clozapine: does it work? analysis of a 15 year experience · clozapine: does it work? analysis of a...

Article ID: WMC002228 ISSN 2046-1690

Clozapine: Does it work? Analysis of a 15 yearexperienceCorresponding Author:Dr. Ennio Piantato,Division Chief / Dept of Mental Health, Azienda Ospedaliera Nazionale , Alessandria, 15121 - Italy

Submitting Author:Dr. Ennio Piantato,Division Chief / Dept of Mental Health, Azienda Ospedaliera Nazionale , Alessandria, 15121 - Italy

Article ID: WMC002228

Article Type: Case Report

Submitted on:24-Sep-2011, 12:17:58 PM GMT

Article URL: http://www.webmedcentral.com/article_view/2228

Subject Categories:PSYCHIATRY

Keywords:Clozapine, Schizophrenia, Results

Source(s) of Funding:

No funding required

Competing Interests:

None

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Clozapine: Does it work? Analysis of a 15 yearexperienceAuthor(s): Piantato E , Sartore F

Abstract

Clozapine: does it work?

Analysis of a 15 year experience.

Ennio PIANTATO and Francesca SARTORE

ABSTRACT

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.

INTRODUCTION

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withdrawn in 1975.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.

MATERIAL 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).

Tab 1: Diagnosis (total group)

Diagnosis TOTAL MEN WOMEN

Schizophrenia 48 37 11

Schizoaffective disorder 4 3 1

Bipolar disorder 2 1 1

Patients affected by schizophrenia are subdivided as follows: paranoid

schizophrenia (19); undifferentiated disorder (12); disorganized

schizophrenia (15); catatonic schizophrenia (1) chronic (1) (Tab 2)

Tab 2 : Schizophrenia sub-types

Sub-type TOTAL MEN WOMEN

Catatonic 1 1 -

Disorganized 15 11 4

Undifferentiated 12 9 3

Paranoid 19 15 4

Chronic 1 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).

Tab 3 : Hospitalizations

TOTAL MEN WOMEN

Total number of hospitalizations 522 447 75

Before treatment with clozapine 413 354 59

After treatment with clozapine 109 93 16

Tab 4 : Patients never re-hospitalized after treatment with Clozapine

TOTAL 22 (41.7%)

MEN 15

WOMEN 7

DISCUSSION

Results

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]

CONCLUSION

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 of these 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.

REFERENCES

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. Mercier C, Bret P, BretMC, Queuille E.: Enquêteobservationelle de

prescription de laclozapine au centrehospitalier Charles-Perrensà Bordeaux, plus de 15 ansaprès l’AMM en France.L’Encéphale. 2009;XXXV (4): 321-9

Ennio Piantato MD,

Servizio Psichiatrico

Azienda OspedalieraNazionale SS Antonio eBiagio,

via Venezia 16

15121 Alessandria

Italy

Tel +39.01.31.20.64.10

Fax +39.01.31.20.66.16


http://www.webmedcentral.com/mpdf/javascript:AL_get(this,%20'jour',%20'Trials.');


Email: [email protected]

Francesca Sartore MD


Azienda OspedalieraNazionale SS Antonio eBiagio

Via Venezia 16

15121 Alessandria

Italy

Tel+39.01.31.20.66.12

Fax +39.01.31.20.66.16

>Email: [email protected]

Both Authors equallycontributed to this article.




ABSTRACT

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

INTRODUCTION

This report contains data about use of Clozapine inour Psychiatric Unit during the period June 1995-June2009.


mailto:[email protected]



Clozapine is an anti-psychotic drug created at the endof 60’s, with a particular receptor profile.

Due to some cases of granulocytopenia noted inFinland the drug was withdrawn in 1975. It wasreintroduced in the 90’s with indication for “resistantschizophrenia” and a recommendation to monitorblood cell counts. Since 1995 Clozapine has beenofficially used in Italy for “resistant schizophrenia”.

In 1995 we started using Clozapine after two of usattended a course at the Psychiatric Clinic of the BernUniversity, Switzerland.

