Ó
2000 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2000 Volume 4 Pages 77 ± 80
77
Long-term efficacy and safety of quetiapine in treatment-refractory schizophrenia: A case report
Int J Psych Clin Pract Downloaded from informahealthcare.com by Universitat de Girona on 12/05/14 For personal use only.
I REZNIK, R BENATOV AND P SIROTA Abarbanel Mental Health Center, Bat-Yam and Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
Correspondence Address Ilya Reznik MD, Y. Abarbanel Mental Health Center, #15, Keren Kayemet Street, Bat-Yam, 59110, Israel Tel: 972-3-555262 6 Fax: 972-3-555262 1 E-mail: [email protected]
Received 22 January 1999; revised 31 March 1999; accepted for publication 1 April 1999
The recent advent of atypical antipsychotics has provided new clinical options and set higher expectation s for the treatment of schizophrenia. Such agents might more effectively prevent relapse because they are more effective against the full spectrum of schizophrenic symptoms, as well as having improved tolerability and leading to improved medication compliance. Quetiapine fumarate (`Seroquel’) is a new dibenzothiaz epine antipsychotic agent with a greater affinity for serotonin receptors than for dopamine receptors and with a lower propensity for producing extrapyrami dal symptoms or increasing prolactin levels. It has recently been approved for the treatment of psychotic disorders; however, the longterm efficacy and safety of quetiapine for treating treatment-refractory schizophrenia is still being investigated. We present a case of a 58-yearold man suffering from chronic therapy-resistant schizophrenia, with both positive and negative symptoms, who was successfully treated with quetiapine for 5 years. To the best of our knowledge, this is the first report of such long beneficial use of quetiapine in a hospital clinical practice. (Int J Psych Clin Pract 2000; 4: 77 ± 80) Keywords atypical antipsychotic s Seroquel treatment resistance
INTRODUCTION
T
he recent advent of atypical antipsychotics has provided new clinical options and set higher expectations for the treatment of schizophreni a. Such agents might more effectively prevent relapse by being more effective for the full spectrum of schizophre nic symptoms, and being better tolerated, so increasing complianc e with medication.1 Quetiapine fumarate (`Seroquel’ , ICI 204,636) is a new dibenzothiaze pine antipsychotic agent with a greater affinity for serotonin 5HT2 than for dopamine D2 receptors and with a lower propensit y for producing extrapyramida l symptoms (EPS) or increasing prolactin levels. It has recently been approved for the treatment of psychotic disorders. 2 In recent years, hundreds of patients with acute exacerbation of chronic or subchronic schizophren ia have entered several double-blind , randomized placebo-controlled trials.3 ,4 However, until now, results of only 1-year or 2-year follow-ups have been published5 ± 7 and therefore
quetiapine schizophrenia
the long-term efficacy and safety of quetiapine for treating therapy-refr actory schizophreni a remained to be determined. 8 We present the case of a 58-year-old man suffering from chronic therapy-resis tant schizophre nia, with both positive and negative symptoms, who was successfull y treated with Seroquel for 5 years. To the best of our knowledge this is the first report of such a long-term successfu l use of quetiapine in hospital clinical practice.
CASE REPORT Mr GS was born in 1940, and grew up normally without any signs of psychiatric disorder until the age of 23. In 1963, he developed an acute psychotic episode and was diagnosed as having schizophre nia. During his first hospitalizatio n, acute `positive’ psychotic symptoms were prominent: persecutor y delusions and delusions of reference, loosening of associations, auditory and visual hallucination s, sleep and
Int J Psych Clin Pract Downloaded from informahealthcare.com by Universitat de Girona on 12/05/14 For personal use only.
