One of the major developments in psychiatry in the last decade is the development and widespread use of the new antipsychotics. The field has moved from the typical dopamine D2-blocking neuroleptics into the new era of antipsychotics with the addition of the serotonin 5-HT2A properties to the classical D2 antagonism. These “atypical” antipsychotic drugs (APDs) provide us with new tools with which to treat our patients. However, do we really know how to make the most of these new medications? Are we equipped with the knowledge to do the best matching between the different APDs and the patients that we will see in an hour's time?

One potential way to get the maximum therapeutic effect of a specific medication is to improve the matching between the compound and the patient that we are seeing, ie, to try and get the best medication for the patient. For example, the medication one would choose for a patient with cognitive decline and a tendency to be overweight, would likely be different from an antipsychotic one would select for a patient with the same diagnosis, but who is slim and has paranoid delusions. It is also intuitively clear to us that we should treat first-episode patients differently from those with a 20-year history of social decline. Similarly, a patient with pronounced affective component would receive a different treatment regimen from a patient who is affectively “flat.”

Although we have been hearing and reading a lot about all the different APDs, it would be quite accurate to postulate that a concise updated summary of the different APDs, examining them around four different critical axes, might be welcomed by our readers.

The topics covered in this supplement are: the differential receptor's profile of APDs and their clinical implications, the issue of cognitive impairment in schizophrenia and APDs, monitoring guidelines to assess metabolic abnormalities that may occur with APDs, and an update on treatment after first-episode psychosis.

Understanding common pharmacologic and clinical “class” actions associated with atypical antipsychotics certainly reveals how these agents are alike, but what about unique differences from one agent to another? Atypical antipsychotics are also a heterogeneous group of agents that have complex pharmacologic entities, acting upon multiple dopamine receptors (D2, D1 (D3, and D4) and multiple serotonin receptors (5-HT2A, 5-HT2C, 5-HT1A, and 5-HT1D, among others). Atypical antipsychotics also interact with noradrenergic (α1- and α2-adrenergic receptor blockade), histaminergic (H1-receptor blockade), and cholinergic (muscarinic M1 blockade) neurotransmitter systems as well as with monoamine (D, 5-HT, and norepinephrine reuptake blockade) transporters. However, no two atypical antipsychotics possess the same portfolio of actions upon all of these additional neurotransmitter systems.

Greater attention has been given to the cognitive dimension in schizophrenia in recent years. This has resulted from increased recognition that cognitive impairment and negative symptoms of the disease have a greater impact on quality of life (QOL) compared to positive symptoms. Successful treatment of positive symptoms in patients with schizophrenia has not been shown to robustly translate into improvements in employment status or social relationships, while cognitive improvements are strongly associated with these important aspects of QOL and independence. These findings are based on extensive testing with standard cognitive tests for measuring executive function, verbal learning and memory, word recall, verbal working memory, spatial working memory, attention, and vigilance. Verbal learning and executive function, in particular, have been found to be valid predictors of employment success independent of the degree of severity of positive symptoms.

Patients with schizophrenia have increased mortality due to higher rates of suicide. However, natural causes of death, such as cardiovascular disease, also contribute greatly to excess mortality. Significant sources of cardiovascular risk in this patient population include high smoking prevalence, inactive lifestyles, poor dietary habits, and the metabolic effects of atypical antipsychotics. These sources of risk interact with underrecognition of common medical conditions by mental health providers, limited access to primary care services, and undertreatment of health conditions in the general medical setting. For many patient with severe mental illness, the mental health setting represents the sole source of medical care, making the psychiatrist the de facto primary care provider for these individuals. With the recent focus on medical consequences of antipsychotic treatment, psychiatrist have an obligation to minimize these adverse effects by choosing antipsychotics with lower risk for metabolic side effects, and becoming familiar with the screening and management of common medical conditions.

Interest in early and preventive interventions in patients with psychotic disorders has increased over the past few years as a result of die intuitive appeal of such interventions. Results of studies point to an association between longer duration of untreated psychosis and poor outcome, atypical antipsychotic agents less likely to cause extrapyramidal side effects, and a shift from hospital to community-based care for many patients with severe mental illness. Treatment strategies specifically directed to firsUepisode psychosis may help to improve outcomes. Such strategies include the use of lower doses of antipsychotic medications, the predominant use of atypical antipsychotic agents, and the deployment of psychological interventions that address the unique needs of young, first-episode patients and their families.