Our Psychiatric Unit is part of a Department of MentalHealth and situated in the Alessandria general hospital,in the region of Piedmont in NW Italy, serving apopulation of 180.000 inhabitants. The unit has 15beds plus 1 bed for Day Hospital service.

Init ially Clozapine was used with so-calledtreatment-resistant schizophrenic patients, showingresistance to traditional and at least two atypicalantipsychotic treatments as reported in internationalguidelines. [1]

Afterwards the treatment with Clozapine was extendedto patients affected by non-schizophrenic disturbancessuch as bipolar disorder.


Our report includes the group of patients currentlytaking Clozapine and attending our centre for bloodtest control. Almost all of them started Clozapine whilehospitalized in our Psychiatric Unit.

At the moment the group is made up of 54 patients: 41males (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 ofour centre.

Average age of patients is 43±9.9 for the total group:for the male group average age is 40, for the femalegroup it is 46.


All patients live at home with 8 exceptions: 6 of themlive in sheltered apartments and 1 is in a nursing home.

Regarding the diagnoses, 48 patients (88.9%) areaffected by schizophrenia, 4 (7.4%) by aschizoaffective disorder and 2 (3.7%) by bipolardisorder with psychotic behaviour. (Tab 1).






Patients affected by schizophrenia are subdivided asfollows: paranoid schizophrenia (19); undifferentiateddisorder (12); disorganized schizophrenia (15);catatonic schizophrenia (1) chronic (1) (Tab 2)



Catatonic 1 1 -



Paranoid 19 15 4

Chronic 1 1 -

Our doses of Clozapine vary from 100 to 900 mg perday: doses are higher – usually - on discharge fromhospital (150 to 900 mg per day) then they tend todiminish 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 otherpsychotropic drugs (sometimes more than one percategory) in remaining cases: more precisely inassociation with mood-stabilizers in 19 patients,antisialorroic drugs in 4 patients, anticholinergicmedications in 19 patients, other antipsychotic drugsin 20 patients, benzodiazepines in 10 patients andantidepressants in 3 patients.

We have observed that the side effects of treatmentwith Clozapine are most frequently:-

sialorrea (excessive salivation); constipation; lowblood pressure; psychomotor slowing; weight increase;



in one case an epileptic fit was controlled by adding ananti-epileptic drug so the global treatment could becontinued without having any other problem; twopatients are affected by epilepsy in co-morbidity andtake anti-epileptic drugs.


We have observed a reduction in hospital admissionsafter beginning treatment with Clozapine, above all inthe male group. In 22 patients (40.7% of the group) wehaven’t had further hospital admissions. (Tab 3 and 4).


TOTAL MEN WOMEN




Tab 4 : Patients never re-hospitalized after treatmentwith Clozapine

TOTAL 22 (41.7%)

MEN 15

WOMEN 7

DISCUSSION

Results

The reduction of hospitalizations is reported [2,3] andexplained as “effect of objective improvement of someclinical parameters and better social and jobadaptability” [4] this is consistent with the selfevaluated subjective improvement registered by ourpatients and by authors. [5]

Clozapine alone isn’t always enough. In our groupClozapine is often associated with other psychotropicdrugs and it is used as the only antipsychotic drug in19 patients; among most frequently used drugs inassociation there are other first and second generationantipsychotics.

Regarding the association between Clozapine andother antipsychotics we found that two patients of thegroup have been included in the CHAT study(experimental cohort with Clozapine enhancedassociating another antipsychotic drug, aripiprazole orhaloperidol). [6]

No patient of ours has tried or succeeded incommitting suicide so far and this is consistent withother reports [7].

Clozapine has also produced good results withpatients whose behaviour had been violent specially ina etero-directed way.

Scientific evidence shows that continuous use ofanti-psychotic drugs in schizophrenics preventsrelapses.

