Depressed? Why a prescription may not be the answer

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Feeling blue? Why a prescription may not be the answer

The escalation in prescription rates for antidepressant drugs over the last decade suggests that rates of depression have reached epidemic proportions, particularly among women. The idea that depression is an illness for which antidepressants are the cure is questioned by Dr. Janet Stoppard, author of Understanding Depression: Feminist Social Constructionist Approaches (Routledge, 2000) and co-editor (with Linda McMullen) of Situating Sadness: Women and Depression in Social Context (New York University Press. 2003).

If you are depressed and seek help from your family doctor, you are likely to leave the doctor's office with a prescription for an antidepressant. In Canada, the number of prescriptions for antidepressants rose from 3.2 million in 1981 to 14.5 million in 2000, a 353 percent increase in two decades.

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Why the sharp increase? Are people more willing to seek help? Are doctors more willing to prescribe antidepressants? The answer to both questions is "yes," but the most important reason for the change has to do with antidepressants themselves.

Antidepressants have been around for several decades, but until the 1990s they often produced unpleasant and sometimes serious side effects.

In the early 1990s, a new class of antidepressants came on the market. Selective serotonin reuptake inhibitors, or SSRIs, produced less serious side effects compared to the older drugs. Prozac was among the first SSRIs approved by the U.S. Food and Drug Administration (FDA). Today, Zoloft and Paxil are prescribed more frequently. SSRIs tend to be better tolerated by patients, so doctors are more willing to prescribe them.

Indeed, if your doctor prescribes an antidepressant, a reasonable expectation is that you will feel better if you take it. And certainly, many women report that antidepressant medication is crucial for their continued sense of well-being.

However, a recent examination of the data from clinical trials for the six most widely prescribed SSRIs, led by Professor Irving Kirsch at the University of Connecticut, revealed some surprising results. Kirsch's 2002 analysis of the results of all 47 clinical trials (involving close to 7,000 patients) submitted to the FDA found that none of the six SSRIs was much better than placebos in treating depressed patients. Patients did respond to the antidepressant drugs by becoming less depressed, but so did patients who received the inert placebos. In nine of the SSRI clinical trials, there was no difference between the effectiveness of the drug and a placebo. For the other 38 trials, a slight difference in favour of the SSRIs was not considered clinically meaningful. On a 50-point scale, there were two points' difference on average between patients receiving antidepressants and those receiving placebos.

There are two significant reasons these findings should concern women. First, although women were among the participants in the clinical trials of SSRI antidepressants, the data from those trials was not analyzed by gender. In other words, no one determined whether the SSRIs are more, less, or equally effective for women compared to men. This is important because men's and women's bodies react quite differently to drugs. One recent study comparing SSRIs with older antidepressants found that women appear to respond better to the newer drugs than men. The differences are complicated by age as well. Women under 40 can respond differently than women over 40 to the same antidepressant drug, a finding that perhaps reflects hormonal changes across the female life cycle. A disturbing finding is that some of these drugs may be less effective with people who experience chronic stress caused by poverty and victimization--conditions that frequently characterize the lives of depressed women.

In the entry for Prozac in the Compendium of Pharmaceuticals and Specialities--the official reference on drugs used by Canadian doctors and pharmacists--the following are included among the side effects listed as frequent: insomnia, anxiety, fatigue, excessive sweating, disturbance of appetite, back pain, painful menstruction and sexual dysfunction. A curious thing about these side effects is that several--insomnia, anxiety, fatigue and appetite disturbance are examples--can also be symptoms of depression. More evidence was documented by British psychiatrist Dr. David Healy (author of the new book, Let Them Eat Prozac), who reported an increased risk of suicide among people taking Prozac. Similar concerns have recently been raised about Paxil.

Women make up an estimated 70 percent of people who are prescribed antidepressants. They may also be more susceptible to the side effects of antidepressants because of the different metabolisms of women's and men's bodies. Antidepressants have slower clearance rates--time to leave the body--in women, so the same dose can result in higher levels of a drug in a woman's body compared to a man's. This means that toxic levels of an antidepressant (and the associated side effects) can occur at lower doses for women.

There are other compounding factors. If a woman is taking the birth control pill along with an antidepressant, the drug's action and the risk of side effects can be accentuated. Recent Canadian research also suggests that long-term use of some SSRIs is associated with an increase in risk for breast cancer.(1) Clearly, long-term research on the effects of drugs and detailed data on their specific effects on women are warranted before products are approved.

In spite of these risks, the message that antidepressant drugs should be the first line of treatment for depression is widely promoted by some medical organizations, government health departments and non-profit mental health groups. It's a message reinforced in advertisements by pharmaceutical companies.

