Selling a Drug: History and ethics

Carl Elliot, M.D., professor in the Center for Bioethics at the University of Minnesota:

There are other options.

Dr. James Gordon, founder and director of the Center for Mind-Body Medicine and author of Unstuck:Your Guide to the Seven Stage Journey out of Depression–and Harvard-trained psychiatrist–discusses alternative therapies for depression and why their popularity is growing:

 

Related material: Alternative therapies for depression

The bone loss connection

Susan Diem, M.D., M.P.H., assistant professor of medicine at the University of Minnesota, discusses her study of the association between antidepressant use and bone loss:

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Risks and side effects
The sleep connection 

The cost to the system

Antidepressants make up the largest expenditure for medications of any category.

In 2000, the domestic sales of antidepressants in the U.S. totaled $10.4 billion, outweighing all other expenditures for medications. Of these sales, three antidepressants stood out in retail sales–fluoxetine (Prozac) at $2.6 billion, sertraline (Zoloft) at $1.9 billion, and paroxetine (Paxil) at $1.8 billion. Although some antidepressants are prescribed more often than others, there is no compelling reason to prescribe any one over another.

In 2004, antidepressants totaled $13 billion worldwide, with only 10 drugs on the market. Nine of these 10 face a loss of patent from 2006 to 2010. Predictions suggest this loss of patent means a nearly 50 percent loss of total revenues, bringing it down to about $7 billion.

Related material: Prescribing antidepressants

Types of antidepressants

About 62 percent of antidepressant prescriptions in the U.S. are selective serotonin reuptake inhibitors (SSRIs), which are the newest class of antidepressants. The other major classes are monoamine oxidase inhibitors (MAOIs) and tricyclics.

These major classes of antidepressants all operate on a similar assumption that mood is regulated in the brain by certain chemicals called neurotransmitters. Research suggests that abnormal activity in the monoamine neurotransmitters (norepinephrine, serotonin, dopamine) can affect mood and behavior. Antidepressants work by blocking nerve cells from reabsorbing these neurotransmitters, thus keeping more of these chemicals in the brain. This enhances neurotransmitter activity, which is thought to improve mood.

Treating depression with drugs

According to the National Institute of Mental Health (NIMH), SSRIs are the first line of treatment for anxiety and depressive disorders. When treating depression, antidepressants typically need to be taken for 6 to 8 weeks before the full therapeutic effect can be felt. Additionally, there is no way to know beforehand which medication will work, so often doctors will start with one for 6 to 8 weeks, then try another. On top of that, it’s recommended to continue medication for 6 to 12 months for full effectiveness and to prevent relapse of depression. In patients with a history of multiple bouts of depression, long-term use is recommended. If the first treatment doesn’t work, different antidepressants can be tried, or the original medication can be augmented with additional medications, such as aripiprazole (Abilify) or mirtazapine (Remeron).

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs work by blocking reabsorption of neurotransmitters in the brain, but this class of drugs specifically target the neurotransmitter serotonin. SSRIs are considered safer than MAOIs and tricyclics. They are less likely to have adverse interactions with other drugs, and they are less dangerous if overdosed.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs block reabsorption of both serotonin and norepinephrine, like the tricyclics. However, more like the SSRIs, these drugs selectively target only these two neurotransmitters. Because these drugs are similar to SSRIs, they share similar side effects. Since SNRIs also block norepinephrine, this creates additional side effects.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs work by preventing certain neurotransmitters from metabolizing, thereby increasing the amount of these chemicals in the brain. Most MAOIs act irreversibly, meaning that once an MAOI has altered the neurotransmitters, they stay altered until the body naturally replaces the affected neurotransmitters, which can take about two weeks.

MAOIs also react with certain foods and alcoholic beverages, such as aged cheeses, foods containing monosodium glutamate (MSG), Chianti and other red wines, and other medications, such as over-the-counter cold and allergy preparations, local anesthetics, amphetamines, insulin, some narcotics, and antiparkinsonian medications. Because of this, patients on MAOIs must adhere to strict diets and be closely monitored for adverse drug interactions.

