Treatment-resistant depression (TRD) is a major public health problem in terms of its prevalence and in terms of individual suffering and cost to society. Best estimates indicate 12-month prevalence rates of approximately 3% for Stage 1 TRD (failure to respond to 1 adequate trial of an antidepressant) and approximately 2% for Stage 2 TRD (failure to respond to 2 adequate trials). The current article provides a brief review of the definitions, prevalence, and various treatment options for TRD, including switching, augmentation, and combination therapies and use of nonpharmacologic treatments. Given the public health importance of TRD, the relative absence of adequately powered, double-blind trials is striking.
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"Two patients in the MDD group and none in the MDDþAUD group had the stabiliser antidepressant lamotrigine added in their treatment schedule, while one patient in each group took two different dibenzo-oxazepine atypical antipsychotics. Three patients in the MDDþAUD group had stage 1 treatment-resistant depression (failure to respond to one adequate trial of an antidepressant ) and the other eight had stage 2 (failure to respond to two adequate antidepressant trials) (Nemeroff, 2007 "
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Co-occurrence of Major Depressive (MDD) and Alcohol Use Disorders (AUDs) is frequent, causing more burden than each disorder separately. Since the dorsolateral prefrontal cortex (DLPFC) is critically involved in both mood and reward and dysfunctional in both conditions, we aimed to evaluate the effects of dTMS stimulation of bilateral DLPFC with left prevalence in patients with MDD with or without concomitant AUD.
Twelve MDD patients and 11 with concomitant MDD and AUD (MDD+AUD) received 20 dTMS sessions. Clinical status was assessed through the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions severity scale (CGIs), craving through the Obsessive Compulsive Drinking Scale (OCDS) in MDD+AUD, and functioning with the Global Assessment of Functioning (GAF).
There were no significant differences between the two groups in sociodemographic (age, sex, years of education and duration of illness) and baseline clinical characteristics, including scores on assessment scales. Per cent drops on HDRS and CGIs scores at the end of the sessions were respectively 62.6% and 78.2% for MDD+AUD, and 55.2% and 67.1% for MDD (p<0.001). HDRS, CGIs and GAF scores remained significantly improved after the 6-month follow-up. HDRS scores dropped significantly earlier in MDD+AUD than in MDD LIMITATIONS: The small sample size and factors inherent to site and background treatment may have affected results.
High frequency bilateral DLPFC dTMS with left preference was well tolerated and effective in patients with MDD, with or without AUD. The antidepressant effect of dTMS is not affected by alcohol abuse in patients with depressive episodes. The potential use of dTMS for mood modulation as an adjunct to treatment in patients with a depressive episode, with or without alcohol abuse, deserves further investigation.
"Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for medication-resistant major depressive disorder (MDD), which affects approximately 2% of the population . The most recent studies of rTMS in MDD have achieved fairly consistent response rates of 50e55% and remission rates of 30e35% in naturalistic case series and open-label trials [2e4]. "
[Show abstract][Hide abstract] ABSTRACT: Background: Conventional rTMS protocols for major depression commonly employ stimulation sessions lasting >30 min. However, recent studies have sought to improve costs, capacities, and outcomes by employing briefer protocols such as theta burst stimulation (iTBS). Objective: To compare safety, effectiveness, and outcome predictors for DMPFC-rTMS with 10 Hz (30 min) versus iTBS (6 min) protocols, in a large, naturalistic, retrospective case series. Methods: A chart review identified 185 patients with a medication-resistant major depressive episode who underwent 20-30 sessions of DMPFC-rTMS (10 Hz, n = 98; iTBS, n = 87) at a single Canadian clinic from 2011 to 2014. Results: Clinical characteristics of 10 Hz and iTBS patients did not differ prior to treatment, aside from significantly higher age in iTBS patients. A total 7912 runs of DMPFC-rTMS (10 Hz, 4274; iTBS, 3638) were administered, without any seizures or other serious adverse events, and no significant differences in rates of premature discontinuation between groups. Dichotomous outcomes did not differ significantly between groups (Response/remission rates: Beck Depression Inventory-II: 10 Hz, 40.6%/29.2%; iTBS, 43.0%/31.0%. 17-item Hamilton Rating Scale for Depression: 10 Hz, 50.6%/38.5%; iTBS, 48.5%/27.9%). On continuous outcomes, there was no significant difference between groups in pre-treatment or post-treatment scores, or percent improvement on either measure. Mixed-effects modeling revealed no significant group-by-time interaction on either measure. Conclusions: Both 10 Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120% resting motor threshold. The effectiveness of 6 min iTBS and 30 min 10 Hz protocols appears comparable. Randomized trials comparing 10 Hz to iTBS may be warranted. (C) 2015 The Authors. Published by Elsevier Inc.
"Similar to epilepsy, pharmacoresistance to antidepressants is defined as non-response to adequate treatment with two or more antidepressants of different mechanism of action (El Hage et al., 2013). Prevalence of non-response to the first trial antidepressant is around 50% (Nemeroff, 2007, Wiborg, 2013). One widely studied mechanism of pharmacoresistance in epilepsy is increased antiepileptic drug efflux mediated by overexpression of multidrug transporters at the blood– brain barrier in the epileptic focus region (Löscher and Potschka, 2005). "
[Show abstract][Hide abstract] ABSTRACT: Among the co-morbidities observed in epilepsy patients depression is the most frequent one. Likewise, depression by itself is accompanied by an increased risk to develop epilepsy. Both epilepsy and depression are characterized by a high incidence of pharmacoresistance, which might be based on overactivity of multidrug transporters like P-glycoprotein at the blood-brain barrier. Using genetically modified mice in preclinical epilepsy research is pivotal for investigating this bidirectional relationship. In the present study, we used the sucrose consumption test (SCT) in the pilocarpine and the intrahippocampal kainate mouse post-status epilepticus model to reveal anhedonic behavior, i.e. hyposensitivity to pleasure, as a key symptom of depression. Mice were repetitively investigated by SCT during early epilepsy and the chronic phase of the disease, during which response to antidepressant drug treatment was assessed. SCT revealed long-lasting anhedonia in both models. Anhedonia appeared to be pharmacoresistant, as neither chronic treatment with imipramine in the pilocarpine model nor chronic treatment with fluoxetine in the kainate model could annihilate the differences in sucrose consumption between control and epileptic mice. Moreover, knock-out of P-glycoprotein did not improve the treatment effect of fluoxetine. In conclusion, our findings show for the first time that the SCT is suited for detection of depression-like behavior in mouse models of temporal-lobe epilepsy. Both models might serve as tools to further investigate the neurobiology and pharmacology of epilepsy-associated pharmacoresistant depression.