Managing Partial Response or Nonresponse: Switching, Augmentation, and Combination Strategies for Major Depressive Disorder
ABSTRACT Despite the multitude of agents approved for the treatment of major depressive disorder, approximately 50% of patients experience no response to treatment with a first-line antidepressant. Clinicians have 4 broad pharmacologic strategies to choose from for treating antidepressant nonresponders: increasing the dose of the antidepressant, switching to a different antidepressant, augmenting the treatment regimen with a nonantidepressant agent, and combining the original antidepressant with a second antidepressant. To date, the most comprehensively studied treatment strategy for nonresponse or partial response to antidepressants is augmentation with atypical antipsychotic agents, including aripiprazole, olanzapine, quetiapine, and risperidone. However, augmentation or combination with other agents such as mirtazapine, mianserin, and omega-3 fatty acids is also supported by considerable efficacy data. Lithium, desipramine, triiodothyronine, and modafinil have mixed data. While more studies are needed, agents such as bupropion, desipramine, mecamylamine, and testosterone look promising. Switching antidepressants, especially to the newer agents, including selective serotonin reuptake inhibitors, bupropion, mirtazapine, and venlafaxine, is also supported by considerable efficacy data. Clinicians should carefully reevaluate patients with major depressive disorder who are nonresponders to treatment, particularly those who have had several adequate trials. When choosing the best treatment strategy for antidepressant nonresponders, clinicians should take into account the efficacy and tolerability of treatment as well as patient preference and treatment history. Finally, the risk of potential loss of partial therapeutic benefit from the first-line antidepressant, as well as the risk of withdrawal symptoms, should be taken into account when considering switching antidepressants, while the risk of drug interactions and poor adherence should be taken into account when considering combination and augmentation treatments.
- SourceAvailable from: Kai G Kahl[Show abstract] [Hide abstract]
ABSTRACT: IntroductionAlthough a growing selection of antidepressants is available, a significant number of patients do not reach clinical remission, despite multiple trials. Data concerning the efficacy and safety of combination therapies with newer antidepressants are limited.Methods Fifteen inpatients with treatment-resistant depression (TRD), defined as Beck Depression Inventory-2 (BDI-2) scores >14 despite treatment with adequate doses of ≥1 antidepressant classes for ≥6 weeks, were treated with agomelatine plus bupropion for ≥6 weeks, and compared to 15 patients on antidepressant monotherapy with TRD matched on age, sex, and TRD stage based on retrospective chart review. The primary outcome was change in BDI-2 scores. Secondary outcomes included treatment response (BDI-2 score decrease by ≥50%), remission (BDI-2 score <13), routinely measured cardiometabolic parameters and adverse effects.ResultsAfter a mean of 6 ± 1 weeks, BDI-2 scores decreased by 20.3 ± 5.6 points in the combination group compared to 12.5 ± 15.1 points in the monotherapy group (P = 0.073; Cohen's d = 0.7). Altogether, 73.3% in the combination group responded compared to 53.3% on monotherapy (P = 0.27). About 60.0% on combination therapy reached remission compared to 40% on monotherapy (P = 0.28), a difference equivalent to a number-needed-to-treat = 4. Treatment response was independent of the degree of TRD (P = 0.27). Bupropion-agomelatine cotreatment was well tolerated and laboratory adverse effect parameters were not altered.Conclusion Despite the small sample and uncontrolled study design, the good remission rate in TRD patients receiving agomelatine plus bupropion, particularly in comparison to the monotherapy group, indicates that this combination treatment should be explored further as a potentially promising strategy for patients with TRD.02/2015; 5(4). DOI:10.1002/brb3.318
- [Show abstract] [Hide abstract]
ABSTRACT: Although well-defined predictors of response are still unclear, clinicians refer a variety of depressed patients for a repetitive Transcranial Magnetic Stimulation (rTMS) treatment. It has been suggested that personality features such as Harm Avoidance (HA) and self-directedness (SD) might provide some guidance for a classical antidepressant treatment outcome. However, to date no such research has been performed in rTMS treatment paradigms. In this open study, we wanted to examine whether these temperament and character scores in particular would predict clinical outcome in refractory unipolar depressed patients when a typical high-frequency (HF)-rTMS treatment protocol is applied. Thirty six unipolar right-handed antidepressant-free treatment resistant depressed (TRD) patients, all of the melancholic subtype, received 10 HF-rTMS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). All patients were classified as at least stage III TRD and were assessed with the Temperament and Character Inventory (TCI) before a HF-rTMS treatment. Only the individual scores on SD predicted clinical outcome. No other personality scales were found to be a predictor of this kind of application. Our results suggest that refractory MDD patients who score higher on the character scale SD may be more responsive to the HF-rTMS treatment.Psychiatry Research 08/2014; 220(1-2). DOI:10.1016/j.psychres.2014.07.084 · 2.68 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Major Depressive Disorder (MDD) is a leading cause of disability globally. Currently available treatments have limited efficacy and combination strategies are frequently used. Several lines of research have demonstrated that MDD patients experience impairments in various components of affective processing, including regulation of affective states. To identify baseline and 1-week neuroimaging predictors of response to a 6-week trial of fluoxetine/olanzapine combination treatment during an affective processing task. Twenty-one MDD patients and 18 healthy controls were enrolled in the study. MDD patients were treated for 6 weeks with fluoxetine (40-60mg/day) and olanzapine (5-12.5mg/day). All participants viewed images from the International Affective Picture Rating System during a functional magnetic resonance (fMRI) scan at baseline and 1 week. There was a 57% response rate (defined as a 50% decrease in Hamilton Rating Scale for Depression-17 item) at 6 weeks. At baseline, responders had increased premotor activity while viewing negative images compared to non-responders and healthy controls. Higher baseline premotor activity was also predictive of greater percent change on the HAMD-17 and improvement in negative disposition and behavioral drive. Non-responders exhibited increased insular activity at baseline compared to responders. Higher activity in the posterior cingulate cortex was also predictive of greater percent change on the HAMD-17. Change from baseline to 1 week did not produce any significant predictive findings. Treatment with fluoxetine/olanzapine demonstrated similar biomarkers of response to monotherapeutic strategies. In particular, posterior cingulate cortex, anterior insula, and premotor cortex may show predictive differences in their response to affective images prior to treatment. Further research needs to be conducted to determine the utility of early changes in emotion circuitry in predicting antidepressant response.Journal of Affective Disorders 08/2013; 151(2). DOI:10.1016/j.jad.2013.06.050 · 3.71 Impact Factor