Tricyclics

Tricyclics work by blocking the reabsorption of neurotransmitters at cell receptor sites. These drugs primarily target serotonin and norepinephrein, but they also affect other neurotransmitters, including dopamine, to a lesser degree. Not much is known about how these drugs work specifically, but they do interfere with other cell receptors, causing many of their side effects.

Tricyclics can interact with thyroid hormone, antihypertensive medications, oral contraceptives, some blood coagulants, some sleeping medications, antipsychotic medications, diuretics, antihistamines, aspirin, bicarbonate of soda, vitamin C, alcohol, and tobacco.

Related material:
Effectiveness of SSRIs
Risks and side effects
Selling a Drug: History and ethics

History of antidepressants

Before the boom of psychopharmacology in the 1950s, the treatments for mood disorders were relatively limited and crude, including shock treatment, insulin coma therapy, and sleep-deprivation therapy. While we’ve come a long way from inducing insulin comas, there are now dozens of antipsychotics on the market to treat depression.

MAOIs and tricyclics were the first antidepressants developed, dating back to the 1950s. These drugs came with numerous side effects and sometimes strict regiments for taking the drugs. Because of this, researchers looked for an alternative with simliar effectiveness but fewer side effects and found this in SSRIs. Even more recently, researhcers have developed another class of drugs, serotonin-norepinephrine reuptake inhibitors (SNRIs), thought to be even more effective but with similar side effects to SSRIs.

Related material:
Types of antidepressants
Cost to the system

Effectiveness of SSRIs

Antidepressant use nearly tripled between 1988 to 1994 and 1999 to 2000, according to the CDC. The large majority of these are SSRIs, but recent studies suggest they are not anymore effective than placebo (dummy) treatment.

Drug vs. placebo

A meta-analysis conducted by the University of Hull found there to be no significant benefit of antidepressants (specifically SSRIs) over placebo, or sugar pill, in moderately depressed patients.

The researchers reviewed all clinical trials of SSRI treatment submitted to the FDA, specifically looking at patient improvement on the Hamilton Rating Scale for Depression (HRSD). The HSRD is a commonly used diagnostic tool for rating severity of depression and involves 17 to 21 questions with a range of possible scores. The most common scoring of the HSRD suggests that scores between 0 and 6 indicate a normal person relative to depression, scores between 7 and 17 indicate mild depression, scores between 18 and 24 indicate moderate depression, and scores over 24 indicate severe depression.

The meta-analysis found that the drug benefit over placebo only reached clinical significance in patients with an initial HSRD score of 28 or higher–a severely depressed population. Moreover, the apparent effect of antidepressants in severely depressed patients was not only small, but it reflected a decrease in responsiveness to placebo rather than an increased response to the antidepressant. In other words, the antidepressant only makes a small difference in the most severely depressed populations, yet the placebo effect is large in treating mild to moderate depression.

A previous meta-analysis of clinical trials submitted to the FDA found that, on average, antidepressants improved patients’ HSRD scores by only 1.8 points, a marginal and in some cases, clinically insignificant improvement. The UK National Institute for Health and Clinical Excellence (NICE) defined clinical significance of drug over placebo as an improvement in HSRD score of 3 points or higher, a standard that most antidepressants fail to meet. Furthermore, about 80 percent of the antidepressant effect was duplicated in placebo treatment.

The STAR*D report

Every year, 9.5 percent of the U.S. population, or roughly 20.9 million people, are affected by depression. Many of these people will try antidepressants, and for those people with treatment-resistant depression, they will likely try multiple antidepressants in search of one that works for that person. The STAR*D study, or Sequenced Treatment Alternatives to Relieve Depression, funded by the NIMH, investigated this method of switching antidepressants in hopes of alleviating depressive symptoms.

The results suggest that patients (with treatment-resistant depression) are more likely to beat depression after trying several treatment strategies. However, those patients who only improved their symptoms, rather than eliminating them, were less likely to remain well, and those who had to try several medications were even more likely to experience a relapse. The study underscores the powerful nature of severe Major Depressive Disorder (MDD) and the need to better understand the underlying mechanisms causing depression so we can find more effective treatment strategies.

