Case outcome: interim follow-ups through nine months

The patient reports that aripiprazole (Abilify) has removed all of her passive suicidal thinking, which has not resolved with any prior treatment over many years. She is very happy with this clinical outcome but still admits to a moderate amount of depressive symptoms

Her chief complaint is of fatigue and relative amotivation despite being on therapeutic SNRI, NDRI, and an atypical antipsychotic

She has no TD/EPS, metabolic or acute side effects, and is tolerating her regimen well

Question

What would you do next?

Increase the aripiprazole (Abilify) upward to 30 mg /d despite the average dose for MDD patients being 11 mg/d

Augment the current regimen with a stimulant medication to treat fatigue and amotivation specifically

As she is still a partial responder only, remove all medications and convert to an MAOI

Attending physician’s mental notes: 9–12 month follow-ups

Despite being still a partial responder and non-remitted, this patient is better than her usual baseline. It may be risky to remove any of her three main antidepressant agents. Adding another medication increases cost and side-effect burden

In targeting her remaining vegetative symptoms, her current medications enhance norepinephrine (NE) by using an SNRI plus an NDRI effectively, and therefore, improving DA neurotransmission may be an important next step

To increase DA activity, classic stimulants might be used but carry addiction risk for this patient. New generation wakefulness-promoting agents such as modafinil (Provigil) or armodafinil (Nuvigil) have less addiction risk and more empirical evidence for treating fatigue symptoms. Direct D2 receptor agonists such as pramipexole (Mirapex) or ropinirole (Requip) might be used but tend to have some sedating side effects

Washing out her medications in order to utilize an MAOI might risk full recurrence of depression and thwart our current gains

• – Interestingly, some MAOI antidepressants have amphetamine-based metabolites, which may better target and improve fatigue

Question

How much do you weigh this patient’s previous addiction to alcohol when determining the next step?

Very much, she will likely become addicted to any controlled substance

Somewhat, her addiction to alcohol may be triggered more by BZ use than stimulant or other controlled drug use as other agents are dissimilar to alcohol pharmacodynamics (GABA-A receptor PAM)

Not much as addiction risk is minimal and can be monitored with pill counts, urine drug screens, and breathalyzer testing, if needed

Case outcome: interim follow-ups through 12 months

Bupropion-XL (Wellbutrin-XL) is discontinued and modafinil (Provigil) is started, as it is less addicting than a formal stimulant and may facilitate wakefulness through the DA system to a greater extent than bupropion, but also theoretically via downstream histamine and orexin pathway facilitation. However, her insurance refuses to cover modafinil

Therefore, the patient is issued the isomer product armodafinil (Nuvigil) due to availability of voucher coupons that enables a therapeutic trial to occur

• – Therapeutically, it was in the patient’s interest to fight for access to modafinil

• – Therapeutically, it was in the patient’s interest for the prescriber to meet with a sales team and procure samples

Armodafinil (Nuvigil) is titrated throughout a full dose range up to 250 mg/d without an antidepressant response and with minimal improvement in her vegetative symptoms. She did not misuse this product

Armodafinil is discontinued and methylphenidate-LA (Ritalin-LA) is started

• – In this manner, the prescriber switches from a less addictive product to a slightly more addictive product

• – Utilizing a slow release preparation of a stimulant allows for slower absorption and less likelihood of withdrawal or intoxication

• – These pharmacokinetic properties allow for less drug-liking properties from the stimulant and theoretically could lower addiction risk overall in this patient

Methylphenidate-LA (Ritalin-LA) is titrated upward to 30 mg/d with very little effect, but again with good tolerability

Blood pressure remains normal, and likely the use of stimulant medication acts as an appetite suppressant minimizing long-term weight gain from her other antidepressants

No abnormal movements are observed and no acute side effects from her complex medication regimen are reported