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I Reznik et al
behavioural disturbances . He responded well to low-tomedium doses of phenothiazine s, was discharged and returned home. Since then, at different times, he has been treated (ambulatory and on the ward) with standard antipsychotic s (thioridazine , haloperidol , chlorpromazine , perphenazin e etc.) at therapeutic doses. Over several years, the median frequency of hospitalization s was about one a year. The patient was unable to work or take care of himself, and spent most of the time alone at home, without contact with the outside world. Although paranoid delusions persisted, marked `negative ’ symptoms (avolition, affective flattening, poverty of speech) and loss of social contacts became more obvious in recent years. Therapeutic interventions also included two series of electroconvul sive therapy (one was partially successfu l and the other failed). Increasing the dosage of `classic’ neuroleptics did not improve the mental status of the patient, but caused significan t EPS. Five years ago he was invited, and agreed, to take part in a 6-week, multicentre double-blind trial (Phase II) evaluating the tolerability and efficacy of ICI 204,636 in the treatment of the positive and negative symptoms of schizophren ia. During the year before he enrolled in the study, he was almost disabled, with prominent deficit signs. He was assessed for efficacy at baseline and weekly using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessmen t of Negative Symptoms (SANS), the Quality of Life Scale (QLS) and the Clinical Global Impression (CGI) scale. Abnormal involuntary movements were assesse d using the Simpson Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). Prolactin levels were determined regularly. The daily dosage of quetiapine was slowly raised from 100 mg/day and gradually titrated up to 700 mg/day. At the beginning of the study, the patient required moderate doses of benzodiazepin es (tab. oxazepam, 10 mg t.i.d) because of tension and anxiety, and small doses of anticholinerg ics (tab. biperiden, 2 mg b.i.d), due to EPS. By the end of the six-week trial period Mr GS’s condition had improved significantl y as evidenced by his rating scale scores, and he continued taking quetiapine. Formal assessment s have continued to be performed by the same raters every 6 months: BPRS and SANS scores decreased by 67% and 28% from baseline, respectively ; his QLS score rose from 3 to 41 and CGI score dropped by two points (Table 1). AIMS and SAS scores decreased to zero (Table 2), and the dosage of both denzodiazepi ne and anticholiner gic medications were gradually reduced until no concomitant medication was required for anxiety or EPS. Prolactin levels decreased from 23.6 ng/ml to 1.3 ng/ml and no clinically significant adverse events were registered, nor was any weight gain observed. Currently, the patient maintains an independent life in the community, participates in a psychosocia l rehabilitativ e programme, continues with follow-up at our mental health centre and has made plans to visit his relatives abroad.
Table 1 Psychiatric and Quality of Life assessments during long-term follow-up
Time of exposure
BPRS (Range: 0 ± 108)
SANS (Range: 24 ± 156)
CGI (Range: 1 ± 7)
QLS (Range: 0 ± 126)
Baseline 6 weeks ˆ year ‰ year 1 year 2 years 3 years 4 years 5 years
62 40 23 35 33 23 20 21 20
90 95 67 83 89 72 69 74 64
6 5 4 4 4 4 4 4 4
3 7 10 13 21 28 40 36 41
BPRS=Brief Psychiatric Rating Scale SANS=Scale for the Assessment of Negative Symptoms CGI=Clinical Global Impression Scale QLS=Quality of Life Scale
Table 2 Assessment of extrapyramidal symptoms and prolactin levels during long-term follow-up Time of AIMS SAS Serum prolactin exposure (Range: 0 - 40) (Range: 10 ± 90) level (ng/ml)a Baseline 6 weeks ˆ year ‰ year 1 year 2 years 3 years 4 years 5 years
16 2 0 0 0 0 0 0 0
24 4 0 0 0 0 0 0 0
23.6 19.9 21.4 27.0 5.9 3.0 1.5 2.0 1.3
AIMS=Abnormal Involuntary Movement Scale SAS=Simpson-Angus Scale a Normal for men: 0 ± 20 ng/ml
DISCUSSION The results of the clinical trials cited3 ± 5 have shown that quetiapine is at least as effective as a standard neuroleptic and is well tolerated, even in the elderly,9 but little data currently exist to determine what benefits it offers to patients with treatment-resi stant schizophreni a.8 An openlabel study describing the effectivenes s of an 8-week trial of oral quetiapine in Japanese treatment-resistant schizophrenic patients with a low incidence of EPS has recently been published. 1 0 The patient we present here appears to meet
Long-term efficacy of quetiapine
the strict treatment-resi stance criteria used by Kane et al1 1 and the Japanese group:
Int J Psych Clin Pract Downloaded from informahealthcare.com by Universitat de Girona on 12/05/14 For personal use only.
