Old and new medications
“New” medications do not necessarily mean the “latest models,” so it is not correct to assume that the newest drug on the market represents an improvement over those that already existed. In theory, there are two main reasons for developing new medications: treatment-resistant conditions, which might respond to drugs with new mechanisms of action, and a better balance between therapeutic benefits and tolerability.
New medications have, of course, all been tested before becoming available on the market, but they nevertheless remain the least familiar to physicians. For this reason, the overall assessment of a new drug’s usefulness and impact is usually made only after a few years. In theory, all new medications can be used as a first treatment attempt, and sometimes studies already exist comparing the new drug with some older ones. It is less common, however, to already have studies confirming the stability of the effect over time, whereas this type of knowledge is available when a medication has been known and used for decades.
Mechanisms of action
Knowing, simply because one has read it somewhere, that a medication acts “on serotonin,” “on dopamine,” or “on adrenaline” does not really explain anything. Neurochemical systems are only partly understood and are inevitably involved, in various ways, in complex functions such as those related to behavior and mood. It can be said that, for each system, there are research findings demonstrating a confirmed or probable role in the regulation of anxiety and mood.
What is important to understand is that the mechanism of the medications currently available for the treatment of anxiety and depressive disorders is not direct. This means that the therapeutic effect does not appear immediately, and that the effects that appear immediately do not correspond to the final therapeutic effect.
Many of these medications, initially—during the first two or three weeks—may simply have no effect, or may even produce symptoms of anxiety or depression, temporarily worsening the clinical picture. This is not a contradiction; rather, it reflects the fact that the final effect is achieved through a kind of desensitization, whereby the brain is, so to speak, stimulated to adapt to and respond to the presence of the medication.
The most effective antidepressant
There is no single “best” antidepressant, partly because each one is better suited to certain types of clinical presentations. Physicians tend to choose certain medications rather than others on the basis of the underlying diagnosis and the type of symptoms that require the most urgent attention, as well as, obviously, what the person has already tried in the past.
Antidepressant dosage
As with all medications, dosage is crucial. It is by no means true that if a medication has not worked at a low dose, it cannot produce a benefit at a full therapeutic dose.
There are “recommended” doses, meaning doses that are effective on average—that is, effective in the majority of patients. Some individuals may not absorb the medication well, or may metabolize it very rapidly, meaning that although the “paper” dose may be, for example, a certain number of milligrams, the amount that actually reaches the body is much lower.
To obtain a normal “effective” dose, these people would probably need to take larger quantities. Ideally, however, one would need a system for measuring the concentration of the medication in the blood, which is not always feasible in ordinary clinical laboratories.
“An antidepressant? But I’m not depressed!”
The label “antidepressant” is simply a way of identifying a particular type of medication. It does not necessarily mean that the medication is used only for depression.
Some people think that their doctor did not want to tell them that their diagnosis was depression, or they do not identify with the term themselves. It may simply be that the medication is indicated for other disorders, unrelated to depression, and that “antidepressant” is merely the pharmaceutical category written in the package leaflet, which does not account for all of the medication’s possible uses.
Antidepressants and mood
Antidepressants are usually introduced onto the market for depression, followed by indications for a range of central nervous system disorders, such as panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, and others.
In practice, antidepressants are then used in a variety of conditions that share certain depressive symptoms, such as sadness or anguish, but this does not necessarily mean that all of these conditions belong to “depression” as a diagnosis.
The most frequent example is bipolar disorder, improperly referred to as “bipolar depression.” Bipolar disorder is not simply a condition closely related to depressive illness, and the fact that depressive phases occur during its course does not mean that it is biologically the same disorder.
Therefore, treatment for bipolar disorder, even during a depressive phase, does not always need to include an antidepressant. Likewise, simply having a “depressed mood” does not necessarily justify or indicate the use of an antidepressant.
In other words, antidepressant does not mean “a drug to lift your mood.” It means “a drug for certain depressive syndromes.”
Moreover, “depression” as an illness is different from “depression” as a temporary state—for example, within bipolar disorder or psychosis—and it is also different from “depression” as a symptom, meaning simply “feeling down.”
Using an antidepressant generically as a symptomatic treatment for low mood in the context of a diagnosis that has nothing to do with anxiety or depressive disorders may result in agitation, an unstable effect (ups and downs), or an effect that persists for a while and then disappears.
Response times
Antidepressants are not, in general, drugs that produce their full therapeutic effect immediately. Improvement may begin during the first few weeks, but clinical response is normally assessed over several weeks. In many cases, a meaningful initial assessment can be made after about 4 weeks, while taking into account the type of drug, the dose reached, the diagnosis, and the course of symptoms.
A feeling of improvement that appears after only a few days does not necessarily mean that the drug has already produced a stable antidepressant effect. It may reflect spontaneous variation in symptoms, an initial effect of the drug, or an improvement in certain aspects of the clinical picture, such as anxiety or sleep. If, on the other hand, marked euphoria, a reduced need for sleep, an unusual increase in energy, accelerated thinking, impulsivity, or other signs of excitement appear rapidly, it is important for the doctor to reassess the diagnosis and treatment, because these phenomena may be compatible with a bipolar spectrum condition.
During the first few weeks, adverse effects or a temporary increase in anxiety, agitation, or insomnia may also occur. This does not necessarily mean that the drug will ultimately fail, but neither does it mean that such symptoms should simply always be tolerated. The doctor needs to distinguish between predictable, transient initial effects and genuine intolerance or clinically significant worsening.
