Mecanismos de acción electrofisiológicos de la terapia electroconvulsiva / Electrophysiological mechanisms of action of electroconvulsive therapy

Pese a la elaboración de guías y consensos sobre sus indicaciones y aplicación, la terapia electroconvulsiva (TEC) sigue siendo uno de los procedimientos terapéuticos con menor certeza en su mecanismo de acción. Es interesante evaluar la manera en la que los factores que modulan la actividad convulsiva pueden ser modificados por esta terapia y su relación con el efecto terapéutico. El objetivo del presente artículo es revisar, en el contexto de las teorías neurobiológicas, la bibliografía existente sobre los mecanismos de acción electrofisiológicos de la TEC, principalmente la hipótesis anticonvulsiva. El mayor conocimiento sobredichos mecanismos, puede conseguir una optimización en la práctica asistencial, así como un punto de partida para buscar tratamientos alternativos basados en las mismas bases físicas. Entre todos los artículos y libros de texto, se han seleccionado aquellos trabajos que, por su metodología y diseño, aportan datos científicamente relevantes respecto al tema principal de esta revisión y que hayan sido publicados entre 1993 y 2007. A fin de aportar mayor consistencia al texto, también se han incluido una serie de artículos, previos a 1993, considerados importantes en el ámbito que se trata, puesto que establecen las bases teóricas de la TEC y han sido citados con frecuencia tras su publicación. Las evidencias científicas obtenidas se sistematizan en tres apartados: conceptos básicos, hipótesis neurofisiológicas y hallazgos electrofisiológicos (AU)

In spite of the guidelines and consensus on its indications and application, electroconvulsive therapy (ECT) continues to be one of the therapeutic procedures with less knowledge on its mechanism of action. It is interesting to evaluate the way in which the factors that modulate the convulsant activity can be modified by this therapy and its relation with the therapeutic effect. The aim of the present article is to review, in the context of neurobiological theories, the bibliography regarding the electrophysiological mechanisms of action of ECT, mainly the anticonvulsant hypothesis. Having better knowledge about these mechanisms can achieve an improvement in the clinical practice and provide a starting point to search for alternative treatments based on the same physical bases. After doing a study of all the papers and reference books, those works which, according to their methodology and design, provide relevant scientific information with regard to the principal topic of this review and that have been published between 1993 and 2007 were selected. In order to provide better consistency to the text, a series of articles prior to 1993 that were considered important within the setting studied have been included, since they establish the theoretical bases of ECT and have been frequently mentioned after their sublication. The scientific evidence obtained is systematized into three sections: basic concepts, neurophysiological hypotheses and electrophysiological findings (AU)

Electrophysiological mechanisms of action of electroconvulsive therapy.

In spite of the guidelines and consensus on its indications and application, electroconvulsive therapy (ECT) continues to be one of the therapeutic procedures with less knowledge on its mechanism of action. It is interesting to evaluate the way in which the factors that modulate the convulsant activity can be modified by this therapy and its relation with the therapeutic effect. The aim of the present article is to review, in the context of neurobiological theories, the bibliography regarding the electrophysiological mechanisms of action of ECT, mainly the anticonvulsant hypothesis. Having better knowledge about these mechanisms can achieve an improvement in the clinical practice and provide a starting point to search for alternative treatments based on the same physical bases. After doing a study of all the papers and reference books, those works which, according to their methodology and design, provide relevant scientific information with regard to the principal topic of this review and that have been published between 1993 and 2007 were selected. In order to provide better consistency to the text, a series of articles prior to 1993 that were considered important within the setting studied have been included, since they establish the theoretical bases of ECT and have been frequently mentioned after their sublication. The scientific evidence obtained is systematized into three sections: basic concepts, neurophysiological hypotheses and electrophysiological findings.

Antidepressant combinations: epidemiological considerations.

OBJECTIVE: To evaluate the treatment options in patients who do not respond appropriately to a single antidepressant alone. METHOD: The medical literature was reviewed. RESULTS: A number of strategies are available if a patient fails to respond adequately to initial antidepressant treatment, including the combination with another psychoactive drug. Evidence published to date appears to suggest that benzodiazepines are the drugs most frequently combined with antidepressants. The combination of two antidepressants together is less common, occurring in approximately 5-15% of cases showing a poor initial response. The key figures involved in such co-prescription are psychiatrists. CONCLUSION: There appears to be considerable variability in the data concerning combined prescription of antidepressants, with differences arising depending on the type of physician, the type of patient or illness and the geographical area. It is also unclear how closely research findings parallel with what doctors do in everyday practice.

Neuropharmacological basis of combining antidepressants.

