In spring 2000, the Missouri Department of Mental Health mandated that its psychiatric inpatient facilities convert patients from trade-name to generic clozapine. The pharmacy department at our facility was encouraged to develop a conversion program to oversee and assess the efficacy and tolerability of the change. A protocol to monitor the conversion of patients to generic clozapine hospitalwide was developed. The primary objective was to determine whether therapeutic response and level of tolerability were the same with generic versus trade-name clozapine. The secondary objective was to determine whether changes in monitoring white blood cell and absolute neutrophil counts were necessary after conversion. Our results showed that most patients did not experience changes greater than a mean of 5 points in their scores on the Brief Psychiatric Rating Scale (BPRS). However, a statistically significant difference was seen in 22 patients who had a mean reduction or an increase of less than 5 points (p=0.0139) in BPRS scores compared with two patients who had a mean increase greater than 5 points. Assessment of percentage change in BPRS scores indicated that 14 (58%) converted patients had a 1-50% decrease in mean BPRS scores, and 10 (42%) had a 1-40% increase. However, of those with a mean BPRS increase, five (50%) had an increase of 10% or less. Our clozapine conversion program resulted in the successful conversion of all 24 patients.

Aripiprazole is a novel antipsychotic with a mechanism of action different from those of traditional first- and second-generation antipsychotics. We describe three patients with long histories of treatment for schizophrenia or schizoaffective disorder in whom conversion to aripiprazole was being attempted. After they started aripiprazole, their psychosis, agitation, anxiety, or aggression worsened. Although the cause of the increased agitation was unclear, it may have been related to long-term use of dopamine-blocking antipsychotics and resultant upregulation of postsynaptic dopamine receptors. The mechanism of partial dopamine agonism observed with aripiprazole may increase dopaminergic activity and worsen positive dopamine-associated symptoms, such as paranoia, agitation, and aggression. The treatment of schizophrenia is often a clinical challenge, particularly when patients have a long history of noncompliance and poor response. Clinicians face difficult decisions in finding an effective and well-tolerated regimen. These cases magnify some of the challenges and provide insight into the clinical implications of converting to therapies with different pharmacodynamic effects.

The management of bipolar disorder has seen significant evolution in terms of the number of treatment options now approved for both the acutely manic phase and the maintenance stages of the illness. In addition, new formulations of traditional agents are available for clinicians to use in their treatment approach. One such example is carbamazepine, which has approval by the United States Food and Drug Administration for the treatment of acute and mixed mania in an extended-release formulation that uses a three-bead delivery system. Although the parent compound has been available for decades, its approval for bipolar disorder is recent despite numerous clinical trials that have supported its use in both the acute and maintenance phases of bipolar disorder. Advantages of the new formulation include less fluctuation in plasma concentration and, in general, improved tolerability. However, issues remain with regard to cytochrome P450 drug-related interactions and the need for therapeutic drug monitoring (e.g., drug concentrations, epoxide metabolite concentrations, hematology, and liver function tests) as part of the treatment and monitoring process. We review the current body of literature describing the use of carbamazepine in bipolar disorder during both the acute and maintenance phases of the disorder, including trials of both monotherapy and combination therapy, as well as findings from trials that included patients with rapid cycling and mixed episodes.