1. Chronic schizophren ia without significan t symptomatic relief over at least the preceding 5 years; 2. At least three cycles of 8-week neuroleptic treatment in the preceding 5 years, with at least three agents from different chemical classes, such as phenothiazine and butyrophenon e, at dosage equivalent to or greater than 21 mg/day of haloperidol (700 mg/day of chlorpromazine); 3. A BPRS total score exceeding 45. Continued treatment of Mr GS restored his impaired social functioning , reducing the risk of repeated hospitalization. The long-term outcome for patients with schizophren ia has been disappointing . Management of treatment-resis tant patients with schizophreni a is still a difficult clinical and therapeutic challenge. Marder1 2 distinguishe d three categories of poor response of patients with schizophren ia to antipsychotic medication. The first category includes patients who continue to demonstrate positive psychotic symptoms when they receive adequate trials of an antipsychotic . The second category consists of patients who are unable to tolerate the side-effects of antipsychotic s. The third category includes patients who have persistent negative symptoms while they are treated with an antipsychotic ; our patient probably belongs to this particular group. The traditional antipsychotics are generally poorly effective or ineffective against the negative symptoms of schizophreni a, and are also associated with extensive sideeffects, which can themselves cause or exacerbate secondary negative symptoms.1 3 There is evidence that treatmentresistant patients demonstrate improvement in longstanding negative symptoms when they receive newer antipsychotics (including clozapine, risperidone , olanzapine, sertindole and quetiapine).1 4 However, few trials have specificall y examined primary negative symptoms, and it has been suggested that the improvemen ts observed with the above agents may be related more to decreases in positive symptoms and/or reduced sedation or EPS. Regardless of whether a unidimensio nal or multidimensiona l approach is used to evaluate treatment
79
response, 1 5 the expectation of superior efficacy, a more benign side-effec t profile and the possibilit y of affecting the longitudina l course of schizophreni a provide a rationale for the use of novel antipsychotic s as a first-line therapy for schizophren ia, even in its treatment-resis tant variant.1 4 The advent of these medications has generally led to better outcomes by facilitating complianc e with drug regimens and rehabilitation programmes .1 6 As our present case has emphasized , long-term maintenance therapy is crucial; as is continuous monitoring for the development of adverse effects. 1 7 The case described here and our review of the relevant literature have allowed us to conclude that the relative lack of EPS, tardive dyskinesi a and elevated prolactin, found with quetiapine, coupled with its positive effect on both positive and negative symptoms, can lead to a significant improvement in the quality of life, social and interpersona l relations, compliance with treatment and clinical outcome in the long-term treatment of therapy-resis tant schizophrenia, primarily by reducing rates of relapse and rehospitaliza tion.
ACKNOWLEDGEMENTS We are grateful to Mr. Aryeh Gordon for his valuable editorial assistance.
KEY POINTS
· · ·
Quetiapine, a novel atypical antipsychotic, like clozapine, shows efficacy in the treatment of schizophreni c patients refractory to conventional neuroleptics Long-term treatment with quetiapine is welltolerated, and is not associated with EPS, prolactin elevation or weight gain Since the long-term maintenanc e therapy of schizophreni a is crucial, quetiapine may be an effective and safe treatment choice even in treatment resistant patients
REFERENCES 1. Andersson C, Chakos M, Mailman R, Lieberman J (1998) Emerging roles for novel antipsychotic medications in the treatment of schizophrenia. Psychiatr Clin North Am 21: 151 ± 79. 2. Hirsch SR, Link CGG, Goldstein JM, Arvanitis LA (1996) ICI 204,636: a new atypical antipsychotic drug. Br J Psychiatry 168 (Suppl 29): 45 ± 56.
3. Fabre LF Jr, Arvanitis L, Pultz J et al (1997) ICI 204,636, a novel, atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia. Clin Ther 17: 366 ± 78.
Int J Psych Clin Pract Downloaded from informahealthcare.com by Universitat de Girona on 12/05/14 For personal use only.
