ABSTRACT
Resumen Lograr la recuperación funcional lo más tempranamente posible en el tratamiento de una depresión monopolar es un desafío que los clínicos de hoy no pueden eludir, pues el retardo en conseguir la remisión sintomática predice mayor número de recaídas y mayor morbimortalidad. Saber cómo escoger, combinar o secuenciar las diferentes estrategias psicofarmacológicas disponibles, como lo son la optimización y el cambio de un antidepresivo son preguntas frecuentes en la práctica cotidiana. Esta revisión comprensiva pretende dilucidar cuándo un clínico deberá optimizar o cambiar un tratamiento antidepresivo en un paciente con un episodio depresivo monopolar que acude a control a las dos a cuatro semanas desde el inicio de su tratamiento, reportando una respuesta parcial al fármaco inicialmente elegido. Analizar adecuadamente los dominios sintomáticos presentes, tener una visión crítica de las guías clínicas imperantes hoy en día y ser enérgico, pero lúcido en esta etapa temprana del tratamiento son, a nuestro juicio, elementos fundamentales para conseguir una recuperación "ad integrum" de nuestros pacientes.
In the current management of monopolar depression, achieving functional recovery as early as possible is a challenge that today's clinicians cannot evade, as the delay in symptom remission predicts a higher number of relapses and increased morbidity and mortality. Knowing how to choose, combine or sequence different psychopharmacological strategies, such as optimization or switching of an antidepressant are frequent questions in everyday clinical practice. This reflective review aims to elucidate when the clinician should optimize or switch an antidepressant treatment in a patient with a monopolar depressive episode that goes to a regular appointment after two to four weeks since the onset of treatment and reports partial response to the initially chosen drug. An adequate analysis of symptomatic domains, having a critical view of contemporary clinical guidelines, and maintaining an active but lucid approach at this early stage of treatment are, in our opinion, fundamental elements for the pursuit of an "ad integrum" recovery.
Subject(s)
Humans , Therapeutics , Depression , Antidepressive AgentsABSTRACT
Background & objectives: Genetic factors have potential of predicting response to antidepressants in patients with major depressive disorder (MDD). In this study, an attempt was made to find an association between response to escitalopram in patients with MDD, and serotonin transporter (SLC6A4) and receptor (5HTR1A, 5HTR2A) polymorphisms. Methods: Fifty five patients diagnosed as suffering from MDD, were selected for the study. The patients were treated with escitalopram over a period of 6-8 wk. Severity of depression, response to treatment and side effects were assessed using standardised instruments. Genetic variations from HTR1A (rs6295), HTR2A (rs6311 and rs6313) and SLC6A4 (44 base-pair insertion/deletion at 5-HTTLPR) were genotyped. The genetic data of the responders and non-responders were compared to assess the role of genetic variants in therapeutic outcome. Results: Thirty six (65.5%) patients responded to treatment, and 19 (34.5%) had complete remission. No association was observed for genotype and allelic frequencies of single nucleotide polymorphisms (SNPs) among remitter/non-remitter and responder/non-responder groups, and six most common side-effects, except memory loss which was significantly associated with rs6311 (p=0.03). Interpretation & conclusions: No significant association was found between the SNPs analysed and response to escitalopram in patients with MDD though a significant association was seen between the side effect of memory loss and rs6311. Studies with larger sample are required to find out genetic basis of antidepressant response in Indian patients.
ABSTRACT
OBJECTIVE: Serotonin transporter (5-HTT) is a key synaptic regulator of serotonergic neurotransmission and a major site of action of most antidepressants. The functional polymorphism of 5-HTT gene is reported to be associated with antidepressant responsiveness. Norepinephrine transporter (NET) and dopamine transporter (DAT) are also the targets for antidepressant drugs, and these biogenic amine transporters share a similar structure and mode of action as 5-HTT. We investigated the association between genetic polymorphisms of biogenic amine transporters and antidepressant response. METHODS: We genotyped 203 patients with major depressive disorder and 147 normal controls, using polymerase chain reaction (PCR) of genomic DNA with primers flanking the second intron and promoter regions of 5-HTT gene, and the 3' untranslated region of DAT. NET-1 (Thr99Ile) and NET-8 (1287 G/A) polymorphism were characterized by amplification and restriction fragment length polymorphisms (RFLP) analysis. RESULTS: VNTR polymorphism in the 3' untranslated region of DAT (p=0.020) was associated with a diagnosis of depression, but was influenced by age effect. We found that NET-8 polymorphism (p=0.015) in NET gene had significant associations with antidepressant response, as did the allelic variations of the promoter (p<0.0001) and intron2 (p=0.023) region in 5-HTT gene. The choice of drug had no effect on drug responsiveness. CONCLUSIONS: These results suggest that allelic variations of 5-HTT and NET genes affect the antidepressant responsiveness.