- Email: [email protected]
Relapse prevention in schizophrenia: attitudes of neurologists-psychiatrists
Eur Psychiatry 2001 ; 16 : 90-8 © 2001 Éditions scientifiques et médicales Elsevier SAS. All rights reserved S0924933801005430/FLA
ORIGINAL ARTICLE
Relapse prevention in schizophrenia: attitudes of neurologists-psychiatrists J.D. Bergiannaki*, J. Hatzimanolis, J. Liappas, P.N. Sakkas, C.N. Stefanis University Mental Health Research Institute, Eginition Hospital, Vas. Sophias Ave. 72-74, GR115 28 Athens, Greece (Received 28 January 1999; accepted 14 September 1999)
Summary – The overall high relapse rates observed in schizophrenia are attributed to several causes. One important factor influencing satisfactory prevention of relapse is the lack of consistent treatment strategies among medical doctors, especially neurologists-psychiatrists. Nearly one-third of the members of the Hellenic Society of Neurology and Psychiatry were asked to fill in anonymously a structured questionnaire on their treatment attitudes and prescribing tactics regarding schizophrenic patients both after the first schizophrenic episode and after multiple episodes. The majority of Greek neurologists-psychiatrists seem to adopt prescribing habits that approximate the current international standards for prevention of schizophrenic relapse. Their attitudes regarding the treatment and prevention of relapse for the first schizophrenic episode and first relapse are determined from multiple factors. These are: the expected relapse rates after the first episode, the expected prevalence of extrapyramidal side effects following a long-term neuroleptic treatment, the patient’s expected treatment compliance after the first episode, the doctor’s experience with treating schizophrenics, and lastly the knowledge of current literature on the topic. These results point to the need for continuing education, especially of the younger mental health professionals and those working in the private sector, addressing the issue of the actual risk of developing side effects from the treatment. In due course, benefits could result for everyday psychiatric practice and the patients’ compliance with treatment. © 2001 Éditions scientifiques et médicales Elsevier SAS neurologists-psychiatrists / prevention / relapse / schizophrenia / treatment attitudes
INTRODUCTION The relapse rate for schizophrenic psychoses still remains high [27], exceeding 50% within the first year [15] and approximating 85% within 5 years after the first episode [19, 45, 55]. Following a successful treatment, every relapse of the schizophrenic psychosis is accompanied by an immense burden on the patient himself, as well as for his family and society at large [20-22, 47, 50, 52]. The actual percentage of relapse is
*Correspondence and reprints. E-mail address: [email protected] (J.D. Bergiannaki).
still unsatisfactory, in contrast to the great progress achieved by the introduction of neuroleptic treatment [7-9, 31] and the application of several psychosocial strategies. According to Kissling [37], this percentage is three times higher than it ought to be. The undertreatment seems to be one major cause for the current high relapse rates in schizophrenia and could be reduced through more consistent relapse prevention [37]. The compliance with neuroleptic treatment is influenced, apart from factors intrinsic to the schizophrenic
Relapse prevention in schizophrenia
process per se, by multiple other determinants as well. The organization of psychiatric services, factors related to medication, the extent of psychosocial education of patients and their relatives [1, 3, 25, 40, 41] and the layman’s prejudice toward treating mental disorders with medication [18] considerably affect compliance. Furthermore, another important factor influencing the success of relapse prevention in schizophrenia is the lack of consistency on treatment strategies among medical doctors [18]. General practitioners and psychiatrists as well often fail to recommend a prophylactic treatment to their schizophrenic patients, or discontinue such a treatment too early [13]. Thus, for many schizophrenic patients the duration of preventive treatment is inadequate or absent [37]. More specifically, only 40–50% of all schizophrenic patients for whom neuroleptic relapse prevention is indicated is prescribed a prophylactic treatment [30, 35], and barely 25% of the patients with a first schizophrenic episode adhere to prevention [14]. This happens more often with patients after the first episode [14], and leads to detrimental effects, because for these patients early prevention of relapse can hamper a long-term poor outcome [6, 16, 26, 27]. The present study aimed at documenting the treatment attitudes and prescribing tactics of neurologistspsychiatrists regarding the prevention of schizophrenic relapse, and checking to what extent these factors relate to their experience, knowledge and personal fears. SUBJECTS AND METHODS The study sample comprised 203 neurologistspsychiatrists (30.6%) out