Last week an article appeared in the Financial Times, Study casts doubt on anti-depressants, that raised serious questions about the efficacy of our current anti-depressant armamentarium:
Prescribing anti-depressants to the vast majority of patients is futile, as the drugs have little or no impact at all, according to researchers.
Almost 50 clinical trials were reviewed by psychologists from the University of Hull who found that new-generation anti-depressants worked no better than a placebo – a dummy pill – for mildly depressed patients.
Even the trials that suggested some clinical benefit for the most severely depressed patients did not produce convincing evidence. Professor Irving Kirsch from the university’s pyschology department said: “The difference in improvement between patients taking placebos and patients taking anti-depressants is not very great.
“This means that depressed people can improve without chemical treatments. Given these results, there seems little reason to prescribe anti-depressant medication to any but the most severely depressed patients.”
There are several salient points in the brief article worth emphasizing. First, the researchers found that the drugs in question, which included Prozac, Paxil, and Effexor, were indistinguishable from placebo for mildly depressed patients. Second, implied but not directly stated, placebos actually have significant usefulness in depression. Third, lurking in the background to this story are elements of diagnostic imprecision, societal and cultural trends, insurance coverage issues, and availability of treatment modalities that effect the balance of any cost-benefit analysis of anti-depressants.
The Iron Shrink took a look at the issue and lists a number of ways in which anti-depressants are being misused. He concludes:
Lest I give you the impression that I stand against antidepressants, let me clarify. I’ve seen them help. I’ve even suggested them for some of my patients. On rare occasions, they are Heaven-sent.
But I have never seen antidepressants fix anything permanently. Sorry for the bad news, but permanent fixes usually involve work and change. Bottom line: if you are suicidal or immobilized by depression, by all means get that prescription. However, if you’re bummed out, anxious, or unhappy, there is a better approach. Start by seeing someone like me who can help you identify and respond to the real problem. Tinkering with your God-given synapses should be a last resort. [Emphasis mine-SW]
His post should be read if only to see an example of an SSRI (Selective Serotonin Re-uptake Inhibitor) working in an unambiguous way. The question of using the newer generation of anti-depressants is actually a bit more complicated that the Financial Times article or Iron Shrink's post imply.
Back in the bad old days of Psychiatry, prior to the 1960s, there were no anti-Depressants. People with severe depressions could be treated with Electro-Convulsant Therapy (ECT) and often responded well, though the treatment sounded (and looked) gruesome and received terrible press. (In even earlier days, the first real treatment, Insulin shock therapy, was so dangerous it was only used when the depression was so bad as to be life threatening.) Less severe depressions were treated with talk therapy, usually Psychoanalysis, later Psychoanalytic Psychotherapy, and now often a combination of approaches including Cognitive Behavioral Therapy. Psychotherapy was difficult, expensive, and time consuming. The invention of the first anti-depressants, the class of Tricyclic Antidepressants (TCAs), was a life saver. People could be given medication and brought out of their depression, in many cases without ECT or long hospital stays. The drugs had quite serious side effects and were reserved for people who were dangerously suicidal or crippled by their depression. Primary Care Physicians were quite reluctant to use such medications since their misuse could easily lead to accidental overdoses and the TCAs were particularly lethal when used in suicide attempts, a constant worry with depressed patients.
In 1987 Prozac was brought to market as the first SSRI available in America. It was extremely safe, well tolerated, with minimal side effects, and was an immediate best seller. Because of its safety profile, Prozac fit well in the medical model defined by the Hippocratic Oath, ie "first, do no harm." Prozac rarely did harm and it seemed to help many people. As time went on it became easier and easier for Doctors to prescribe Prozac and later others in its class, to patients who complained of "depression." Unfortunately as time went on and the drugs were used more easily and sometimes cavalierly, many people who did not have classical "major depression" were given the drugs. By the 1990s. it was common practice for Physicians to give an SSRI to anyone who was unhappy and complained of depression.
In brief there is a significant difference between unhappiness and depression. Depression is an illness which includes a change of state and the constellation of sadness, guilt, self-reproach, complete with diminished ability to not only feel pleasure but to perform their usual activities; for such patients restoring prior functionality is one of the key goals of anti-Depressant treatment. In contrast, too often unhappy people come to a Doctor or clinic complaining of depression, when they mean they are unhappy, and the easiest and quickest response is to offer a drug. Certainly, unhappy people do sometimes descend into depression but for many people who by virtue of their character, temperament, and/or limited abilities remain stuck in unhappy lives, such unhappiness does not constitute a depressive disorder. So, does this mean these people should not be offered a SSRI?
Again, there are complicated issues. Fore example, placebos work and active placebos work even better. There is also evidence that a costly placebo works better than cheap one. In other words, whenever anti-depressants are tested on large groups of depressed people the response rate for the active anti-depressant often approaches 30-50% yet the placebo response rate often is almost half that. Further, in the limited number of studies in which an active placebo is used (an active placebo is a drug that is not an anti-depressant but may be sedating, like Benedryl) the response rate approaches that of the active anti-depressants. The usual rationale for preferring an SSRI to an active placebo long term is that active placebo response rates diminish over time. This, too, can be questioned.
Placebos work for a great many unhappy people who believe they are receiving an anti-depressant. They feel better able to bear up under the burden of their unhappiness and often function marginally better. If SSRIs are primarily acting for such people as active placebos, this is not an altogether negative outcome. After all, they are safe and well tolerated and now that they are no longer under patent, are relatively inexpensive. Furthermore, the placebo effect is intimately related to the unconscious connections to the Psychiatrist and that means that even with only relatively infrequent brief contacts, the effect can last indefinitely.
To be very clear, SSRIs are never my first recommendation. When I see an unhappy person in the clinic or my office, I always do an assessment for evidence of severe depression and, in its absence and if their unhappiness is impinging upon their ability to function, I then look for evidence that the person is interested, motivated, and shows some capacity for engaging in Psychotherapy. If the person does not just want medication, I may offer a hierarchy of recommendations.
- A trial of Psychotherapy alone to gauge their response to an interpretative and supportive relationship.
- If the therapy suggests the existence of more problematic character pathology that would require a more intensive Psychotherapy which is unavailable in the clinic or too expensive for them to see me privately, a referral to a therapist or clinic able to provide such treatment, up to and including low fee Psychoanalysis, can be offered.
- If they feel that they cannot cope with their present level of discomfort and it interferes with their lives or their therapy, adjunctive use of medication can be helpful and is offered.
Psychotherapy should always be part of a recommendation for medication, yet too many people have neither the interest, the motivation, the time, or the money to invest in a treatment that can actually help them change their dysfunctional lives. In such cases, perhaps the use of an active placebo can be warranted.
In addition, the SSRIs do in fact have physiological effects. Though they are rarely described as such, in fact they tend, in many people, to decrease the intensity of all affects. They are helpful in that they lessen the intensity of unhappiness and depression, but they often also limit the intensity of joy. This is often a tolerable trade-off for someone who s miserable (and has unconscious guilt and masochism.) Not everyone is ready or willing to spend the time and energy required to reflect on why they are unhappy and change those aspects of their lives that lead to unhappiness.
When academics complain that SSRIs are being over-prescribed, they are expressly talking about those with mild depression or chronic unhappiness, for whom anti-depressants are not the treatment of choice. I would always encourage people to take the harder path because the rewards are so much higher and what is lost when one chooses partial psychic numbing over learning to be more engaged in life is always a tragedy of lost potential. Unfortunately, Psychotherapy doesn't work for everyone and if a pill helps them feel better and tolerate the intolerable, and it is their choice, it is hard to argue with them.