Compliance with treatment is important in all chronicpathologies and in our group especially an interruptionof treatment provokes various consequences, first ofall the risk of a relapse with hospitalization (up to“revolving-door” conditions) plus blockage of thepersonal therapeutic and rehabilitation project. Thereduction in hospitalization observed in our group isthe verification of good compliance with treatmentincluded the regular carrying out of their blood tests.Moreover patients have been also monitored viaanalysis of plasma levels of Clozapine.

We have begun to use metformin in some of ourpatients to control weight gain due to the treatmentwith Clozapine: so far the results appear good but thetime of observation (4 months) is too short to allow usto be more specific. [8,9]

CONCLUSION

Clozapine is an antipsychotic whose use is limited bysome side effects, some of which are potentiallydeadly.

Many clinical studies have confirmed its efficacyespecially on positive schizophrenic symptoms in thelong term treatment and in drug-resistantschizophrenia, moreover it is the antipsychotic used incase of psychoses in patients with Parkinson’sdisease. [10,11,12,13]

Our considerations, based on our clinical group, are inline with results of these studies: this is particularlyevident in pat ients who have never beenre-hospitalized after taking Clozapine notwithstandingthe gravity of their mental pathology: i.e. two women



had even previously been treated with convulsivetherapy, so far both of them have had good healthsince 1995 after since using Clozapine.

REFERENCES

1. Società Italiana di Psicopatologia, ConsensusConference: Linee guida per la Farmacoterapia


2.Breier A, Buchanan RW, Irish D, Carpenter WT Jr.:Clozapine Treatment of Outpat ients WithSchizophrenia: Outcome and Long-Term ResponsePatterns. 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 theQuality of Life of Chronic Schizophrenic Patients.Hosp Community Psychiatry 1990; 41: 892-897

4. Meltzer HY, Cola P, Way L, Thompson PA, BastaniB, Davies MA, Snitz Beth: Cost Effectiveness ofClozapine in Neuroleptic-Resistant Schizophrenia. AmJ Psychiatry 1993; 150: 1630-1638

5. Waserman J, Criollo: M. Subjective Experience ofClozapine Treatment by Patients With ChronicSchizophrenia. 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 IndependentRandomised Controlled Trial Evaluating theEffectiveness of Aripiprazole or Haloperidol inCombination with Clozapine for Treatment-ResistantSchizophrenia. Trials. 2009 May 15;10-31

7. Llorca PM, Perez JJ.: Leponex, 10 ans après. Unerevue clinique. L’Encéphale, 2004; XXX: 474-479

8. Schumann SA, Ewigman B.: Can Metformin UndoWeight Gain Induced by Antipsychotics? J Fam Pract.2008 Aug; 57 (8): 526-30

9.Ness-Abramof R, Apovian CM.: Drug-inducedWeight Gain. Drugs Today. 2005 Aug; 41 (8): 547-55

10. Buchanan RW, Breier A, Kirkpatrick B, Ball P,Carpenter WT Jr.: Positive and Negative SymptomResponse to Clozapine in Schizophrenic Patients Withand Without Deficit Syndrome. Am J Psychiatry 1998;155: 6: 751-760

11. Leiderman EA.: Effectiveness Trials in ChronicSchizophrenic 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 forSchizophrenia. Cochrane Database Syst Rev. 2009;Jan 21; (1): CD000059

13. Mercier C, Bret P,Bret MC, Queuille E.:Enquête observationellede prescription de laclozapine au centrehospitalierCharles-Perrens àBordeaux, plus de 15ans après l’AMM enFrance. L’Encéphale.2009; XXXV (4): 321-9

Ennio Piantato MD,






via Venezia 16

15121 Alessandria

Italy

Tel +39.01.31.20.64.10

Fax +39.01.31.20.66.16





Via Venezia 16

15121 Alessandria

Italy

Tel+39.01.31.20.66.12

Fax +39.01.31.20.66.16










ABSTRACT


INTRODUCTION

This report contains data about use of Clozapine inour Psychiatric Unit during the period June 1995-June2009.

Clozapine is an anti-psychotic drug created at the endof 60’s, with a particular receptor profile.

