What are the next steps for a patient with major depression who is not responding to Zoloft (sertraline) 100mg?

From the Guidelines

For a patient with major depression not responding to Zoloft (sertraline) 100mg, the next steps should include optimizing the current medication by increasing the dose to the maximum recommended amount of 200mg daily, as many patients require higher doses for therapeutic effect, as suggested by the American College of Physicians 1. If dose optimization fails after 4-6 weeks, switching to another antidepressant from a different class such as an SNRI like venlafaxine (starting at 37.5mg twice daily and titrating up) or mirtazapine (starting at 15mg at bedtime) would be appropriate. Alternatively, augmentation strategies could be employed by adding medications like bupropion (150mg daily initially) or an atypical antipsychotic such as aripiprazole (2-5mg daily), considering the patient's response and tolerability to these medications, as recommended by the American College of Physicians 1. Referral to a psychiatrist is warranted for treatment-resistant cases, especially if considering more specialized approaches like transcranial magnetic stimulation or electroconvulsive therapy, as suggested by the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline 1. Throughout this process, it's essential to reassess for complicating factors such as substance use, medical conditions, or bipolar disorder that might be affecting treatment response. These approaches are based on the understanding that depression involves multiple neurotransmitter systems, and patients often require individualized approaches targeting different neurochemical pathways when first-line treatments fail. Some key considerations include:

• Monitoring for suicidal thoughts and behaviors, especially during the first 1 to 2 months of treatment, as advised by the U.S. Food and Drug Administration 1.
• Evaluating the effectiveness of combination therapy and considering whether any second-generation antidepressant is better than another in patients who either did not respond to or could not tolerate a first-line treatment, as recommended by the American College of Physicians 1.
• Considering the use of ketamine and esketamine in patients who have not responded to other treatments, as suggested by the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline 1.

From the FDA Drug Label

Patients not responding to a 50 mg dose may benefit from dose increases up to a maximum of 200 mg/day.

• The patient is currently on Zoloft 100mg, which is within the recommended dose range for major depressive disorder.
• Since the patient is not responding to the current dose, a dose increase to a maximum of 200 mg/day may be considered.
• However, it is essential to note that the patient is already on a dose of 100mg, and any further increases should be made with caution and under close monitoring.
• The FDA label does not provide specific guidance on adding additional antidepressants, so this option is not directly supported by the label 2.

From the Research

Next Steps for Treatment-Resistant Depression

For a patient with major depression who is not responding to Zoloft (sertraline) 100mg, several strategies can be considered:

• Augmentation with another medication: Adding another medication to the existing treatment regimen, such as lithium, thyroid hormone, or atypical antipsychotics, may be effective 3, 4.
• Switching to a different antidepressant: Switching to a different antidepressant, such as bupropion or mirtazapine, may be considered 5.
• Increasing the dose of sertraline: Increasing the dose of sertraline to 200 mg/day may be effective, but the response rate may be lower compared to continuing the treatment with 100 mg/day sertraline 6.
• Extending the duration of treatment: Continuing the treatment with 100 mg/day sertraline for a longer period, at least until week 8, may result in a substantial increase in the accumulated response rate 6.

Considerations for Augmentation Strategies

When considering augmentation strategies, it is essential to note that:

• Atypical antipsychotics may have higher response rates compared to antidepressant monotherapy and placebo, but also have more withdrawals due to adverse events 3.
• Lithium and thyroid hormone have substantial controlled evidence to support their use as augmentors 4.
• Buspirone, testosterone, methylphenidate, yohimbine, inositol, and atomoxetine have no evidence of clinical efficacy as measured by response in augmentation 3.

Patient-Specific Factors

Patient-specific factors, such as the presence of melancholic features, do not appear to influence the overall post-randomisation response rate 6. However, patients who complete an initial treatment of 12 weeks or more and have a partial response with residual mild depressive severity may benefit more from augmentation relative to switching 5.