Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines

Abstract

Background Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression. This review provides a definitive overview of pharmacological augmentation recommendations by assessing the quality of guidelines for depression and comparing the recommendations made. Methods A systematic literature search identified current treatment guidelines for depression published in English. Guidelines were quality assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Data relating to the prescription of pharmacological augmenters were extracted from those developed with sufficient rigor, and the included recommendations compared. Results Total of 1696 records were identified, 19 guidelines were assessed for quality, and 10 were included. Guidelines differed in their quality, the stage at which augmentation was recommended, the agents included, and the evidence base cited. Lithium and atypical antipsychotics were recommended by all 10, though the specific advice was not consistent. Of the 15 augmenters identified, no others were universally recommended. Conclusions This review provides a comprehensive overview of current pharmacological augmentation recommendations for major depression and will support clinicians in selecting appropriate treatment guidance. Although some variation can be accounted for by date of guideline publication, and limited evidence from clinical trials, there is a clear need for greater consistency across guidelines to ensure patients receive consistent evidence-based care.

The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders: Major depression summary

“…37,38 Again, it is important to note that the augmenting agent is acting upon the primary antidepressant effect of the initial antidepressant prescribed and so if one augmentation strategy is ineffective, another augmenting agent can be trialled. 39 However, if augmentation as a strategy is ineffective, then all the medications that have been prescribed as part of the strategy should be removed when switching to another medication. 40 Generally speaking, as per Figure 6, agents with a broader spectrum of action generally have greater efficacy but are also more likely to produce side-effects.…”

“…akathisia in the short‐term and weight gain, metabolic disruption and tardive dyskinesia in the long‐term) 37,38 . Again, it is important to note that the augmenting agent is acting upon the primary antidepressant effect of the initial antidepressant prescribed and so if one augmentation strategy is ineffective, another augmenting agent can be trialled 39 . However, if augmentation as a strategy is ineffective, then all the medications that have been prescribed as part of the strategy should be removed when switching to another medication 40 .…”

A retrospective examination of care pathways in individuals with treatment-resistant depression

“…Therefore, the LQD sample may have selectively recruited a sample not treated in line with guidance for this step. Having said that, many other first- and second-line adjunctive treatments are commonly used in TRD, 14 , 23 and even allowing for the exclusion of lithium and quetiapine, given the current episode duration and number of treatments trialled within the episode, a higher rate of adjunctive treatment would have been expected in these patients.…”

“…6 This was identified as a treatment gap by Wiles et al 10 The fourth treatment gap is 'steps to adjunctive treatment'. As part of the best-practice stepped care treatment pathways, all the major UK prescribing guidelines recommend augmentation with atypical antipsychotics or lithium when individuals with depression have failed to adequately respond to two first-line treatments, 14 and this is supported by meta-analysis. 15 After two unsuccessful monotherapy trials of antidepressants, switching to a third tends to result in reduced response rates, 16 whereas augmenting increases response rates.…”

Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression

“…Depression, once diagnosed, is clinically treated with anti-depressants and cognitive behavioral therapy (CBT). In patients where the anti-depressant regimen is not eliciting a response, an additional drug from a different pharmaceutical group has proved to have a significant effect [19,20]. However, long-term and extensive pharmacotherapy are almost always associated with the extent of undesirable effects on the patient like the risk of major adverse cardiovascular events, decline in cognitive functioning over time, behavioral changes including but not limited to sexual problems, and feeling of "emotional numbness."…”