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I Reznik et al
4. Borison RL, Arvanitis LA, Miller BG (1996) ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. J Clin Psychopharmac ol 16: 158 ± 69. 5. Arvanitis LA, Miller BG (1997) Multiple fixed doses of `Seroquel’ (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry 42: 233 ± 46. 6. Reznik I, Benatov R, Sirota P (1996) Seroquel in a resistant schizophrenic with negative and positive symptoms (in Hebrew). Harefuah 130: 675 ± 77. 7. Arvanitis LA, Rak IW (1997) The long-term efficacy and safety of quetiapine. In: New Research Program and Abstracts of the 150 Annual Meeting of the American Psychiatric Association, May 1997, San Diego, CA. (Abstract NR230). APA, Washington, DC. 8. Meats P (1997) Quetiapine (Seroquel); an effective and welltolerated atypical antipsychotic. Int J Psych Clin Pract 1: 231 ± 9. 9. Goldstein JM (1998) Inaccurate information on quetiapine (letter). J Clin Psychiatry 59: 687. 10. Maeda H, Kotorii T, Nakamura J, Uchimura N (1998) Clinical evaluation of quetiapine (ICI 204,636), a novel antipsychotic agent, in treatment-resistant schizophrenic patients. In: Proceedings of XXI CINP Congress, Glasgow, 12 ± 16 July 1998; The Scientific Program and Book of Abstracts. Abstract: PT 07099.
11. Kane JM, Honigfeld G, Singer J, Meltzer HY and the Clozaril Collaborative Study Group (1988) Clozapine for the treatmentresistant schizophrenic: A double-blind comparison with chlorpromazine.Arch Gen Psychiatry 45: 789 ± 96. 12. Marder SR (1996) Management of treatment-resistant patients with schizophrenia. J Clin Psychiatry 57 (suppl 11): 26 ± 30. 13. King DJ (1998) Drug treatment of the negative symptoms of schizophrenia.Eur Neuropsychoph armacol 8: 33 ± 42. 14. Tamminga CA, Lahti AC (1996) The new generation of antipsychotic drugs. Int Clin Psychopharmaco l 11 (suppl 2): 73 ± 6. 15. Meltzer HY (1997) Treatment-resistant schizophrenia ± the role of clozapine. Curr Med Res Opin 14: 1 ± 20. 16. Stip E (1996) Memory impairment in schizophrenia: perspectives from psychopathology and pharmacotherapy. Can J Psychiatry 41 (suppl 2): S27 ± S34. 17. Fleischhacker WW, Hummer M (1997) Drug treatment of schizophrenia in the 1990s. Achievements and future possibilities in optimizing outcomes. Drugs 53: 915 ± 29.
2000 Martin Dunitz Ltd
International Journal of Psychiatry in Clinical Practice 2000 Volume 4 Pages 77 ± 80
77
Long-term efficacy and safety of quetiapine in treatment-refractory schizophrenia: A case report
Int J Psych Clin Pract Downloaded from informahealthcare.com by Universitat de Girona on 12/05/14 For personal use only.
I REZNIK, R BENATOV AND P SIROTA Abarbanel Mental Health Center, Bat-Yam and Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
Correspondence Address Ilya Reznik MD, Y. Abarbanel Mental Health Center, #15, Keren Kayemet Street, Bat-Yam, 59110, Israel Tel: 972-3-555262 6 Fax: 972-3-555262 1 E-mail: [email protected]
Received 22 January 1999; revised 31 March 1999; accepted for publication 1 April 1999
The recent advent of atypical antipsychotics has provided new clinical options and set higher expectation s for the treatment of schizophrenia. Such agents might more effectively prevent relapse because they are more effective against the full spectrum of schizophrenic symptoms, as well as having improved tolerability and leading to improved medication compliance. Quetiapine fumarate (`Seroquel’) is a new dibenzothiaz epine antipsychotic agent with a greater affinity for serotonin receptors than for dopamine receptors and with a lower propensity for producing extrapyrami dal symptoms or increasing prolactin levels. It has recently been approved for the treatment of psychotic disorders; however, the longterm efficacy and safety of quetiapine for treating treatment-refractory schizophrenia is still being investigated. We present a case of a 58-yearold man suffering from chronic therapy-resistant schizophrenia, with both positive and negative symptoms, who was successfully treated with quetiapine for 5 years. To the best of our knowledge, this is the first report of such long beneficial use of quetiapine in a hospital clinical practice. (Int J Psych Clin Pract 2000; 4: 77 ± 80) Keywords atypical antipsychotic s Seroquel treatment resistance
INTRODUCTION
T
he recent advent of atypical antipsychotics has provided new clinical options and set higher expectations for the treatment of schizophreni a. Such agents might more effectively prevent relapse by being more effective for the full spectrum of schizophre nic symptoms, and being better tolerated, so increasing complianc e with medication.1 Quetiapine fumarate (`Seroquel’ , ICI 204,636) is a new dibenzothiaze pine antipsychotic agent with a greater affinity for serotonin 5HT2 than for dopamine D2 receptors and with a lower propensit y for producing extrapyramida l symptoms (EPS) or increasing prolactin levels. It has recently been approved for the treatment of psychotic disorders. 2 In recent years, hundreds of patients with acute exacerbation of chronic or subchronic schizophren ia have entered several double-blind , randomized placebo-controlled trials.3 ,4 However, until now, results of only 1-year or 2-year follow-ups have been published5 ± 7 and therefore
quetiapine schizophrenia
the long-term efficacy and safety of quetiapine for treating therapy-refr actory schizophreni a remained to be determined. 8 We present the case of a 58-year-old man suffering from chronic therapy-resis tant schizophre nia, with both positive and negative symptoms, who was successfull y treated with Seroquel for 5 years. To the best of our knowledge this is the first report of such a long-term successfu l use of quetiapine in hospital clinical practice.