of a total of 673 members of the Hellenic Society of Neurology and Psychiatry, who were asked to fill in anonymously a structured questionnaire. This questionnaire, similar to Kissling’s [37], consisted of a pair of well-defined case histories of schizophrenic patients: one following a first schizophrenic episode and the other after multiple episodes. Respondents were asked to recommend a treatment for both situations. Likewise, they had to note the treatment duration they would usually consider, and the optimal pertinent dose of a classic neuroleptic like haloperidol. They were also asked their opinion about the lower effective neuroleptic dose for prevention of relapse. Additional information was obtained on the patient’s expected compliance after the first and after multiple schizophrenic episodes, the expected prevalence of development of mild and severe tardive dyskiEur Psychiatry 2001 ; 16 : 90–8
91
nesia (TD) and the percentage of relapse rates according to their knowledge of the current literature and their personal experience. The respondents were either in private practice or in the public sector for at least five years. Four groups were formed according to age: group 1 (up to 30 years), group 2 (31–40 years), group 3 (41–50 years) and group 4 (above 51 years). The student t-test (paired and unpaired) was used for comparisons between means (± SEM) and the χ2 was applied for non-parametric variables. To estimate the distribution of frequencies, the mean, median, skewness and kurtosis of the variables, the normality test (Kolmogorow-Smirnof) was used. Multiple linear regression analysis was applied to detect the potential relationship between various dependent and independent variables. RESULTS The majority of subjects were males (males: 135 vs females: 65, P < 0.05). Females were younger than males (in age group 2: females: 55.4% vs males: 47.0%, P < 0.01) and were in psychiatric practice significantly fewer years than males (7.67 ± 0.79 vs 10.34 ± 0.77, P < 0.05). The rate of working hours in private practice/ mental health institutions, the percentage of the neurologic and psychiatric patients’ ratio, and the percentage of schizophrenic patients treated, did not differ between genders. The majority of their practice was psychiatric patients (91.43%), mostly schizophrenics (35%) (table I). Treatment of the first schizophrenic episode During the acute phase of the first paranoid-type schizophrenic episode, with hallucinations but no agitation or disrupting behavior and insomnia, the recommended mean haloperidol dosage was 19.8 ± 11.21 mg/daily, the median 17.50 mg/daily, and the mode 15 mg/daily. The distribution curve exhibited a skewness of 1.41 ± 0.171 and had a kurtosis of 2.769 ± 0.341. Linear regression analysis showed that the recommended haloperidol dosage for the treatment of the first schizophrenic episode related positively to the expected relapse rates and ratio of schizophrenics among patients, and negatively to the percentage of psychiatric patients treated by the respondent (table II). In the event that the psychotic symptoms proved resistant to haloperidol treatment, the majority of the respondents turned to another neuroleptic after 30
92
J.D. Bergiannaki et al.
Table I. Demographic and occupational characteristics of respondents. Number Age group 30–40 years No of years in psychiatric practice Occupation in psychiatric institutions (% of time) Occupation in private practice (% of time) Turnout of psychiatric patients (%) Prevalence of schizophrenic patients (%)
Total
Males
Females
200 100 9.54 ± 0.58 60.84 ± 2.55 37.95 ± 2.52 91.43 ± 1.12 34.83 ± 1.50
135 (67.5%) 64 (47.0%) 10.34 ± 0.77 59.22 ± 3.0 39.04 ± 2.93 91.11 ± 1.4 33.85 ± 1.83
65 (32.5%) 36 (55.4%) 7.67 ± 0.79 65.39 ± 4.77 34.27 ± 4.91 92.03 ± 1.92 37.40 ± 2.65
days. The frequency distribution of the number of days for a change of neuroleptic medication exhibited a normal curve (mean 29.34 ± 1.09 days, median = 30.00, mode = 30, skewness = 1.42 ± 0.171, and kurtosis = 2.77 ± 0.341). Two months after the first schizophrenic episode with paranoid and hallucinatory symptoms and while in remission, the maintenance of neuroleptic treatment for several months, the majority of psychiatrists (85.7%) recommended the maintenance of neuroleptic treatment for several months (figure 1). The gradual tapering of the neuroleptic medication after 2–3 months was proposed by 11.7% of the respondents; only 2.6% would consider discontinuation over a period of 2–3 weeks (figure 1). More precisely, 39.9% of neurologistspsychiatrists would recommend maintenance treatment for up to seven months, 42.9% for up to one year, and 17.35% for a period longer than one year and a half (figure 2). The last group comprised professionals over 40 years of age, who had been active for more than 10 years in the field of psychiatry, worked mostly in mental health institutions (80%), who had treated plenty of schizophrenic patients (75%) and believed that the
