Clozapine for schizophrenia

Your patient is prescribed clozapine for schizophrenia that has not responded to other drugs. You must discuss this new therapy with the family. Discuss what points to include in this family teaching session. 

Tuunainen A, Wahlbeck A, Gilbody SM. Newer atypical antipsychotic medication versus clozapine for schizophrenia. Cochrane Database of Systematic Reviews 2000. Issue 2. 

Blanz, B., and Schmidt, M.H. (1993) Clozapine for schizophrenia [letter comment]. / Am Acad Child Adolesc Psychiatry 32 223-224. 

The potential of lithium to prevent or treat clozapine-induced granulocytopenia has been reviewed (39). In a study of 38 patients on clozapine for schizophrenia or schizoaffective disorder, the addition of lithium increased the leukocyte count (42). A 20-year-old man with olanzapine-induced neutropenia 5 mg/day was able to tolerate 20 mg/day while taking lithium (43). 

There is a potentially dangerous interaction with cancer treatment in patients with schizophrenia taking clozapine, because of the unpredictable risk of myelotoxicity. However, a 37-year-old patient taking clozapine for schizophrenia was given full-dose cisplatin and concomitant radiotherapy for an undifferentiated nasopharyngeal carcinoma, without significant neutropenia (250). 

K (nM) values for clozapine at D2 and Di receptors are 56 and 141 compared with 0.5 and 27 for haloperidol giving D1/D2 ratios of 2.5 and 54 for the two drugs. A relatively strong block of Di compared with D2 receptors may not be the answer for schizophrenia but it could reduce the tendency to produce dyskinesias, if this depends on Di receptor activation (see Fig. 17.2). 

Psychopharmaco-epidemiology investigation in China in 2002 showed that the first six antipsychotic drugs used for schizophrenia were clozapine, risperidone,... 

The first of the second-generation, or atypical, antipsychotics was clozapine. Clozapine (Clozaril) is relatively free of the movement disorders that characterize the first-generation drugs. This is true of, and defines, second-generation, atypical antipsychotics. It was a significant breakthrough for schizophrenia patients. 

Dose adjustment - Continue daily dosing on a divided basis to an effective and tolerable dose level. Do not exceed 900 mg/day. The mean and median clozapine doses are approximately 600 mg/day for schizophrenia and 300... 

Wahlbeck K, Cheine M, Essali MA. Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database Syst Rev 1999. Issue 4. 

Anisette Doe, a 28-year old woman, went to the emergency department with abdominal bloating and inability to void her bladder she had been unable to urinate for 16 hours. A urinary catheter was inserted and 2.5 L of urine was withdrawn. Subsequent testing revealed no calculi or masses in the bladder, urethra, ureters, or kidneys. Ms. Doe s medical records indicated that she was being treated with clozapine for paranoid schizophrenia. She reported no signihcant side effects as a result of this treatment. For 2 days prior to admission to the hospital, Ms. Doe complained of a cold and was taking diphenhydramine Benadryl)... 

TABLE 5-11. Clozapine versus neuroleptics for schizophrenia acute treatment... 

Clozapine, risperidone, olanzapine, quetiapine, and ziprasidone have all been approved for the treatment of schizophrenia. Data from long-term open evaluations of clozapine demonstrate that improvement is maintained over time, even when the dose is reduced. Further, patients did not develop tolerance to its antipsychotic effect. Naturalistic reports indicate that an adequate trial for acute response in some patients may be at least 6 months. Further, a small number (8 of 14) of previously refractory patients were successfully maintained on clozapine for up to 2 years ( 215). 

Green Al, Zimmet SV, Strous RD, et al. Clozapine for comorbid substance use disorder and schizophrenia do patients with schizophrenia have a reward deficiency syndrome that can be ameliorated by clozapine Harvard Rev Psychiatry 1999 6 287-296. 

Bondolfi G, Baumann P, Paths M, et al. A randomized double-blind trial of risperidone versus clozapine for treatment-resistant chronic schizophrenia. Presented at the 148th Annual Meeting of the American Psychiatric Association, Miami, May 1995. 

FIGURE 11-52. Positive symptom pharmacy. First-line treatment of positive symptoms is now atypical antipsychotics (SDA), not only for schizophrenia but also for positive symptoms associated with bipolar disorder, Alzheimer s disease, childhood psychoses, and other psychotic disorders. However, conventional antipsychotics (D2) and benzodiazepines (BZ) are still useful for acute intramuscular administration (in case of emergency), and D2 for monthly depot injections for noncompliant patients, as well as for second-line use after several atypical agents fail. Clozapine (C), polypharmacy, and combinations (combos) are relegated to second- and third-line treatment for positive symptoms of psychosis. 

Goff DC, Tsai G, Manoach DS, Flood J, Darby D, et al. 1996. D-cycloserine added to clozapine for patients with schizophrenia. Am J Psychiatry 153 1628-1630. 

Tsai GE, Yang P, Chung LC, Tsai IC, Tsai CW, et al. 1999. D-serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry 156 1822-1825. 

Squires RF, Saederup E. 2000. Additivities of compounds that increase the numbers of high affinity [3H] muscimol binding sites by different amounts define more than 9 GABA(A) receptor complexes in rat forebrain Implications for schizophrenia and clozapine research. Neurochem Res 25 1587-1601. 

Clozapine and SSRIs are often used together, because depressive syndromes are common in patients with schizophrenia. Clozapine carries a relatively high risk of agranulocytosis, but this adverse effect is very rarely seen with SSRIs, although a case of possible fluoxetine-induced neutropenia has been described (SEDA-22, 15). Two cases in which the addition of paroxetine to clozapine was associated with neutropenia have been reported (11). The patients had been taking stable doses of clozapine for 6-12 months and had previously tolerated other SSRIs without adverse hematological consequences. In both cases the white cell count recovered when clozapine was withdrawn, although paroxetine was continued. 

Moldavsky M, Stein D, Benatov R, Sirota P, Elizur A, Matzner Y, Weizman A. Combined clozapine-lithium treatment for schizophrenia and schizoaffective disorder. Eur Psychiatry 1998 13 104-6. 

Hummer M, Kemmler G, Kurz M, Kurzthaler I, Oberbauer H, Fleischhacker WW. Sexual disturbances during clozapine and haloperidol treatment for schizophrenia. Am J Psychiatry 1999 156(4) 631-3. 

Patients with aggressive schizophrenia (n = 29) improved when treated with clozapine one was withdrawn after the development of leukopenia. In 10 mentally retarded patients taking clozapine for 15 days to 46 months improvement was observed. Half of the patients developed sedation and hypersalivation, and one discontinued the drug after 2 weeks because of neutropenia. The putative neurotoxicity of clozapine in moderately to... 

In a retrospective study, 27 of 61 Chinese patients who took clozapine for more than 3 months developed urinary incontinence, persistent in 15 cases (193). The reaction could not be related to age, sex, clozapine dosage, duration of clozapine use, duration of hospitalization, duration of illness, age at onset of schizophrenia, or concurrent treatment with other psychiatric drugs. 

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