Vieta E, Colom F. Therapeutic options in treatment-resistant depression. Ann Med 43: 512-530

Bipolar Disorders Program, Hospital Clinic, University of Barcelona , Catalonia, Spain.
Annals of Medicine (Impact Factor: 3.89). 05/2011; 43(7):512-30. DOI: 10.3109/07853890.2011.583675
Source: PubMed


The phenomenon of treatment-resistant depression (TRD), described as the occurrence of an inadequate response after an adequate treatment with antidepressant agents (in terms of dose, duration, and adherence), is very common in clinical practice. It has been broadly defined in the context of unipolar major depression, but alternative definitions for bipolar depression have also been suggested. In both cases, there is a remarkable lack of consensus amongst professionals concerning its operative definition. A relatively wide variety of treatment options for unipolar TRD are available, whilst the evidence is very scanty for bipolar TRD. TRD is associated to poor clinical, functional, and social outcomes. Several novel therapeutic options are currently being investigated as promising alternatives, targeting the neurotransmitter system outside of the standard monoamine hypothesis. Augmentation or combination with lithium or atypical antipsychotics appears as a valid option for both conditions, and the same occurs with electroconvulsive therapy. Other non-pharmacological strategies such as deep brain stimulation may be promising alternatives for the future. The use of cognitive behaviour therapy is recommended for unipolar TRD, but there is no evidence supporting its use in bipolar TRD.