Related material: Types of antidepressants

What does the FDA say?

The Food and Drug Administration approves drugs, such as antidepressants and specifically SSRIs, to treat specific health conditions that are recognized and diagnosed. However, many people who take antidepressants have never been diagnosed with depression–their main tested and approved use.

Media reports have estimated that 43 percent of people prescribed antidepressants have never been diagnosed with any psychiatric condition and have never had other mental health care.

And one study of Medicaid enrollees found that three-quarters of the people taking antidepressants were using the drugs for an “off-label” reason–one that is not approved by the FDA.

Related material: Risks and side effects

Prescribing antidepressants

According to the CDC, antidepressants are the most commonly prescribed drug in the U.S.–118 million prescriptions in 2005. About 11 percent of women and 5 percent of men currently use antidepressants.

Media have reported that for women in 2002, more than 1 in 3 doctor’s visits involved either a new antidepressant prescription or monitoring an existing one.

Where do they get them? Less than one-third of antidepressants are prescribed by psychiatrists–doctors who have been specially trained in the drugs’ prescription and use.

And psychiatrists, according to a Johns Hopkins University study, spend 71 percent of their time during office visits prescribing medications and only 29 percent on talk therapy (likely due to higher insurance reimbursement for the former).

Source: Medical Expenditure Panel Survey (2008), Agency for Healthcare Research and Quality

Though antidepressants have proven side-effects, some serious, the New York Times reported that only 1 in 5 people on the medications have any kind of follow-up appointment after prescription. More than 80 percent of adults do not see a doctor or therapist for mental health care in the first month after starting an antidepressant, according to research by Medco Health Solutions.

Diagnosing depression

According to the CDC, more than 1 in 20 Americans over age 11 had current depression in a 2005-2006 household survey, the highest rates being among the middle-aged, women and blacks. Among poor Americans, the number rose to 1 in 7.

Less than one-third of all people with depression–and nearly 40 percent of people with severe depression–sought help from a mental health professional in the past year.

And media reports have estimated that 40 percent of mental health complaints in the U.S. result in a depression diagnosis.

Life changes and depressive symptoms

A 2007 study from New York University found that 1 in 4 people diagnosed with and treated for depression is dealing with a major life change such as the loss of a job or end of a marriage.

Depression or depressive symptoms can also be common in young people who are going through transitions such as moving away from home or starting college. At the University of Minnesota in 2004, 1 in 5 female students and 1 in 10 male students reported being diagnosed with depression at some point in their lives. Nearly 8 percent of students were taking medication for depression, and 8 percent were seeing a mental health counselor or therapist.

Insurance coverage of antidepressants

The “official” depression diagnosis

What exactly constitutes depression? A valid question considering 40 percent of mental health complaints to health providers end in a depression diagnosis, according to the CDC.

Are most people being treating for depression technically depressed? And do the official diagnostic criteria encourage under- or over-diagnosis?

See what you think: View the official diagnostic criteria for depression from the Diagnostic and Statistical Manual of Mental Disorders, version four.

The Patient Health Questionnaire, or PHQ-9, is a depression scale based off of the DSM criteria that is also commonly used to diagnose patients with depression. See a sample.

Related material: Have the Internet? Self-diagnose.

Have the Internet? Self-diagnose.

Though a true diagnosis of depression can be complex and serious, many institutions promote free self-screening tools to determine whether a person is–or may be–depressed and should seek professional evaluation and treatment.

The University of Minnesota’s counseling center recommends this online depression screening to students concerned about their mental health.

New York University created this depression screening test.

And Google “depression screening”–the first hit is a free test from Depression-Screening.org, who has clearly made its name in this “business.”

I took the test. “I” being a happy, healthy 20-something with no reason to suspect I might be depressed. But I am in my first semester of graduate school–a total lifestyle change. In the thick of midterms.

And, according to this test, my “screening results are consistent with moderately severe depression”: 

 

depression-screening.org

Related material: The “official” depression diagnosis