Antipsychotics guidelines

The seeds of this transformation were sown some years ago. The first so-called atypical antipsychotic, clozapine (Clozaril), was devised in the 1960s. Clozapine was used widely in Europe until a series of deaths from a toxic hematological (blood) side effect called agranulocytosis occurred in the mid-1970s. Clozapine resurfaced in the 1980s and was approved for use (under strict guidelines) in the United States in 1990. Since that time, several other atypical antipsychotics have been approved, and others loom on the horizon. 

Efficacy in short-term treatment. From studies in adult schizophrenia, it is evident that clozapine treatment has at least the same or superior antipsychotic effect, compared to typical antipsychotics. In some studies, clozapine was superior with regard to symptom reduction in severe and acute schizophrenic patients. As the guidelines do not allow the use of clozapine as a first-choice drug, most patients have been treated before with at least two atypical or typical antipsychotics. Only one controlled trial has assessed the efficacy of clozapine in child and adolescent psychiatry. In this study (Kumra et ah, 1996), clozapine was found to be superior to haloperidol in all measures of psychosis, and showed a striking superiority for both positive and negative symptoms. 

The following guidelines are suggested with regard to the use of antipsychotic medication ... 

As with antidepressant therapy, reversal of psychosis is often gradual and may occur over several weeks to several months. Guidelines for the acute use of antipsychotic drugs are summarized in Table 4— 2 usual dosages for each of the commonly used antipsychotic drugs are summarized in Table 4—1. 

The 2004 Practice Guideline for the Treatment of Patients With Schizophrenia recommends indefinite maintenance treatment for patients who have had at least two episodes of psychosis within 5 years or who have had multiple previous episodes (Lehman et al. 2004). Maintenance therapy should involve the lowest possible doses of antipsychotic drugs, and patients should be monitored closely for symptoms of relapse. If the patient is compliant with treatment, oral medications are usually sufficient. However, if the patient s treatment history suggests that the patient may not reliably take daily oral medication, a long-acting depot preparation may be indicated. 

Antipsychotics. Clear guidelines for measuring therapeutic serum concentrations of antipsychotics have not yet been established. There may, however, be specific situations in which they may be of value (e.g., monitoring of haloperidol [HPDL] levels might be useful in patients on concurrent carbamazepine therapy because the latter agent can substantially reduce serum HPDL concentrations). These issues are discussed in greater detail in the Pharmacokinetics/Plasma Level section in Chapter 5. 

Stahl, S.M. (1999) Selecting an atypical antipsychotic by combining clinical experience with guidelines from clinical trials. Journal of Clinical Psychiatry 60(Suppl 10), 31—41. 

Note. None of these medications have FDA indication for the treatment of Alzheimer s disease. The literature and practice guidelines support the use of these medications for specific target symptoms. The FDA has issued a black box warning regarding the use of certain antipsychotic medications in the elderly, especially haloperidol, olanzapine, and risperidone. The warning notes that the use of these drugs is associated with an increase in death rates when used by the elderly patients with dementia. 

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