Significance P < 0.05 P < 0.01 P < 0.01 Non-significant Non-significant Non-significant Non-significant
patient’s cooperation increases after multiple relapses. Eighty to 90 percent of them were aware of the risk for development of mild or serious tardive dyskinesia (TD) under long-term neuroleptic treatment and used a moderate dose of haloperidol for relapse prevention (mean dose: 22.03 ± 1.89 mg/d). Multiple linear regression analysis showed a positive relationship between the duration of the recommended treatment (in months) and the age group in which the respondent belonged; furthermore, a negative relationship was observed with the expected prevalence of mild reversible tardive dyskinesia five years after initiation of neuroleptic treatment (table III). Almost all respondents (94.9%) prescribed more than one neuroleptic for the prevention of relapse. In case haloperidol was selected for prevention, a minimal dose of 5 mg/daily was prescribed by 46.7% of neurologistspsychiatrists; 37.4% would administer 6–10 mg of haloperidol per day and the remaining 15.9% would prescribe a higher dosage. Linear regression analysis showed that the recommended dosage (in mg/d) of haloperidol used for long-term prevention related negatively to the percentage of expected compliance with
Table II. Treatment of the acute phase of the first schizophrenic episode of paranoid-hallucinatory schizophrenia: linear regression analysis of the recommended haloperidol dosage (mg/day) in relation to several independent variables. Dependent variable: recommended dose of haloperidol (mg/day) Independent variables Sex: (Female: 0 – Male: 1) Age group (1, 2, 3, 4) No of years in psychiatric practice Occupation in private practice (% of time) % of psychiatric patients in treatment % of schizophrenics among patients % of estimated relapse rate after the first schizophrenic episode (according to experience) % of anticipated mild reversible tardive dyskinesia after 5 years of neuroleptic treatment % of expected patient’s cooperation after the first schizophrenic episode Satisfied by present state of relapse prevention in schizophrenia
Regression’s coef. Beta
Significance P
–0.014 –0.036 0.148 0.042 –0.160 0.165 0.176 –0.436 –0.087 –0.076
0.84 0.76 0.21 0.60 0.03 0.04 0.03 0.56 0.25 0.32
Eur Psychiatry 2001 ; 16 : 90–8
Relapse prevention in schizophrenia
93
Figure 1. Percentages of neurologists-psychiatrists (vertical axis) and time elapsed before recommendation of neuroleptic treatment discontinuation (horizontal axis), a), after the first schizophrenic episode and b) after the first relapse.
medication of the schizophrenic patients after the first episode (table IV). First post-relapse period Mental health professionals significantly modified their attitudes towards neuroleptic relapse prevention as soon as a relapse occurred after a one-year remission of the first schizophrenic episode. In this event, the majority of psychiatrists (87.5%) increased the period of neuroleptics (figures 1 and 2) from 10.70 ± 0.60 months after the first episode, to 19.37 ± 1.10 months after the first relapse (P < 0.01). The number of psychiatristsneurologists who did not recommend neuroleptic relapse prevention following both the first schizophrenic episode and the first relapse did not change significantly (33 vs 29) (figure 1). This particular group comprised private practitioners who had few schizophrenics among their clients. They also underestimated the relapse rates both after the first episode and after multiple relapses and were not informed on the relapse rates reported in the literature. Furthermore, they usually administered lower doses of haloperidol during the acute phase of the first schizophrenic episode, and turned earlier to another Eur Psychiatry 2001 ; 16 : 90–8
neuroleptic when no immediate improvement was achieved (table V). According to their personal experience, psychiatristsneurologists reported that the rate of relapse after the first schizophrenic episode was significantly lower than that 5 years after illness onset and multiple relapses (paired t-test 53.33 ± 1.52 vs 60.17 ± 1.70, P < 0.000). No divergence was observed between the relapse rates noted as derived from their personal experience and those actually reported in the literature, either after the first schizophrenic episode (53.06 ± 1.60 vs 53.89 ± 1.33, NS), or after five years of illness and multiple relapses (59.99 ± 1.80 vs 58.66 ± 1.62, NS). The percentage of expected occurrence of mild and reversible tardive dyskinesia after 5 years of continuous neuroleptic administration was significantly higher than that expected for severe and irreversible tardive dyskinesia (14.39 ± 1.026 vs 6.33 ± 0.748, P < 0.000). Concerning the patient’s cooperation after multiple relapses, respondents’ estimations, in mean percentages, were significantly higher than those after the first episode (54.18 ± 1.57 vs 44.97 ± 1.83, P < 0.05). Finally, the majority of neurologists-psychiatrists (54.5%) were not satisfied with the present state of relapse prevention in
94
J.D. Bergiannaki et al.
