Precision Psychiatry in Practice: 3 Therapeutic Drug Monitoring Pearls

“It’s just so important to not guess when we are practicing medicine, and we have tools like therapeutic drug monitoring [TDM], which can aid our decision-making,” Jonathan Meyer, MD, said in a recent Psychiatric Times “Insights” video program.

Meyer, voluntary clinical professor of psychiatry at the University of California, San Diego, said with TDM, “everyone benefits. The patient benefits, because either they get better, or they get the appropriate care because they’re nonadherent.”

To support clinicians in implementing TDM, Meyer offered a clear, pragmatic road map for how TDM can improve outcomes in psychiatric care. He walked clinicians through the fundamentals of TDM, how it has evolved, and where the field is headed. Although the principles apply broadly, he focused the discussion on clozapine, where TDM has the greatest clinical impact.

1. TDM Helps Solve Variability in Metabolism, Adherence, and Clinical Response

“TDM really is measuring drug levels,” Meyer explained. He stressed that oral medications are particularly vulnerable to tremendous variations in adherence seen across patient populations. At the same time, patients exhibit wide biological variability in how they metabolize psychotropics, meaning that standard dosing may not yield standard plasma concentrations.

For these reasons, Meyer explained that TDM is helpful whenever “patients aren’t getting better the way we expect;” for example, when adverse effects don’t match the dose or when adherence is uncertain. He added that clozapine remains the clearest use case due to its well-established therapeutic threshold, with levels below about 350 ng/mL significantly reducing the odds of response. But reaching this level is only the beginning of the process, he said, noting “just getting toward the minimum response…does not always mean that the person is going to respond.”

Having the data and information available to avoid educated guesses is “the biggest value of therapeutic drug monitoring, and this is true for all antipsychotics,” Meyer added. “This is a group of people with a very serious mental illness. Why would you guess about what’s going on? Or even if they’re stable on oral therapy, why would you guess if they’re still adherent? Not everyone relapses when they stop their oral medications right away…. Why would you want to guess when you have measurement-based care that can assist your decision-making?”

TDM, then, becomes a precision-oriented tool, he added. It supports efficacy, clarifies failures, and protects patients from unnecessary toxicity.

2. TDM Has Evolved: Faster Turnaround, Better Technology, and Growing Guidelines

Meyer emphasized that the evidence supporting TDM has grown substantially. He referenced the 2020 joint consensus statement from the American Society of Clinical Psychopharmacology and the Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie.¹ It provided clear guidance on when and how to use TDM for psychiatric medications. Still, he noted there is a disconnect in its use in clinical practice, largely due to the lack of tools to apply TDM routinely.

A major cause of such has been the logistics. Traditional methods often required a couple of weeks before results were available, leaving clinicians without actionable data in real time. “Much of the frustration many of us have as clinicians has to do with the slow turnaround of clozapine plasma levels,” he said. Fortunately, Meyer highlighted that a shift is underway, with modern immunoassay methods allowing for results within a day instead of the traditional 1 to 2 weeks.

Rapid testing could transform TDM from an occasional troubleshooting tool into a standard part of titration and ongoing management, he added.

3. Certain Populations Warrant Special Considerations

TDM is particularly valuable because metabolism is not uniform across populations. Meyer highlighted several clinically important groups and special considerations.

Patients Who Smoke

Smoking induces CYP1A2 and dramatically increases clozapine metabolism. This means:

• Smokers may have unexpectedly low levels at standard doses.
• Abrupt smoking cessation—common during hospitalization—can rapidly elevate levels into the toxic range.

Patients often do not disclose their smoking habits, Meyer emphasized, and adherence and smoking are “dynamic, not static.” Routine TDM can catch these shifts early on.

Slow Metabolizers

“You will want to have a sense of how…genetic backgrounds modify those concentration-dose relationships,” Meyer told Psychiatric Times. For example, he explained that women, Indigenous Americans, and patients with East or South Asian ancestry are likely to be slow metabolizers and so have much higher drug levels for any given dose.

Looking Ahead: The Future of TDM in Psychiatry

For clinicians and patients interested in personalized medicine, TDM is a great tool, Meyer concluded. “I don’t always know everyone’s genetics, and I think we’ve come to appreciate that ordering routine genetic testing is not always that helpful because sometimes people are simply nonadherent, and the genetics don’t tell you that. Or they are on complex regimens, some of which are inhibitors of various strengths, [with] maybe even an inducer thrown in,” he said. “The plasma level gives you the sum of all those inputs. And, more importantly, it is accurate.”

He is hopeful that the FDA will approve modular assays for other anitpsychotics, so clinicians won’t have to rely on educated guesses when developing and fine-tuning treatment strategies. As turnaround times improve and immunoassay platforms become more widely available, TDM is moving from niche to mainstream, he added. The next phase will likely integrate rapid assays into routine titration, ongoing monitoring, and real-time risk mitigation.

Meyer’s message is clear: TDM is no longer a specialized tool—it is becoming an essential component of precision psychopharmacology. With better technology, clearer guidelines, and growing awareness, the future points toward more personalized, safer, and more effective psychiatric treatment, he said.

“If I took away lithium levels from your practice, you’d be very unhappy, and you’d think, ‘How can I make good decisions?’ The same is true for antipsychotics,” Meyer said. “Once you start incorporating this information into your practice, I think you’ll realize, ‘How did I ever do without it?’”

Reference

1. Howes OD, McCutcheon R, Agid O, et al. Treatment-resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174(3):216-229.