Case Report

By Dr. Ennio Piantato , Dr. Francesca Sartore
Corresponding Author Dr. Ennio Piantato
Azienda Ospedaliera Nazionale , Alessandria - Italy 15121
Submitting Author Dr. Ennio Piantato
Other Authors Dr. Francesca Sartore
Dept Mental health, via Venezia 16nAlessandria - Italy 15121


Clozapine, Schizophrenia, Results

Piantato E, Sartore F. Clozapine: Does it work? Analysis of a 15 year experience. WebmedCentral PSYCHIATRY 2011;2(9):WMC002256
doi: 10.9754/journal.wmc.2011.002256
Submitted on: 24 Sep 2011 06:42:23 PM GMT
Published on: 25 Sep 2011 03:38:01 PM GMT


This is an overview of results after a 15 year follow-up of psychotic patients treated mainly with Clozapine. We have found out that their quality of life has improved, they are good compliant in taking their medications and the number of hospitalizations is greatly reduced after beginning treatment with Clozapine.


This report contains data about use of Clozapine in our Psychiatric Unit during the period June 1995-June 2009. Clozapine is an anti-psychotic drug created at the end of 60’s, with a particular receptor profile. Due to some cases of granulocytopenia noted in Finland the drug was withdrawn in 1975. It was reintroduced in the 90’s with indication for “resistant schizophrenia” and a recommendation to monitor blood cell counts. Since 1995 Clozapine has been officially used in Italy for “resistant schizophrenia”. In 1995 we started using Clozapine after two of us attended a course at the Psychiatric Clinic of the Bern University, Switzerland.
Our Psychiatric Unit is part of a Department of Mental Health and situated in the Alessandria general hospital, in the region of Piedmont in NW Italy, serving a population of 180.000 inhabitants. The unit has 15 beds plus 1 bed for Day Hospital service. Initially Clozapine was used with so-called treatment-resistant schizophrenic patients, showing resistance to traditional and at least two atypical antipsychotic treatments as reported in international guidelines. [1] Afterwards the treatment with Clozapine was extended to patients affected by non-schizophrenic disturbances such as bipolar disorder.

Materials and Methods

Our report includes the group of patients currently taking Clozapine and attending our centre for blood test control. Almost all of them started Clozapine while hospitalized in our Psychiatric Unit.
At the moment the group is made up of 54 patients: 41 males (76%) and 13 females (24%).
Originally the use of Clozapine began with 6 patients (4 males and 2 females) who are still under the care of our centre.
Average age of patients is 43±9.9 for the total group: for the male group average age is 40, for the female group it is 46. Age range is from 26 to 69 years.All patients live at home with 8 exceptions: 6 of them live in sheltered apartments and 1 is in a nursing home. Regarding the diagnoses, 48 patients (88.9%) are affected by schizophrenia, 4 (7.4%) by a schizoaffective disorder and 2 (3.7%) by bipolar disorder with psychotic behaviour. (Tab 1). Our doses of Clozapine vary from 100 to 900 mg per day: doses are higher – usually - on discharge from hospital (150 to 900 mg per day) then they tend to diminish to a medium 75 to 600 mg per day.
Clozapine is used as monotherapy in 19 patients (35.1%) . It’s also used in association with other psychotropic drugs (sometimes more than one per category) in remaining cases: more precisely in association with mood-stabilizers in 19 patients, antisialorroic drugs in 4 patients, anticholinergic medications in 19 patients, other antipsychotic drugs in 20 patients, benzodiazepines in 10 patients and antidepressants in 3 patients.
We have observed that the side effects of treatment with Clozapine are most frequently:-sialorrea (excessive salivation); constipation; low blood pressure; psychomotor slowing; weight increase; in one case an epileptic fit was controlled by adding an anti-epileptic drug so the global treatment could be continued without having any other problem; two patients are affected by epilepsy in co-morbidity and take anti-epileptic drugs. In this group we have not had any granulocytopenia. We have observed a reduction in hospital admissions after beginning treatment with Clozapine, above all in the male group. In 22 patients (40.7% of the group) we haven’t had further hospital admissions. (Tab 3 and 4).