Figure 2. Percentages of neurologists-psychiatrists (vertical axis), and duration of maintenance neuroleptic treatment (horizontal axis), a) after the first schizophrenic episode, and b) after the first relapse.
schizophrenia. All of them (97.5%) believe that compliance with treatment may improve by way of educational actions. DISCUSSION The aim of the present study was to assess the attitudes of neurologists-psychiatrists pertaining to the treatment of schizophrenic patients, with a specific focus on the recommended dosage and maintenance treatment with neuroleptics for prevention of relapse. First, it is
difficult to form a clear opinion about treatment attitudes towards the schizophrenic patient, because psychiatrists adjust their treatment to the particularities of any individual case. The presentation of identical case reports to all interviewed neurologists-psychiatrists allowed differences in prescribing tactics to be more adequately identified [37], and permitted reliable comparisons with the questionnaires administered by other investigators [12, 36]. In our sample males were overrepresented, reflecting the composition of the enlisted members of the Hel-
Table III. Two months after full remission of the first schizophrenic episode with paranoid and hallucinatory symptoms: linear regression analysis of the duration (in months) of the recommended neuroleptic preventive treatment in relation to several independent variables. Dependent variable: duration (in months) of recommended neuroleptic preventive treatment after the first schizophrenic episode Independent variables Regression’s coef. Significance Beta P Sex: (Female: 0 – Male: 1) Age group (1, 2, 3, 4) No of years in psychiatric practice Occupation in psychiatric institutions (% of time) % of schizophrenics among patients % of estimated relapse rate after the first schizophrenic episode (according to experience) % of expected patient’s cooperation after the first schizophrenic episode % of anticipated mild reversible tardive dyskinesia (TD) after 5 years of neuroleptic treatment
0.067 0.274 0.063 0.160 0.036 0.047 –0.021 –0.164
0.43 0.01 0.52 0.64 0.67 0.58 0.80 0.04
Eur Psychiatry 2001 ; 16 : 90–8
95
Relapse prevention in schizophrenia
Table IV. Post-remission phase after the first schizophrenic episode: linear regression analysis of the recommended minimal dosage of haloperidol (mg/day) for relapse prevention in relation to several independent variables. Dependent variable: recommended minimal dose of haloperidol (mg/day) Independent variables
Regression’s coef. Beta
Significance P
0.004 0.137 0.029 0.184 0.063 –0.066 –0.192 –0.068
0.95 0.16 0.75 0.50 0.46 0.42 0.01 0.39
Sex: (Female: 0 – Male: 1) Age group (1, 2, 3, 4) No of years in psychiatric practice Occupation in psychiatric institutions (% of time) % of schizophrenics among patients % of estimated relapse rate after the first schizophrenic episode (according to experience) % of expected patient’s cooperation after the first schizophrenic episode % of anticipated mild reversible tardive dyskinesia (TD) after 5 years of neuroleptic treatment
lenic Society for Neurology and Psychiatry up to 1994 (males: 75.9% vs females: 24.1%). Males were older than females on the average, a difference reflecting the predilection of Greek female medical doctors for the psychiatric specialty during the last two decades. However, according to our results, age and gender did not influence significantly the treatment attitudes of respondents (tables II-IV). The decision on the optimal dosage of an antipsychotic agent for treatment of the acute schizophrenic episode is quite difficult [26]. More than half of the respondents would recommend for management of the first schizophrenic episode with paranoid and hallucinatory symptoms a mean dose of 20 mg/d of a classic neuroleptic like haloperidol. This dosage is within the range proposed by the PORT treatment recommenda-
tion [39], but it is somewhat higher than the one reported by Baldessarini et al. [2]. However, the frequencies distribution curve of haloperidol dosage in our sample was normal, suggesting a considerable agreement in the prescribing tactics. The choice of unusually high doses of haloperidol was characteristic of neurologists-psychiatrists who did not attend to many psychiatric patients. This observation illustrates the difficulty of medical doctors lacking adequate experience to appropriately treat the schizophrenic patient. Whenever the psychotic symptoms proved to be resistant to haloperidol, the majority of professionals turned to another medication within 30 days, a practice that is in accordance with the established norm [44]. Although Greek respondents maintained the preventive treatment for numerous months following the first
Table V. Characteristics of psychiatrists who do not modify their treatment attitudes (no modification), compared to psychiatrists who modify/extend their preventive treatment (modification), following the first relapse after a year of full and stable remission of a first episode of paranoid-hallucinatory schizophrenia.