CASE REPORT Mr GS was born in 1940, and grew up normally without any signs of psychiatric disorder until the age of 23. In 1963, he developed an acute psychotic episode and was diagnosed as having schizophre nia. During his first hospitalizatio n, acute `positive’ psychotic symptoms were prominent: persecutor y delusions and delusions of reference, loosening of associations, auditory and visual hallucination s, sleep and
Int J Psych Clin Pract Downloaded from informahealthcare.com by Universitat de Girona on 12/05/14 For personal use only.
78
I Reznik et al
behavioural disturbances . He responded well to low-tomedium doses of phenothiazine s, was discharged and returned home. Since then, at different times, he has been treated (ambulatory and on the ward) with standard antipsychotic s (thioridazine , haloperidol , chlorpromazine , perphenazin e etc.) at therapeutic doses. Over several years, the median frequency of hospitalization s was about one a year. The patient was unable to work or take care of himself, and spent most of the time alone at home, without contact with the outside world. Although paranoid delusions persisted, marked `negative ’ symptoms (avolition, affective flattening, poverty of speech) and loss of social contacts became more obvious in recent years. Therapeutic interventions also included two series of electroconvul sive therapy (one was partially successfu l and the other failed). Increasing the dosage of `classic’ neuroleptics did not improve the mental status of the patient, but caused significan t EPS. Five years ago he was invited, and agreed, to take part in a 6-week, multicentre double-blind trial (Phase II) evaluating the tolerability and efficacy of ICI 204,636 in the treatment of the positive and negative symptoms of schizophren ia. During the year before he enrolled in the study, he was almost disabled, with prominent deficit signs. He was assessed for efficacy at baseline and weekly using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessmen t of Negative Symptoms (SANS), the Quality of Life Scale (QLS) and the Clinical Global Impression (CGI) scale. Abnormal involuntary movements were assesse d using the Simpson Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). Prolactin levels were determined regularly. The daily dosage of quetiapine was slowly raised from 100 mg/day and gradually titrated up to 700 mg/day. At the beginning of the study, the patient required moderate doses of benzodiazepin es (tab. oxazepam, 10 mg t.i.d) because of tension and anxiety, and small doses of anticholinerg ics (tab. biperiden, 2 mg b.i.d), due to EPS. By the end of the six-week trial period Mr GS’s condition had improved significantl y as evidenced by his rating scale scores, and he continued taking quetiapine. Formal assessment s have continued to be performed by the same raters every 6 months: BPRS and SANS scores decreased by 67% and 28% from baseline, respectively ; his QLS score rose from 3 to 41 and CGI score dropped by two points (Table 1). AIMS and SAS scores decreased to zero (Table 2), and the dosage of both denzodiazepi ne and anticholiner gic medications were gradually reduced until no concomitant medication was required for anxiety or EPS. Prolactin levels decreased from 23.6 ng/ml to 1.3 ng/ml and no clinically significant adverse events were registered, nor was any weight gain observed. Currently, the patient maintains an independent life in the community, participates in a psychosocia l rehabilitativ e programme, continues with follow-up at our mental health centre and has made plans to visit his relatives abroad.
