear who was making the misdiagnoses: a psychiatrist, non-psychiatrist physician or other provider, like a nurse practitioner.

    But while a psychiatrist may spend up to 90 minutes with a patient before making a diagnosis, patients often are more comfortable with their primary care doctors, who rarely have that kind of time.

    Dr. Lieberman suggested watchful waiting may be appropriate in some cases, and more integrated forms of health care may soon make it easier to send patients to a mental health provider “down the hall.”

    Doctors need to improve their diagnostic skills, Dr. Mojtabai said, and must resist the temptation “to take out the prescription pad and write down an antidepressant and hand it to the patient.”


    Copyright 2013 The New York Times Company

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    A Dry Pipeline for Psychiatric Drugs


    Published: August 19, 2013 NYT

    Fully 1 in 5 Americans take at least one psychiatric medication. Yet when it comes to mental health, we are facing a crisis in drug innovation.

    Sure, we have many antidepressants, antipsychotics, hypnotic medications and the like. But their popularity masks two serious problems.

    First, each of these drug classes is filled with “me too” drugs, which are essentially just copies of one another; we have six S.S.R.I. antidepressants that essentially do the same thing, and likewise for the 10 new atypical antipsychotic drugs.

    Second, the available drugs leave a lot to be desired: patients with illnesses like schizophrenia, major depression and bipolar disorder often fail to respond adequately to these medications or cannot tolerate their side effects.

    Yet even though 25 percent of Americans suffer from a diagnosable mental illness in any year, there are few signs of innovation from the major drug makers.

    After a series of failed clinical trials in which novel antidepressants and antipsychotics did little or no better than placebos, the companies seem to have concluded that developing new psychiatric drugs is too risky and too expensive. This trend was obvious at the 2011 meeting of the American Society for Clinical Pharmacology and Therapeutics, where only 13 of 300 abstracts related to psychopharmacology and none related to novel drugs. Instead, they are spending most of their research dollars on illnesses like cancer, heart disease and diabetes, which have well-defined biological markers and are easier to study than mental disorders.

    To understand this predicament, it helps to know how we got here.

    All of our current antidepressants, antipsychotics and anti-anxiety drugs share the same molecular targets in the brain as their prototypes from the 1950s. For example, the new antipsychotic drugs block dopamine receptors in critical brain regions, just like the first antipsychotic, Thorazine, synthesized in 1950. And all of our current antidepressants increase the levels of one or more of the neurotransmitters serotonin, dopamine or norepinephrine, just like the early tricyclic antidepressants.

    With rare exceptions, it is hard to think of a single truly novel psychotropic drug that has emerged in the last 30 years. True, the new psychotropic drugs are generally safer and more tolerable than older prototypes, but they are no more effective. So why has the pharmaceutical industry churned out so many copycat drugs?

    The simple answer is that we don’t yet understand the fundamental cause of most psychiatric disorders, in part because the brain is uniquely difficult to study; you can’t just biopsy the brain and analyze it. That is why scientists have had great trouble identifying new targets for psychiatric drugs.

    Also, knowing how a drug works in the brain doesn’t necessarily reveal the cause of the illness. For example, just because an S.S.R.I. antidepressant increases serotonin in the brain and improves mood, that does not mean that serotonin deficiency is the cause of the disease; many depressed patients get better with medications that have no effect on serotonin.

    Until very recently, scientists have relied on the same animal models to screen for potential psychotropic drugs that had been used for decades, which predictably yielded a raft of “me too” medications that shared the same mode of action as the old drugs.

    Sure, this old method of drug development has produced commercially successful blockbuster drugs, like the antipsychotics Seroquel and Abilify. But soon the patents on these medicines will expire, and there is little new in the pipeline.

    Perhaps, though, the pharmaceutical industry is making a mistake, running away from the brain just when things are getting interesting. Consider ketamine (known on the street as Special K), an anesthetic agent that has recently shown unusually powerful antidepressant effects.

    Ketamine acts on a target in the brain where no other drug in psychiatry currently does: the NMDA receptor, which it blocks. The receptor is the site of action of glutamate, a neurotransmitter critically important in learning and memory — and, it turns out, in depression.

    Several promising early studies found that depressed patients who had failed to respond to multiple antidepressants experienced rapid resolution of their symptoms within a few hours of ketamine infusion.

    Unlike standard antidepressants, which typically take weeks to work, ketamine’s effect is rapid because its target, the NMDA receptor, is fast-acting. But this is a tricky biological system to modulate: too little glutamate function at this receptor can produce psychosis, and too much can kill neurons.

    Whether ketamine, or a similar compound, will ultimately prove safe and effective as an antidepressant is unclear. Presently, though, the pharmaceutical industry has little taste for the long-term financial risk of discovering new psychotropic drugs.

    In contrast, academic researchers, who are not beholden to shareholders, are much freer to do high-risk, high-gain experiments that can fail. Large multisite research programs like the Brain Activity Map, along with the latest gene-sequencing technology, can help identify the circuits and genes that are linked to various psychiatric disorders and find promising new targets for drugs. These discoveries, in turn, may entice the drug makers to reinvest in psychiatric drug development.

    As consumers desire new treatments, they have to recognize that innovation carries risks. Drugs are approved by the Food and Drug Administration on the basis of short-term studies, so there is always limited knowledge about the long-term safety of new medications. This is particularly true for drugs that act on new targets in the brain about which relatively less is known.

    But if we are to find better medical solutions for the mental illnesses that disrupt and destroy so many lives, we need to acknowledge a simple truth: there can be no innovation without financial — and medical — risk.

    Dr. Richard A. Friedman is a professor of clinical psychiatry at Weill Cornell Medical College

    © 2013 The New York Times Company