Selecting the Appropriate Strategy for an Acute Psychotic Episode

Philip G. Janicak, MD, Frank J. Ayd, Jr, MD, John M. Davis, MD

Medscape Psychiatry & Mental Health eJournal. 1997;2(4) 

In This Article

Abstract & Introduction

Choosing the optimal drug therapy for an acute psychotic episode has become much more complex, particularly with the advent of the novel antipsychotics. Now, physicians must carefully consider the risk-benefit ratio of both the conventional and novel agents for each patient, depending on his or her specific needs. Data from PET imaging, dose-response, and plasma level-response studies can offer useful guides in this decision-making process. Copharmacy with other agents (eg, benzodiazepines), the combination of different antipsychotic classes, or electroconvulsive therapy may also be appropriate in carefully chosen situations.

The goal of all drug therapies is to achieve optimal outcome with the lowest effective dose. When agents with rapid onset of action, such as anesthetics, are administered, the intended effect can be carefully observed and loose titrated as necessary. Unfortunately, antipsychotics have a much longer interval (ie, weeks to months) between the initiation of treatment and intended effect, which makes developing dosing strategies much more difficult. Furthermore, the end point with antipsychotic therapy is less well defined (eg, improvement in positive symptoms, negative symptoms, general psychopathology). The prolonged lag time between the initiation of drug therapy and response, as well as the indefinite nature of the response, often leads to a rate of dose escalation that can quickly surpass the optimal dose range for many drugs.[1]

Even though the need for accurate dose-response data are critical, it is generally lacking for the conventional neuroleptics. In this light, plasma level-response studies and positron emission tomography (PET) imaging of receptor occupancy can offer some guidance. Fortunately, dose-response information for newer agents such as risperidone, olanzapine, and sertindole has been more carefully collected in large multicenter trials conducted to obtain FDA approval for clinical use. Even with agents such as risperidone, however, widespread clinical experience has already tempered the initial dosing recommendations, which were based primarily on more chronically ill schizophrenic populations. For example, it appears that many patients with mood disorders may have a better outcome with risperidone doses well below the 4- to 8-mg range that appeared optimal in the North American and the international multicenter trials.[2,3]

We will draw on information from these various sources (ie, PET imaging, dose-response, and plasma level-response data) to develop guidelines for the optimal dosing strategies of both conventional and novel antipsychotics during an acute psychotic exacerbation. In this context, we will also consider the potential for extrapyramidal side effects (EPS) with the conventional agents as well as other common adverse effects associated with the novel agents.