Due to some cases of granulocytopenia noted inFinland the drug was withdrawn in 1975. It wasreintroduced in the 90’s with indication for “resistantschizophrenia” and a recommendation to monitorblood cell counts. Since 1995 Clozapine has beenofficially used in Italy for “resistant schizophrenia”.

In 1995 we started using Clozapine after two of usattended a course at the Psychiatric Clinic of the BernUniversity, Switzerland.

Our Psychiatric Unit is part of a Department of MentalHealth and situated in the Alessandria general hospital,in the region of Piedmont in NW Italy, serving apopulation of 180.000 inhabitants. The unit has 15beds plus 1 bed for Day Hospital service.

Init ially Clozapine was used with so-calledtreatment-resistant schizophrenic patients, showingresistance to traditional and at least two atypicalantipsychotic treatments as reported in internationalguidelines. [1]

Afterwards the treatment with Clozapine was extendedto patients affected by non-schizophrenic disturbancessuch as bipolar disorder.














Patients affected by schizophrenia are subdivided asfollows: paranoid schizophrenia (19); undifferentiateddisorder (12); disorganized schizophrenia (15);catatonic schizophrenia (1) chronic (1) (Tab 2)





Catatonic 1 1 -



Paranoid 19 15 4

Chronic 1 1 -


Clozapine is used as monotherapy in 19 patients(35.1%) . It’s also used in association with otherpsychotropic drugs (sometimes more than one percategory) in remaining cases: more precisely inassociation with mood-stabilizers in 19 patients,antisialorroic drugs in 4 patients, anticholinergicmedications in 19 patients, other antipsychotic drugsin 20 patients, benzodiazepines in 10 patients andantidepressants in 3 patients.


sialorrea (excessive salivation); constipation; lowblood pressure; psychomotor slowing; weight increase;in one case an epileptic fit was controlled by adding ananti-epileptic drug so the global treatment could becontinued without having any other problem; twopatients are affected by epilepsy in co-morbidity andtake anti-epileptic drugs.




TOTAL MEN WOMEN




Tab 4 : Patients never re-hospitalized after treatmentwith Clozapine

TOTAL 22 (41.7%)

MEN 15

WOMEN 7

DISCUSSION

Results







Compliance with treatment is important in all chronicpathologies and in our group especially an interruptionof treatment provokes various consequences, first ofall the risk of a relapse with hospitalization (up to“revolving-door” conditions) plus blockage of thepersonal therapeutic and rehabilitation project. Thereduction in hospitalization observed in our group isthe verification of good compliance with treatment



included the regular carrying out of their blood tests.Moreover patients have been also monitored viaanalysis of plasma levels of Clozapine.


CONCLUSION



Our considerations, based on our clinical group, are inline with results of these studies: this is particularlyevident in pat ients who have never beenre-hospitalized after taking Clozapine notwithstandingthe gravity of their mental pathology: i.e. two womenhad even previously been treated with convulsivetherapy, so far both of them have had good healthsince 1995 after since using Clozapine.

REFERENCES

1. Società Italiana di Psicopatologia, ConsensusConference: Linee guida per la Farmacoterapia


2.Breier A, Buchanan RW, Irish D, Carpenter WT Jr.:Clozapine Treatment of Outpat ients WithSchizophrenia: Outcome and Long-Term ResponsePatterns. 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 theQuality of Life of Chronic Schizophrenic Patients.Hosp Community Psychiatry 1990; 41: 892-897

4. Meltzer HY, Cola P, Way L, Thompson PA, BastaniB, Davies MA, Snitz Beth: Cost Effectiveness ofClozapine in Neuroleptic-Resistant Schizophrenia. AmJ Psychiatry 1993; 150: 1630-1638

5. Waserman J, Criollo: M. Subjective Experience ofClozapine Treatment by Patients With ChronicSchizophrenia. 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 IndependentRandomised Controlled Trial Evaluating theEffectiveness of Aripiprazole or Haloperidol inCombination with Clozapine for Treatment-ResistantSchizophrenia. Trials. 2009 May 15;10-31

