The term “antidepressants” refers to a group of medications that are useful in the treatment of major and minor depressive syndromes. Here we will try to clarify some basic concepts that may help explain the potential and limitations of this type of medication.
One important limitation is the name itself. “Antidepressant” is a term that suggests treatment “for depression” without further qualification, but things are not quite that straightforward.
Almost all studies are conducted on depression as a syndrome rather than as a disease. Several neuropsychiatric disorders include depressive episodes at some point during their course, or at their onset, but subsequently develop according to their own specific characteristics.
In antidepressant studies, researchers attempt to isolate and study the effect of the antidepressant on “depressive illness,” that is, on single or recurrent episodes of depression.
However, “single-episode depression” and recurrent depression are not stable diagnoses over time, because the subsequent appearance of additional features often justifies changing the diagnosis to a more specific disorder.
Clinical trials do not have time to establish this, because they typically end after a few weeks and therefore only allow researchers to determine what happens to that particular depression after one to three months of treatment.
The most typical development is that single or recurrent depression subsequently becomes associated with features of an excitatory nature, leading to a diagnosis of bipolar disorder, corresponding to a different model of illness.
Therefore, even when antidepressant treatment has been successful, it should nevertheless be reassessed after a certain period to determine whether treatment needs to be “redirected” toward a different understanding of the disorder.
There is no single antidepressant that is better or “stronger” than the others. Some appear to act more rapidly, but in general the effect of an antidepressant is assessed at the end of the first month, sometimes with a delay of a couple of weeks.
There are several classes of antidepressants that work better or worse for different types of depression.
Even among single depressive episodes, there are different “diseases” that respond to different neurochemical models.
People who experience periods of low mood usually ask themselves which symptom should be regarded as the “main” one, in order to give themselves a label and understand where to start in order to solve the problem.
Am I depressed or am I anxious? Am I more depressed or more anxious? Is anxiety causing my depression, or is it the other way around?
These questions are based on a mistaken assumption: namely, that the symptom of feeling “negative, low, or melancholy” is itself depression.
By “depression,” however, one does not mean the symptom itself, but rather a collection of symptoms—that is, a depressive syndrome, which simply means a situation involving several symptoms, one of which is depressed mood.
A depressive syndrome itself can correspond to several different types of illness. It is therefore not surprising if a friend or acquaintance who says they suffer from depression is taking completely different treatments or subsequently displays completely different behaviors.
Anxiety is typically also present in depressive syndromes, so there is no contradiction or opposition between the two, nor do the symptoms necessarily cause one another.
The two types of symptoms occur together so frequently that people often speak of an “anxious-depressive syndrome,” which is a very provisional entity that may ultimately correspond to completely different disorders, or constitute only one part of the clinical picture—the part that the patient identifies as the core of their suffering.
Antidepressants produce a response over the course of approximately one month, on average.
In technical terms, “response” means an overall improvement of more than 50%—for example, if each symptom were assigned a score from 0 to 10 and the scores were compared after one month.
After one month of treatment, therefore, one should not necessarily expect complete improvement, and there is nothing unusual about substantial but incomplete improvement.
Treatment continues after a response has been achieved. There is no switch-like mechanism whereby depression suddenly disappears and treatment is over.
Treatment always continues for many weeks after the initial improvement.
On the other hand, continuing treatment makes little sense if no response has been achieved within two or three months. In such cases, treatment is usually modified, either by increasing the dose or changing the medication.
Response to an antidepressant consists of the reduction or disappearance of the symptoms expected for the diagnosis.
The fact that mood may still occasionally be negative, even though it is never as bad as before, is therefore not necessarily something that should be “treated harder,” because in a person who is not depressed, mood is not always positive and naturally fluctuates in response to external events within certain limits.
Feeling better “immediately” after starting an antidepressant—that is, from the first few days—is an unreliable effect because it is usually not stable.
Although some medications tend to produce faster responses, feeling extremely well after only one week of treatment, as though the depression had “disappeared,” is not necessarily a good sign.
This type of response should instead raise the suspicion that the true diagnosis may not be simple depression, but bipolar disorder.
Conversely, during the first few weeks the response may be “intermittent”: a person may experience several days of feeling better, perhaps almost reasonably well as early as the first week, and then return to their previous state.
In fact, this course can be expected. What matters is that there should not be an immediate miraculous improvement or euphoria, which could indicate that the antidepressant is not producing a stable and beneficial effect for that person.
To be clear, if symptoms are measured after one month, the depression itself might still appear to have improved. Over time, however, mood may become unstable, frequent relapses may occur even while taking the antidepressant, the person may stop responding to the same antidepressant even at higher doses, or may fail to respond when the medication is restarted during a relapse.
People who have taken antidepressants for years or repeatedly for periods of varying length may therefore, paradoxically, have experienced more depressive episodes than people who have not taken them.
This does not change the initial antidepressant effect, but it can change the long-term course, sometimes for the worse.
More specifically, this paradox is due to the fact that many depressions initially treated as straightforward depression were actually part of the course of bipolar illness—alternating depression and excitation—in which the antidepressant has something of the effect of accelerating a car along a road full of bumps and dips.
The energy produced by the acceleration is there, but instead of moving the person forward, it is distributed in swings upward and downward.
Some depressive episodes are short, lasting only two weeks or a month.
