Antidepresivos

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Salud Mental 2008;31:307-319

Los antidepresivos inhibidores selectivos de recaptura de serotonina

Los antidepresivos inhibidores selectivos de recaptura de serotonina (ISRS, ISR-5HT)
Enrique Chávez- León1, Martha Patricia Ontiveros Uribe2, Carlos Serrano Gómez3
Actualización por temas

SUMMARY
Depression is a frequent mental disorder in the general population. Approximately 3.7% of thepopulation will suffer a major depressive episode throughout life. Pharmacological treatment with selective serotonin receptor inhibitors (SSRIs) is useful to treat this condition and other mental disorders. Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, which constitute this group, are characterized by having an easy way of administration and a very extensivesecurity profile. Objectives The objectives in this revision were: 1. To establish current indications of selective serotonin receptor inhibitors, using as basis those authorized by the Food and Drug Administration (FDA) of the United States of America. 2. To describe the mechanisms that explain antidepressant action. Initially, the SSRIs inhibit the reuptake of serotonin at the synaptic cleft; laterthere is a downregulation of the 5HT1A receptors; and finally antidepressants raise the levels of brain derived neurotrophic factor (BDNF). 3. To present its way of administration and dosage. 4. To describe frequent collateral effects and those specifically associated to this group of antidepressants and the recommended treatment. Results SSRIs antidepressants are the first choice treatment indepression, in the anxiety disorder, the obsessive-compulsive disorder, the posttraumatic stress disorder, bulimia nervosa and the premenstrual dysphoric disorder. At present, SSRIs displace benzodiacepines in the treatment of generalized anxiety disorder, just as they displaced tricyclic antidepressants in the past. Depressed patients show less activity than normal of the serotonin neurotransmitter(serotonergic hypothesis of depression) and the reuptake blockade at the site of the serotonergic presinaptic receptors 5HT1A , 5HT2C and 5HT3C increases neurotransmission in this system. Desensitization of autoreceptors 5HT1A and the downregulation of the 5HT2 receptors coupled to the G protein, a late effect of the SSRIs, result in the improvement of the

depressive symptoms. The mechanism thatexplains the relatively late antidepressant effect seems to be different to the acute and fast serotonergic effect responsible of improvement in the premenstrual dysphoric disorder. Moreover, these antidepressants, in the same way than mood stabilizers and electroconvulsive therapy, increase serum levels of the brain-derived neuronal growth factor, as well as other neurotrophic factors. Althoughthe SSRIs dosages are variable, it is possible to start antidepressant treatment with therapeutic doses in the majority of cases; at the same time, if necessary, it is possible to augment them gradually up to the largest dose, with a wide security margin. Their most frequent collateral effects occur in the gastrointestinal system, in the sexual response and on bone density. Nevertheless, there arecollateral effects specifically related to the use of these antidepressant medications: 1. The serotonergic syndrome, characterized by changes in the mental status, autonomic hyperactivity and neuromuscular anomalies. 2. The syndrome of inappropriate secretion of antidiuretic hormone, which occurs in 25% of the elder depressed patients treated, and which is characterized by a high serumosmolarity, low urinary osmolarity and hyponatremia. Its manifestations are malaise, myalgias, drowsiness and headache, but it may produce also confusion, convulsions and coma. 3. Gastrointestinal bleeding mainly and cutaneous bleeding: Use of SSRIs raises 2 to 4 times the risk of bleeding. When the patient takes aspirin it is raised up to 7 times, and with the concomitant use of anti-inflammatory drugs,...
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