The reduction of hospitalizations is reported [2,3] and explained as “effect of objective improvement of some clinical parameters and better social and job adaptability” [4] this is consistent with the self evaluated subjective improvement registered by our patients and by authors. [5]
Clozapine alone isn’t always enough. In our group Clozapine is often associated with other psychotropic drugs and it is used as the only antipsychotic drug in 19 patients; among most frequently used drugs in association there are other first and second generation antipsychotics.
Regarding the association between Clozapine and other antipsychotics we found that two patients of the group have been included in the CHAT study (experimental cohort with Clozapine enhanced associating another antipsychotic drug, aripiprazole or haloperidol). [6]
No patient of ours has tried or succeeded in committing suicide so far and this is consistent with other reports [7]. Clozapine has also produced good results with patients whose behaviour had been violent specially in a etero-directed way. Scientific evidence shows that continuous use of anti-psychotic drugs in schizophrenics prevents relapses.
Compliance with treatment is important in all chronic pathologies and in our group especially an interruption of treatment provokes various consequences, first of all the risk of a relapse with hospitalization (up to “revolving-door” conditions) plus blockage of the personal therapeutic and rehabilitation project. The reduction in hospitalization observed in our group is the verification of good compliance with treatment included the regular carrying out of their blood tests. Moreover patients have been also monitored via analysis of plasma levels of Clozapine.
We have begun to use metformin in some of our patients to control weight gain due to the treatment with Clozapine: so far the results appear good but the time of observation (4 months) is too short to allow us to be more specific. [8,9]


Clozapine is an antipsychotic whose use is limited by some side effects, some of which are potentially deadly. Many clinical studies have confirmed its efficacy especially on positive schizophrenic symptoms in the long term treatment and in drug-resistant schizophrenia, moreover it is the antipsychotic used in case of psychoses in patients with Parkinson’s disease. [10,11,12,13]
Our considerations, based on our clinical group, are in line with results ofthese studies: this is particularly evident in patients who have never been re-hospitalized after taking Clozapine notwithstanding the gravity of their mental pathology: i.e. two women had even previously been treated with convulsive therapy, so far both of them have had good health since 1995 after since using Clozapine.


1. Società Italiana di Psicopatologia,  Consensus Conference: Linee guida per la Farmacoterapia della schizofrenia, Roma, 14-15 aprile 2000
2.Breier A, Buchanan RW, Irish D, Carpenter WT Jr.: Clozapine Treatment of Outpatients With Schizophrenia: Outcome and Long-Term Response Patterns. Hosp Community Psychiatry 1993; 44: 12: 1145-1149
3. Meltzer HY, Burnett S, Bastani B, Ramirez LF.: Effects of Six Months of Clozapine Treatment on the Quality of Life of Chronic Schizophrenic Patients. Hosp Community Psychiatry 1990; 41: 892-897
4. Meltzer HY, Cola P, Way L, Thompson PA, Bastani B, Davies MA, Snitz Beth: Cost Effectiveness of Clozapine in Neuroleptic-Resistant Schizophrenia. Am J Psychiatry 1993; 150: 1630-1638
5. Waserman J, Criollo: M. Subjective Experience of Clozapine Treatment by Patients With Chronic Schizophrenia. Psychiatric Services 2000; 51: 5: 666-668
6. Nosè M, Accordini S, Artioli P, Barale F, Barbui C. et Alii: Rationale and Design of an Independent Randomised Controlled Trial Evaluating the Effectiveness of Aripiprazole or Haloperidol in Combination with Clozapine for Treatment-Resistant Schizophrenia. Trials. 2009 May 15;10-31
7. Llorca PM, Perez JJ.: Leponex, 10 ans après. Une revue clinique. L’Encéphale, 2004; XXX: 474-479
8. Schumann SA, Ewigman B.: Can Metformin Undo Weight Gain Induced by Antipsychotics?  J Fam Pract. 2008 Aug; 57 (8): 526-30 
9.Ness-Abramof R, Apovian CM.: Drug-induced Weight Gain. Drugs Today. 2005 Aug; 41 (8): 547-55
10. Buchanan RW, Breier A, Kirkpatrick B, Ball P, Carpenter WT Jr.: Positive and Negative Symptom Response to Clozapine in Schizophrenic Patients With and Without Deficit Syndrome. Am J Psychiatry 1998; 155: 6: 751-760
11. Leiderman EA.: Effectiveness Trials in Chronic Schizophrenic Patients: CATIE. What can we learn? Vertex 2009; 20;(84); 129-35
12. Essali A, Al-Haj Haasan N, Li C, Rathbone J.: Clozapine vs Typical Neuroleptic Medication for Schizophrenia. Cochrane Database Syst Rev. 2009; Jan 21; (1): CD000059
13. MercierC, Bret P, Bret MC, Queuille E: Enquête observationelle de prescription de la clozapine au centre hospitalier Charles-Perrens à Bordeaux, plus de 15 ans a près l'AMM en France, L'Encéphale, 2009: XXXV (4): 321-9.

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Competing Interests



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