Neuroleptics treatment-resistant patients

Efficacy of high doses of "classical" neuroleptics in the treatment-resistant patient... 

ECT was generally inferior or equivalent to treatment with neuroleptics alone in terms of short-term outcome 2) in contrast, long-term outcome in these early studies appeared to favor ECT over medications 3] the combination of ECT and neuroleptic may be more effective than ECT or neuroleptic alone and 4] although we lack controlled studies, several reports have indicated that ECT may be of benefit in neuroleptic-resistant patients with schizophrenia. 

The aforementioned study had insufficient power to determine whether patients with SRI-resistant OCD with comorbid schizotypal personality show a significant improvement after addition of neuroleptic. Despite the widespread clinical impression that neuroleptics are useful in treating OCD with psychotic symptoms, no controlled trials have been performed with this population. Further controlled studies with other SRls are needed to confirm the findings of McDougle et al. [1994] and to better define the appropriate target population for neuroleptic addition. The prescribing physician should be wary about exposing patients unnecessarily to the risks of chronic neuroleptic treatment. 

Goff DC, Brotman AW, Waites M, et al. Trial of fluoxetine added to neuroleptics for treatment-resistant schizophrenic patients. Am J Psychiatry 1990 147 492-494. 

The concept of treatment-resistant schizophrenia, which was developed to delineate a market for the relaunch of clozapine, has lead to public acknowledgment of the extent of non-response to treatment with other neuroleptic drugs. It is now widely admitted that at least 25% of patients do not show any significant clinical improvement with drug treatment. A recent comparison of two of the newer neuroleptic drugs, risperidone and olanzapine, found that 46% and 56% of patients, respectively, did not respond after four months of treatment (Robinson et al. 2006). In addition, the majority of inpatients with psychosis are treated with other sedative drugs in addition to... 

Combinations are often used in patients with treatment-resistant schizophrenia and schizoaffective disorders, and the published data (29 case reports and case series, n = 172, and one double-blind placebo-controlled trial, n = 28) between 1985 and 2003 has been reviewed (22). Significant adverse effects were rarely reported (by only 36 of the 200 subjects) and did not appear to be different in nature from those of monotherapy regimens hypersalivation (n = 6), mild akathisia (n = 4), exacerbation of hoarding behavior (n = 2), neuroleptic malignant syndrome (n = 2), and neutropenia, agranulocytosis, oculogyric crises, atrial extra beats, and aggravation of previous tardive dyskinesia (n = 1 each). 

Rates of hospitalization with clozapine have been analysed by Novartis, the manufacturers, based on two retrospective studies of hospitalization among patients with treatment-resistant schizophrenia (2). All the patients who began clozapine treatment in Texas State psychiatric facilities during the early 1990s (n = 299) were compared with controls who received traditional neuroleptic drugs (n = 223), matched for severity, age, and sex. More patients in the latter group required continuous hospitalization at 4 years, four times as many patients taking a... 

In Connecticut in the USA, Essock and co-workers randomized 227 patients to treatment with clozapine or to usual care and observed treatment outcome for 24 months (Essock et al, 1996). At the end of this period 88 (64%) of the original clozapine group ( = 138) were still taking clozapine. All randomized participants were in-patients who were resistant to or intolerant of conventional neuroleptics. The authors presented only brief results. Discharge rates for the two treatment groups were similar, but stark differences were observed in readmission rates 3% of patients taking clozapine were readmitted within 6 months of discharge, compared with 29% of... 

Also supportive of DA involvement in the pathophysiology of OCD are observations that adjunctive therapy with the older conventional antipsychotics-neuroleptics (which block DA receptors) added to ongoing SSRI treatment reduces the severity of OCD symptoms in OCD patients resistant to SSRI treatment alone, especially in those with concomitant Tourette syndrome. 

The hormone leptin is synthesized by adipocytes and is important in controlling body weight plasma leptin concentrations correlate with fat mass and insulin resistance. Leptin could be a link between obesity, insulin resistance syndrome, and treatment with some neuroleptic drugs. Plasma leptin concentrations are raised, regardless of weight, in patients taking clozapine (793). 

In clinical studies, remoxipride has been shown to improve both positive and negative symptoms of schizophrenia and may have a place in the treatment of resistant schizophrenic patients. In addition such side effects as the neuroleptic-induced deficit syndrome, sedation and extrapyramidal side effects are apparently absent in patients treated with the drug. 

These observations suggest that insulin resistance might be responsible for the development of diabetes during treatment with atypical neuroleptic drugs, but it may not be the only factor, since the rapid development of diabetes in many of these patients suggests a direct and possibly toxic effect of neuroleptic drugs. 

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