7. Llorca PM, Perez JJ.: Leponex, 10 ans après. Unerevue clinique. L’Encéphale, 2004; XXX: 474-479

8. Schumann SA, Ewigman B.: Can Metformin UndoWeight Gain Induced by Antipsychotics? J Fam Pract.2008 Aug; 57 (8): 526-30

9.Ness-Abramof R, Apovian CM.: Drug-inducedWeight Gain. Drugs Today. 2005 Aug; 41 (8): 547-55

10. Buchanan RW, Breier A, Kirkpatrick B, Ball P,Carpenter WT Jr.: Positive and Negative SymptomResponse to Clozapine in Schizophrenic Patients Withand Without Deficit Syndrome. Am J Psychiatry 1998;155: 6: 751-760

11. Leiderman EA.: Effectiveness Trials in ChronicSchizophrenic 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 forSchizophrenia. Cochrane Database Syst Rev. 2009;Jan 21; (1): CD000059

13. Mercier C, Bret P,Bret MC, Queuille E.:




Enquête observationellede prescription de laclozapine au centrehospitalierCharles-Perrens àBordeaux, plus de 15ans après l’AMM enFrance. L’Encéphale.2009; XXXV (4): 321-9

Ennio Piantato MD,



via Venezia 16

15121 Alessandria

Italy

Tel +39.01.31.20.64.10

Fax +39.01.31.20.66.16





Via Venezia 16

15121 Alessandria

Italy

Tel+39.01.31.20.66.12

Fax +39.01.31.20.66.16







Introduction

This report contains data about use of Clozapine inour Psychiatric Unit during the period June 1995-June2009.Clozapine is an anti-psychotic drug created at the endof 60’s, with a particular receptor profile.Due to some cases of granulocytopenia noted inFinland the drug was withdrawn in 1975. It was

reintroduced in the 90’s with indication for “resistantschizophrenia” and a recommendation to monitorblood cell counts. Since 1995 Clozapine has beenofficially used in Italy for “resistant schizophrenia”.In 1995 we started using Clozapine after two of usattended a course at the Psychiatric Clinic of the BernUniversity, Switzerland.Our Psychiatric Unit is part of a Department of MentalHealth and situated in the Alessandria general hospital,in the region of Piedmont in NW Italy, serving apopulation of 180.000 inhabitants. The unit has 15beds plus 1 bed for Day Hospital service.Init ially Clozapine was used with so-calledtreatment-resistant schizophrenic patients, showingresistance to traditional and at least two atypicalantipsychotic treatments as reported in internationalguidelines. [1]Afterwards the treatment with Clozapine was extendedto patients affected by non-schizophrenic disturbancessuch as bipolar disorder.

Materials and Methods









Clozapine is used as monotherapy in 19 patients(35.1%) . It’s also used in association with otherpsychotropic drugs (sometimes more than one percategory) in remaining cases: more precisely inassociation with mood-stabilizers in 19 patients,




antisialorroic drugs in 4 patients, anticholinergicmedications in 19 patients, other antipsychotic drugsin 20 patients, benzodiazepines in 10 patients andantidepressants in 3 patients.


sialorrea (excessive salivation); constipation; lowblood pressure; psychomotor slowing; weight increase;in one case an epileptic fit was controlled by adding ananti-epileptic drug so the global treatment could becontinued without having any other problem; twopatients are affected by epilepsy in co-morbidity andtake anti-epileptic drugs.



Discussion

Results







Compliance with treatment is important in all chronic

pathologies and in our group especially an interruptionof treatment provokes various consequences, first ofall the risk of a relapse with hospitalization (up to“revolving-door” conditions) plus blockage of thepersonal therapeutic and rehabilitation project. Thereduction in hospitalization observed in our group isthe verification of good compliance with treatmentincluded the regular carrying out of their blood tests.Moreover patients have been also monitored viaanalysis of plasma levels of Clozapine.