% of relapse after the first schizophrenic episode (according to experience) % of relapse after the first schizophrenic episode (according to literature) % of relapse after multiple episodes (according to experience) % of relapse after multiple episodes (according to literature) % of expected mild–reversible tardive dyskinesia after 5 years of neuroleptic treatment % of expected severe tardive dyskinesia after 5 years of neuroleptic treatment Recommended dosage of haloperidol (mg/day) during the acute phase of the first schizophrenic episode Days elapsed before turning to another neuroleptic No of years in psychiatric practice Occupation in private practice (% of time) Occupation in psychiatric institutions (% of time) Turnout of psychiatric patients (%) Prevalence of schizophrenic patients (%) Eur Psychiatry 2001 ; 16 : 90–8
No modification N = 29
Modification N = 174
Significance P
26.33 ± 5.31 39.64 ± 4.27 31.88 ± 6.34 43.67 ± 5.51 12.94 ± 3.88 6.00 ± 1.49 11.35 ± 2.13
55.38 ± 1.48 55.22 ± 1.35 62.20 ± 1.66 60.66 ± 1.66 15.20 ± 1.14 6.36 ± 0.81 20.52 ± 0.82
P < 0.01 P < 0.01 P < 0.01 P < 0.01 Non-significant Non-significant P < 0.01
20.65 ± 3.60 10.59 ± 1.73 66.47 ± 8.18 30.81 ± 7.47 89.59 ± 4.15 25.94 ± 4.43
30.14 ± 1.12 9.44 ± 0.61 35.22 ± 2.57 34.39 ± 2.57 91.61 ± 1.16 35.65 ± 1.57
P < 0.01 P < 0.01 P < 0.01 Non-significant P < 0.01 P < 0.01
96
J.D. Bergiannaki et al.
schizophrenic episode, they did not meet the standards of the consensus of Bruges [38] and the PORT treatment recommendations [39], which propose treatment maintenance for 1–2 years after the first episode, and for at least 5 years after multiple episodes [56]. According to our results, the more experienced professionals, who worked at psychiatric institutions and had attended to a large number of schizophrenics, were in tune to the above international standards. The recommended duration of treatment was in negative relation to the expected prevalence of moderate tardive dyskinesia and in positive relation to the age of the respondent. This finding points out that the worry of emergence of side effects was greater among younger psychiatrists who curtail the duration of preventive treatment. This is in agreement with a previous study that holds that the main reason for the widespread nonconforming of doctors to the above standards is due to underestimation of the relapse risk for untreated schizophrenics and overestimation of the potential risks of side effects [37]. It is well known that side effects, i.e., heavy sedation, anticholinergic effects and dystonias [29, 53, 57] need to be minimized to enhance compliance and prevent relapse [5, 48]. Therefore, our findings imply that systematic information on the actual prevalence of TD could improve prophylactic treatment. Inasmuch as atypical neuroleptics have been recently introduced to medical practice, apt information of young psychiatrists and professionals in private practice with limited schizophrenic clientele could be a promising policy for reducing relapse rates. The dosage of haloperidol proposed for prevention subsequent to the first schizophrenic episode was higher than the one reported in American studies [46], but conformed with that reported in European studies [10, 12]. Certain divergences observed within small subgroups of our sample have also been noted by others [12, 32, 37]. These differences obviously reflect the lack of common consent on the relapse risk, as well as the controversies concerning the treatment guidelines for the first schizophrenic episode [4, 6, 24, 28, 43] and the duration of maintenance on neuroleptics [18]. The recommended haloperidol dosage for relapse prevention following remission of the first schizophrenic episode was in negative relation to the expected compliance from the patient. A likely reason for this phenomenon is that the doctor’s urge for a rapid and efficient therapeutic outcome is coupled to poor expectations for adequate compliance and therefore to a precocious treatment discontinuation. This finding is discordant
