Mood stabilizers, most derived from neurological AEDpractice, are a notable exception. Plasma levels are readily available for AED's whether for seizure or mood control.

For the bulk of psychiatric prescriptions, plasma levels were not found to reliably reflect potency or bioavailbility.

There is more awareness as there are now tests available for fast metabolizers. However these are expensive and are not widely used other than in research or academic institutions.

Well in my point of view without going into CYP450 and other drug metabolism/ interaction related issues, a simplest explaination would be the training of the medical doctors. I guess a minimal exposure to pharmacology and then therapeutics is the most strongest reason for such understandings. Nevertheless it is the role and responsibility of the pharmacist (Clinical pharmacists in particular) to look into therapeutical aspects of disease managment and to provide appropriate recommendations both to physician and patients, based on individualised need of each patient.

As a medical researcher with a specialization in pharmacokinetics, let me note that there are actually three strands here, and the second two, as I show below, have far graver implications than suggested by the first (insufficient knowledge). These are the critical issues re pharmacokinetic expertise:

(1) INADEQUATE TRAINING in pharmacokinetics.

The contributors above have addressed this well, as has - graphically but accurately (the analogy chosen is both humorous and trenchant) - our moderator, Barry Turner.

(2) SELECTIVE BIAS in the application of adverse pharmacokinetic warnings:

Example: Oncologists typically argue strongly against co-administration of antioxidants and oncotherapeutic agents, yet on the balance of the evidence, the preponderance of data suggests a synergistic or at least harmless effect with most high-dose dietary antioxidants and chemotherapy, and claims to the contrary are inconsistent and not supported by the evidence data, as per my extensive evaluation of this issue in review [1].

(3) DEVALUATION OF THE CLINICAL RELEVANCE of adverse pharmacokinetic interactions:

Example: We draw attention to the example of cimetidine (Tagamet) for stomach GI acid complaints: cimetidine is a known and powerful CYP3A4 inhibitor, and dozens and dozens of chemotherapy drugs are metabolized by the same enzyme, making for clinical relevant adverse interactions, yet numerous studies we have reviewed found that oncologists showed no professional caution, or even interest in this, among hundreds of other common adverse interactions among their patients.

So researchers at the H. Lee Moffitt Cancer Center and the New Hope Cancer Center [2] found that 19% - one in five - of cancer patients were taking cimetidine yet when oncologists involved were informed about the potentially harmful clinically relevant drug combinations - which bore FDA warnings to that effect - not one made any changes in their patients prescriptions. Similarly, Rachel Riechelmann and colleagues in Sao Paulo [3] concluded in comparable circumstances that "Curiously, no oncologist made any change in patients’ prescriptions despite being alerted about such interactions by the authors".

This suggests that the objection to CAM interventions may be more doctrinal than founded any rational scientific basis, and its selective application against CAM modalities without any comparable inquiry into or prohibition against dozens of traditional medicines far more likely to raise adverse interactions with cancer therapies reflects unfavorably on the sincerity of oncologists' prohibitions against CAM agents. It is inescapable that if one is sincerely concerned to minimize the potential for adverse interactions than that should apply to traditional and non-traditional interventions alike, and indifferently, yet regrettably we see no such equity in display. This ultimately leaves the decision in the hands of patients, not a burden they should have to bare alone.

Thus, vastly more alarming and consequential than knowledge inadequacy in the domain of potentially adverse pharmacokinetic interactions, is:

(1) the selective bias shown of putative great concern for such potential when CAM/natural agents are involved versus when conventional agents are involved in drug-drug interactions (DDIs), and

(2) the failure of professional and ethical response - warnings, substitution of agents, etc, - when medical professionals are confronted with clear evidence of such potential at a clinically relevant level, as the Moffitt Cancer Center and Riechelmann studies I cited (among many others) clearly demonstrate.

REFERENCES

1. Kaniklidis C. Drug Interactions in Oncology - Review. [pending publication]. Available on the authors ResearchGate profile (at: http://www.researchgate.net/profile/Constantine_Kaniklidis/‎.

2. Sokol KC, Knudsen JF, Li MM. Polypharmacy in older oncology patients and the need for an interdisciplinary approach to side-effect management. J Clin Pharm Ther 2007; 32: 169–175.

3. Riechelmann RP, Del Giglio A. Drug interactions in oncology: how common are they? Ann Oncol 2009; 20(12):1907-12.

I believe that pharmacists can and do play a major role in informing prescribers regarding the effects of CYP on drug metabolism. There are countless drug interactions related to the CYP system, but most if not all software systems used in a US pharmacy dispensing will alert the pharmacist. It is then up to the pharmacist to decide what to do next. We find that using two or more prescribers to the same patient greatly increases the chance for CYP-related drug interactions. Unfortunately, using more than 1 pharmacy may also contribute to the frequency of these interactions, for the same reason.

This is the field of pharmacogenomics. Many psychiatrists I know will ask for a CYP profile blood test (usually only available in tertiary teaching hospitals) to determine the metabolism status of the patient which helps in drug selection and dosage adjustment.

Antony, I would love to talk to about that sometime. It has not been my experience that psychiatrists consider this at all.

Dear Barry, Where I work we order a "Cytochrome P450 genotyping" blood test through pathology. I understand that the test originated as part of a PhD student's research and was so useful that it was retained. This is from the Department of Psychiatry (I am not a psychiatrist rather a paediatrician and pharmacist) so I do not know much further, only that it is used by certain personnel with good effect.

It may be that there will be greater consumer demand in this area. In this month's Australian pharmacy news:

Pharmacy genetic test

In a pharmacy first, Chemmart Pharmacy has partnered with genetic testing company, GenesFX Health, to offer a once off, pharmacogenomic test that identifies gene variants in four major enzyme systems, how these genes metabolise medications and the clinical implications of discovered slow or fast drug metabolism. The service will be rolled out in selected Chemmart Pharmacy stores nationally throughout the year and costs $225.

A consumer article about this is here: http://cranbournenews.starcommunity.com.au/news/2014-04-03/dna-test-on-medicine-response/

Also Tobacco smoking induces CYP1A2 so there are implications when starting and stopping smoking (thankfully not with bupropion which is metabolised by CYP2B6).

In India, in 3 semesters, students have to learn about pharmacology of all the drugs. And this is simultaneously with two more subjects. all subjects are vast - and hence the focus is on salient points - and some important practical issues often get ignored.

-Parimal

Its astonishing to tell many prescribers are even unaware of the maximum doses of the commonly prescribed drugs,let alone the metabolizing enzyme C P450. The reason which is commonly attributed to this the physicians are busy and have little time for the pharmacology. The only solution for this is make it a mandatory continuing medical education programme (CME) in pharmacology which is done quarterly.