The outcome of treatment in schizophrenia is best considered as a multidimensional construct. This report lists thirteen categories of outcome measures that have been studied in schizophrenia research, among the most important of which are psychopathology, cognitive function, interpersonal social function, quality of life, extrapyramidal function, the suicide tendeccy and the need for hospitalisation. Clozapine is effective in achieving improved outcome in all these measures in a high percentage of neuroleptic-resistant patients. Ninety-two of 180 (51.1%) clozapine-treated neuroleptic-resistant patients achieved a decrease of 20% in Brief Psychiatric Rating Scale total scores at six weeks using the 0–6 scaling system. Cognitive function contributes importantly to overall function for schizophrenia. Clozapine has been shown to improve some types of cognition in schizophrenia, especially semantic memory and some tests of executive function. Clozapine has also been shown to decrease the incidence of suicide and hospitalisation. The task of deciding which therapies to use in schizophrenia should encompass the spectrum of benefits of each therapy, their risks and costs, in relation to all alternatives.

A meta-analysis of the published literature was performed in order to quantify the efficacy of low-dose neuroleptic therapy in reducing extrapyramidal side effects in schizophrenic patients. A low-dose regimen between 50–100 mg equivalents of chlorpromazine, in comparison to a standard-dose regimen between 200–500 mg reduced extrapyramidal side effects by a 0.30 (±0.12) standard deviation, which is only a limited effect.

Consensus was reached on the five following points: (1) “Treatment resistance” is a term which is widely used, but not adequately defined. In particular, definitions of “responders” and “non-responders” need to be more precise. (2) There is a need to extend the assessment of the results of treatment to include factors such as quality of life and the subjective evaluation by the patient and relatives. (3) Clozapine (Clozaril®/Leponex®) has become the standard for atypical antipsychotic drugs. The adjective “atypical” is not an exact descriptor. The vague nature of the term leads to confusion with other drugs that are putative atypical antipsychotic agents but have different properties. D2 dopamine receptor antagonism is the single factor common to all antipsychotic drugs. Antagonism at a specific D2-like receptor may underlie the atypical antipsychotic actions of clozapine. Drugs described as being atypical antipsychotics share a relatively low incidence of extrapyramidal side effects. (4) Clozapine is the only drug that produces antipsychotic (therapeutic) effects at doses that do not result, in significant extrapyramidal side effects. This may be due to the fact that antipsychotic efficacy is obtained with clozapine in doses that result in significantly less striatal D2 occupancy. Other factors including concomitant 5-HT2 antagonism, may contribute to the lack of motor side effects observed with clozapine treatment. (5) Clozapine is the only drug currently well proven in therapy-resistant schizophrenia, and there is a case for its earlier use in patients who can be anticipated to become therapy resistant. Other antipsychotic therapies remain unproven in this group of patients.

The authors describe the cases of three patients presenting a major extrapyramidal symptom with rising CPK, inconstant hyperthermia and autonomic dysfunction. Through a brief review of the literature, the authors question the unity of the malignant syndrome. If hypertonia is quite constant, the rise in the seric CPK is aspecific and hyperthermia is inconstant.

There is evidence in the literature that cognitive functions in schizophrenia (SC) may be improved by atypical neuroleptics (NLPs) in contrast to typical medication, but there is still controversy regarding this apparent superiority of atypical drugs. In this study, we assessed the differential effects of risperidone and haloperidol on verbal memory, attention, and psychiatric symptoms in SC. The performance of 28 SC participants, randomly assigned to risperidone (2–6 mg/day) or haloperidol (2–40 mg/day), was compared with that of healthy controls. The California Verbal Learning Test (CVLT), the d2 Cancellation Test, and the Positive and Negative Symptoms Scale were administered at baseline and 3, 6, and 12 months. Relative to controls, all SC participants showed markedly impaired verbal memory and processing speed at each assessment period. There was no differential effect between the two NLPs on CVLT and d2 performance. However, risperidone was more effective than haloperidol in reducing psychiatric symptoms. Improvement in symptom severity was not associated with improvement in neurocognitive performance on these specific tests. Neither conventional nor atypical neuroleptic medications improved neurocognitive functioning over a 12-month follow-up, suggesting that psychopathological improvement under risperidone is independent of cognitive function. (JINS, 2008, 14, 110–118.)

The recent development of an isometric instrument for the precise quantification of hand force persistence has created a novel opportunity for the evaluation of potential motor asymmetries in schizophrenia and their response to treatment. A study of asymmetries in the unmedicated state may provide insight into the pathogenesis of schizophrenia, whereas alterations of asymmetries in response to antipsychotic medication could assist the delineation of a cerebral mechanism for the effects of pharmacotherapy. The hand force persistence of 21 unmedicated patients with schizophrenia was compared to 21 age, gender, and handedness matched normal controls. The effect of neuroleptic treatment on hand force persistence was then evaluated on a subset of 10 patients after at least 30 days of treatment. The anticipated asymmetry was evident in the unmedicated sample that showed impaired right hand force persistence compared to the normal control sample. The prospective comparison showed an alleviation of the asymmetry resulting from an improvement of right hand force persistence with treatment. In addition to providing further support to a primary left hemisphere cerebral involvement in schizophrenia, the present results suggest that prior investigations of motor asymmetry may have been compromised by the study of medicated patients. The apparently paradoxical improvement of motor skill may relate to the substantial number of patients treated with 2nd generation neuroleptic medications which may implicate an improvement in left hemisphere physiology in the cognitive advantages of the novel treatments. (JINS, 2001, 7, 606–614.)

Three cases of neuroleptic induced blepharospasm successfully treated by botulinum toxin type A are reported.