Schizophrenia: Crafting a New Approach to Treatment Tolerability


Genotyping and access to more genetic information about patients may allow clinicians to minimize side effects associated with treatment for schizophrenia by choosing antipsychotic agents based on their unique molecular binding profiles and using the lowest effective doses.

One of the major challenges associated with treating patients with schizophrenia is the high rate of treatment nonadherence. According to Andrew J. Cutler, MD, Courtesy Assistant Professor, Department of Psychiatry, University of Florida, Gainesville, and CEO and Chief Medical Officer, Florida Clinical Research Center, LLC, the first thing clinicians should examine when a schizophrenic patient comes in after a relapse or rehospitalization is incomplete adherence to their medication regimen. Reasons for nonadherence center around the simple fact that patients cannot tolerate the negative side effects of antipsychotics, including cardiometabolic issues in terms of weight gain, sedation or sleepiness, cognitive dysfunction, and extrapyramidal symptoms (movement disorders such as Parkinsonism or akathisia). Cutler said, “Tolerability is the primary cause for 20% of all drug discontinuation” in patients with schizophrenia.

Fortunately, the new generation of genotyping allows clinicians to access information that may “predispose or protect individuals from the adverse effects of antipsychotics.” For example, in terms of movement disorders, Rs6280 polymorphisms in the DRD3 gene (specifically a serine to glycine substitution) is a mutation known to be associated with an increased risk for tardive dyskinesia mediated by a four-fold greater affinity for dopamine by this receptor.

If clinicians can be made aware of such connections ahead of time, they may be able to take individualized treatment to a whole new level. Potentially, they could predict which patients might be expected to experience more difficulties with certain side effects. Cutler said, “side effects that may be intolerable for the individual can often be minimized by choosing antipsychotic agents based on their unique molecular binding profiles and using the lowest effective doses.”The genetic information that is currently being collected about antipsychotics will no doubt be vital in the future treatment of patients.

However, Culter was quick to point out that clinicians can also simply examine and promote healthy lifestyle changes such as improving diet and exercise as a way to further provide individualized treatment, especially in patients who are experiencing adverse cardiometabolic issues and do not have the ability to change their medication.

In regards to drug intolerability, he advised that, “If an antipsychotic agent is intolerable, treatment strategies include switching to a different antipsychotic agent or augmenting with a side effect-mitigating agent.” When switching antipsychotic agents, he advised clinicians to be vigilant when designing the switching protocol. He said drugs within the same category such as the “pines” (clozapine, olanzapine or quetiapine) can be switched over the course of only one week. The same is true for the “dones” (risperidone or lurasidone). However, when switching between categories, Cutler advised clinicians to stop the “pine” drug slowly and use a minimum of two weeks to complete the switch. Similarly a “done” to “pine” switch should be done over a minimum of two weeks, introducing the “pine” class slowly.

In conclusion, Cutler stressed that successful treatment of schizophrenia and subsequent proper adherence to medication requires increased individualized treatment utilizing modern genetic information and careful deliberation of patient tolerance to side effects.

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