Obviously, in these cases antidepressant treatment makes little sense, given that it takes approximately a month to work.
People often started taking antidepressants because they felt better after only a few days, and therefore the episode was actually resolving immediately.
Over time, however, this response may deteriorate, or the phenomenon described above may occur.
The term “bipolar depression” is widely used and is understandable to patients because the initial diagnosis was depression and was subsequently changed to bipolar disorder.
Alternatively, the diagnosis may be made during a depressive episode, and the term “depression” with the additional qualification “bipolar” is used to make the diagnosis easier for the person to understand.
Even in textbooks, chapters on depression usually present simple (unipolar) depression first and bipolar depression afterward.
This view, however, is limited.
In reality, one should speak of bipolar disorder, rather than depression, because bipolar disorder is fundamentally different in terms of its course, response to treatment, priorities, the patient’s experience of the illness, and rehabilitation pathways when these are necessary.
With some experience, it is possible to distinguish, even without additional information, whether an ongoing depressive episode is unipolar or bipolar.
However, the best information for making this judgment actually comes from the person’s psychiatric family history, previous treatments and responses to them, and the person’s overall biography.
Bipolar depression—or, more appropriately, bipolar disorder—can sometimes be prevented and, in some cases, treated using medications that are not classified as antidepressants, but rather as anti-bipolar medications or mood stabilizers.
Are external events important?
This question is already poorly formulated.
As episodes recur, they increasingly begin for weaker reasons, or for no apparent reason at all.
The same thing can happen from the very beginning, although people may be inclined to search their recent past for some reason that would logically justify the depression.
Typically, many possible reasons can be found, but these are reasons for depressed mood as a common human experience, whereas depression should be understood as a disorder that has little to do with an ordinary reaction of demoralization.
Experiences such as bereavement, for example, are not typically associated with depression. Otherwise, 100% of people would experience a depressive episode at some point in their lives.
Some people use expressions such as “endogenous depression,” “exogenous depression,” or “reactive depression” to indicate that some forms occur “on their own,” whereas others follow stressful events.
In reality, the fact that those events are stressful is either reported by the person from the perspective of their current depression, or determined by the examiner through comparison with non-depressed people—that is, according to the logic of ordinary demoralization rather than that of depression.
Reasons such as a recent infectious illness or abuse of euphoric substances are much more directly understandable as potential sources of depression than events for which there is often no clear “biological” translation and which are highly subjective.
Some people, in response to negative events such as failing at school or bereavement, instead develop periods of euphoria.
There is therefore no such simple logic.
In practice, treatment is based on symptoms rather than on the reasons behind them.
It should also be said that, depending on their personality characteristics, people tend to find themselves in circumstances similar to those they have experienced before, to choose similar risks and sources of stress, and therefore, for the same individual, the weight and type of environmental events often have to be considered a kind of “constant.”
Some antidepressants are particularly suitable for tolerating what is commonly called “stress”—that is, the effort associated with the need to avoid social or individual decline, or to obtain minimal benefits that are conditional on productive outcomes or achievements, in other words, on not disappointing expectations.
Furthermore, some antidepressants are useful in buffering physiological reactions of anger, anguish, and demoralization in response to unfavorable, hostile, or loss-related circumstances.
This property radically changes the way people perceive the reasons that led to the depression itself, because with treatment they are able to tolerate higher levels of stress and environmental demands—perhaps levels that previously seemed impossible—without developing depressive symptoms.
There is no dependence on antidepressants in the sense of drug addiction.
Sometimes there is a discontinuation syndrome, but this does not generally motivate people to continue taking the medication indefinitely, since people generally do not like the idea of taking medication for a long time or for life, even when they have experienced significant and unexpected benefits.
There is, however, a condition that is not pathological at all but may be perceived as an unnatural “bond” with antidepressants.
This occurs when symptoms return every time the medication is discontinued, after a certain period, causing people to restart treatment or continue taking it while feeling well, but with a sense of discomfort about this apparent “dependence” on treatment.
One truth is that treatment enables people to “do” more and therefore exposes them to more stimuli, some of which are stressful.
Being accustomed to functioning well also means that one can no longer afford periods of poorer functioning.
Sometimes, however, people lose sight of the fact that, in the overall balance of life, stressful events need to provide some form of return in terms of gratification or fulfillment.
Otherwise, they are simply “negative entries on the balance sheet,” against which the antidepressant acts as a counterweight without producing any genuine improvement in quality of life.
In other words: with the antidepressant I can tolerate what I do not like; without it, I cannot. But in the end, I still do not like it.
In this discussion, we have not focused on the technical differences between the various medications, because in reality this is not the most interesting aspect of the issue, particularly for patients.
Whether there are “natural” antidepressants—that is, non-pharmacological ones—is an interesting question, but one that has been relatively little studied.
Keep in mind that most psychological interventions offered to depressed people are designed as though they were not dealing with depressed people, but rather with people who are simply going through “a difficult period.”
From the classic “cheer up” and “pull yourself together,” to antidepressant vacations organized by family members, these interventions—which fail to take into account the neurological nature of depression—are largely futile.
There are, however, “psychotherapeutic antidepressants,” meaning techniques that can be useful in improving symptoms, particularly during the “rehabilitation” phase of depression, or in helping a person wait for the end of short episodes for which no better treatment is available, while limiting certain forms of suffering or environmental difficulties.