When switching antipsychotics for patients with schizophrenia, you can ease this potentially perilous passage by choosing the right time to switch and preventing psychotic relapse. This article describes four keys to a smooth transition:
- assess response and side effects with the existing medication
- weigh the pros and cons of switching, with input from the patient or caregiver
- select a replacement with characteristics that could improve patient function
- choose a switching strategy while considering safety and efficacy data.
RISKS AND BENEFITS OF SWITCHING
The two most compelling reasons to switch antipsychotics are enhanced clinical response and improved tolerability. Others may include lower medication cost, less-frequent monitoring, fewer drug interactions, or easier administration (such as once-daily versus twice-daily dosing).
Table 1
Sample response criteria to evaluate an antipsychotic switch
Improved functioning
|
Decreased symptoms
|
Improved tolerability
|
The greatest risk in a relatively stable patient is for psychotic symptoms to re-emerge. Be very careful when switching patients who:
- might harm themselves or others if their psychosis re-emerges during the switch
- were recently stabilized after an acute psychotic episode and have been maintained for less than 6 months on the medication that controlled their symptoms
- cannot adhere to oral medications and are being maintained on long-acting depot formulations.1
Other factors to consider include:
- the need for more-frequent patient visits during the transition to monitor for adverse effects
- the patient’s willingness to switch
- influence of external stressors—such as recent bereavement—or aspects of the patient’s workplace or living environment that may interfere with adherence to a new regimen
- medication cost and coverage by third-party payers.
Establishing specific response criteria for each patient (Table 1) will help you know when to continue or terminate a switch.
INADEQUATE RESPONSE
Because antipsychotics do not eliminate all positive and negative symptoms, an adequate response is considered a reasonable therapeutic goal. Many patients with schizophrenia respond adequately to traditional or atypical antipsychotics, but approximately one-third do not.2
What is an “adequate” response? No advisory groups or consensus panels have defined this term or set standards for when to switch. Therefore, psychiatrists must evaluate a patient’s response to an antipsychotic by using clinical judgment and patient/caregiver input. To gather the information you need, it is important to:
- identify target symptoms at baseline
- regularly monitor symptom severity, frequency, and intrusion on activities of daily living and quality of life.
Quantitative measures. In research, response is measured as a percent reduction in scores on standard assessments such as the Positive and Negative Syndrome Scales (PANSS). Using the PANSS, however, is too time-consuming for clinical practice.
The Brief Psychiatric Rating Scale (BPRS) is simpler than PANSS and can be administered more quickly but is less specific for negative symptoms. Even so, using the BPRS can help quantify baseline symptoms and monitor clinical response. It is useful to complete a BPRS rating prior to a switch and at subsequent visits during the transition. A >20% reduction in the total score is considered an adequate response.
Qualitative measures. Rating scales do not measure patients’ and sfamilies’ subjective feelings. One patient may view a 50% decrease in psychotic symptoms as extremely favorable and another as unacceptable. Switching therefore may be reasonable for one patient but not for another with a similar clinical response.
Table 2
Treatment-limiting antipsychotic side effects and options for switching
| Treatment-limiting factor | Atypical antipsychotic options |
|---|---|
| Akathisia/activation | Clozapine, olanzapine, quetiapine |
| Hyperprolactinemia | Any atypical antipsychotic except risperidone |
| Insomnia | Olanzapine, quetiapine |
| Orthostatic hypotension | Ziprasidone |
| Pre-existing cardiac dysfunction | Aripiprazole, olanzapine, quetiapine, risperidone |
| Pre-existing diabetes | Aripiprazole, quetiapine, ziprasidone |
| Sedation | Aripiprazole, risperidone, ziprasidone |
| Excessive weight gain | Aripiprazole, quetiapine, risperidone, ziprasidone |
Underdosing contributes to inadequate response, so assess whether an antipsychotic has been given a sufficient trial. For example, 400 to 800 mg/d of quetiapine is considered a therapeutic dosage, assuming adequate tolerability, but some clinicians stop increasing the dosage below that range. Similarly, the usual antipsychotic trial continues at least 3 to 4 weeks at a therapeutic dosage.
TREATMENT-LIMITING EFFECTS
Antipsychotic side effects that justify switching may be treatment-limiting or simply bothersome. For example, switching is necessary for antipsychotic-induced QTc prolongation in a patient with a history of cardiac dysrhythmias and reasonable for excessive daytime sedation in a patient who is working or attending school.
Extrapyramidal symptoms (EPS) and hyperprolactinemia may limit a patient’s tolerance of an antipsychotic. Patients who are especially sensitive to EPS may not tolerate high-potency agents such an haloperidol or even low to moderate dosages of risperidone. Others may not develop EPS while receiving haloperidol or higher dosages of risperidone.