Table 1 Psychiatric and Quality of Life assessments during long-term follow-up
Time of exposure
BPRS (Range: 0 ± 108)
SANS (Range: 24 ± 156)
CGI (Range: 1 ± 7)
QLS (Range: 0 ± 126)
Baseline 6 weeks ˆ year ‰ year 1 year 2 years 3 years 4 years 5 years
62 40 23 35 33 23 20 21 20
90 95 67 83 89 72 69 74 64
6 5 4 4 4 4 4 4 4
3 7 10 13 21 28 40 36 41
BPRS=Brief Psychiatric Rating Scale SANS=Scale for the Assessment of Negative Symptoms CGI=Clinical Global Impression Scale QLS=Quality of Life Scale
Table 2 Assessment of extrapyramidal symptoms and prolactin levels during long-term follow-up Time of AIMS SAS Serum prolactin exposure (Range: 0 - 40) (Range: 10 ± 90) level (ng/ml)a Baseline 6 weeks ˆ year ‰ year 1 year 2 years 3 years 4 years 5 years
16 2 0 0 0 0 0 0 0
24 4 0 0 0 0 0 0 0
23.6 19.9 21.4 27.0 5.9 3.0 1.5 2.0 1.3
AIMS=Abnormal Involuntary Movement Scale SAS=Simpson-Angus Scale a Normal for men: 0 ± 20 ng/ml
DISCUSSION The results of the clinical trials cited3 ± 5 have shown that quetiapine is at least as effective as a standard neuroleptic and is well tolerated, even in the elderly,9 but little data currently exist to determine what benefits it offers to patients with treatment-resi stant schizophreni a.8 An openlabel study describing the effectivenes s of an 8-week trial of oral quetiapine in Japanese treatment-resistant schizophrenic patients with a low incidence of EPS has recently been published. 1 0 The patient we present here appears to meet
Long-term efficacy of quetiapine
the strict treatment-resi stance criteria used by Kane et al1 1 and the Japanese group:
Int J Psych Clin Pract Downloaded from informahealthcare.com by Universitat de Girona on 12/05/14 For personal use only.
1. Chronic schizophren ia without significan t symptomatic relief over at least the preceding 5 years; 2. At least three cycles of 8-week neuroleptic treatment in the preceding 5 years, with at least three agents from different chemical classes, such as phenothiazine and butyrophenon e, at dosage equivalent to or greater than 21 mg/day of haloperidol (700 mg/day of chlorpromazine); 3. A BPRS total score exceeding 45. Continued treatment of Mr GS restored his impaired social functioning , reducing the risk of repeated hospitalization. The long-term outcome for patients with schizophren ia has been disappointing . Management of treatment-resis tant patients with schizophreni a is still a difficult clinical and therapeutic challenge. Marder1 2 distinguishe d three categories of poor response of patients with schizophren ia to antipsychotic medication. The first category includes patients who continue to demonstrate positive psychotic symptoms when they receive adequate trials of an antipsychotic . The second category consists of patients who are unable to tolerate the side-effects of antipsychotic s. The third category includes patients who have persistent negative symptoms while they are treated with an antipsychotic ; our patient probably belongs to this particular group. The traditional antipsychotics are generally poorly effective or ineffective against the negative symptoms of schizophreni a, and are also associated with extensive sideeffects, which can themselves cause or exacerbate secondary negative symptoms.1 3 There is evidence that treatmentresistant patients demonstrate improvement in longstanding negative symptoms when they receive newer antipsychotics (including clozapine, risperidone , olanzapine, sertindole and quetiapine).1 4 However, few trials have specificall y examined primary negative symptoms, and it has been suggested that the improvemen ts observed with the above agents may be related more to decreases in positive symptoms and/or reduced sedation or EPS. Regardless of whether a unidimensio nal or multidimensiona l approach is used to evaluate treatment
79
response, 1 5 the expectation of superior efficacy, a more benign side-effec t profile and the possibilit y of affecting the longitudina l course of schizophreni a provide a rationale for the use of novel antipsychotic s as a first-line therapy for schizophren ia, even in its treatment-resis tant variant.1 4 The advent of these medications has generally led to better outcomes by facilitating complianc e with drug regimens and rehabilitation programmes .1 6 As our present case has emphasized , long-term maintenance therapy is crucial; as is continuous monitoring for the development of adverse effects. 1 7 The case described here and our review of the relevant literature have allowed us to conclude that the relative lack of EPS, tardive dyskinesi a and elevated prolactin, found with quetiapine, coupled with its positive effect on both positive and negative symptoms, can lead to a significant improvement in the quality of life, social and interpersona l relations, compliance with treatment and clinical outcome in the long-term treatment of therapy-resis tant schizophrenia, primarily by reducing rates of relapse and rehospitaliza tion.
