Performance in practice: confessions of a psychopharmacologist

What could have been done better here?

• – Possibly using augmentation strategies sooner

• – Obtain a second opinion to see if any strategies were overlooked

• – More aggressive use of clozapine (Clozaril) despite side-effect burden and day-to-day intolerability issues may have been warranted

Possible action items for improvement in practice

• – Read more review articles on treatment-refractory schizophrenia

• – Attend more educational events to develop new treatment ideas/plans and to increase confidence in prescribing rational off-label treatments

• – Be familiar with approved dosing strategies and also those super-dosing strategies outlined in the evidence-based literature

Tips and pearls

At least three antipsychotics carry distinct warnings about QTc prolongation: ~20 ms for ziprasidone (Geodon), ~90 ms for thioridazine (Mellaril), ~9 ms for iloperdione (Fanapt)

In practice, QTc prolongation has been seen with many of the atypical antipsychotics, some of the typical antipsychotics, and may be case specific

More caution and EKG monitoring are warranted in those cases with cardiac histories, those who take other medications that prolong QTc (TCAs), those who are dosed above the approved limits, and those on antipsychotic polypharmacy

EKG monitoring is not required specifically for any antipsychotic, but clinical rationale suggests monitoring similar to guidelines for TCA or lithium use

Two-minute tutorial

Switching atypical antipsychotics in this case?

Early in this case, a classical titration switch strategy was utilized. The first or failing antipsychotic was tapered off gradually, while simultaneously the new antipsychotic was added at a roughly equal pace

• – Pros: The patient is never on two full-dosed antipsychotics at the same time

  • This lowers risk of EPS and other side effects. This lowers cost

• – Cons: There may be a window, when both antipsychotics are subtherapeutic during the crossover

  • This may leave the patient with lower levels of D2 antagonism and psychosis may worsen in the middle of the cross-titration

  • This may make the clinician feel that the second agent is also failing

Later in this case, the current/failing antipsychotic was maintained at an approved, top antipsychotic dose while the new antipsychotic was added gradually. Once the second antipsychotic reached a minimally therapeutic dose, the initial, failing agent was discontinued

• – Pros: In this strategy, essential therapeutic doses of two antipsychotics are reached before any drug tapering off

  • This might allow for better psychosis control and no breakthrough psychosis window to occur

• – Cons: Extra side-effect risks and increased cost, being on two medications at once

  • Sometimes clinicians feel that the antipsychotic response was due to both agents. Both agents are maintained at full doses, gaining the prescriber the notoriety of being an atypical antipsychotic polypharmacist

  • Again, this increases cost and side effect risk

  • Guidelines and available data suggest this practice does not boost antipsychotic effects