What is the recommended treatment for treatment-resistant depression in a patient taking gabapentin (Neurontin) 600 milligrams three times a day (TID), sertraline (Zoloft) 150 milligrams every day (qday), and bupropion (Wellbutrin) 300 milligrams daily?

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Last updated: May 6, 2025 • View editorial policy

From the Guidelines

For treatment-resistant depression in a patient already on gabapentin 600 mg TID, sertraline 150 mg daily, and bupropion 300 mg daily, augmentation with an atypical antipsychotic such as aripiprazole (starting at 2-5 mg daily, titrating up to 5-15 mg daily as needed) would be recommended. This approach is supported by the most recent and highest quality study available, which suggests that augmenting with another medication can be effective in treating treatment-resistant depression 1.

Key Considerations

  • The patient's current medication regimen includes gabapentin, sertraline, and bupropion, which target different neurotransmitter systems, and augmentation with an atypical antipsychotic may help address the underlying neurobiological mechanisms of the depression.
  • The American College of Physicians recommends that clinicians assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy 2.
  • Non-pharmacological approaches, including cognitive behavioral therapy and regular exercise, should be implemented concurrently to target different aspects of the depression.

Alternative Approaches

  • Adding lithium (starting at 300 mg twice daily, titrating based on levels to 0.6-1.0 mEq/L) could be an effective alternative approach if augmentation with an atypical antipsychotic is not feasible or effective.
  • Switching to a different antidepressant class like venlafaxine (starting at 37.5 mg twice daily, gradually increasing to 150-225 mg daily) might help if the current regimen is not effective.
  • For patients with severe symptoms unresponsive to medication changes, electroconvulsive therapy (ECT) should be considered as a last resort.

Monitoring and Follow-up

  • Regular monitoring for side effects and therapeutic response is essential, with assessment at 4-6 week intervals to determine effectiveness.
  • The patient's response to treatment should be closely monitored, and adjustments to the treatment plan should be made as needed to ensure optimal outcomes.

From the Research

Treatment Options for Treatment-Resistant Depression

The patient is currently on gabapentin 600 mg TID, sertraline 150 mg qday, and bupropion 300 mg daily. Considering the treatment-resistant depression, the following options can be explored:

  • Switching to a different antidepressant: This can be considered if the current medication is not effective 3.
  • Combining more than one antidepressant: Combining bupropion with other antidepressants like mirtazapine or tricyclics may be effective 3.
  • Augmenting an antidepressant with another medication: Augmentation with certain second-generation antipsychotics like quetiapine or aripiprazole, lithium, liothyronine (T3), or lamotrigine may be effective 3, 4, 5.
  • Somatic therapies: Electroconvulsive therapy, repetitive transcranial magnetic stimulation, or other modalities of brain stimulation may be considered 4, 6.

Augmentation Strategies

Augmentation with certain medications has shown efficacy in treatment-resistant depression:

  • Atypical antipsychotics: Aripiprazole, brexpiprazole, quetiapine, and olanzapine (fluoxetine) have shown significant response and remission rates 5.
  • Thyroid hormones: Liothyronine and levothyroxine (T4) have shown efficacy in augmentation therapy 5.
  • Lithium: Augmentation with lithium has shown significant response and remission rates 3, 5.
  • Dopamine compounds: Modafinil and lisdexamfetamine have shown efficacy in augmentation therapy 5.

Considerations

When selecting a treatment option, it is essential to consider the patient's individual needs and preferences 3. A shared decision-making approach is recommended to guide treatment selection. The patient's current medication regimen, medical history, and potential side effects should be taken into account when exploring new treatment options.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.