Conclusion



Our considerations, based on our clinical group, are inline with results of these studies: this is particularlyevident in pat ients who have never beenre-hospitalized after taking Clozapine notwithstandingthe gravity of their mental pathology: i.e. two womenhad even previously been treated with convulsivetherapy, so far both of them have had good healthsince 1995 after since using Clozapine.

References

1.Società Italiana di Psicopatologia, ConsensusConference: Linee guida per la Farmacoterapiadellaschizofrenia, Roma, 14-15 aprile 20002.Breier A,Buchanan RW, Irish D, Carpenter WT Jr.: ClozapineTreatment of Outpatients With Schizophrenia:Outcome and Long-Term Response Patterns. HospC o m m u n i t y P s y c h i a t r y 1 9 9 3 ; 4 4 : 1 2 :1145-11493.Meltzer HY, Burnett S, Bastani B,Ramirez LF.: Effects of Six Months of ClozapineTreatment on the Quality of Life of ChronicSchizophrenic Patients. Hosp Community Psychiatry1990; 41: 892-8974.Meltzer HY, Cola P, Way L,Thompson PA, Bastani B, Davies MA, Snitz Beth:



C o s t E f f e c t i v e n e s s o f C l o z a p i n e i nNeuroleptic-Resistant Schizophrenia. Am J Psychiatry1993; 150: 1630-1638 5.Waserman J, Criollo: M.Subjective Experience of Clozapine Treatment byPatients With Chronic Schizophrenia. PsychiatricServices 2000; 51: 5: 666-6686.Nosè M, Accordini S,Artioli P, Barale F, Barbui C. et Alii: Rationale andDesign of an Independent Randomised ControlledTrial Evaluating the Effectiveness of Aripiprazole orHaloperidol in Combination with Clozapine forTreatment-Resistant Schizophrenia. Trials. 2009 May15;10-317.Llorca PM, Perez JJ.: Leponex, 10 ansaprès. Une revue clinique. L’Encéphale, 2004; XXX:474-4798.Schumann SA, Ewigman B.: Can MetforminUndo Weight Gain Induced by Antipsychotics? J FamPract. 2008 Aug; 57 (8): 526-30 9.Ness-Abramof R,Apovian CM.: Drug-induced Weight Gain. DrugsToday. 2005 Aug; 41 (8): 547-5510.Buchanan RW,Breier A, Kirkpatrick B, Ball P, Carpenter WT Jr.:Positive and Negative Symptom Response toClozapine in Schizophrenic Patients With and WithoutDeficit Syndrome. Am J Psychiatry 1998; 155: 6:751-76011.Leiderman EA.: Effectiveness Trials inChronic Schizophrenic Patients: CATIE. What can welearn? Vertex 2009; 20;(84); 129-3512.Essali A, Al-HajHaasan N, Li C, Rathbone J.: Clozapine vs TypicalNeuroleptic Medication for Schizophrenia. CochraneDatabase Sys t Rev . 2009; Jan 21 ; (1 ) :CD00005913.Mercier C, Bret P, Bret MC, Queuille E.:Enquête observationelle de prescription de laclozapine au centre hospitalier Charles-Perrens àBordeaux, plus de 15 ans après l’AMM en France.L’Encéphale. 2009; XXXV (4): 321-9



Diagnosis TOTAL MEN WOMENSchizophrenia 48 37 11Schizoaffectivedisorder

4 3 1


Patients affected by schizophrenia are subdivided as follows: paranoid schizophrenia (19);undifferentiated disorder (12); disorganized schizophrenia (15); catatonic schizophrenia (1)chronic (1) (Tab 2)

Illustrations

Illustration 1




Sub-type TOTAL MEN WOMENCatatonic 1 1 -Disorganized 15 11 4Undifferentiated 12 9 3Paranoid 19 15 4Chronic 1 1 -

Illustration 2




TOTAL MEN WOMENTotal number ofhospitalizations

522 447 75

Before treatment withclozapine

413 354 59

After treatment withclozapine

109 93 16

Illustration 3




TOTAL 22 (41.7%)MEN 15WOMEN 7

Illustration 4

Tab 4 : Patients never re-hospitalized after treatment with Clozapine



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