Withdrawal from clozapine

Clozapine. Withdrawal symptoms after the abrupt discontinuation of clozapine differ from those noted with other antipsychotics ( 98, 477). Thus, rapid discontinuation may result in the following ... 

Clozapine withdrawal symptoms occur after stopping therapeutic doses (range 200 to 900 mg/day) administered from 4 months to several years. In a study, one-third of patients who were switched directly from clozapine to risperidone remained stable, one-third had to be switched back to clozapine, and one-third were treated with combined risperidone-clozapine or risperidone-neuroleptic ( 480). 

The accumulating data from reports on clozapine withdrawal support these important facts ... 

Stanilla et al. (1997) described three cases of delirium with psychotic symptoms due to clozapine withdrawal (see also Adams et al., 1991, for an early report of clozapine withdrawal psychosis). They believed that clozapine produces more severe withdrawal symptoms than typical antipsychotic agents. In a 3-year open label study of quetiapine, Margolese et al. (2004) switched 23 male patients from classical antipsychotics and risperidone to quetiapine Six of the seven patients who relapsed after being stabilized on quetiapine for at least three months met the criteria for supersensitivity psychosis. This is a very high rate, again raising questions about whether atypicals may be more prone to cause tardive psychosis. 

Caffeine has been associated with changes in the metabolism of clozapine (SEDA-20, 50 SEDA-22, 61). Seven schizophrenic patients taking clozapine monotherapy participated in a study of the effects of caffeine withdrawal from the diet (247). After a caffeine-free diet for 5 days, clozapine plasma concentrations fell by 50%. The authors suggested that schizophrenic patients treated with clozapine should have their caffeine intake medically supervised, and that monitoring of concentrations of clozapine and its metabolite may be warranted. 

Carrillo JA, Herraiz AG, Ramos SI, Benitez J. Effects of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients. J Clin Psychopharmacol 1998 18(4) 311-6. 

Seeman P, Tallerico T (1999) Rapid release of antipsychotic drugs from dopamine d2 receptors An explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. Am J Psychiatry 156(6) 876-884... 

Withdrawal of clozapine can lead to resolution of agranulocytosis, but not always. Granulocytopenia, presumably induced by clozapine, persisted in a 53-year-old woman after she switched from clozapine to quetiapine (159). 

Data from an open study (n = 329) have suggested that patients aged 55-64 years may have a better response to clozapine than those aged 65 and older, but there were no significant differences between the two age groups in the number of patients remaining on clozapine therapy and the number in whom therapy was discontinued (n = 134) (223). The mean duration of clozapine therapy was 278 days. The most common adverse effects that required withdrawal were sedation (n = 12), hematological adverse effects (n = 7), and cardiovascular adverse effects (n = 6). 

Caffeine 2. Chaste tree 3. Green tea 4. Plantain 1. Lithium 2. Phenothiazines (e.g. chlorpromazine, promazine, levomepromazine, pericyazine, pipotiazine, fluphenazine, perphenazine, trifluphenazine) 3. Clozapine L blood lithium levels with 1 clinical effects. 1 effects of phenothiazines Unknown mechanism (caffeine) Contains dopamine agonists (chaste tree) Induction of metabolizing enzymes (green tea may induce CYP1A2, which metabolizes clozapine) l absorption from the gut (plantain may l absorption of lithium) Be aware. Caffeine withdrawal may precipitate lithium toxicity, so avoid sudden caffeine withdrawal. Avoid concomitant use if possible... 

Delayed onset of clozapine-induced leucopenia is reported in a 51-year-old male after 11 years of treatment necessitating discontinuation of clozapine [125 ]. A second case of delayed onset of clozapine-induced leucopenia is reported in a 57-year-old female after 6 years of treatment also leading to discontinuation [126 ]. Two cases, a 45-year-old male and a 50-year-old female who developed neutropenia but successfully responded and tolerated high-dose quetiapine, are reported [127 ]. A case series reporting the withdrawal and reintroduction of clozapine in patients suffering from dengue fever is described [128 ]. 

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