The sleep connection

Dr. Mark Mahowald notes some unusual and disturbing side effects in sleep caused by antidepressants, some temporary and some permanent. In particular, antidepressants are the leading medical cause of REM sleep behavior disorder, where people act out their dreams and can end up seriously injuring themselves. Additionally, antidepressants cause abnormal eye movements during non-REM sleep (what sleep specialists informally call “Prozac eyes“) and this side effect is permanent.

Mark Mahowald, M.D., is a neurologist and medical director of the Minnesota Regional Sleep Disorders Center and professor for the University of Minnesota Medical School.

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The bone loss connection

Experts talk about drug advertising

What’s in this video: A discussion of how direct to consumer advertising affects how care providers treat depression.

William Robiner, Ph.D., A.B.P.P., L.P., is a health psychologist and director of health psychology at the University of Minnesota Medical School.

Linda Muldoon, Ph.D., L.P., L.G.P., is a senior pychologist for the University Counseling & Consulting Services at the University of Minnesota.

David Adson, M.D., is a psychiatrist and associate professor for the University of Minnesota Medical School.

Jon Hallberg, M.D., is a family physician and medical director of Mill City Clinic, as well as creative director of the Center for Arts and Medicine, both in Minneapolis, MN.

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What does the FDA say?

Experts discuss insurance concerns

What’s in this video: A discussion of the insurance issues both patients and care providers face when treating depression.

William Robiner, Ph.D., A.B.P.P., L.P., is a health psychologist and director of health psychology at the University of Minnesota Medical School.

Linda Muldoon, Ph.D., L.P., L.G.P., is a senior pychologist for the University Counseling & Consulting Services at the University of Minnesota.

David Adson, M.D., is a psychiatrist and associate professor for the University of Minnesota Medical School.

Jon Hallberg, M.D., is a family physician and medical director of Mill City Clinic, as well as creative director of the Center for Arts and Medicine, both in Minneapolis, MN.

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Insurance coverage

Experts tell us about their professions

If you feel you have depression, you have a choice of who to go to–a psychologist, a psychiatrist or your family doctor–but who should you choose? Psychiatrists have the most in-depth training on antidepressants but they generally don’t spend much time doing psychotherapy with their patients. On the other hand, psychologists strictly do psychotherapy and cannot prescribe medications. Family physicians do have training on antidepressants and diagnosing depression, though it tends to be more limited.

What’s in this video: An overview of the difference between psychology, psychiatry and family medicine, what type of training these fields receive in diagnosing depression and prescribing antidepressants, whether they refer to psychologists or psychiatrists for additional help in treating depressed patients, and a discussion of the cost of psychotherapy.

William Robiner, Ph.D., A.B.P.P., L.P., is a health psychologist and director of health psychology at the University of Minnesota Medical School.

Linda Muldoon, Ph.D., L.P., L.G.P., is a senior pychologist for the University Counseling & Consulting Services at the University of Minnesota.

David Adson, M.D., is a psychiatrist and associate professor for the University of Minnesota Medical School.

Jon Hallberg, M.D., is a family physician and medical director of Mill City Clinic, as well as creative director of the Center for Arts and Medicine, both in Minneapolis, MN.

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Experts discuss antidepressants

What’s in this video: How SSRIs work, the side effects of antidepressants, their effectiveness, the effect of placebo (dummy) treatment, and what else antidepressants are prescribed for.

William Robiner, Ph.D., A.B.P.P., L.P., is a health psychologist and director of health psychology at the University of Minnesota Medical School.

Linda Muldoon, Ph.D., L.P., L.G.P., is a senior pychologist for the University Counseling & Consulting Services at the University of Minnesota.

David Adson, M.D., is a psychiatrist and associate professor for the University of Minnesota Medical School.

Jon Hallberg, M.D., is a family physician and medical director of Mill City Clinic, as well as creative director of the Center for Arts and Medicine, both in Minneapolis, MN.

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Experts talk about treating depression

What’s covered in this video: The different methods for beginning treatment, who prescribes medication, and other considerations for treating depression.