When they report depression to their family physician, women are often informed that they are depressed because of a "biochemical imbalance" in their brain. The idea that depression results from a biochemical imbalance vastly oversimplifies a complex set of research findings. Over the years, various biochemical theories have been put forward to explain depression, but none of these theories has received consistent support. Indeed, the more fundamental assumption that depression is caused by biological changes in the brain has not been established. There are changes in the brains of people who are depressed, but a person's mood can also affect their brain function, and an important factor in mood is how people perceive things going on in their lives. Antidepressant drugs do have an impact on the brain, but it is far from certain that this impact corrects a biochemical imbalance. The metabolic changes found in depressed people who respond to antidepressant drugs also occur in depressed people who respond to chemically inert placebos. These metabolic changes are found as well in depressed people who improve with non-drug forms of treatment, such as therapy or counselling.

Similarly, it is possible that patients in clinical trials improve when they receive a placebo because they have regular contact with a doctor who takes an interest in how they are feeling. The effect of having a doctor's attention and interest, coupled with a belief in the effectiveness of a drug, may help explain why some people report improvement in their mood while participating in clinical trials.

Treating depression is complicated and there is no one single treatment that works for everyone. Some studies suggest that combining medication with psychotherapy is the most beneficial. Other studies have found that psychotherapy (particularly cognitive and interpersonal forms of therapy) is as effective as medication in the short term, even for severe depression. Although many patients are told they will need to take antidepressants after they no longer feel depressed (possibly for the rest of their lives), there are encouraging studies that suggest therapy is superior to drugs in the longer term.

This points to another troubling aspect of SSRIs. The decision to stop taking an antidepressant is difficult for many because of withdrawal effects--recently renamed "discontinuation syndrome." Once the brain has adapted to a certain level of an antidepressant, withdrawal can generate symptoms that may be confused with the depressive symptoms that lead to the drug being taken in the first place. Withdrawal symptoms with SSRIs can include anxiety, sweating, confusion and trouble sleeping. This situation can create a cycle of drug dependency where drug withdrawal is followed by further drug use to treat withdrawal symptoms. Thus, reducing the dose of an antidepressant, or withdrawing from the drug altogether, is something that needs to take place gradually, usually under medical supervision.

Kirsch's analysis of SSRI antidepressants revealed another important finding: patients on the highest doses did not improve more compared to those on the lowest doses. This has particular implications for women prescribed antidepressants because they may be more susceptible to their side effects. In other words, increasing the dose is unlikely to be an effective strategy for someone taking medication for more than a few weeks and who still feels depressed. A higher dose may even increase the risk of side effects and make it harder to stop taking the drug. If an antidepressant isn't working, it may be time to consider non-drug alternatives.

Another concern is that clinical trials for antidepressants require patients to meet diagnostic criteria for depressive disorder, a diagnosis termed "major depression" by the official diagnostic code book--the Diagnostic and Statistical Manual of Mental Disorders (the DSM)--published by the American Psychiatric Association. So, while antidepressants are usually tested on patients diagnosed with major depression, this is not the most common diagnosis among depressed women. Mixed forms of anxiety and depression, and "atypical depression" (depression that does not fit the diagnostic categories included in the DSM) are more common among women. Therefore, many women are taking antidepressants, even though the distress they are experiencing does not fit the diagnostic template for which these drugs were initially developed.

In contrast to this medicalized view of depression, our concept of depression expanded so much in recent years that categorizing depression as an illness makes less and less sense. Partly due to the extensive marketing of antidepressants by pharmaceutical companies, our notion of depression now includes a wide range of experiences, from everyday unhappiness and demoralization, to severe forms of depression that affect a small number of people. Depression has also become gendered, and women are more likely than men to experience distress and to feel unhappy and discouraged. Thus, women form a large and ready market for antidepressants. This market is being extended even more widely with the inclusion of pre-menstrual syndrome, eating disorders and menopausal hot flashes among the indications for the prescription of antidepressants.

The idea that the solution to feeling depressed is to take a drug is also part of a cultural shift toward individualism--a trend marked by the belief that everyone is responsible for their own course in life, including both successes and failures. It's a belief that says life's setbacks are also to be overcome alone, without seeking help from others--even though the root causes of many sources of hardship lie beyond people's control, and are beyond their ability to change without help.

Under these conditions, taking a pill to change one's internal environment may seem an easier solution than trying to change the external environment. However, rather than channelling research efforts ever more narrowly toward the goal of developing temporary biochemical fixes, a healthier prescription is to improve the fundamental social conditions that compound the experience of depression in women's lives.

Janet Stoppard is a professor of psychology at the University of New Brunswick in Fredericton. She has worked as a clinical psychologist and has published widely on women, mental health and depression.

A HIGHER DOSE MAY EVEN INCREASE THE RISK OF SIDE EFFECTS AND MAKE IT HARDER TO STOP TAKING THE DRUG.