1. Copyright Notice
This presentation is copyrighted by the Psychopharmacology Institute.
Subscribers can download it and use it for professional use.
The contents of the presentation may be modified, but the Psychopharmacology Institute logo must remain visible in all slides.

2. Node 1a Intolerance or Inadequate Trial of a Node 1 Antipsychotic
David N. Osser, MD
Associate Professor of Psychiatry
Harvard Medical School
Brockton Division of the VA Boston Healthcare System
General Editor - Psychopharmacology Algorithm Project
Harvard South Shore Residency Training Program

3. Incomplete trial: What to do?
Now, Node 1a is if they are not tolerating or you can’t give an adequate trial of that first choice that you made. What if they just couldn’t complete that trial? What should you do?

4. Incomplete trial: What to do?
Adequate trial?
Dose
Duration
As allowed by side effects
Adherence reports
Patient and caretakers
Assess presence of enzyme inducers
Assess substance abuse
Well, first of all, you got to be sure this trial was adequate. How do you decide that? Well, first of all, there’s adequate dose and duration as allowed by side effects.

5. Incomplete trial: What to do?
Adequate trial?
Dose
Duration
As allowed by side effects
Adherence reports
Patient and caretakers
Assess presence of enzyme inducers
Assess substance abuse
You consider the patient’s reports of adherence and that of any caretakers who may be observing them.

6. Incomplete trial: What to do?
Adequate trial?
Dose
Duration
As allowed by side effects
Adherence reports
Patient and caretakers
Assess presence of enzyme inducers
Assess substance abuse
You assess for the presence of any known enzyme inducers that they may be on that could have changed the metabolism and rendered them to have too low a blood level like an inducer like carbamazepine, for example.

7. Incomplete trial: What to do?
Adequate trial?
Dose
Duration
As allowed by side effects
Adherence reports
Patient and caretakers
Assess presence of enzyme inducers
Assess substance abuse
You assess for the presence of substance abuse that could make the drug less likely to work.

8. Incomplete trial: What to do?
Plasma levels
No side effects, low plasma levels
Suspect poor adherence
Rare: rapid metabolism
Side effects, low plasma levels
Somatization or nocebo effect
And then if you’re getting no side effects, I think it’s very reasonable to get a plasma level. And if the level is well below the range usually seen in patients on typical doses of that drug, you certainly should suspect poor adherence that you have somehow missed or the rare cases of rapid metabolism.

9. Incomplete trial: What to do?
Plasma levels
No side effects, low plasma levels
Suspect poor adherence
Rare: rapid metabolism
Side effects, low plasma levels
Somatization or nocebo effect
On the other hand, if they report severe side effects that are not objectively apparent, the plasma level helps you sort that out too to see whether that’s a somatization or a nocebo effect.
They really don’t want this medication and they’re telling you about all these awful side effects which they may feel they’re having. But if their blood level is 0, that’s a different understanding of it than if they’ve got maybe a high blood level suggesting that they’re slow metabolizers of it and that these side effects are real and you could do something about it by lowering the dose

10. Specific plasma levels
150 to 210 ng/ml
Aripiprazole:
20-40 ng/ml
Olanzapine
Amisulpride: ng/ml [121]
Risperidone: ng/ml [52]
Haloperidol 5-15 ng/ml
Other, but less well delineated:
Aripiprazole has probably the best delineated optimal range of 150 to 210 ng/mL taken at trough like 12 hours after their last dose. I strongly recommend getting aripiprazole levels to help your dosage not only for adherence issues but to actually try to get the patient into this therapeutic window relationship range that Sparshatt and colleagues described in their review.
Sparshatt, A., Taylor, D., Patel, M. X., & Kapur, S. (2010). A systematic review of aripiprazole--dose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. The Journal of clinical psychiatry, 71(11),

11. Specific plasma levels
150 to 210 ng/ml
Aripiprazole:
20-40 ng/ml
Olanzapine
Amisulpride: ng/ml [121]
Risperidone: ng/ml [52]
Haloperidol 5-15 ng/ml
Other, but less well delineated:
Olanzapine, if you have used that, seems to have a range of
Bishara, D., Olofinjana, O., Sparshatt, A., Kapur, S., Taylor, D., & Patel, M. X. (2013). Olanzapine: a systematic review and meta-regression of the relationships between dose, plasma concentration, receptor occupancy, and response. Journal of clinical psychopharmacology, 33(3),
Citrome, L., Stauffer, V. L., et al (2009). Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/d in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration. Journal of clinical psychopharmacology,
Patel, M. X., et al (2011). Plasma olanzapine in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, Journal of clinical psychopharmacology, 31(4),

12. Specific plasma levels
150 to 210 ng/ml
Aripiprazole:
20-40 ng/ml
Olanzapine
Amisulpride: ng/ml
Risperidone: ng/ml
Haloperidol 5-15 ng/ml
Other, but less well delineated:
And other possible ranges less well-delineated are amisulpride , risperidone 20-60, haloperidol 5-15.
Sparshatt, A., Taylor, D., Patel, M. X., & Kapur, S. (2009). Amisulpride–dose, plasma concentration, occupancy and response: implications for therapeutic drug monitoring. Acta psychiatrica Scandinavica, 120(6),
Taylor D, Paton C, Kapur S. The Maudsley prescribing guidelines in psychiatry. 12nd ed. Padstow, UK: Wiley-Blackwell, 2015.

13. If no adequate trial possible
Try a different antipsychotic from Node 1
Adequate trial, unsatisfactory response
Node 2: Second Antipsychotic Trial
If they didn’t get an adequate trial and you can’t give them an adequate trial because of side effects, then we would just try another one from the choices in Node 1. You still haven’t completed an adequate trial of a first-line agent. So pick another one from the same group that we originally gave you earlier in the talk.

14. If no adequate trial possible
Try a different antipsychotic from Node 1
Adequate trial, unsatisfactory response
Node 2: Second Antipsychotic Trial
But if it was an adequate trial and the response was unsatisfactory, you are now ready for Node 2 or the second antipsychotic trial.

15. Next Video: Node 2: Unsatisfactory Response to an Adequate Trial