What’s covered in this video: The nature of treatment schedules for antidepressants and psychotherapy, how many medications doctors try before finding the right balance, how long the duration of treatment typically lasts, and how to go about stopping antidepressant treatment.

William Robiner, Ph.D., A.B.P.P., L.P., is a health psychologist and director of health psychology at the University of Minnesota Medical School.

Linda Muldoon, Ph.D., L.P., L.G.P., is a senior pychologist for the University Counseling & Consulting Services at the University of Minnesota.

David Adson, M.D., is a psychiatrist and associate professor for the University of Minnesota Medical School.

Jon Hallberg, M.D., is a family physician and medical director of Mill City Clinic, as well as creative director of the Center for Arts and Medicine, both in Minneapolis, MN.

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SSRIs, SNRIs and triptans

Psychotherapy

There are many different types of psychotherapy, but they all have one thing in common: talking.

Cognitive behavioral therapy, or CBT, is the most common psychotherapy treatment for depression–and is effective. The National Alliance on Mental Illness defines CBT as a treatment “that focuses on patterns of thinking that are maladaptive and the beliefs that underline such thinking.”

Therapists help patients view their beliefs as hypotheses that must be tested instead of fact and ask them to monitor automatic thoughts in order to find patterns and biases. Ultimately, they try to replace negative thoughts with positive ones, working from the foundation that thought influences mood.

CBT has been shown to be as effective as antidepressants in treating depression. It also significantly reduces depression relapse rates–and does so better than some antidepressant medications.

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Who should I go to?

Out-of-pocket cost of therapy

The cost of antidepressants varies by type, between brand name and generic (if available) and by where they are purchased:

The cost of psychotherapy varies by therapist. Psychology Today provides an online therapy directory where you can find theraptists in your area and even sort them by specialty. A list of therapists in Minneapolis, Minn. specializing in depression shows that the out-of-pocket cost for psychotherapy ranges from $60 to $200 per session.

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Risks and side effects

While the specific cause of depression is not well understood, most researchers think that brain chemistry has something to do with it. Antidepressants work by altering the balance of certain chemicals in the brain, but with that come some risks and side effects that you should know about.

Most common side effects

Antidepressants carry with them a host of unpleasant side effects, some of which can turn into serious problems of their own. Some other side effects, like abnormal eye movement during non-REM phases of sleep (referred to as “Prozac eyes” by many sleep specialists), are permanent. A 2002 Toxic Exposure Surveillance System report revealed that of 26,733 patients on SSRIs, 27 percent developed significant morbidity and 93 died.

Most of these side effects are relatively benign, but there are more serious side effects to worry about. One study by University of Manchester outlined the many more severe side effects of antipsychotics and antidepressants, including: acute dystonia (brief or sustained muscle spasms), parkinsonism (neurological syndrome characterized by tremors), akathisia (extreme restlessness), tardive dyskinesia (involuntary, repetitive movements caused by medication), tardive dystonia (sustained muscle contractions as a result of medication), increased risk of seizure, serotonin toxicity (see below) and discontinuation symptoms (see below). Antidepressants can also cause REM sleep behavior disorder, which causes you to act out your dreams and can result in serious injuries.

Serotonin syndrome

This can be a life-threatening condition caused by high levels of serotonin in the body. It’s typically caused by combining drugs that affect serotonin levels, though it can also occur when you first start or increase medication that affects serotonin. A common dangerous combination is taking SSRIs or SNRIs (used to treat depression) with triptans (used to treat migraines). Even taking certain cough medicines (dextromethorphan) can increase this risk in combination with other serotonin medications. For a list of SSRIs, SNRIs and triptans <<click here>>.

Research done at Washington State University earlier this year (2008) found that during 2003 to 2004, 1.3 percent of patients prescribed a triptan or an SSRI or SNRI were prescribed the potentially fatal combination of the two together, a total of 694,276 patients affected.

