There are 12 Food and Drug Administration–approved atypical antipsychotics for schizophrenia, which can be overwhelming for clinicians who do not specialize in treating the disorder. “While these meds are not perfect, each of these can help some people who are not helped otherwise, and each of these has a different side effect profile,” Dr. Weiden said. “So while we can’t completely cure schizophrenia, we will have a lot more luck in getting a patient on a medication that is not too burdensome for them. The downside is that we don’t have any biologic predictors as to who will respond to what agent.”
Dr. Weiden said he thinks of recovery from schizophrenia as a process in which the choice of goals is decided primarily by the patient and guided by the clinician. “The good thing is, there’s no shortage of symptoms you can work on,” he said. “You don’t have to fix everything, but you and the patient should come together to goal-set and pick one or two that are the priorities. That will keep you from getting overwhelmed and burned out trying to ‘fix’ everything at once.”
Nonpharmacologic causes of persistent symptoms warrant investigation as well, such as substance comorbidities, medical comorbidities such as obstructive sleep apnea, treatment access barriers, and adherence challenges. While discontinuation of the medication class is not an option, “We have dose adjustment; we can substitute, go from one antipsychotic to another; we have route of delivery, you can add a new medication to the regimen, either within the class or a new class, and we can discontinue one or more medications from the current regimen,” Dr. Weiden said. “That is one strategy we often forget: getting the person off a medication that may be causing a problem.”
When positive symptoms persist, make sure that the patient’s current antipsychotic medicine is optimized. “The dose response of these different antipsychotics is not the same,” he said. “Some meds have a very steep dose response; others are more flat. How far you push may depend on the specific agent. You want to do what’s easy first. So raising the dose for persistent positive symptoms is a good idea, except if you think it’s behavioral toxicity.”
Switching to a new agent takes more work than changing the dose of a current agent. He characterized clozapine as “the anchor” for persistent positive symptoms. “No patient is clearly refractory of positive symptoms until they’ve either failed or refused clozapine,” he said. “Combining antipsychotics is not a substitute for clozapine. It’s a lot easier to do, but it’s not a substitute.
“Should the patient seem to have suboptimal response to a few first-line antipsychotics, it is important to tell the patient and family about clozapine even if you are not ready to recommend it right now. Likewise, it is crucial to inform all stakeholders about the suicide prevention indication of clozapine for any schizophrenia patient with any suicide history, even if the overall circumstances are not yet amenable to starting clozapine right away.”
During a separate presentation, Dr. Weiden encouraged meeting attendees to think about adherence to antipsychotics as not an outcome, but rather as an important mediator of outcome.
“As clinicians, we get stuck on [the notion of] ‘you’re not doing what I recommended,’ ” he said. One indirect consequence of adherence is poor information, which obscures assessment of treatment response, and also creates safety risks. When Dr. Weiden meets with patients for the first time, he tells them, “It’s very important that I know what you’re really doing, both in terms of your drugs and the drugs I’ve prescribed for you,” he said. “I make it safe for them. I say, ‘I may disagree, but I’m not going to get mad.’ I give them advance information about how I would respond, because different clinicians respond differently. Some take it personally and some don’t. I don’t take it personally.
“The other thing I say is that, ‘It’s not just about you’re obeying me, but it’s for your safety. It’s less safe if you don’t tell me.’ Safety is less pejorative than adherence.” Other strategies that can be used to track adherence include recommending long-acting therapies such as routine, supervision of oral therapy, and using pharmacy refill data. “Many patients don’t pick up their medications or don’t fill their prescriptions,” he said.
Gradual dose lowering is a feasible strategy, he said. “It can be successful, but not always. We have to advise patients that even brief medication gaps are a bad thing, but gradual dose lowering may be achievable and helpful.”