Combinations of antipsychotics are widely used clinically (about 15 to 20 percent of patients, with a clear trend toward increasing popularity), though no studies of their efficacy or safety are available. Thus, although combinations such as clozapine plus a high-potency conventional drug or clozapine plus an atypical agent have been suggested, their utility remains unclear. Despite these concerns, some situations may lend themselves to the concurrent use of more than one antipsychotic. A common dilemma faced in the clinic is the patient who responds well to clozapine but is consistently noncompliant and thus risks relapse. A combination of clozapine plus a depot neu-roleptic (as a "safety net") may prove superior to either agent alone, by offering the patient the benefit of clozapine, yet providing some degree of protection from relapse by the presence of the depot medication. Another common clinical situation is the patient being tapered off one antipsychotic and simultaneously titrated onto another who shows dramatic improvement midway through the process on moderate doses of the two medications. There is no clear basis to decide whether to continue the cross titration to monotherapy with the new agent or maintain the patient on lower doses of the two medications together. At this time, however, it is recommended that all patients receive a trial of monotherapy on the new antipsychotic agent with the precaution of slow cross titration (over 6 to 12 weeks), and optimal dosing with the newer agent. As we await controlled studies of this practice, it is important to systematically document the specific reasons for the use of multiple antipsychotics in a particular patient, describe the response of defined target symptoms, and assess adverse effects on an ongoing basis.
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