Although today they are less used than SSRIs and other more modern antidepressants, tricyclics were for many decades the pharmacological treatment of choice for depressive disorders.
In this article we will describe what are tricyclic antidepressants what they are used for and what are their most common side effects.
Tricyclics are psychotropic drugs that are used to treat depressive disorders s, although in many countries they have been replaced as medications of choice by other, more effective antidepressants. The effects of drugs useful for treating depression are usually related to serotonin and norepinephrine agonism.
The name of these drugs comes from their chemical structure: they are made up of three rings of atoms. Years after the appearance of tricyclic antidepressants, tetracyclic antidepressants also emerged, which are made up of four rings instead of three.
From the moment it appeared imipramine, the first antidepressant of this class, a large number of tricyclics have been manufactured with some differential characteristics. Among the most common are clomipramine, amitriptyline, nortriptyline, desipramine, maprotiline, doxepin, amoxapine, protriptyline and trimipramine.
What is your mecanism of action?
Tricyclic antidepressants are agonists of monoamines, a type of neurotransmitter that is very relevant in the human nervous system. These enhancing effects affect serotonin, noradrenaline and, less significantly, dopamine.
Its main therapeutic activity is due to the inhibition of the reuptake of these neurotransmitters, which increases the availability of monoamines in the synaptic space. However, also collaterally affect histamine and acetylcholine on which they exert an antagonizing effect.
Due to the low specificity of their mechanism of action, which does not target only the most relevant neurotransmitters as happens with other antidepressants, tricyclics can be useful in relieving symptoms of depression but they also cause very significant side effects and adverse reactions.
History of these drugs
Tricyclics were discovered in the manufacturing process of antipsychotic medications. In 1950, clomipramine, a neuroleptic with a tricyclic structure, was synthesized Information about this drug soon led to the creation of imipramine, the first tricyclic used specifically to treat depression.
In recent decades, the popularity of tricyclics has declined in most of the world due to the discovery of more effective and safer antidepressant drugs, particularly selective serotonin reuptake inhibitors (SSRIs) and fourth-generation antidepressants, such as venlafaxine and reboxetine.
Its functions
Despite their name, tricyclic antidepressants are not only used in cases of depression, but throughout their history they have been applied to a large number of different psychological disorders.
1. Depressive disorders
The main indication of tricyclics is treatment of depressive disorders, both major depression and other milder variants, particularly dysthymia. Currently they are prescribed especially in melancholic depression and in cases that do not improve through the consumption of other antidepressants with fewer side effects.
2. Anxiety disorders
Some tricyclics are occasionally used to treat different anxiety disorders: imipramine has been shown to be effective in generalized anxiety disorder and panic disorder, while clomipramine is still used in cases of obsessive-compulsive disorder (closely related to depression) and amitriptyline in post-traumatic stress.
Among the disorders related to chronic pain that have been treated with tricyclics, fibromyalgia and neuropathic pain stand out; It is believed that serotonin and norepinephrine agonism indirectly influences the production of endogenous opioids, which have analgesic effects. Amitriptyline seems to be especially useful in this regard.
4. Insomnia
The sedative side effects of tricyclic antidepressants have led to their sometimes being used to treat symptoms of insomnia. However, it is important to keep in mind that there are other more specific drugs for these problems, and above all that psychological therapy is the most recommended way to deal with sleeping difficulties.
5. Eating disorders
Again, the therapeutic effects of tricyclics in eating disorders are associated with one of its most frequent side effects: weight gain. In particular, clomipramine is sometimes prescribed as part of therapy for anorexia nervosa.
6. Nocturnal enuresis and night terrors
Imipramine is effective in treating two childhood sleep disorders: nocturnal enuresis and night terrors. These effects are related to the decreased delta or slow wave sleep during which said episodes appear.
Side effects of tricyclic antidepressants
Although the side effects associated with the use of tricyclic antidepressants largely depend on their agonism or antagonism toward certain neurotransmitters, in this section we will focus on the side reactions most commonly associated with this class of psychotropic drugs as a whole.
As we have mentioned in the previous section, between The most common side effects of tricyclic antidepressants we find sedation and weight gain; both are due to inhibition of histamine activity.
Blocking acetylcholine receptors causes side effects such as constipation, urinary retention, dry mouth, blurred vision, and memory problems On the other hand, inhibition of alpha-adrenergic receptors is related to alterations in blood circulation, especially dizziness and orthostatic hypotension.
Among the serious adverse reactions to the consumption of tricyclics highlights neuroleptic malignant syndrome, consisting of the appearance of respiratory, cardiac and muscular alterations that can cause coma and, in approximately one fifth of cases, death. This syndrome seems to be more common in people over 50 years of age.
It is also worth highlighting the high addictive potential of tricyclics, because pharmacological tolerance develops easily. The appearance of an intense withdrawal syndrome after suddenly stopping consumption is also a consequence of tolerance. In addition, the risk of overdose and suicide is strikingly high
