Antipsychotics: To Switch or Not to Switch?

Jeffrey A. Lieberman, MD


August 26, 2011

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Hello. This is Dr. Jeffrey Lieberman of Columbia University speaking to you for Medscape. Today, I want to address the question of how and when to switch from one antipsychotic medication or medications to another and what to expect when switching. This is a standard practice in the course of treating individuals with psychotic disorders such as schizophrenia and can be occasioned by a variety of occurrences. You could switch medication because it is not effective and is not controlling symptoms adequately, or, when it is effective, it is not achieving the level of therapeutic response that is desired, meaning that some residual symptoms persist. The medication may be producing unwanted side effects that are posing tolerability or safety problems. For these reasons, you can consider switching to another medication to improve efficacy and symptom control, or to improve tolerability and safety.

Recently, 3 papers reported very rigorous studies that bear on the question of switching.[1,2,3] Let me comment on these as a way of illustrating the advantages and disadvantages of switching. Generally, when a patient is relatively stable on an antipsychotic medication, albeit with some level of residual symptoms, we tend to think that we can try another medication to see whether it can do better in terms of symptom control, and assuming that other medications will have equivalent or comparable efficacy, there will not be any loss of the ability to maintain the level of response that has been achieved thus far, and medications will produce this cross-tolerance in terms of efficacy. This assumption presumes that switching will have no downside. It may not improve the level of symptom control over that of the prior antipsychotic medication, but it could improve side effects, and it could prove to be more effective, although we can't be sure of that in terms of symptom control. The only medication that we know has a substantial likelihood of being more effective is the switch to clozapine for residual or refractory symptoms.

However, in 2006 Essock and colleagues[1] reported on outcomes derived from patients enrolled in CATIE [Clinical Antipsychotic Trials of Intervention Effectiveness]. These patients had been randomly assigned to 1 of 5 assigned medications. Thus, some patients were switched from the medication that they were taking when they entered the study to another medication, and some patients stayed on the same medication because they were randomly assigned to the medication that they were previously receiving. Essock and colleagues[1] found that when patients who were stable, albeit residually symptomatic, were switched, there was a higher rate of treatment discontinuation due to destabilization or new side effects associated with switching. This was particularly the case if patients were switched from treatment with olanzapine or risperidone. What this meant was that switching from one medication to another carried some significant risk for destabilization and then required either a switch back to the previous medicine or a switch to a new medication to stabilize patients again. This was an important lesson that switching has risks and that the reason for switching must justify those risks.

A second publication by Essock and colleagues[2] analyzed the practice of trying to reduce patients taking multiple antipsychotic drugs to monotherapy with a single antipsychotic medication. Patients who were receiving multiple antipsychotic medications were randomly assigned to continue these multiple medications or to have one of their medications tapered and discontinued, leaving them on just a single antipsychotic drug. This study found that a proportion of individuals who were taking 2 antipsychotic medications and were assigned to taper and discontinue one of those destabilized and needed to be returned to their polypharmacy regimen. This only occurred in one third of the patients assigned to eliminate 1 medication; two thirds were able to tolerate monotherapy, and stability was sustained on 1 medication or side effects improved.

Thus, this study supports efforts to try and simplify pharmacologic regimens by reducing polypharmacy with antipsychotic medications. This needs to be accomplished carefully and gradually, with the understanding that a proportion of patients will not tolerate that reduction and may need to be returned to their polytherapeutic regimen. Again, there is a risk in simplifying a regimen from poly- to monotherapy.

In a third study, Stroup and colleagues[3] asked this question: Is switching them from their current antipsychotic medication to an antipsychotic medication with low metabolic liability the correct course of action for patients who suffer from the side effects of obesity, a high BMI [body mass index], high body weight, or metabolic syndrome? These investigators randomly assigned patients who met the criteria for metabolic syndrome to either switch to aripiprazole; a weight-neutral or low-liability antipsychotic drug; or to stay on their existing regimen with olanzapine, quetiapine, or risperidone. They found that the individuals who switched to aripiprazole experienced statistically significant reductions in weight and alleviation of their metabolic syndrome, but that a substantial number of these patients destabilized and needed to be either returned to their previous medication or treated with additional medications to stabilize them.

The message from this study is that switching from an antipsychotic medication that causes weight gain or metabolic disturbances in glucose and lipids can alleviate those side effects, but there is a potential risk in terms of not being able to maintain the psychiatric stability or level of remission that had previously been achieved. Such a switch will work for some patients but not for all patients. When switching, one has to justify the reasons for switching, make sure that they warrant the risk, and in doing so be prepared to either backtrack or take additional measures to treat and stabilize patients if their mental status or clinical status deteriorates or worsens.

As Oscar Wilde said, "the truth is rarely simple and never pure," and such is the case with switching antipsychotic drugs. It's something that we must consider in the course of clinical management of patients, but it's not a simple or uncomplicated maneuver to accomplish.

This is Dr. Jeffrey Lieberman at Columbia University speaking to you today for Medscape. Thank you very much, and see you soon.


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