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Available from: Eduard Vieta, Aug 15, 2014
    • "With a worldwide point prevalence of 4.7 %, major depression disorder (MDD) is a widespread mental health problem (Ferrari et al. 2013). It is estimated that approximately 70 % of MDD patients do not remit after adequate first-line antidepressant (AD) treatment (Carvalho et al. 2014), and that roughly for 20 % of such patients this leads to refractory MDD (Vieta and Colom 2011;van Randenborgh et al. 2012;Trevino et al. 2014). For some years now, repetitive transcranial magnetic stimulation (rTMS) has been clinically available and it has been acknowledged by the American Psychiatric Association (APA), the Canadian Network for Mood and Anxiety Treatments (CANMAT), and the World Federation of Societies of Biological Psychiatry (WFSBP) as an evidence-based and accepted treatment option to treat patients suffering from major depression disorder (MDD). "
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    ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is an evidence based neurostimulation modality used to treat patients with Major Depressive Disorder (MDD). In spite that the duration of current a depressive episode has been put forward as a negative predictor for clinical outcome, little is known about the underlying neurobiological mechanisms of this phenomenon. To address this important issue, in a sample of 43 melancholic stage III treatment resistant antidepressant-free refractory MDD patients, we reanalysed regional cerebral glucose metabolism (CMRglc) before high frequency (HF)-rTMS treatment, applied to the left dorsolateral prefrontal cortex (DLPFC). Besides that a lower baseline cerebellar metabolic activity indicated negative clinical response, a longer duration of the depressive episode was a negative indicator for recovery and negatively influenced cerebellar CMRglc. This exploratory 18FDG PET study is the first to demonstrate that the clinical response of HF-rTMS treatment in TRD patients may depend on the metabolic state of the cerebellum. Our observations could imply that for left DLPFC HF-rTMS non-responders other brain localisations for stimulation, more specifically the cerebellum, may be warranted.
    No preview · Article · Jan 2016 · Brain Imaging and Behavior
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    • "Recent clinical trials indicated that only approximately half of depressed patients with initial antidepressant monotherapy showed a favorable treatment response, and only about one-third achieved remission of symptoms (Trivedi et al., 2006); thus, there is need for additional treatment strategies for those patients with TRD. One common alternative approach to the treatment of patients with TRD is augmentation strategies for those who failed to respond to the initial antidepressant (Vieta and Colom, 2011). The use of atypical antipsychotics has rapidly increased worldwide in the last decade. "
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    ABSTRACT: Previous meta-analyses of atypical antipsychotics for depression were limited by few trials with direct comparisons between two treatments. We performed a network meta-analysis, which integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD). Systematic searches resulted in 18 RCTs (total N=4422) of seven different types and different dosages of atypical antipsychotics and placebo that were included in the review. All standard-dose atypical antipsychotics were significantly more efficacious than placebo in the efficacy (SMDs ranged from -0.27 to -0.43). There were no significant differences between these drugs. Low-dose atypical antipsychotics were not significantly more efficacious than placebo. In terms of tolerability, all standard-dose atypical antipsychotics, apart from risperidone, had significantly more side-effect discontinuations than placebo (ORs ranged from 2.72 to 6.40). In terms of acceptability, only quetiapine (mean 250-350 mg daily) had a significantly more all-cause discontinuation than placebo (OR = 1.89). In terms of quality of life/functioning, standard-dose risperidone and standard-dose aripiprazole were more beneficial than placebo (SMD = -0.38; SMD = -0.26, respectively), and standard-dose risperidone was superior to quetiapine (mean 250-350 mg daily). All standard-dose atypical antipsychotics for the adjunctive treatment of TRD are efficacious in reducing depressive symptoms. Risperidone and aripiprazole also showed benefits in improving the quality of life of patients. Atypical antipsychotics should be prescribed with caution due to abundant evidence of side effects. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · May 2015 · The International Journal of Neuropsychopharmacology
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    • "Since the introduction of newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors, there have been great advances in treatments for major depressive disorder (MDD; Garnock- Jones and McCormack, 2010; Nichols et al., 2010; Choi et al. 2012; Rocha et al., 2012; Citrome, 2013). However, many patients with MDD have shown inadequate responses to standard antidepressant therapy (Rush et al., 2006; Nelson and Papakostas, 2009; Vieta and Colom, 2011; Turner et al., 2014). As a result, many researchers have sought to develop better treatment strategies for treatment-resistant MDD (Bauer et al., 2014; Carvalho et al., 2014; Fond et al., 2014; McIntyre et al., 2014; McNamara et al., 2014); one such is augmentation treatment with atypical antipsychotic agents (Nelson and Papakostas, 2009). "
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    ABSTRACT: Atypical antipsychotic augmentation was demonstrated to be efficacious in treatment resistant depression (TRD) in previous meta-analyses. We investigate whether there are differences in the effect size of atypical antipsychotic augmentation in major depressive disorder according to the degree of treatment resistance. A comprehensive search of four databases identified eleven randomized controlled trials. The eleven trials, which included 3,341 participants, were pooled using a random-effects meta-analysis. Atypical antipsychotic augmentation of antidepressant therapy showed superior efficacy compared to antidepressant monotherapy in TRD in terms of both response and remission rates (response, risk ratio (RR) = 1.38 (95% CI= 1.25 to 1.53); remission, RR = 1.62 (95% CI= 1.42 to 1.85)). In addition, regarding response rates in the TRD trials, atypical antipsychotic augmentation exhibited significantly different effect sizes according to the degree of treatment resistance (TRD 1: RR= 1.24; TRD 2: RR=1.37; TRD 2-4: RR=1.58). In non-TRD trials, atypical antipsychotic augmentation failed to show superior efficacy over antidepressant monotherapy in terms of remission rates (RR = 0.89 (95% CI= 0.69 to 1.14)). Atypical antipsychotic augmentation of antidepressant therapy exhibits greater effect size in patients with a higher degree of treatment resistance. This finding strengthens the rationale for considering atypical antipsychotic augmentation among depressed patients with multiple previous treatment failures in clinical practice. The efficacy of atypical antipsychotic augmentation for non-TRD seems to be different from that for TRD, and, thus, further studies of non-TRD populations are needed. © The Author 2014. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · Mar 2015 · The International Journal of Neuropsychopharmacology
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