OBJECTIVE: To review the neuropharmacological basis of antidepressant combination therapy. METHOD: Literature searches and other relevant material were obtained and reviewed. RESULTS: The overall clinical aim of combining antidepressants is to increase the efficacy whilst minimizing the side effects. Although such prescriptions are frequently based on the previous experience and knowledge, a sound neuropharmacological basis to support these combinations is desirable. When combining antidepressants, it is important to combine mechanisms of action, rather than simply one drug with another, and to aim for synergistic effects. The possibilities of combining mechanisms of action should also be exploited to the full if necessary, and the potential exists for combining two independent actions that have synergistic effects on the serotonergic, noradrenergic and even the dopaminergic systems. CONCLUSION: Unfortunately, there are still, as yet, insufficient data to categorically justify choosing one or other combination based only on the neuropharmacological evidence.

Combined antidepressants: clinical experience.

OBJECTIVE: To review the current literature on the use of combinations of antidepressive agents. METHOD: Literature searches were undertaken and reviewed on the use of combinations of antidepressants. RESULTS: Data sources included surveys, analyses of prescription records, decision algorithms, clinical reports, and studies comparing the monotherapy with combination therapy. More recent surveys recommend combining different selective serotonin reuptake inhibitors (SSRIs), an SSRI plus bupropion or dual action antidepressants plus an SSRI. Decision algorithms recommend an SSRI plus tricyclic antidepressant (TCA) and more recently bupropion plus venlafaxine or mirtazapine. Few controlled clinical trials comparing the combined therapy with monotherapy have been conducted. Beneficial effects have been reported with combinations of TCAs plus mianserin or SSRIs plus mirtazapine. CONCLUSION: Adding or combining antidepressant medications has advantages for the speed of onset and maintaining the existing response. More rigorous clinical trials comparing combination therapy with monotherapy and for the development of rational treatment guidelines are required.

Potentiation strategies for treatment-resistant depression.

OBJECTIVE: To review the pharmacological basis of antidepressant potentiation in combination therapy and the clinical evidence for its efficacy. METHOD: Literature searches were undertaken and the results reviewed. RESULTS: Treatment-resistant depression is common (15-30%). Various strategies exist for dealing with resistant depression, including pharmacological potentiation, i.e. adding a treatment that itself does not have antidepressant actions but that enhances the efficacy of the original treatment. Lithium, triiodothyronine (T3) and buspirone are the best studied potentiating drugs, although other options include pindolol, dopaminergic agents, second-generation antipsychotics, psychostimulants, hormones and anticonvulsants. CONCLUSION: Several pharmacological potentiation strategies exist. Whilst good evidence exists for lithium combined with antidepressants, although good results have also been reported with augmentation strategies involving T3 or buspirone.

Use of antidepressant combinations: which, when and why? Results of a Spanish survey.

OBJECTIVE: The present study uses the data from a large survey conducted to examine the general practice of Spanish psychiatrists on the use of antidepressant combinations in the treatment of depressive disorders. METHOD: The sample was drawn from specialists and psychiatric residents practicing in Spain who were respondents to a questionnaire distributed during an annual national psychiatry meeting and sent by mail. RESULTS: A total of 1032 questionnaires were collected; following the data-filtering, 831 were analysed. Most psychiatrists (89%) believe that many patients do not respond to the first treatment; in such cases of non-response, 58% choose a combination of antidepressants as the next treatment option. Reasons for using the combined treatments include greater efficacy (57%), overcoming resistance to the first antidepressant (27%), faster onset of action (21%) and avoidance of side effects (17%). The most sought after pharmacological profile was serotonergic-noradrenergic (96%) and the most popular combinations were selective serotonin reuptake inhibitor (SSRI) + mirtazapine, SSRI + reboxetine and SSRI + tricyclic antidepressant. CONCLUSION: Antidepressant combinations are frequently used in clinical practice. Pharmacological profiles are always considered and SSRIs + mirtazapine is the option usually chosen.

Onset of antidepressant action: a pharmacological question?

OBJECTIVE: This study was conducted to analyse the onset of action of antidepressants in naturalistic conditions. METHOD: Multicenter, prospective, open-label, non-comparative naturalistic study among 582 depressed outpatients treated with mirtazapine. The patients were assessed at screening, and after 1, 2 and 4 weeks by the 17-item Hamilton depression rating scale (17-HAM-D) and clinical global impression (CGI). Onset of action was measured by traditional analyses based on the time to a persistent reduction of more than 50% from baseline on the 17-HAM-D. Patients were grouped into four groups: very fast responders, fast responders, traditional responders and partial or non-responders. The non-parametric Kruskall-Wallis test was used to assess differences between the groups and logistic regression to predict response after 1 week of treatment. RESULTS: 16% of patients had a very fast response, 42.1% a fast response, 26.5% a traditional response and 15.5% a partial or non-response. There were no significant differences between these groups with regard to dose of mirtazapine or sociodemographic characteristics. The baseline total 17-HAM-D was lower in the faster groups than in the slower groups. The evolution of 17-HAM-D items was similar in each responder group. CONCLUSION: Time to response varied from early faster response to late slower response. The evolution of 17-HAM-D for each type of response was similar, but occurred at a different time in each group.