Clozapine in the treatment of 121 out-patients

Abstract

Retrospectively, effects of long-term therapy with clozapine were evaluated in 121 out-patients. They were treated for 32 +/- 43 months in a daily dosage of 131 +/- 99 mg. Sixty nine patients were schizophrenic and had previously received one or more neuroleptics but with insufficient response or severe side effects. Nine patients suffered from tardive dyskinesia (TD), 44 patients had other diagnoses. Twenty two per cent of the schizophrenic patients improved slightly, 65% markedly and in 13% the symptoms nearly totally disappeared. Fourty per cent of chronic schizophrenics showed improvement of anergia. Eleven per cent of the patients with TD did not improve, 22% showed slight and 67% marked improvement. Clinically relevant side-effects occurred in 64% of patients: Generally sedation/hypotension, EG and ECG alterations, changes of white blood cell count, increase of liver enzymes and weight gain. EEG alteration correlated significantly with dosage of clozapine (P less than 0.01). In 6% of patients, severe side-effects led to discontinuation of clozapine treatment. No case of agranulocytosis occurred. Most patients tolerated the drug well and were compliant. Under careful control of hematological and other variables, the benefit/risk ratio of clozapine long-term treatment appears to be high and acceptable.

Atypical antipsychotics and mood stabilization in bipolar disorder

“…Case reports suggested the antidepressant efficacy of clozapine in bipolar (Calabrese et al 1991;Privitera et al 1993;Suppes et al 1994) and unipolar (Leppig et al 1989;Naber et al 1992;Ranjan and Meltzer 1996) patients. No open-label or controlled data are available with the use of clozapine in bipolar depression.…”

“…Clozapine has been suggested to be effective in the long-term management of treatment-resistant bipolar patients in case reports (Calabrese et al 1991;Frankenburg 1993;Suppes et al 1994;Puri et al 1995;Frye et al 1996;Calabrese and Gajwani 2000) and in open-label studies (Battegay et al 1977;Leppig et al 1989;McElroy et al 1991;Banov et al 1994;Frankenburg and Zanarini 1994;Calabrese et al 1996;Ciapparelli et al 2000), in most cases used as an adjunctive agent (Table 5). In the study by Calabrese et al (1996), among 11 bipolar patients taking clozapine monotherapy, increasing clozapine dose was sufficient to manage the re-emergence of manic symptoms in 5 of them, whereas coadministration of antidepressants was needed to treat major depression in 5 of them.…”

“…The main reasons for discontinuation were lack of efficacy, non-compliance, or side effects. When considering together the available uncontrolled studies that reported the number of responders (Battegay et al 1977;Leppig et al 1989;McElroy et al 1991;Banov et al 1994;Calabrese et al 1996;Ciapparelli et al 2000), clozapine was effective in 70% of bipolar patients (92 of 131 patients), at a mean dose of 250 mg/day, and over an average time of 18.2 months (Table 6).…”

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment

“…There have been reports that conventional antipsychotics are used in around one-third of patients receiving clozapine in some European countries. 51,52 For example, McCarthy and Terkelsen 53 reported that a conventional antipsychotic was added to clozapine in 30-35% of cases in Denmark. This is despite the lack of convincing research evidence to justify the addition of another antipsychotic in patients with only a partial response to clozapine monotherapy.…”

Clozapine as Add-On Medication in the Maintenance Treatment of Bipolar and Schizoaffective Disorders

“…Atypical antipsychotics such as clozapine, olanzapine, risperidone or quetiapine are considered as relatively safe alternatives used as add-on med- Hummel/Dittmann/Forsthoff/Matzner/ Amann/Grunze ication in the maintenance treatment of bipolar and schizoaffective disorders [9]. Hints at efficacy of clozapine in schizoaffective [10][11][12] and bipolar disorders [13][14][15] were reported by several authors. However, controlled trials of clozapine in maintenance treatment are still missing.…”