Case outcome: first interim follow-up visit four weeks later

Patient was tolerating the low-dose mirtazapine (Remeron) except for carbohydrate-craving side effects

• – It was increased to 30 mg/d

Next, she is placed on chromium picolinate 200 mcg/d as an antidote to her carbohydrate cravings

• – Evidence base suggests that use of this agent up to 1000 mcg/d may reduce carbohydrate cravings in MDD patients

• – Anecdotal reports suggest it may reduce AAWG

• – A larger evidence base suggests it improves insulin sensitivity and may be mildly effective in treating some diabetes patients

Between sessions insomnia escalates and she calls reporting that she had to take extra zolpidem (Ambien) to compensate

• – She panics more when she cannot sleep and her depressive symptoms worsen as a result

• – She does not seem to be abusing the hypnotic agent but the pattern is worrisome

Upon return, there is slightly less dysphoria and agitation

Affect is moderately brighter

Carbohydrate craving is moderately diminished

Insomnia is evaluated and appears partially driven by the MDD symptoms, but also has a phobic, fear-like quality more consistent with insomnia as if it were a clear comorbidity in itself

• – DSM-5 allows insomnia to be a comorbid diagnosis if it is a focus of clinical attention even if, in part, the insomnia is felt to be secondary to MDD

Admits now to mixing her zolpidem and zolpidem-CR and overusing them as she wakes up in the middle of the night sometimes

Question

What would you do next?

Increase the mirtazapine (Remeron) as she seems to be responding better with each dose escalation

Change her hypnotic agent to another with a longer half-life to allow better sleep maintenance

Change her hypnotic agent from her current, sleep center-selective BZRA zolpidem to a true BZ hypnotic that is less selective and possibly able to allow for hypnosis, anxiolysis, and muscle relaxation

Change her hypnotic to one that is not a controlled substance due to fear of pending addiction

Leave medications the same as she is appearing to respond to moderate-dose mirtazapine

Attending physician’s mental notes: second interim follow-up visit at two months

Despite being a little better, she is not a full responder to full-dose mirtazapine (Remeron)

This drug is involved in the CYP450 system, but its metabolism is divided among different enzymatic pathways

• – The patient is not deficient on all pathways and has tolerated this medication well, except for her reported hair loss

• – She does not seem to be having any major systemic side effects but is growing wary of the medication

• – It is possible that she is having side effects from her CYP450 enzymatic 2C19 deficiency regarding mirtazapine metabolism, but more likely at this point, is highly somatic and suffers anxiety-induced side effects

  • These are erroneously attributed to the medicine

  • These are often called “nocebo” effects as they are placebo-induced

She is particularly fixed on the hair loss (approved package insert suggests 1/10,000 chance), refuses augmentation with zinc or selenium, and refuses to accept that it might be related to her stress, that in turn requires more aggressive treatment

She states that she is “fed up” with antidepressants and just needs her sleep and wants to focus on treating her insomnia

She believes that her insomnia drives her MDD symptoms and that her MDD will resolve if she sleeps better