Drug treatment of depression


The choice of drug can be guided by the past response to a specific antidepressant. Otherwise, serotonin reuptake inhibitors are often the initial drugs of choice. Although the different serotonin reuptake inhibitors are equally effective in typical cases, some properties of the drugs make them more or less appropriate for certain individuals (see table Antidepressants and Depressive Disorders: Treatment).

Antidepressants and suicide risk

Patients and their loved ones should be warned that some patients may appear more agitated, depressed and anxious within one week of starting an antidepressant or increasing the dose; symptoms that worsen with treatment should be reported to the doctor. This situation must be closely monitored because some patients, particularly children and adolescents, increase their suicidal risk if agitation, increased depression and anxiety are not quickly detected and treated.

Several analyzes on the Food and Drug Administration (FDA) database of pharmaceutical industry sponsored studies have led to a “black box warning” on antidepressants which, in general, appear to be associated with an increased risk of developing suicidal ideation and attempts to suicide in patients aged ≤ 24 years. However, subsequent analyzes by the Food and Drug Administration (FDA) and other data have cast doubt on this conclusion.

Selective reuptake inhibitors of

These drugs prevent the reuptake of serotonin (5-hydroxytryptamine [5-HT]). Serotonin reuptake inhibitors include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and vilazodone. Although they have the same mechanism of action, the differences in their clinical properties make the choice important. Serotonin reuptake inhibitors have a wide therapeutic margin; they are relatively easy to use and need little dosage adjustments (except for fluvoxamine).

Modulators of (5-HT 2 blockers)

These substances first block 5-HT2 receptors and inhibit the reuptake of 5-hydroxytryptamine and noradrenaline. Serotonin modulators include Trazodone Mirtazapine Serotonin modulators have antidepressant and anxiolytic effects but do not cause sexual dysfunction.

Trazodone does not inhibit the reuptake of 5-hydroxytryptamine at the presynaptic level. It causes priapism (in 1/1000) and, as an alpha-1-noradrenergic-blocker, can cause orthostatic (postural) hypotension. It is extremely sedative, so its use in antidepressant doses (> 200 mg / day) is limited. It is usually given in doses of 50 to 100 mg at bedtime for depressed patients with insomnia.

Serotonin-noradrenaline reuptake inhibitors

These drugs (eg, desvenlafaxine, duloxetine, levomilnacipran, venlafaxine, vortioxetine) also have dual mechanisms of action on 5-hydroxytryptamine and norepinephrine, as do tricyclic antidepressants.

However, their toxicity approximates that of serotonin reuptake inhibitors. Nausea is the biggest problem during the first 2 weeks; modest dose-dependent increases in blood pressure can occur at high doses. Withdrawal signs (eg, irritability, restlessness, nausea) occur frequently if the drug is stopped suddenly.


This group of drugs, which was once the mainstay of treatment, includes tricyclics (the tertiary amines amitriptyline and imipramine and their secondary amine metabolites nortriptyline and desipramine), modified tricyclics, and tetracyclic antidepressants.

Acutely, heterocyclic antidepressants increase the availability of norepinephrine in the first place and to some degree of 5-hydroxytryptamine, blocking their reuptake into the synaptic wall. Long-term administration desensitizes alpha-1-adrenergic receptors on the post-synaptic membrane, a possible final common route of their antidepressant activity.


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