Case outcome: interim follow-up visits through four months

The patient appreciates his improvements so far and states his hands are not as problematic

Agrees to final maximization of sertraline (Zoloft) up to 200 mg/d

Appears to have resolution of a few MDD symptoms and others are felt to be moderately improved

Now is considered a responder but not in remission from the maximal dose SSRI monotherapy

Question

What would you do next?

Switch to a new SSRI

Switch to an antidepressant that is not an SSRI

Combine his current SSRI with a non-SSRI antidepressant

Augment his current SSRI

Refer for MDD-specific IPT

Case outcome: interim follow-up visits through six months

Patient continues the SSRI and agrees to combine with the NDRI bupropion-XL (Wellbutrin-XL) starting at 150 mg/d

• – There is an initial boost in energy and alertness, but that falters after two weeks

Bupropion-XL is increased to the minimum effective approved monotherapy dose of 300 mg/d

• – There is no additional benefit now but he is tolerating it well

The bupropion-XL is increased to the maximum approved dose of 450 mg/d

• – Sertraline (Zoloft) is lowered down to 100 mg/d

  • This is done partially as the 200 mg/d dose was not felt to be robustly different from the 100 mg/d dose clinically, in retrospect

• – Additionally, sertraline is a weak to moderate CYP450 2D6 hepatic enzyme inhibitor

  • Bupropion is also a 2D6 inhibitor and a substrate

  • Bupropion at doses greater than 450 mg/d are known to cause seizures

• – This patient is not in a contraindicated group, but his sertraline is lowered to attempt to keep his bupropion plasma levels below theoretically dangerous levels

• – Despite this, he returns with intention hand tremors and tinnitus side effects. Interestingly, his hand paresthesias have dissipated

• – He stops smoking unexpectedly

Question

How did this patient stop smoking unexpectedly? Without trying?

Some patients just stop

Some bupropion preparations are approved as antidepressants (Wellbutrin-IR, -SR, -XL) and one is approved and marketed as a smoking cessation agent (bupropion-SR [Zyban])

Most often when used with smoking cessation, bupropion-SR is paired with a behavioral intervention of determining a smoking cessation date, identifying triggers for smoking relapse, and preparing for change

Sometimes patients lose the drive to smoke without these behavioral interventions, suggesting a purely neurochemical anti-smoking effect

Attending physician’s mental notes: visits through six months

This appeared initially to be a simple, moderate episode of MDD

The patient is now resistant to SSRI plus NDRI combination therapy and only is a responder, not a remitter

There are increasing side-effect problems and tolerating high doses of the NDRI was not possible

There were some vegetative symptom improvements while on the NDRI

Case outcome: interim follow-up visits through nine months

The problematic bupropion (Wellbutrin-XL) is discontinued

He is maintained on the sertraline (Zoloft) 100 mg/d as it has given him a solid, sustained response

Next, he is augmented with the approved ADHD medication atomoxetine (Strattera), and this off-label approach is explained to the patient in that

• – It may be warranted as some of his residual MDD symptoms include poor memory, concentration, and inattention

• – Atomoxetine is approved for treating inattention and poor concentration associated with ADHD and these symptoms appear similar to some of his MDD symptoms

• – Atomoxetine is an NRI, which is one of bupropion’s mechanisms of action and might be used in the hope of continuing better effectiveness with less tremor and tinnitus