Question

Would you continue her aripiprazole (Abilify) for her TRD?

Yes

No

Attending physician’s mental notes: nine-month follow-ups

TD can become permanent, thus discontinuing the atypical antipsychotic makes sense to the clinician and the patient

The patient is aware that her MDD may recur and that increased visits and monitoring are needed as recurrence rate could be as high as 90% within a year

To avoid MDD recurrence and withdrawal dyskinesia, the atypical antipsychotic is discontinued over two to three weeks. The jaw movements subside over a few months. She is now diagnosed with temperomandibular joint (TMJ) syndrome as a result of her previously excessive jaw movements

The PMEs exacerbate, her stress-induced interpersonal issues escalate, but her depression is relatively stable while she is off the atypical antipsychotic and only on the SNRI

Question

If she gradually relapses into MDD, what would you consider?

Add a formal psychotherapy such as PDP or dialectical behavioral psychotherapy (DBT)

Add another atypical antipsychotic at risk of recurrent TD

Try another monotherapy (non-SSRI, non-SNRI) antidepressant approach

Try another augmentation approach (lithium, buspirone [BuSpar]), mood stabilizer such as gabapentin (Neurontin) or divalproex (Depakote)

None of these

Attending physician’s mental notes: interim follow-up through nine months (continued)

Lithium

• – Could help to boost her mood and mitigate risk of future relapse

• – If added, may still need to watch for weight gain and lithium toxicity

• – Will need laboratory follow-ups (cell blood count, creatinine, thyroid panel, drug levels, etc.)

Buspirone (BuSpar)

• – May help boost mood, as this has been an effective augmentation strategy for patients with MDD in some off-label trials and in clinical practice. The aripiprazole (Abilify) utilized a similar 5-HT1A partial receptor agonism so that buspirone may be the closest, non-TD-inducing mechanistic relative to aripiprazole

• – However, it does not have 5-HT2A or dopamine-2 (D2) receptor antagonism

• – Therefore, it may not be as calming, sleep promoting, or mood lability dampening

Other atypical antipsychotics (quetiapine [Seroquel-XR], lurasidone [Latuda])

• – Another trial is too risky given her recent TD remission, unless other non-TD-inducing treatments fail first

• – Clozapine (Clozaril) could be an option if an antipsychotic is clinically warranted

Mood stabilizers

• – The epilepsy drugs may be used as mood stabilizers and some can help mood lability in bipolar patients (per the FDA). Off-label data suggests this may help in personality disorders as well. Consider bipolar-approved sodium channel blocking lamotrigine (Lamictal) or carbamazepine (Equetro) or GABAergic divalproex (Depakote) as such. The calcium channel blocking medications gabapentin (Neurontin) and pregabalin (Lyrica) have off-label data suggesting more anxiolytic properties instead of mood stabilization properties

Case outcome and multiple interim follow-ups to 24 months

The patient was encouraged to add the 5-HT1A receptor partial agonist, buspirone (BuSpar), to her duloxetine (Cymbalta) and it was titrated to 45 mg/d

This failed and her MDD re-emerged at moderate levels with clear PMEs

Instead of combining other medications or augmenting her duloxetine (Cymbalta) again, the patient chose to taper off all medications and “start from scratch” as she had lost faith in the duloxetine, which was only marginally effective before the atypical antipsychotic augmentation

TD has fully resolved

Other monotherapies are offered, such as an NDRI, bupropion (Wellbutrin-XL), a noradrenergic and specific serotonergic antidepressant (NaSSA), mirtazapine (Remeron), or another SNRI (venlafaxine [Effexor-XR], desvenlafaxine [Pristiq], levomilnacipran [Fetzima])

The patient was switched from her SNRI plus Buspirone combination onto initial monotherapy with desvenlafaxine (Pristiq), another SNRI

• – This SNRI is utilized as it may have greater norepinephrine transporter (NET) inhibition properties. In other words, it may be a more effective norepineprhine reuptake inhibitor (NRI)

Titrated initially to 100 mg/d with minimal effect

Simultaneously, the patient’s obstetrician/gynecologist placed her on low-dose diazepam (Valium) 5–10 mg/d as needed as a muscle relaxant given her complaints of PMS to that clinician

Desvenlafaxine (Pristiq) was raised to 200 mg/d with a solid clinical response and no side effects. Unfortunately, mood lability with PMEs continued despite depression symptoms being remarkably lowered

It was suggested to take 200 mg/d desvenlafaxine routinely but to raise it to 300 mg/d during her luteal phase PMEs

This alternating dosing approach plus low-dose BZ was effective and she was maintained on this combination of SNRI plus BZ with very good symptom control (depression, PMEs, personality disorder-related lability, hallucinations)