From the Guidelines
Antipsychotic augmentation is a viable treatment strategy for mixed depressive episodes with comorbid anxiety disorders, particularly when first-line treatments have failed, as evidenced by the most recent and highest quality study 1. When considering antipsychotic augmentation, it is essential to weigh the potential benefits against the risks, taking into account the patient's medical history, current medications, and response to prior treatment, as well as patient preference 1. The treatment approach should be tailored to the individual patient, using a stepped care model that considers variables such as current symptomatology level, presence or absence of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) diagnosis, level of functional impairment, presence or absence of risk factors, history of and response to previous treatments, and patient preference 1. Some key points to consider when implementing antipsychotic augmentation include:
- Initiating treatment with low-dose atypical antipsychotics, such as aripiprazole (2.5-5mg daily), quetiapine (25-300mg daily), or brexpiprazole (0.5-2mg daily), as adjuncts to antidepressants
- Gradually titrating the dose over 2-4 weeks to minimize side effects
- Monitoring treatment efficacy with a 4-8 week trial, and continuing treatment for 6-12 months if beneficial
- Close monitoring for metabolic effects, extrapyramidal symptoms, and sedation, with baseline and follow-up measurements of weight, blood pressure, fasting glucose, and lipids
- Regular reassessment of the need for continued antipsychotic treatment to minimize long-term exposure and potential adverse effects It is crucial to note that the certainty of evidence for most comparisons is low, and findings should be interpreted cautiously, as highlighted in the systematic review and network meta-analysis by the American College of Physicians 1. However, antipsychotic augmentation can be an effective strategy for treating mixed depression and anxiety, particularly in patients with treatment-resistant symptoms, prominent anxiety features, or those experiencing breakthrough symptoms despite adequate antidepressant therapy.
From the Research
Antipsychotic Augmentation in Treating Mixed Depressive Episodes
- Antipsychotic augmentation is a potential treatment strategy for patients with major depressive disorder (MDD) and comorbid anxiety disorders who have not responded to initial antidepressant treatment 2, 3, 4, 5, 6.
- Studies have shown that atypical antipsychotics, such as aripiprazole, quetiapine, and olanzapine, may be effective as adjunctive therapy in MDD, particularly in patients with treatment-resistant depression 3, 5, 6.
- Aripiprazole, in particular, has been found to be effective in improving depressive and anxiety symptoms in patients with MDD and comorbid anxiety disorders 2, 5, 6.
Efficacy and Safety of Antipsychotic Augmentation
- The efficacy of antipsychotic augmentation in treating MDD with comorbid anxiety disorders is supported by several studies, including randomized controlled trials and systematic reviews 3, 5, 6.
- However, antipsychotic augmentation may also be associated with increased adverse effects, such as metabolic side effects, which can lead to discontinuation of treatment 3, 5, 6.
- The safety and efficacy of antipsychotic augmentation should be frequently reassessed, and dosage should be individualized to minimize adverse effects 3.
Treatment Approaches for Comorbid Anxiety and Depression
- Treatment of comorbid anxiety and depression may require specific psychopharmacological adjustments, including the use of serotonin reuptake inhibitors, atypical antipsychotics, and benzodiazepines 4.
- Combination and augmentation therapies may be necessary for positive outcomes in patients with comorbid anxiety and depression 4, 5.
- A "stacking approach" may be recommended for treatment-resistant patients, involving the use of multiple medications and therapies to achieve optimal treatment outcomes 4, 5.