If, after an adequate period of treatment, at an adequate dose and with good adherence, there is not enough improvement, the treatment strategy is generally reassessed. Options may include adjusting the dose, switching medication, combining or augmenting treatment and, above all, verifying that the diagnosis is correct.
Simply increasing the starting dose does not necessarily produce a faster response. For many antidepressants, it is preferable to start at relatively low doses and increase gradually, particularly to improve tolerability during the first weeks.
Intolerance to antidepressants
Tolerability varies considerably from person to person. During the early stages, nausea, gastrointestinal symptoms, insomnia or sleepiness, agitation, headache, changes in appetite, and other adverse effects may occur. Their presence does not automatically mean that the drug is “intolerable”: they may depend on the dose, the speed at which the dose is increased, and individual characteristics.
When adverse effects are significant, the doctor may decide to slow the dose increase, temporarily reduce the dose, change the time of administration, switch medications, or, when appropriate, use temporary treatment to control certain symptoms. Antidepressants should not be stopped abruptly without medical advice, because some can cause discontinuation symptoms if stopped suddenly.
Anxiety related to taking medication can also amplify the perception of certain bodily sensations. This phenomenon is real and can contribute to difficulty starting treatment, but it does not mean that the symptoms are “imaginary”: they should be clinically assessed and distinguished from genuine pharmacological effects.
Depression or anxiety?
Patients with anxiety or depressive disorders often find themselves wondering: “Is it more anxiety or more depression?” or “Am I more anxious or more depressed?” Technically, these questions do not mean much in terms of diagnosis. In simple terms, however, they are asking whether mood or anxiety is the aspect that is “driving” their distress.
Every depressive disorder has anxiety symptoms to some degree, while an anxiety disorder that does not resolve on its own can also demoralize patients. A core feature of depression is precisely the feeling of being “helpless” and “in danger” when faced with ordinary events, responsibilities, commitments, and, more generally, with the day ahead. This entails a state of anxiety, which can be intense and clearly visible. Having anxiety as a symptom during depression is therefore compatible with depression itself as a diagnosis.
Medications do not act simply as symptomatic treatments, targeting one symptom or another. Rather, they act on underlying biological mechanisms and, by correcting them, can improve both mood and anxiety.
Insomnia
Sleep disturbances are generally a symptom of disorders that involve more than sleep itself. Insomnia can precede the first depressive episode or the full development of anxiety symptoms by months or even years.
Moreover, people experiencing anxiety or depression often seek treatment precisely because, among all their symptoms, insomnia is one of the most alarming or urgent. Antidepressants generally tend to improve sleep quality because, overall, they improve the person’s mental condition. Some have relatively rapid sedative properties and can make it easier to fall asleep or help maintain deeper, more stable sleep; this can be one of the factors considered when choosing one antidepressant over another.
Sleep should not necessarily be treated as a separate problem. During the early stages of treatment, particularly the first 2–3 weeks, it may not improve immediately, just as other symptoms may not improve immediately either.
Time of administration
Generally speaking, the time of day at which an antidepressant is taken is not what determines its therapeutic effect. Initially, the timing may be chosen to make certain side effects more tolerable—for example, taking it in the evening if it causes drowsiness, or in the morning if it causes insomnia.
These considerations mainly concern initial and potentially transient effects. As treatment continues, the medication is generally present in the bloodstream throughout the day. Some medications require two daily doses, while for others one daily dose is sufficient.
Some people reason that if they feel worse in the morning, it would make sense to take their medication in the morning, or conversely to take it in the evening if they feel worse in the evening. This is not how the mechanism works. Symptoms improve with a delay and are not directly linked to the time at which the medication is taken.
For example, if someone is already feeling better after 15 days of treatment but still experiences several hours of anxiety and low mood in the morning, this does not necessarily mean that they are “uncovered” by the medication in the morning. It therefore does not necessarily follow that the medication should be moved to the morning, or that another medication or an additional dose should be added in the morning.
Non-antidepressant medications and depression
Sometimes people with depression are treated with medications that do not belong to the antidepressant category. This is not a contradiction, because treatment should be based on the diagnosis.
Some depressive episodes may improve with mood stabilizers or atypical antipsychotics. This can happen for two reasons:
- Some medications that are not officially classified as antidepressants nevertheless have useful effects on depressive symptoms, particularly in the disorders for which they are indicated—for example, lithium in bipolar disorder.
- Some medications treat key symptoms of the specific disorder—for example, delusions or hallucinations in psychotic disorders, or anxiety in bipolar disorder—and the depression consequently improves.
Resistance to antidepressants
There are cases of depression that do not respond to several antidepressants. “Treatment-resistant depression” is an area of ongoing research, and there are several ways to improve the response, either by switching antidepressants or by adding other treatments. This naturally also involves considering whether a more precise diagnosis may be appropriate.
Depression was already a treatable illness before the first antidepressants were developed, through electroconvulsive therapy (ECT), commonly known as electroshock. Today, ECT remains an effective antidepressant treatment, particularly for severe depression with marked psychomotor retardation, and it can also be administered in a day-hospital setting.
Other, newer non-pharmacological treatments have also been developed, although their effectiveness is less clearly established and standardized. One example is vagus nerve stimulation (VNS), which requires a surgical procedure involving implantation of a device in the neck and chest.