What is a good next option for treating depression and anxiety when a patient is maximized on Zoloft (sertraline)?

From the Guidelines

When a patient is maximized on Zoloft (sertraline) for depression and anxiety, adding bupropion (Wellbutrin) at 150-300 mg daily is a good next option, as it works on different neurotransmitters (dopamine and norepinephrine) than sertraline (serotonin), potentially addressing symptoms that sertraline alone doesn't manage. This approach is supported by low-quality evidence from a trial that showed no difference in response or remission for augmentation of citalopram treatment with bupropion compared with augmentation with buspirone, but augmenting with bupropion decreases depression severity more than augmentation with buspirone 1.

Some key points to consider when making this decision include:

• The patient's response to sertraline, including any partial response or lack of response
• The presence of any side effects or adverse events associated with sertraline
• The patient's preferences and values regarding treatment options
• The potential benefits and risks of adding bupropion or switching to another medication

Alternatively, switching to another SSRI like escitalopram (Lexapro) 10-20 mg daily or an SNRI such as venlafaxine (Effexor XR) 75-225 mg daily or duloxetine (Cymbalta) 30-60 mg daily may help patients who had partial response to sertraline. Augmentation with low-dose atypical antipsychotics like aripiprazole (Abilify) 2-5 mg daily or quetiapine (Seroquel) 25-300 mg daily can be particularly effective for treatment-resistant depression. For anxiety symptoms specifically, adding buspirone (BuSpar) 15-30 mg daily in divided doses can enhance anxiolytic effects without significant side effects. Any medication change should be implemented gradually, with careful cross-titration when switching medications to minimize discontinuation symptoms and side effects. Non-pharmacological approaches like cognitive behavioral therapy should be continued or initiated alongside medication adjustments, as the combination typically produces better outcomes than either approach alone 1.

From the Research

Next Steps for Treating Depression and Anxiety

When a patient is maximized on Zoloft (sertraline) and still experiencing symptoms of depression and anxiety, several options can be considered:

• Switching medications: Clinicians may choose to switch to a different antidepressant within the same class or to a different class to obtain a different neurochemical effect 2.
• Augmentation therapy: Adding another medication to the current treatment, such as atypical antipsychotics (e.g., aripiprazole, olanzapine, risperidone) 3, buspirone, lithium, or triiodothyronine, can be effective.
• Combining antidepressants: Combining two antidepressants with different mechanisms of action (e.g., bupropion + SSRI or mirtazapine + venlafaxine) can be considered 4.
• Adding cognitive behavioral psychotherapy: Adding cognitive behavioral psychotherapy to the treatment plan can be beneficial 5, 4.
• Using newer antidepressants: Newer antidepressants, such as mirtazapine, nefazodone, and venlafaxine XR, may provide benefits across the broad spectrum of anxiety disorders with improved safety and tolerability 6.

Considerations for Treatment-Resistant Depression

For patients with treatment-resistant depression, it is essential to:

• Optimize SSRI dosing: Ensure an adequate trial of the SSRI before switching to a different drug 5.
• Consider augmentation therapy: Augmentation therapy with medications like benzodiazepines, buspirone, beta blockers, tricyclic antidepressants, or valproate sodium can be effective 5.
• Take a step-wise approach: Take one or more additional steps to attempt to achieve remission, considering the comfort level of the primary care practitioner and the availability of psychiatry referral 4.