Pathogenesis and Clinical Picture of Depression
Depression (from Latin depressio — suppression) is a severe psychiatric disorder that significantly impairs social adaptation and reduces the patient's quality of life. The leading clinical symptom is hypothymia, which is a persistent depressed mood.
The psychological status of the patient is characterized by a pessimistic evaluation of their personality and surrounding reality, a sharp decrease in drive, and a high probability of suicidal attempts. At the psychomotor and physiological levels, there is marked inhibition of motor activity and intellectual function, along with various somatovegetative disturbances.
Current concepts of etiology rely on several factors. Genetic predisposition has been proven, and in reactive depressions, negative social and emotional influences play a significant role. However, the foundational concept is the biochemical (monoamine) theory. According to this theory, the primary cause lies in decreased monoaminergic activity—a deficiency of norepinephrine and serotonin in the central nervous system. In response to this deficiency, a compensatory receptor response is triggered: up-regulation occurs (an increase in the number and altered sensitivity of receptors, especially postsynaptic adrenoceptors). Additionally, intracellular disturbances are documented at the postsynaptic membrane level, closely linked to G-protein function.
Classification by Clinical Effect
Drug selection largely depends on whether excitation or inhibition predominates in the clinical presentation. Based on their clinical effect, antidepressants are divided into two main groups:
- Tymeretics. These are medications with a stimulating component. Their main indication is the treatment of depressions accompanied by persistent inhibition.
- Thymoleptics. Drugs with a pronounced sedative (calming) effect. They are indicated for treating depressions accompanied by signs of agitation.
Monoamine Reuptake Inhibitors
The pharmacological action of antidepressants targets specific synaptic sites. The pathogenesis involves noradrenergic synapses (mediator: norepinephrine) and serotonergic synapses (mediator: serotonin). Normally, the inactivation of these neurotransmitters occurs via neuronal reuptake by transport proteins or enzymatic degradation within the nerve terminal.
The first major group of drugs consists of monoamine reuptake inhibitors:
- Non-selective agents. They predominantly inhibit the reuptake of two neurotransmitters simultaneously: serotonin and norepinephrine. The primary group here is the tricyclic antidepressants (TCAs). Notable examples include amitriptyline, imipramine, clomipramine, and pipofezine.
- Selective agents. They act specifically on the reuptake of particular neurotransmitters. These include selective serotonin reuptake inhibitors (SSRIs — fluoxetine, paroxetine, fluvoxamine, sertraline), norepinephrine reuptake inhibitors (maprotiline), and serotonin-norepinephrine reuptake inhibitors (venlafaxine).
MAO Inhibitors and Drug Profiles
The second major group is monoamine oxidase inhibitors (MAOIs). They prevent the enzymatic degradation of neurotransmitters by the mitochondrial enzyme MAO, thereby increasing their concentration.
- Selective MAO-A inhibitors. An example is moclobemide. The mechanism involves the predominant inhibition of MAO type A, which targetedly increases the concentration of serotonin and norepinephrine.
- Non-selective MAO inhibitors. An example is nialamide. It is characterized by the non-selective blockade of both enzyme types (MAO-A and MAO-B). This fundamentally distinguishes it from selective drugs and accounts for a broader spectrum of adverse effects.
Each drug possesses a unique pharmacodynamic profile. For instance, fluoxetine (an SSRI) has a pronounced psychostimulating effect, but can cause akathisia—a distressing motor restlessness and inability to sit still. Amitriptyline (a TCA) exhibits muscarinic receptor antagonism, leading to xerostomia (dry mouth). Furthermore, it affects the cardiovascular system: lowering blood pressure (hypotension) and carrying a dangerous arrhythmogenic potential. Modern classifications also include tetracyclic antidepressants (NaSSAs), represented by mirtazapine.