Case debrief

This patient suffered from an index MDD episode that was moderate to severe

She had no previous treatment or family history to guide psychopharmacologic care

Any first-tier antidepressant or psychotherapy could be selected in her case

Genetic testing was ordered; suggested where her neurobiological vulnerabilities might lie and also indicated that many antidepressants could be ineffective

Instead of going back to randomly choosing an antidepressant, or even choosing one that is more risky, second- or third-tier to start with, the fMRI allowed for a decision to opt out of psychopharmacology and advise the patient toward psychotherapy, specifically CBT in this case

This could save weeks of non-response to unlikely psychopharmacologic agents

This could save weeks of untoward side effects and medication intolerability

Take-home points

Genetic testing as a clinical tool is still in its infancy, but has the potential to inform treatment decisions

Genotyping may be especially useful for patients who do not respond to or tolerate a drug as expected

Caution is essential when adopting genetic testing into the selection of treatments in clinical practice as the science is still in its infancy

fMRI use is also in its infancy and its use clinically has not come to fruition in practice as there is less fMRI availability and it is expensive compared to genetic testing

It is unlikely at this juncture that new patients with first-episode MDD will obtain genetic and functional neuroanatomic testing to delineate their genotype and endophenotype, but academically, the use of this science and technology could eventually guide the psychopharmacologist to more accurate and personalized treatment as is found in oncology practice

Eventually, software could also be developed and used to calculate the percent chance of response, remission, side effects, etc. for each specific medication, psychotherapy, and device-based treatment. At initial or first follow-up encounters, the psychopharmacologist could have very clear guidance and direction as to which type of treatment to try first

Posttest self-assessment question and answer

A 23-year-old patient with her first depression has the S/S genotype for the SERT gene, the Del/Del alleles for the D2 receptor gene, the VAL/VAL alleles for the COMT gene, the T/T alleles for the MTHFR gene, and the A/A alleles for the CACNA1C gene. She also had a brain fMRI completed and it shows that her right insular cortex was hypoactive. Based only on these genetic results and neuroimaging findings, what treatment might be preferred for this patient?

A. SSRI

B. An atypical antipsychotic

C. Lithium

D. NDRI like bupropion

E. A noradrenergic TCA like desipramine

F. A mood stabilizer like lamotrigine

G. A folate-boosting product such as L-methylfolate

H. CBT

Answer: H

All of the medications listed may be fraught with greater side effects and greater ineffectiveness, given the alleles this patient has inherited from her parents. There is no easy or perfect choice for an antidepressant. The fMRI finding suggests similarly, at least, that SSRI will likely not help alleviate depression but CBT will.

For this final case of this psychopharmacology case-based textbook, the answer may not be to institute a psychotropic at all. This patient likely should be referred to a CBT specialist for psychotherapy.

References

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