The most widely prescribed drugs in the U.S. are not for pain management, cholesterol lowering, heartburn or hypertension.

They’re for depression.

Last year doctors wrote $232.7 million prescriptions for antidepressants. That’s an increase of 25 million prescriptions since 2003 and translates into an estimated 30 million patients in the United States who spent $12 billion on antidepressants in 2007.

With numbers like these, a person might make these assumptions:

• Antidepressants are effective treatments for depression
• There are few, if any, effective alternatives to antidepressants

As reasonable as these assumptions would be based on the popularity of antidepressants, they are both wrong.

In my preceding articles in this ongoing series on depression and antidepressants, I’ve presented clear evidence that antidepressants are not effective for treating depression.

In this article and the following two, I will present evidence that several non-drug treatments for depression are at least as effective as antidepressants, with few (if any) of their side effects, risks and costs.

As you may recall from the previous articles in this series, recent meta-analyses have shown that antidepressants have no clinically meaningful advantage over placebos. What I have not yet pointed out is that the effectiveness of antidepressant drugs has probably been overstated due to methodological factors in the studies.

In the studies performed on antidepressant drugs, the people taking the drugs also received supportive weekly visits with doctors or researchers along with the medication. The resulting “therapeutic alliance” may have enhanced the efficacy of these drugs and given an inaccurate picture of their effectiveness in a managed care environment where antidepressants are often delivered in conjunction with infrequent visits to a physician or mental health professional.

We know from placebo research that the contact which occurs between the patient and practitioner can be a powerful treatment in itself. Therefore, the supportive visits that patients received during the drug trials could have easily amplified the effect of the drug and made it seem far more effective than it would be in a “normal” clinical situation where visits to a physician or psychiatrist are not regular or frequent.

With this in mind, it is very likely that antidepressants are less effective than placebos in normal clinical practice. Indeed, researcher Joanne Moncrieff has repeatedly pointed out that the term “antidepressant” is a misnomer. The drugs collectively referred to as “antidepressants” do not specifically treat depression (any more than placebo), and therefore should not be called “antidepressants” at all.

What are the alternatives, then, to treating depression? Imagine having a choice between five treatments. Treatment A produces a therapeutic response but also a large number of adverse effects including diarrhea, nausea, anorexia, sweating, forgetfulness, bleeding, seizures, anxiety, mania, sleep disruption and sexual dysfunction. Treatments B, C, D & E produce therapeutic responses similar to Treatment A, but with far fewer adverse effects and costs. Treatments B & C, in fact, have no adverse effects at all and have been shown to be significantly more effective than Treatment A in the long-term.

This is not, of course, simply a hypothetical question. Treatment A corresponds to the selective serotonin reuptake inhibitors (SSRIs) that have become so overwhelmingly popular. Treatment B is psychotherapy, which is as effective as antidepressants in the short term (even for serious depression), and is more effective in the long term. Treatment C is exercise, which has been reported to have lasting therapeutic benefits in the treatment of major depression with no “side effects” except for improved physiological and mental health. Treatment D is light therapy, which has been recently assessed in several clinical studies and is just as effective as antidepressant medication. Treatment E is St. John’s Wort, an herb that has been extensively studied and shown to be similar in efficacy to antidepressants with 10 times fewer adverse effects.

As depression researcher David Antonuccio points out, “whether one subscribes to the Hippocratic dictum ‘first do no harm’ or takes a cost-benefit approach to treatment, it is impossible to ignore the fact that antidepressants are not medically benign treatments. Antidepressants have serious side effects (listed above) as well as medical risks (including increased risk of dying) when combined with other medications – as is often the case in clinical settings. Antidepressants have been shown to cause potentially permanent changes to the brain that can predispose a patient to depression in the future, and the withdrawal symptoms of SSRIs are substantial for many, if not most, patients.