ACKNOWLEDGEMENTS We are grateful to Mr. Aryeh Gordon for his valuable editorial assistance.
KEY POINTS
· · ·
Quetiapine, a novel atypical antipsychotic, like clozapine, shows efficacy in the treatment of schizophreni c patients refractory to conventional neuroleptics Long-term treatment with quetiapine is welltolerated, and is not associated with EPS, prolactin elevation or weight gain Since the long-term maintenanc e therapy of schizophreni a is crucial, quetiapine may be an effective and safe treatment choice even in treatment resistant patients
REFERENCES 1. Andersson C, Chakos M, Mailman R, Lieberman J (1998) Emerging roles for novel antipsychotic medications in the treatment of schizophrenia. Psychiatr Clin North Am 21: 151 ± 79. 2. Hirsch SR, Link CGG, Goldstein JM, Arvanitis LA (1996) ICI 204,636: a new atypical antipsychotic drug. Br J Psychiatry 168 (Suppl 29): 45 ± 56.
3. Fabre LF Jr, Arvanitis L, Pultz J et al (1997) ICI 204,636, a novel, atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia. Clin Ther 17: 366 ± 78.
Int J Psych Clin Pract Downloaded from informahealthcare.com by Universitat de Girona on 12/05/14 For personal use only.
80
I Reznik et al
4. Borison RL, Arvanitis LA, Miller BG (1996) ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. J Clin Psychopharmac ol 16: 158 ± 69. 5. Arvanitis LA, Miller BG (1997) Multiple fixed doses of `Seroquel’ (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry 42: 233 ± 46. 6. Reznik I, Benatov R, Sirota P (1996) Seroquel in a resistant schizophrenic with negative and positive symptoms (in Hebrew). Harefuah 130: 675 ± 77. 7. Arvanitis LA, Rak IW (1997) The long-term efficacy and safety of quetiapine. In: New Research Program and Abstracts of the 150 Annual Meeting of the American Psychiatric Association, May 1997, San Diego, CA. (Abstract NR230). APA, Washington, DC. 8. Meats P (1997) Quetiapine (Seroquel); an effective and welltolerated atypical antipsychotic. Int J Psych Clin Pract 1: 231 ± 9. 9. Goldstein JM (1998) Inaccurate information on quetiapine (letter). J Clin Psychiatry 59: 687. 10. Maeda H, Kotorii T, Nakamura J, Uchimura N (1998) Clinical evaluation of quetiapine (ICI 204,636), a novel antipsychotic agent, in treatment-resistant schizophrenic patients. In: Proceedings of XXI CINP Congress, Glasgow, 12 ± 16 July 1998; The Scientific Program and Book of Abstracts. Abstract: PT 07099.
11. Kane JM, Honigfeld G, Singer J, Meltzer HY and the Clozaril Collaborative Study Group (1988) Clozapine for the treatmentresistant schizophrenic: A double-blind comparison with chlorpromazine.Arch Gen Psychiatry 45: 789 ± 96. 12. Marder SR (1996) Management of treatment-resistant patients with schizophrenia. J Clin Psychiatry 57 (suppl 11): 26 ± 30. 13. King DJ (1998) Drug treatment of the negative symptoms of schizophrenia.Eur Neuropsychoph armacol 8: 33 ± 42. 14. Tamminga CA, Lahti AC (1996) The new generation of antipsychotic drugs. Int Clin Psychopharmaco l 11 (suppl 2): 73 ± 6. 15. Meltzer HY (1997) Treatment-resistant schizophrenia ± the role of clozapine. Curr Med Res Opin 14: 1 ± 20. 16. Stip E (1996) Memory impairment in schizophrenia: perspectives from psychopathology and pharmacotherapy. Can J Psychiatry 41 (suppl 2): S27 ± S34. 17. Fleischhacker WW, Hummer M (1997) Drug treatment of schizophrenia in the 1990s. Achievements and future possibilities in optimizing outcomes. Drugs 53: 915 ± 29.
