Definición e impacto de las depresiones resistentes/refractarias al tratamiento

Salud Mental (Impact Factor: 0.42). 05/2011; 34(3):247-255.


Major depressive disorder (MDD) is characterized by high rates of
medical morbidity, low productivity, low life expectancy, and high rates
of suicide. Therefore, the treatment of depressed patients involves,
among others, an early diagnosis and treatment of the disease.
Although an increasing number of antidepressants to treat MDD are
available, approximately half of the patients do not respond, and near
of two-thirds do not achieve remission after a first treatment attempt.
For this project, it was conducted a detailed review using several
databases such as MEDLINE, PsycINFO, EMBASE, the Cochrane
Library, and LILACS from 1949 to March 2011 crossing terms related
to the diagnosis and impact of the DRT. Unfortunately, original
publications on DRT in Latin America are scarce and the findings
and conclusions of this review have been based almost entirely on
Anglo-Saxon scientific evidence.
In a similar manner as described by medical microbiology, a
major depressive episode (MDE) can be considered refractory when
it has not responded to an adequate treatment with an established
therapy. What constitutes an inadequate treatment has been the
subject of considerable debate, but most experts would probably say
it is the failure to achieve remission. The rationale for this approach
is that not achieving remission often results in changes in work
performance, increased risk of recurrences, chronicity, suicide, and
impaired social functioning.
Before considering a patient as TRD, is necessary to confirm the
diagnosis of unipolar MDD ruling out other psychiatric disorders such
as bipolar disorder, or other non-psychiatric medical diseases. After
clarifying the diagnosis, and in the absence of remission, the physician
is confronted with a great diversity of definitions and clinical criteria
suggested for DRT. This variety of diagnostic alternatives, rather than
enrich the portfolio of treatment options for DRT, often leads to serious
discrepancies that hinder the effective management of the DRT.
Unfortunately, more than 50 years after the discovery of the first
antidepressants and increased knowledge about the neurobiological
mechanisms of MDD and their interactions with the environment, for
now there are no uniform guidelines on the definition and treatment
of patients with DRT. Perhaps, the most accepted definition of DRT in
the literature is that in which an inadequate response after one or two
courses of antidepressant treatment with dose optimization, appropriate
time of administration (usually between 8 and 12 weeks) and high
level of adherence and compliance can be assured.
Among the models proposed for the diagnosis of the DRT, Thase
and Rush developed a frequently used tool, although with a predictive
value, regarding the outcome of treatment, not systematically evaluated.
It is based on five steps or levels that arbitrarily assume that the lack of
remission after one single trial with an appropriate treatment is just
enough to make a diagnosis of DRT. In addition, certain interventions
such as tricyclic antidepressants or monoamine oxidase inhibitors are
considered superior to first-line strategies available today.
This review also defines the differential diagnosis of DRT such
as pseudo-resistance, chronic depression, bipolar depression and
tachyphylaxis, and describes the costs and consequences of DRT with
an inadequate intervention.

