Switching antipsychotics A balanced approach 52 Current VOL. 2, NO. 8 / AUGUST 2003 p SYCHIATRY Current p SYCHIATRY to ease the transition Elizabeth A. Winans, PharmD hen switching antipsychotics Clinical assistant professor for patients with schizophre- Departments of pharmacy practice nia, you can ease this potentially perilous passage and psychiatry W University of Illinois at Chicago by choosing the right time to switch and prevent- ing psychotic relapse. This article describes four keys to a smooth transition: • assess response and side effects with the existing medication With no standards or guidelines, • weigh the pros and cons of switching, you’re working without a net. with input from the patient or caregiver • select a replacement with characteristics Here’s evidence you need to that could improve patient function hone your clinical judgment • choose a switching strategy while consid- ering safety and efficacy data. and help patients switch safely. 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). The greatest risk in a relatively stable patient VOL. 2, NO. 8 / AUGUST 2003 53 Switching antipsychotics Table 1 patient’s workplace or living environment Sample response criteria that may interfere with adherence to a new to evaluate an antipsychotic switch regimen • medication cost and coverage by third- Improved functioning party payers. • Able to be discharged from inpatient care Establishing specific response criteria for • Transition from nursing home to group home each patient (Table 1) will help you know when to • Able to hold a job or tolerate longer work continue or terminate a switch. periods • Improvement in self-care INADEQUATE RESPONSE Decreased symptoms Because antipsychotics do not eliminate all posi- • Hallucinations less frequent and bothersome tive and negative symptoms, an adequate • Delusions held less tenaciously or interfere response is considered a reasonable therapeutic less often with thinking goal. Many patients with schizophrenia respond • Less withdrawn or isolative • Initiates social contact adequately to traditional or atypical antipsy- 2 • Interacts appropriately with others chotics, but approximately one-third do not. Improved tolerability What is an “adequate” response? No adviso- • Tardive dyskinesia reduced ry groups or consensus panels have defined this • Anticholinergic or beta-blocking agents term or set standards for when to switch. no longer needed Therefore, psychiatrists must evaluate a patient’s • Weight gain subsides response to an antipsychotic by using clinical • Patient reports feeling more energetic judgment and patient/caregiver input. To gather the information you need, it is important to: • identify target symptoms at baseline • regularly monitor symptom severity, fre- is for psychotic symptoms to re-emerge. Be very quency, and intrusion on activities of careful when switching patients who: daily living and quality of life. • might harm themselves or others if their Quantitative measures. In research, response is psychosis re-emerges during the switch measured as a percent reduction in scores on • were recently stabilized after an acute standard assessments such as the Positive and psychotic episode and have been maintained Negative Syndrome Scales (PANSS). Using the for less than 6 months on the medication PANSS, however, is too time-consuming for clin- that controlled their symptoms ical practice. • cannot adhere to oral medications and are The Brief Psychiatric Rating Scale (BPRS) is being maintained on long-acting depot simpler than PANSS and can be administered formulations.1 more quickly but is less specific for negative Other factors to consider include: symptoms. Even so, using the BPRS can help • the need for more-frequent patient visits quantify baseline symptoms and monitor clinical during the transition to monitor for adverse response. It is useful to complete a BPRS rating effects prior to a switch and at subsequent visits during • the patient’s willingness to switch the transition. A >20% reduction in the total • influence of external stressors—such as score is considered an adequate response. recent bereavement—or aspects of the Qualitative measures. Rating scales do not mea- continued on page 60 54 Current VOL. 2, NO. 8 / AUGUST 2003 p SYCHIATRY Switching antipsychotics continued from page 54 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 sure patients’ and families’ subjective feelings. Extrapyramidal symptoms (EPS) and hyper- One patient may view a 50% decrease in psychot- prolactinemia may limit a patient’s tolerance of ic symptoms as extremely favorable and another an antipsychotic. Patients who are especially sen- as unacceptable. Switching therefore may be rea- sitive to EPS may not tolerate high-potency sonable for one patient but not for another with a agents such an haloperidol similar clinical response. or even low to moderate Underdosing contributes to inade- dosages of risperidone. Others quate response, so assess whether Patients may view may not develop EPS while receiv- an antipsychotic has been given a a 50% decrease ing haloperidol or higher dosages of sufficient trial. For example, 400 in symptoms risperidone. to 800 mg/d of quetiapine is con- as very favorable Switching to an antipsychotic with sidered a therapeutic dosage, relatively less histamine or alpha-adrener- or unacceptable assuming adequate tolerability, gic blockade may reduce problematic side but some clinicians stop increasing effects such as sedation and orthostatic the dosage below that range. Similarly, the hypotension, respectively (Table 2). usual antipsychotic trial continues at least 3 to 4 Patients vary in how well they weeks at a therapeutic dosage. tolerate other side effects, such as weight gain. For example, a 10-lb weight gain may be accept- TREATMENT-LIMITING EFFECTS able to one patient and unacceptable to another. Antipsychotic side effects that justify switching The decision to switch may be more obvious in a may be treatment-limiting or simply bothersome. patient with diabetes, for whom substantial For example, switching is necessary for antipsy- weight gain is unacceptable. chotic-induced QTc prolongation in a patient with a history of cardiac dysrhythmias and rea- SWITCHING STRATEGIES sonable for excessive daytime sedation in a No method is universally accepted for switching patient who is working or attending school. from one antipsychotic to another. In clinical 60 Current VOL. 2, NO. 8 / AUGUST 2003 p SYCHIATRY Current p SYCHIATRY practice and research, three common methods Figure (Figure) are used: 3 common antipsychotic • immediately discontinuing drug A while switching strategies starting drug B at full dosage • slowly tapering drug A while starting Strategy A drug B at full dosage • slowly tapering drug A while slowly increasing drug B to full dosage. Each method has advantages and disadvan- Drug A tages. Gradual cross-titration and tapering may Full dosage reduce the risk of relapse but increase the risk of Drug B side effects. Elaborate regimens may confuse some patients—especially those with cognitive Time impairment—and increase the risk for adverse Discontinue drug A immediately while simulta- events and nonadherence. neously beginning drug B at full dosage Abruptly discontinuing an agent is less con- fusing and more convenient than gradual taper- ing, but patients may experience acute withdraw- Strategy B al (as with clozapine). Finally, no guidelines exist on how quickly to make the transition when one or both medications are cross-titrated and tapered. For inpatients receiving intense monitoring, a transition may be completed in 3 to 7 days, where- Drug A Full dosage as outpatients may require 1 to 3 weeks. Drug B Recommendation. The evidence cited in the next Overlap in drug A & B section of this article suggests that any of the three methods can be used when switching Time antipsychotics, except clozapine. When switch- Slowly discontinue drug A while starting drug B at full dosage ing from clozapine, extend the cross-taper period to help minimize or eliminate rebound psychosis and cholinergic symptoms. Strategy C SWITCHING FROM DEPOT TO ORAL AGENTS For patients switching from depot to oral antipsy- chotics, a 1-month cross-titration taper has been shown to be efficient and safe. Drug A Full dosage 3 Godleski et al randomized 26 patients who had Drug B received IM depot antipsychotics (haloperidol or Overlap in drug A & B fluphenazine decanoate) for at least 3 years to either continue the IM depot antipsychotic or switch to Time olanzapine. Although the study was designed to Slowly discontinue drug A while slowly starting assess the safety and efficacy of the switch, it also and increasing drug B to full dosage provided data on the transition