Antidepressant drugs: what they are, what they are for and what types exist
Antidepressants are a class of drugs, belonging to the category of psychopharmaceuticals, used in the treatment of various psychiatric conditions
Despite their name, antidepressants have proven effective not only in the treatment of depression, but also in the treatment of other conditions such as anxiety disorders (generalised anxiety and panic attacks), obsessive compulsive disorder, eating disorders, post-traumatic stress disorder, some sexual disorders (such as premature ejaculation or pathological paraphilias) and some hormone-mediated disorders (such as dysmenorrhoea, post-menopausal flushes or premenstrual dysphoric disorder).
Alone or together with anticonvulsants (e.g. carbamazepine or valproate), some of these drugs may be used to treat attention deficit hyperactivity disorder (ADHD) and substance abuse.
Antidepressants are sometimes used to treat other non-psychiatric conditions such as migraines, chronic pain, nocturnal enuresis, fibromyalgia, sleep disorders or snoring.
The drugs most commonly associated with this class are monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs), and atypical (or second-generation) antidepressants.
Their efficacy, mechanism of action and side effects are continuously being investigated, making them one of the most studied classes of drugs.
Types of antidepressants
There are many compounds approved for the treatment of depression that can be classified according to their basic mechanism of action, mainly into monoamine reuptake inhibitors (which block the recovery processes of these neurotransmitters), degradative enzyme inhibitors (such as MAOIs) and receptor agonists/antagonists (i.e. drugs that can activate or deactivate particular biological ‘switches’).
Other drugs formally approved for other disorders and which do not fall into the category of antidepressants also have an antidepressant effect, but the limitations of their use (e.g. due to a poor side-effect profile, potential for abuse, poor long-term tolerability) have caused controversy about their use for this purpose and, moreover, prescription for conditions other than those officially approved always represents a risk, despite possible superior efficacy.
For example, low-dose antipsychotics and benzodiazepines may be used for the management of depression (even in addition to an antidepressant), although the use of benzodiazepines may cause dependence and that of antipsychotics other side effects.
Opioids were used to treat major depression until the late 1950s and amphetamines until the mid-1960s.
Both opioids and amphetamines induce a very fast therapeutic response, showing results within twenty-four to forty-eight hours, and their therapeutic indexes are greater than those of tricyclic antidepressants.
In a small study published in 1995, the opioid buprenorphine was shown to be a good candidate for the treatment of severe, treatment-resistant depression.
Recently, other substances of abuse such as ketamine or psilocybin, used appropriately, have shown marked and rapid antidepressant effects and their derivatives are likely to form the basis of a future generation of drugs.
Some extracts of natural origin, often classified as a food supplement, also show an antidepressant effect (although the extent of their effect has sometimes been questioned): e.g. St. John’s wort extract is commonly used as an antidepressant especially in Europe; some probiotics have been shown to improve symptoms of anxiety and depression in clinical trials and animal models, highlighting the link between gut and mental health; Acetyl l-Carnitine showed in one study rapid effect in the treatment of dysthymia; Inositol showed in one study an anxiolytic effect comparable to that of fluoxetine; Adenosyl Methionine (SAMe) is widely publicised as a natural alterative to antidepressants; Nicotine acts as an antidepressant by stimulating the release of Dopamine and Norepinephrine and desensitising nicotine receptors as a result of tolerance.
Main antidepressants drugs
In the following table we list the main classes of antidepressants with their respective active ingredients:
- TCAs (tricyclic antidepressants)
- Imipramine, Amitriptyline, Clomipramine, Doxepine, Dosulepine, Trimipramine, Nortriptyline,
- MAOIs (monoamine oxidase inhibitors)
- Tranylcypromine, Phenelzine, Isocarboxazide, Moclobemide
- SSRIs (selective serotonin reuptake inhibitors)
- Citalopram, Escitalopram, Paroxetine, Fluoxetine, Fluvoxamine, Sertraline
- NaRIs (NorAdrenalin Reuptake Inhibitors)
- Reboxetine
- SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
- Venlafaxine, Duloxetine
- NDRIs (noradrenaline-dopamine reuptake inhibitors)
- Bupropion
- Others
Myrtazapine, Trazodone, Agomelatine, Tianeptine, Sulpiride\Amilsupride, Mianserin
Criteria for prescribing an antidepressant drug
It is currently not possible to determine which particular alteration in brain functioning is the cause of a depressive disorder in a given patient, so it is not possible to predict which drug will be most effective in treating the condition.
