Question

Considering her current medication failures (SSRI, SNRI, stimulant, and antiepileptic), what would you consider next?

Discontinue current ineffective medications and

• – Start a new SNRI and consider combining with an NDRI such as bupropion-XL (Wellbutrin-XL), which all together continue to facilitate synaptic DA, NE, and serotonin (5-HT), albeit with a different combination of medications

• – Remove lamotrigine (Lamictal), maintain the SNRI, and add mirtazapine (Remeron), a NaSSA, instead seeking a “California rocket fuel” combination to maximize synaptic NE and 5-HT

• – Remove all agents, washout, start an MAOI

• – Refer for ECT, VNS, TMS treatments

• – Refer for a course of group CBT

Attending physician’s mental notes: four months

The patient has been compliant with visits and medications

She now has several failed full medication trials where the drugs inhibit monoamine reuptake pumps

Weight-gain potential medications like mirtazapine (Remeron), the TCAs, and the atypical antipsychotics will not be appreciated by the patient

The newer MAOI transdermal patch selegiline (Emsam) has data suggesting minimal weight gain and utilizes a novel mechanism of action elevating all three monoamines in one monotherapy, and may be a rational choice

Case outcome: interim follow-ups through six months

The patient accepts education and the risks of drug and diet interactions and starts this MAOI after appropriate washout of her previous antidepressants

• – An appropriate washout in this case was a gradual taper off of each medication to avoid withdrawal, followed by five half-life duration waiting periods specific to each agent prior to MAOI initiation

Selegiline (Emsam) patch is escalated eventually to the full 12 mg/d maximal dose but without any clinical response

This drug is discontinued and appropriate washout implemented

• – Two weeks must lapse prior to a contraindicated medication being started

• – This allows for adequate replenishment of MAO enzymes to be synthesized and return of drug metabolism to normal capability

She elects, despite some weight-gain potential, to take a TCA and is titrated to therapeutic doses and levels of nortriptyline (Pamelor), but also without clinical response

Weight begins to increase

Metformin (Glucophage) is a diabetes medicine known to cause weight loss and is initiated and titrated to 2000 mg/d, and weight gain is halted but not reversed

• – There is a reasonable evidence base to support the use of metformin prophylactically or after the fact to lower or inhibit AAWG

She has gained 15 lbs

Laboratory blood samples are drawn and renal function is normal and there is no acidosis with metformin use. Blood glucose is normal

The wakefulness-promoting agent modafinil (Provigil) is added now to her current TCA as a depression augmentation, and titrated eventually to 400 mg/d

Her chief symptoms continue to be anhedonia, blunted affect, and low energy

There was only a minimal response and weight starts to increase on this combination again

Orlistat (Xenical) is an approved weight-loss medication, which patient agrees to start (360 mg/d). It is a fat-blocking (intraluminal lipase inhibitor) drug with two-year regulatory effectiveness in overweight patients but has a minimum of evidence for its use in iatrogenic weight gain from psychotropic administration