The Canadian Journal of Psychiatry

To examine research and clinical interest in the first episode of schizophrenia. Pathobiological features have been shown to be a consequence of the disorder rather than the effects of chronicity, drug treatment or institutionalization. There is increasing evidence that ventricular enlargement is a robust finding and hypofrontality on PET and SPECT is associated more with symptomatology than with neuroleptic treatment.

Neuroleptic threshold studies suggest that lower daily dosages and onset of medication may be the most important response prediction parameters.

The role of novel antipsychotics in the treatment of first-onset schizophrenia merits investigation for lower rates of extrapyramidal syndromes and tardive dyskinesia. To reduce relapse rates, psychiatrists need to introduce practice standards employing those biopsychosocial features in the management of first-episode schizophrenia.

To recommend dose range and therapeutic plasma concentration for several neuroleptics, and to discuss conditions under which neuroleptic plasma levels are clinically useful.

Neuroleptic drug therapy is a major component of the acute and maintenance treatment of schizophrenia. However, there is no consensus on what constitutes an appropriate or optimal dose of antipsychotic drug in individual patients. Low-dose medication has the potential to improve psychosocial function and reduces the frequency of side effects but can lead to an increase in positive symptoms and schizophrenic relapse. High doses may be associated with behavioural toxicity, symptom exacerbation, a worsening of secondary deficit symptoms, impaired social functioning and increased adverse effects such as acute extrapyramidal symptoms and tardive dyskinesia. Numerous clinical studies have attempted to determine the degree of correlation between dose, neuroleptic blood levels, and clinical response.

To date, this approach has met with only limited success: neuroleptic dose overall appears to be a poor predictor of clinical outcome, and the suggested therapeutic plasma level concentrations of some antipsychotic drugs cannot be regarded as established by any means. Furthermore, the ability to conduct neuroleptic plasma levels is not readily accessible in the usual clinical setting. In the acute treatment phase, titrating the dose until the onset of minimal cogwheel rigidity or hypokinesia (neuroleptic threshold dose) has met with some success and is preferable to standard dosing as a means of individualizing pharmacotherapy. During the maintenance phase, a slow and gradual dosage reduction with adjunctive psychosocial and psychotherapeutic intervention is the preferred strategy.

Reinforcing patient and physician compliance is a key element in achieving an optimal treatment regimen.

To review recent research findings on tardive dyskinesia (TD) with relevance to clinical practice.

TD is a syndrome of involuntary movements that can occur in association with chronic neuroleptic use. It is of unknown pathophysiology. It can be irreversible, is cosmetically disfiguring, and can be functionally disabling.

There is as yet no treatment of demonstrated efficacy for TD. It is an iatrogenic disorder whose incidence is increased by age and total cumulative dose of typical neuroleptics. It has been the source of successful litigation in some jurisdictions but, until very recently, there has been no effective antipsychotic agent without this effect.

This litigation in some jurisdictions has been a major impetus to the development of novel antipsychotic agents. It is less well known that a similar, possibly identical, movement disorder occurs spontaneously particularly in the elderly and inpatients with schizophrenia, and that TD is often reversible.

To review the data and discuss clinical recommendations for treating negative symptoms of schizophrenia. Negative symptoms (e.g., poverty of thought, affective blunting) have been regarded as part of schizophrenia since Kraepelin's early descriptions, although they remain a subject of controversy. For example, it is unclear if negative symptoms are distinct from other psychiatric symptoms such as depression, or are in actuality depression within schizophrenia. Recent evidence suggests that negative symptoms are independent of depression.

Factor analytic studies have suggested that a negative factor (loss of affect, volition, poverty of thinking) may be distinguished from other components and is separable from a depression factor. Experimental use of vignettes have also been useful in the assessment of negative symptoms. A second controversial area is whether or not the presence or absence of affect is the fundamental issue separating schizophrenia from other psychoses.

A continuum of psychosis has been hypothesized, with unipolar psychotic depression at one pole and schizophrenia with defect state at the other. Within this proposed continuum, negative symptoms are associated only with schizophrenia without affect and with defect state schizophrenia. As such, variation in affect could be a primary determinant of the type of psychosis.

It appears that negative symptoms are a distinct aspect of schizophrenia and may aid in our understanding of psychotic disorders.

To discuss the costs associated with mental illnesses that constitute a significant percentage of the total direct health care costs, currently estimated at $1605 per person per year (9% of the gross national product). The cost of all mental illness in the US has been estimated at US$103.7 billion (1985 dollars), of which schizophrenia alone accounts for US$22.7 billion.

A number of studies that have attempted to evaluate the cost of therapies in schizophrenia are examined.

While schizophrenia affects only 1% of the population, it accounts for 2.5% of total health care expenditures in the US. For first-admission patients suffering from schizophrenia, it would appear to cost less to provide the most clinically-effective treatments than to provide a good level of milieu care with special treatment.

Community-based care can be less costly than conventional hospital-based programs and can improve patient quality of life. Inhospital programs that reduce length of stay with the use of medication clinics or day hospital care may achieve significant cost savings. A special challenge is the subgroup of patients suffering from schizophrenia that is neuroleptic-resistant. New drugs, such as the atypical neuroleptics, clozapine and risperidone, may prove to be highly cost-effective in treating schizophrenia by preventing relapse and reducing hospital lengths of stay.