Discontinuation syndrome

Although not common, some patients may experience withdrawal symptoms when stopping an antidepressant, particularly if the treatment is stopped too abruptly. The Mayo Clinic notes that it can be difficult to distinguish withdrawal symptoms from reemergence of depression, but that this should not be considered the same as withdrawal from an addictive substance. For these reasons, the NIMH advises gradual withdrawal of antidepressants when discontinuing treatment.

One study noted that many patients are continuing use of SSRIs well beyond the recommended duration of treatment in part due to fear of withdrawal symptoms. However, an article written by King’s College London indicated that withdrawal symptoms are in fact milder than the public generally assumes and can be easily managed by slowly tapering off medication.

Paroxetine (Paxil) appears to be the most prone to discontinuation syndrome, perhaps because it is the most potent inhibitor of serotonin reuptake among SSRIs. Paroxetine efficacy is similar to other SSRIs, though it is approved for a wider variety of disorders, including major depression, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, post-traumatic sterss disorder and social phobia.

Risk of suicidality

The FDA reported results from a series of clinical trials that showed a 4 percent risk of suicidality in children and adolescents taking antidepressants, as compared to a 2 percent risk with placebo.

According to the NIMH, fluoxetine (Prozac) is currently the only antidepressant approved by the FDA for use in children ages 8 and older.

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Experts talk about diagnosing depression

What’s covered in this video: The criteria for diagnosing Major Depressive Disorder, related depressive symptoms, what the experts think about that criteria, the type of people more often diagnosed, and how they go about diagnosing depression.

What’s in this video: Discussion of whether depression is over-diagnosed, misdiagnosed, or over-medicated.

William Robiner, Ph.D., A.B.P.P., L.P., is a health psychologist and director of health psychology at the University of Minnesota Medical School.

Linda Muldoon, Ph.D., L.P., L.G.P., is a senior pychologist for the University Counseling & Consulting Services at the University of Minnesota.

David Adson, M.D., is a psychiatrist and associate professor for the University of Minnesota Medical School.

Jon Hallberg, M.D., is a family physician and medical director of Mill City Clinic, as well as creative director of the Center for Arts and Medicine, both in Minneapolis, MN.

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Insurance coverage

Antidepressants are prescription medications that are covered by insurance in the same way and at the same rate as other prescription drugs. However, other treatments for depression–such as psychotherapy, other behavioral therapy and alternative treatments–are not always covered as fully as biomedical services.

Two major providers of health insurance in Minnesota, HealthPartners and Blue Cross and Blue Shield of Minnesota, appear to cover mental and behavior health services as well as biomedical services in their most popular plans.

HealthPartners’ Traditional plan, at a $1,000 deductible level, and Blue Cross’ comparable Aware Care, also with a $1,000 deductible, both cover 80 percent of mental and behavioral health services (after deductible, and up to the out-of-pocket maximum)–the same coverage they afford to most other services. While some companies and plans restrict the number of psychotherapy appointments that are covered, for example, both the HealthPartners and Blue Cross plans cover unlimited appointments within their provider networks.

Coverage for mental health services should improve across the board, thanks to a new law passed along with the recent government bailout bill that, for the first time, requires mental and physical health to be covered equally by insurance.

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The culture of depression and treatment

Mac Baird M.D., M.S., professor and head of Family Medicine and Community Health at the University of Minnesota, discusses the American culture surrounding depression diagnosis and treatment–and how that differs from the rest of world’s:

Alternative therapies for depression

Though they are understudied compared to drugs, several alternative therapies have shown promise in the treatment of depression. Perhaps their largest draw is that while it can be unclear whether or how much they help, they usually don’t hurt.

Side effects are minimal, and alternative therapies are often less expensive than biomedical treatment. According to a 2004 brief by the Center for Studying Health System Change, 6 million Americans sought alternative treatments in 2002 because of concerns about the rising cost of traditional health care.

Promising alternative therapies include:

• Supplements (such as St. John’s wort and S-adenosyl- L-methionine, or SAMe)
• Physical activity
• Stress reduction techniques (such as meditation)
• Acupuncture
• Massage
• Diet and nutrition
• Music therapy
• Art therapy

Related material: There are other options.

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:

 

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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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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.

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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.

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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.

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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

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