Question

What would you do next?

Increase the dose of her olanzapine (Zyprexa) augmentation

Switch the mirtazapine to an SSRI, which may mimic the approved olanzapine–fluoxetine combination drug (Symbyax), which is approved specifically for TRD

As she is a partial responder and has failed many therapeutic trials, could combine with a second approved antidepressant such as bupropion (NDRI), or trazodone (SARI), or an SNRI

As she is a partial responder with a minimal response and has failed many therapeutic trials, could augment with a stimulant or a nutraceutical

• – L-methylfolate (Deplin) 15 mg/d

• – SAMe 400–800 mg twice a day

• – N-acetyl cysteine (NAC) 1000 mg twice a day

Continue to wait on the current regimen and PDP for full effectiveness to occur

Attending physician’s mental notes: second interim follow-up visit at three months (continued)

The patient seems to be losing some ground after her hospitalization in that she is experiencing increased guilt and recurrent negative thoughts

• – This seems triggered by the sedating side effects

Her affect did appear better after the addition of the atypical antipsychotic, which is dosed low at this point

Likely now is sedated by medications and needs to be addressed

Case outcome: interim follow-up visits through six months

To honor the patient’s request for less fatigue-based side effects, she is tapered off the zolpidem-CR hypnotic agent in the hope of alleviating the morning sedation, but the lorazepam is continued for anxiolysis

The relatively ineffective mirtazapine and lamotrigine are discontinued

Next is switched to olanzapine–fluoxetine combination (Symbyax) and titrated to the 6 mg/50 mg/d dose

• – This combination agent is approved for TRD

• – The insomnia returns and a SARI, trazodone(Desyrel) 150 mg at bedtime, is added to the regimen to treat insomnia, but may also act as an antidepressant augmentation

She ultimately improves and is considered a responder as she is 50% improved

• – There is less symptom severity and she starts exercising and socializing again

• – Anxiety is no longer felt to be chronic and pervasive but appears situational and more manageable

Question

What would you do next?

Make no changes as she is a responder to her medications and PDP is ongoing and should improve her symptoms gradually with time

Escalate the olanzapine–fluoxetine (Symbyax) combination dose to better gain remission

Augment the current regimen with lithium or thyroid hormone to better gain remission

Augment the current regimen with a stimulant

Augment her current regimen with a nutraceutical

Attending physician’s mental notes: interim follow-up visits through six months

Patient is 50% better on a regimen essentially of an atypical antipsychotic, an SSRI, a BZ, and an alpha-adrenergic-1 receptor antagonizing hypnotic/SARI antidepressant

Given her recurrent MDD, and previous attempts with at least four medication trials to obtain a response, she unfortunately is likely to relapse into MDD within the next 6 to twelve months, even if continuing current treatment, especially as she is not in full MDD remission now

Will need to monitor her closely and intervene if relapse is pending

It is likely worth pushing forward with more aggressive antidepressant augmentation now, to better aim for remission, which is needed to better avoid a depressive relapse