Case debrief

Interferon is well known to induce depression. This patient seems to have developed her first MDE after interferon

She was highly anxious and agitated as well

Throughout sessions it became clear that her anxiety was interfering with her ability to tolerate her medications more so than her well-known CYP450 vulnerabilities

However, both of these needed to be taken into consideration routinely during her treatment

The primary focus turned toward providing relief from her insomnia and anxiety target symptoms, only to be thwarted in that sedative–hypnotics were mildly effective but caused sedation, preventing her from being dose-escalated but better treated

Finally, after being advised to take lithium, the patient terminated care as she was unwilling to be put on other medications

She was essentially left on the zolpidem BZRA preparations, which was similar to her situation when she came to her first office visit

Interestingly, during one session, device-based MDD treatments (ECT, VNS, TMS) were discussed

• – The patient later remembered the TMS discussion and inquired about this with an outside provider

• – She had a modest antidepressant response but not remission after she proceeded with a course of TMS therapy

  • Daily right DLPFC stimulation for three to four weeks

• – TMS became a good choice as it has no drug interactions, is not a “medication,” thus allowing for fewer side effects in her mind, and it matched her idea of what a better tolerated treatment would be

This case shows that a patient’s fear about taking medication can thwart his/her compliance, leaving him/her undertreated and remaining symptomatic

Despite best efforts in psychoeducation, bibliotherapy, allowing patient freedom of choice and control of medication in a partnership fashion, micro-titrating at very subtherapeutic doses, using medications that would not interfere greatly with her CYP450 enzymatic deficiencies, enlisting help of a psychotherapist for psychotherapy, and use of much patience and countertransference containment, she continued with poor compliance and almost no sustained partial response at all

TMS allowed for a good MDD response (nearly 70% symptom improvement)

Take-home points

Anxious patients often do not respond well to medication management and often develop amplified side effects or even nocebo effects, where just the thought of being on a medication increases placebo-based side effects

Many supportive techniques are often needed to help compliance and thus improve outcome

Sometimes treating a chief complaint or prioritized symptom, instead of the syndrome or disorder, may be helpful at first

Performance in practice: confessions of a psychopharmacologist

What could have been done better here?

• – Despite a change in strategy to treat her insomnia and agitation symptomatically, this approach did not work

  • This patient likely required higher doses of sedative

  • Even though she tolerated sedatives better than antidepressants, she was still left with fatigue, which was disheartening

  • Perhaps trying a myriad of different sedatives with differing absorption and half-lives may have worked better for her and the dose may have been escalated for better clinical effectiveness

Should TMS or device-based treatment been suggested sooner?

• – ECT actually could have been utilized effectively, but the patient was fairly rigid that ECT was too frightening and too severe a treatment

• – VNS could be helpful but she really did not meet regulatory criteria of four failed, full antidepressant trials, and VNS could take months to work

• – TMS fits fairly well in this case in that she had one full antidepressant failure and a few very subtherapeutic trials

Possible action items for improvement in practice

• – Research data for device-based treatments, specifically TMS, as it is the latest approved modality and contains regulatory wording for patients who have found antidepressants intolerable

• – Research the CYP450 enzyme systems or become more aware of available resources to use in patients with laboratory-based or clinically based diagnoses of CYP450 deficiencies

• – A simple technique is to internet search the drug’s name plus the word “metabolism.” Notice the many references at the end of this case

• – CYP450 drug interaction tables may also be searched and utilized, but sometimes these are more complicating and confusing