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Available from: Jorge M Tamayo,
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    • "Aunque un número creciente de agentes antidepresivos está disponible para tratar la depresión, aproximadamente la mitad de los pacientes no responden y hasta dos tercios no logran la remisión después del tratamiento de primera línea. En estos casos nos referimos a la depresión refractaria/ resistente al tratamiento (DRT) tal como es definida en un artículo publicado en este número de la revista (Tamayo JM et al., 2011). La DRT es una de las condiciones más complejas en psiquiatría desde el punto de vista terapéutico debido a diferentes definiciones, algoritmos y criterios de respuesta que hacen difícil ofrecer alternativas eficaces, especialmente en América Latina donde los procedimientos basados en las necesidades regionales o el consenso son escasos y no siempre basados en la evidencia. "
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    ABSTRACT: Major depressive disorder (MDD) is a prevalent and costly disease that is usually associated with high rates of disability. The target for the treatment of MDD is to achieve and maintain remission or complete control of depressive symptoms by the choice of an effective antidepressant. Sometimes, despite evidence based-treatment, it is possible that the patient does not have a favorable response. Although there is an increasing number of antidepressants available to treat depression, approximately half of the patients do not respond and two-thirds do not achieve remission after first-line treatment. In these cases we refer to treatment-resistant depression (TRD) as is defined in an article in this issue of Salud Mental. The TRD is one of the most complex conditions in psychiatry from the therapeutic point of view due to different definitions, algorithms, and response criteria, especially in Latin America where the procedures based on regional needs and consensus are scarce and not always based on evidence. It was conducted a systematic review using several databases such as MEDLINE, PsycINFO, EMBASE, the Cochrane Library and LILACS from 1949 to March 2011 crossing terms which allowed the inclusion of relevant articles in the management of the TRD. Unfortunately, the original publications in Latin America are often based on TRD case report, so the results and conclusions of this review have been based entirely on Anglo-Saxon scientific production. The therapeutic strategies used in the TRD are many, and include combinations of antidepressants or other psychotropic agents, in some cases addition of psychotherapy and, in extreme cases, neurostimulation techniques such as electroconvulsive therapy (ECT). The study Sequenced Treatment Alternatives to Relieve Depression (STARD) is the largest trial of treatment for MDD conducted in real practice settings, and the first to study remission as a measure of pre-defined primary outcome. It consists of four different stages of resistance. It is clear that there are diminishing remission rates as the number of treatment trials increases. The strategies include: antidepressant dose optimization, addition of medications like thyroid hormone, lithium, or nutritional supplements, a combination of antidepressants, and addition of second-generation antipsychotics (SGAs). Evidence suggests that remission rates can be from 25% to 50%, although with some differences among the drugs recommended. Evidence supports the use of SGAs for increasing the level of remission of new-generation antidepressants, although neither the profit nor the long-term benefits of this strategy have been well established. Neuro-modulation techniques include ECT, repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). ECT remains a first line option for the treatment of DRT with response rates ranging from 50% to 89%. Finally, the effectiveness of cognitive-behavioral therapy (CBT) in the management of the DRT could be a useful alternative when practiced in conjunction with any of the pharmacological strategies. However, further studies are needed to recommend it as first line treatment
    Salud Mental 05/2011; 34(3):257-266. · 0.42 Impact Factor
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    Salud Mental 03/2011; 34(3):267-273. · 0.42 Impact Factor
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    ABSTRACT: Objective: we conducted a systematic review to evaluate the evidence for the efficacy and safety of olanzapine-fluoxetine combined (OFC) in patients with treatment-resistant depression (TRD). Methods: MEDLINE, EMBASE, Cochrane Library,, and were searched (28 February 2014) using terms related to TRD and OFC (no language restrictions). All prospective studies of OFC treatment of TRD were included. Results: we included 16 studies (5 meta-analyses, 3 pooled analyses, 7 randomized controlled trials [RCTs], 1 nonrandomized, open-label trial); unpublished data of open-label extensions were available for 4 RCTs. The definition of TRD varied; most studies defined TRD as response failure after 2 antidepressant trials of4 weeks. All RCTs compared OFC with fluoxetine. Treatment duration was 4 12 weeks in RCTs, and 8 76 weeks in open-label studies. Depressive symptoms improved with OFC treatment in all studies; improvement was generally greater and occurred earlier than with fluoxetine and was sustained during longer-term treatment. Response (27.5%-80%) and remission (16.9%-73.3%) rates were generally greater than with fluoxetine. Weight gain and changes in metabolic parameters were generally more common in patients treated with OFC than with fluoxetine. Other adverse events and discontinuation rates were similar to those seen with fluoxetine. Conclusions: evidence from prospective studies supports the efficacy of OFC in the treatment of TRD, which is sustained with longer-term treatment. However, there may be a greater risk of weight gain and changes in metabolic parameters. Physicians may consider OFC as treatment for TRD, provided the risks of weight gain and metabolic changes are actively managed.
    Archivos de Neurociencias 01/2015; 20(1):17-33.