A frequent argument made by supporters of antidepressants is that patients with serious depression need antidepressants to stave off suicide. However, there is no evidence whatsoever that antidepressants reduce the risk of suicide or suicide attempts in comparison with placebo in clinical trials. On the contrary, in a recent analysis of the data that compensated for erroneous methodologies, Dr. Grace Jackson found that antidepressants increased the risk of suicide by two to four times in adults, and by three times in children (Jackson 2005, p.122)

It has also been demonstrated that recent sharp increases in antidepressant use have been accompanied by increased prevalence and duration of depressive episodes and rising levels of sickness absence (Patten 2004). Naturalistic studies have also shown that depressive episodes are more frequent and last longer among antidepressant users than among nonusers, and that sickness absence is more prolonged (Moncrieff 2006). Finally, long-term follow-up studies show very poor outcomes for people treated for depression with drugs, and the overall prevalence of depression is rising despite increased use of antidepressants (Fombonne 1994).

Please allow me to summarize the research and simplify the preceding paragraphs:

Antidepressants don’t work. If anything, they make things worse.

Now that we have firmly established the ineffectiveness and dangers of antidepressants, let’s look more closely at the alternatives. We will evaluate each treatment based on Antonuccio’s criteria above:

• Does the treatment do any harm?
• How do the “costs” compare with the “benefits”?

and we will also compare their efficacy with that of antidepressants.

Psychotherapy

Several studies show that psychotherapy (particularly cognitive therapy, behavioral activation, and interpersonal therapy) compares favorably with medication in the short-term, even when the depression is severe, and appears superior to medications over the long term (Antonuccio 2002). When medical cost offset, relapse and side effects are considered in a cost-benefit analysis, psychotherapy can be very cost-effective – particularly in a psychoeducational (e.g. therapist-assisted bibliotherapy) or group format (Antonuccio et al. 1997). Finally, studies show that most patients prefer psychotherapeutic intervention to drugs when given the choice. (Unfortunately, they are rarely given the choice; today, fewer than 10% of psychiatrists offer psychotherapy to their patients.)

It is important to note that several studies have shown that combined treatment (psychotherapy + medication, exercise + medication) produces inferior results when compared to the non-drug modality alone (Hollon et al. 1992). The failure of this combined approach is not surprising when one considers the counter-productive effects of invasive chemical interventions (e.g. suppression of REM sleep, elevation of cortisol, induction of mania).

Unfortunately, the mental health profession remains largely ignorant to this “tragedy of its own making”:

Exercise

Several studies have shown that aerobic exercise is at least as effective as antidepressants in treating depression. For example, one recent study published in the American Journal of Preventative Medicine in 2005 indicated that the “public health dose” (5x/week frequency burning 17.5 kcal/kg/week) of exercise led to remission rates of 42%. For the sake of comparison, the Collaborative Depression Study, conducted by the National Institute for Mental Health, indicated remission rates of 36% for cognitive behavioral therapy and 42% for antidepressant medication.

A frequent criticism of exercise as a treatment for depression is the supposed lack of compliance in patients. The argument is that people who are depressed are too depressed to exercise. While this may be true in some cases, adherence rates in exercise studies were comparable to many medication trials, where rates vary from 60%-80%. Thus, evidence does not support the notion that exercise is not a feasible treatment for depressed patients.

Another benefit of exercise as a treatment for depression is that the only “side effects” are improved physiological and mental health. In contrast to antidepressants, exercise has no adverse effects whatsoever. Instead, it has a moderate reducing effect on anxiety, can improve physical self-perceptions and in some cases global self-esteem, and can enhance mood states and – in older adults – improve cognitive function.

In a study published in Psychosomatic Medicine in 2000, another important advantage of exercise over antidepressants was revealed. Participants in the exercise group were less likely to relapse than participants in the two groups receiving medication. Other studies have confirmed this effect, demonstrating that aerobic exercise is especially helpful in the prevention of relapse and recurrence of depression.

Once again, as was the case with psychotherapy, there was no benefit when combining antidepressant drugs with exercise. In fact, the opposite was the case, at least with respect to relapse for patients who initially responded well to treatment. According to the authors of the study:

The authors go on to speculate on why antidepressant drugs would decrease the exercise’s beneficial effects on depression:

It is also possible that the metabolic and physiological effects of antidepressants described above (suppression of REM sleep, elevated cortisol levels, etc.) could counteract the positive benefits of exercise to a certain degree.

In part II of this article I will discuss light therapy, St. John’s Wort and acupuncture as treatments for depression. In Part III I will examine other lifestyle modifications that can both prevent and treat depression, such as proper nutrition, stress management, getting adequate sleep, the experience of pleasure and prayer or spiritual practice.