with the standing treatment guidelines that regard the optimal neuroleptic threshold dosage to be generally fairly adequate for an effective antipsychotic treatment without causing extrapyramidal side effects [46]. Consequently, this practice may be attributed to a sort of ‘reaction formation’ that contributes to the establishment of a ‘vicious circle’ between the expected poor compliance of the patient, the administration of an unexpectedly high dosage of neuroleptics, the development of side effects, and the incitement/sustenance of poor compliance. This phenomenon should be made explicit in any future educational program for psychiatrists, because of the obvious importance for the enhancement of the doctor-patient relationship [11]. It is well known that the optimal dosage and duration of treatment cannot be easily established and that patients at low risk for relapse following neuroleptic withdrawal cannot be safely identified [54]. The fact that the first schizophrenic relapse modified the attitudes of the majority of the psychiatrists-neurologists with respect to neuroleptic relapse prevention indicates that this is a potentially self-resolved problem. According to our results the respondents who did not change their treatment attitudes after the first relapse consisted of a minority with limited experience with schizophrenic patients and poor knowledge of the relevant treatment and relapse risk (table V). Moreover, the majority of respondents were well informed on the actual relapse rates for the first schizophrenic episode, which were in accordance with those reported by previous studies [6, 33, 49]. Conversely, they underestimated the relapse rates after multiple episodes compared to those accounted for in the literature [23, 49]. The reason apparently was lack of adequate information. Besides, the respondents were aware of the actual prevalence rates of mild and severe tardive dyskinesia as reported elsewhere [17, 31, 34, 42]. Finally, the estimated percentage of cooperation and compliance of patients after the first schizophrenic episode was similar to that reported by other investigators [51]; the reported increase of these percentages after multiple relapses was in partial agreement with previous studies [15]. CONCLUSION The majority of Greek neurologists-psychiatrists seem to hold views and take up attitudes towards relapse prevention that approximate the current international standards. Divergences were identified in particular subgroups composed of respondents oriented to private Eur Psychiatry 2001 ; 16 : 90–8
Relapse prevention in schizophrenia
practice, active both in the fields of neurology and psychiatry, and less informed on the current scientific literature. The attitudes of medical doctors regarding the treatment and prevention of relapse of the first schizophrenic episode were determined by the anticipated rate of relapse and treatment compliance after the first episode; the expected prevalence of extrapyramidal side effects after long-term neuroleptic prevention; the knowledge of current literature on the topic; and personal experience of attending to schizophrenic patients. In this context, continuing educational programs addressing the issue of the actual risk of side effects, especially designed for young professionals and those working in private practice, could prove to be particularly useful in improving everyday psychiatric practice and patient compliance.
13 14 15 16 17 18 19 20
ACKNOWLEDGEMENTS This study was partly supported by a grant by Lundbeck Hellas SA (1995). REFERENCES 1 Angermeyer MC, Siara CS. Effects on assassination attempts on Lafontaine and Schauble on public opinion about psychiatric patients. Part 2: 1991 development. Nervenarzt 1994 ; 65 (Suppl 382) : 49-56. 2 Baldessarini RJ, Cohen BM, Teicher MH. Significance of neuroleptic dose and plasma levels in the pharmacological treatment of psychoses. Arch Gen Psychiatry 1988 ; 45 : 79-91. 3 Baüml J, Kissling W, Meurer C, Wais A, Lauter H. Informationszentrierte Angehörigengruppen zur Complianceverbesserung bei schizophrenen Patienten. Psychiat Prax 1991 ; 18 : 48-54. 