From the Guidelines
Treatment for treatment-resistant depression should prioritize a combination of medication adjustments, psychotherapy, and intensive interventions, with electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) being highly effective options, as supported by the most recent and highest quality study 1. When managing treatment-resistant depression, it's essential to consider the patient's history of previous treatment attempts and the severity of their symptoms. The definition of treatment-resistant depression can vary, but most studies agree that it involves a lack of response to at least two adequate pharmacologic treatment trials 1. Some key considerations for treatment include:
- Switching antidepressants to a different class, such as from an SSRI to an SNRI like venlafaxine
- Augmenting current medication with additional agents, such as atypical antipsychotics like aripiprazole or quetiapine, or combining with lithium
- Adding bupropion to an existing SSRI
- Considering ECT or TMS for patients who don't respond to medication changes
- Continuing psychotherapy, particularly cognitive behavioral therapy, and addressing lifestyle factors like sleep, exercise, and social support The most recent study 1 found that rTMS had a significantly higher response and remission rate compared to sham treatment, with a number needed to treat of 3.4 to 9 patients for response and 5 to 7 patients for remission. However, another study found no significant differences between rTMS and sham treatment in a veteran population with high rates of comorbid posttraumatic stress disorder and substance use disorder 1. Overall, the treatment of treatment-resistant depression requires a comprehensive and individualized approach, taking into account the patient's unique needs and circumstances, and prioritizing the most effective and evidence-based treatments, as supported by the most recent and highest quality studies 1.
From the Research
Treatment-Resistant Depression
Treatment-resistant depression (TRD) is defined as the absence of remission despite trials of two or more antidepressant medications and can occur in up to 31% of patients with major depressive disorder 2.
Management Strategies
Management strategies for TRD include:
- Adding psychotherapy
- Switching antidepressant medication class
- Augmenting with additional medications
- Current guidelines recommend augmentation with a second-generation antidepressant, an atypical antipsychotic, tricyclic antidepressants, lithium, or a triiodothyronine medication as pharmacologic options 2
- Ketamine and esketamine can also be used as augmentation for treatment-resistant depression and may help reduce suicidal ideation 2
- Electroconvulsive therapy and repetitive transcranial magnetic stimulation may be effective 2
Psychotherapies for TRD
Psychotherapies for TRD include:
- Cognitive-behavioural therapy (CBT)
- Intensive short-term dynamic psychotherapy (ISTDP)
- Interpersonal therapy (IPT)
- Group dialectical behavioural therapy (DBT)
- Moderate-quality evidence shows that psychotherapy added to usual care (with antidepressants) is beneficial for depressive symptoms and for response and remission rates over the short term for patients with TRD 3
Pharmacological Interventions
Pharmacological interventions for TRD include:
- Augmenting current antidepressant therapy with mianserin or with an antipsychotic (cariprazine, olanzapine, quetiapine or ziprasidone) improves depressive symptoms over the short-term (8 to 12 weeks) 4
- Augmentation with buspirone provides no evidence of a benefit in terms of a reduction in depressive symptoms or numbers of drop-outs 4
- Serotonin and norepinephrine reuptake inhibitors, such as venlafaxine and duloxetine, are also used to treat TRD 5
Challenges and Strategies
Challenges in managing TRD include:
- Confounds in the definitions and staging models of TRD
- Difficulties inherent in assessing the illness
- Further large-scale work is necessary to understand the appropriate treatment pathways for TRD and to prescribe effective therapeutic options for patients suffering from TRD 6