Treatment delays reduce efficacy
Importantly, the delays before receiving clozapine are not inconsequential – data show that each outpatient antipsychotic trial prior to clozapine reduces the likelihood of response by 8%-11%, and each hospital admission further reduces the likelihood of response by 4%-8%, underscoring the need to identify treatment resistance as early as possible, Dr. Kane said.
“It’s critically important to try to identify treatment resistance earlier than we usually do because if we can get it under control sooner, we have a better chance of improving the patient’s outcome, and this has been shown in a number of studies,” he said.
“The longer you wait, the less likely you are to see a good response even to clozapine.”
Despite the concerns about clozapine, Dr. Kane notes that even the blood monitoring does not appear to be a big complaint for patients, especially they are improving.
“In our experience, the patients who benefit from clozapine don’t really have a problem with the monitoring,” he said.
“In fact, patients who benefit from clozapine are much more adherent to the medication than other patients that we see, which is understandable, because if you feel you’re really getting a benefit from medicine, you’re going to be much more motivated to take it even if it has side effects.”
A recent systematic review of 13 studies and 1,487 patients backs that up, concluding that “patients generally have a favorable experience when being treated with clozapine,” with the caveat that “conclusions are limited by the risk of bias, particularly survivorship bias.”
Preference for clozapine over other antipsychotic medications was reported by 54%-86% of patients in the review, with specific improvements in mood (11%-78%) and cognition (5%-68%).
Clinicians the biggest ‘obstacle’
Dr. Kane notes that an important factor in underutilization could indeed be the manner in which clinicians discuss clozapine with their patients – often opening the discussion by focusing on the negative aspects that, without the context of the potential benefits, can be deal-breakers for patient from the start.
“The clinicians in my opinion are really the obstacle,” Dr. Kane said. “What we always hear from clinicians is ‘I can’t do it because the patient refuses, or the patient doesn’t like the side effects’.”
Dr. Kane notes that most side effects can indeed be managed – regarding the risk for metabolic syndrome, for instance, he recommends that patients should be given metformin from the beginning when they’re started on clozapine.
He adds that in most cases, a 3-month trial is enough to answer the question of whether clozapine is working or not.
“Three months is a good trial, but it may not even tell you the total response to clozapine because that may actually accrue over time,” he said. “We’ve seen patients who actually get better and better beyond 3 months.”
Not offering the drug to patients, however, is doing them a serious disservice, Dr. Kane added.
“What I tell patients and families is that it would be a shame to miss this opportunity for a potential treatment that could be life-changing,” he said. “Does it have potential side effects? Yes. Do you have to get blood tests? Yes. And I can’t tell by evaluating a patient’s history or examining that patient whether or not they’re going to be a good responder. But would you really want to miss an opportunity to find that out?”
“To me the argument is – let’s try this drug for 3 months and see what effect it has, and at that point you’ll be in a much better position to make a decision about the benefits versus risk,” Dr. Kane said.