Question

What could you have done instead of using this off-label augmentation to obtain the same mechanism of action of SRI plus NRI?

Switching to an SNRI, such as duloxetine (Cymbalta), venlafaxine-ER (Effexor-XR), desvenlafaxine (Pristiq), or levomilnacipran (Fetzima), would accomplish the same dual mechanism of action in a monotherapy

Add a noradrenergic TCA, such as desipramine (Norpramin), protriptyline (Vivactil), or nortriptyline (Pamelor), in order to add NRI properties to his current SSRI

Case outcome: interim follow-up visits through nine months (continued)

Patient now takes sertraline 100 mg/d and atomoxetine 80 mg/d

• – There are minimal to no side-effect complaints now

• – He is perhaps 70% better overall, reporting improvements in every residual symptom

• – Has bouts of low energy, poor memory, and concentration

• – Atomoxetine is a CYP450 2D6 substrate and his plasma levels may be higher than his oral dose suggests, due to sertraline’s concomitant use

He is leery of adding a third prescription antidepressant agent as he has been side effect free

Nutraceuticals are discussed as an option and he agrees to augment the given two medications, based upon a recent literature search suggesting that SAMe 800–1200 mg/d can augment SSRI with minimal side effects, as it is an over-the-counter product found in the vitamin section of most pharmacies

He is titrated to 800 mg twice a day

He returns and states that his MDD symptoms are in remission and he is without any adverse effects

Case debrief

The patient suffered from a single episode of MDD that was moderate in intensity

He was a partial responder to SSRI monotherapy

With assurance, he was able to tolerate the SSRI, and over time, his initial paresthesia-like side effects resolved and he was able to carry through with a full therapeutic SSRI trial

He was a responder to SSRI plus NRI augmentation

He remitted with the addition of SAMe

Take-home points

In treating MDD, starting with aggressive SSRI monotherapy can be effective

With recent approvals for atypical antipsychotic augmentations for MDD, sometimes clinicians forgo clinically reasonable and now classic combinations such as adding bupropion or buspirone

If NRI facilitation is not tolerated with the bupropion product line, there are other NRI-possessing agents in the armamentarium that may be added instead

Certain nutraceuticals (vitamins, minerals, cofactors, supplements) are beginning to develop an evidence base that contains in its literature some moderate-sized, randomized, and controlled studies

These agents often have a more benign side-effect profile and might be used effectively to foster remission in those patients who are 70%–80% less depressed, but require final fine tuning, or improvement, of tenuous residual symptoms without imposing a major side-effect burden

Performance in practice: confessions of a psychopharmacologist

What could have been done better here?

• – Instead of three medications being used to foster remission, perhaps an SNRI monotherapy may have worked if started initially instead of the SSRI

• – IPT, if available, would have been an ideal, side-effect-free approach

Possible action items for improvement in practice

• – Research the availability and evidence base for nutraceutical use in treating MDD

• – Review textbooks to remember and maintain how antidepressant combinations and augmentations act mechanistically so that polypharmacy is rational with regard to agent selection