The various antidepressant drugs have shown an approximately comparable ability to bring about a reduction in symptoms (in the case of severe and persistent disorder) and to prevent depressive relapses (compared to placebo) while showing significant differences essentially in the profile of side and secondary effects (activation, sedation, anxiolysis etc.).
Based on this, the choice of antidepressant is mainly based on the assessment of its side effect profile and tolerability for a given patient, which is why the choice usually falls on an SSRI\SNRI.
In this regard, in 2003 the SOPSI (Italian Society of Psychopathology) carried out a survey on a sample of 750 Italian psychiatrists, who were given 28 multiple-choice questions exploring the area of diagnosis and that of pharmacological treatment of depressive disorders.
Among the various aspects explored by the survey, one particular aspect evaluated was the criteria for choosing between an SSRI and a drug acting on Noradrenalin.
According to the results, the prescription of an SSRI antidepressant would be preferable in pictures characterised by a marked anxiety and agitation component, while noradrenergic drugs would be more indicated in melancholic pictures and in avoidant and passive premorbid personalities.
The treatment is usually prolonged for a few weeks before its efficacy can be assessed (which sets in and increases during the first few weeks of treatment) and if there is no substantial improvement, a therapeutic adjustment (change in dosage or switch to another drug) can be opted for following the trial-and-error method.
A usable treatment protocol may be the one suggested by the results of the STAR*D Trial (Sequenced Treatment Alternatives to Relieve Depression), one of the largest studies conducted on the subject.
Some authors and institutions criticise the use of SSRIs\SNRIs as first-line treatment for depression because of the poor ratio of efficacy to side effects.
Selective serotonin reuptake inhibitors (SSRIs)
Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants considered to be the current standard for the pharmacological treatment of depression because they are characterised by a favourable side-effect profile and low toxicity.
A possible cause (or concomitant cause) of depression is an inadequate amount of serotonin, a neurotransmitter also used in the brain to transmit signals between neurons.
SSRIs are believed to work by increasing the concentration of serotonin at synapses by preventing its reuptake (a biological process of neurotransmitter retrieval and recycling).
The first to discover an SSRI, fluoxetine, were Klaus Schmiegel and Bryan Molloy of Eli Lilly.
This class of drugs includes:
- Citalopram (Elopram, Seropram in Italy; Celexa in the USA)
- Escitalopram (Cipralex, Entact in Italy; Lexapro in the USA)
- Fluoxetine (Fluoxeren, generic Fluoxetine in Italy; Prozac in Italy and the USA)
- Fluvoxamine (Dumirox, Fevarin, Maveral, generic Fluvoxamine in Italy; Luvox in the USA)
- Paroxetine (Daparox, Eutimil, Sereupin, Seroxat, Stiliden, generic Paroxetine in Italy; Paxil in the USA)
- Sertraline (Tatig, generic Sertraline in Italy; Zoloft in Italy and the USA)
Typically, these antidepressants have fewer adverse effects than tricyclics or monoamine oxidase inhibitors, although side effects such as drowsiness, dry mouth, irritability, anxiety, insomnia, decreased appetite, and decreased drive and sexual capacity may occur.
Some side effects may diminish as a person gets used to the drug, but other side effects may be persistent.
Although safer than the first generation of antidepressants, SSRIs may not work for many patients, with lower efficacy than previous classes of antidepressants.
A paper by two researchers questioned the link between serotonin deficiency and symptoms of depression, pointing out that the efficacy of SSRI treatment does not prove such a link.
Research indicates that these drugs may interact with transcription factors known as ‘clock genes’, which may play a role in the addictive properties of drugs (drug abuse) and possibly obesity.
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