4 Bleuler M. The schizophrenic disorders–long-term patient and family studies. New Haven: Yale University Press; 1978. 5 Citrome L. New antipsychotic medications: what advantages do they offer? Postgrad Med 1997 ; 101 : 207-10. 6 Crow TJ, McMillan JF, Johnson AL, Johnstone EC. The Northwick Park study of first episodes of schizophrenia: II. A randomized controlled trial of prophylactic neuroleptic treatment. Br J Psychiatry 1986 ; 148 : 120-7. 7 Davis JM. Overview: maintenance of therapy in psychiatry. Am J Psychiatry 1975 ; 132 : 1237-45. 8 Davis JM. Antipsychotic drugs. In: Kaplan HI, Freedman AM, Sadock BJ, Eds. Comprehensive textbook of psychiatry. 3rd ed. Baltimore: Williams and Wilkins; 1980. p. 2257-89. 9 Davis J. Maintenance medication. In: Barnes TRE, Ed. Depot neuroleptics: a consensus. London: Mediscript; 1988. p. 47-52. 10 Denker SJ, May PRA. The treatment of acute psychosis. Copenhagen: Lundbeck; 1986. 11 Fenton WS, Blyler CR, Heinssen RK. Determinants of medication compliance in schizophrenia: empirical and clinical findings. Schizophr Bull 1997 ; 23 : 637-51. 12 Fleischhacker WW, Meise U. The current status of maintenance treatment in schizophrenia. In: Kissling W, Ed. GuideEur Psychiatry 2001 ; 16 : 90–8
21 22 23 24
25
26 27
28 29 30 31 32
33 34
97
lines for neuroleptic relapse prevention in schizophrenia. New York: Springer-Verlag; 1991. p. 13-5. Gäbel W. Towards the improvement of compliance: the significance of psycho-education and new antipsychotic drugs. Int Clin Psychopharmacol 1997 ; 12 (Suppl 1) : S37-S42. Gäbel W, Pietzcker A. Indikation zur neuroleptischen Langzeitmedikation – standardverfahren oder individualprognostisch geleitete Intervention? Nervenarzt 1983 ; 54 : 467-76. Gäbel W, Pietzcker A. One-year outcome of schizophrenic patients – the interaction of chronicity and neuroleptic treatment. Pharmacopsychiatry 1985 ; 18 : 235-9. Gäbel W, Marder S. Conclusions and treatment recommendations for the acute episode in schizophrenia. Int Clin Psychopharmacol 1996 ; 11 (Suppl 2) : 93-100. Gerlach J, Casey DE. Tardive dyskinesia. Acta Psychiatr Scand 1988 ; 77 : 369-78. Gjerris A, Kissling W. Concluding remarks. Acta Psychiatr Scand 1994 ; 89 (Suppl 382) : 93. Gmür M, Tschopp A. Die Behandlungskontinuität bei schizophrenen Patienten in der Ambulanz. Eine Fünfjahresnachuntersuchung. Nervenarzt 1988 ; 59 : 727-30. Guenther V, Meise U. Compliance – Ein Komplexes Problem. Wien Med Wochenschr 1990 ; 140 : 265-9. Gunderson JG, Mosher LR. The cost of schizophrenia. Am J Psychiatry 1975 ; 132 : 901-6. Hall W, Goldstein G, Andrews G, Lapsley H, Bartels R, Silove D. Estimating the economic costs of schizophrenia. Schizophr Bull 1985 ; 11 : 598-610. Hogarty GE, Goldberg SC, Collaborative Study Group. Drug and sociotherapy in the aftercare of schizophrenic patients: one year relapse rates. Arch Gen Psychiatry 1974 ; 28 : 54-64. Hogarty GE. Resistance of schizophrenic patients to social and vocational rehabilitation. In: Dencker SJ, Kulhanek F, Eds. Treatment resistance in schizophrenia. Wiesbaden: Braunschweig; 1988. Hornung WP, Kieserg A, Feldmann R, Buchkremer G. Psychoeducational training for schizophrenic patients: background, procedure and empirical findings. Patient Educ Couns 1996 ; 29 : 257-68. Janicak PG, Davis JM. Antipsychotic dosing strategies in acute schizophrenia. Int Clin Psychopharmacol 1996 ; 11 (Suppl 2) : 35-40. Johnstone EC, Crow TJ, Johnson AL, Macmillan JF. The Northwick Park study of first episodes of schizophrenia. I. Presentation of the illness and problems relating to admission. Br J Psychiatry 1986 ; 148 : 115-20. Johnstone EC, Geddes J. How high is the relapse rate in schizophrenia? Acta Psychiatr Scand 1994 ; 89 (Suppl 382) : 6-10. Kane JM. Problems of compliance in the outpatient treatment of schizophrenia. J Clin Psychiatry 1983 ; 1 : 3-6. Kane JM. Compliance issues in outpatient treatment. J Clin Psychopharmacol 1985 ; 5 : 225-75. Kane JM. Treatment of schizophrenia. Schizophr Bull 1987 ; 13 : 133-56. Kane JM. Dosage and route of administration of neuroleptic drugs during different phases of a schizophrenic illness. In: Kissling W, Ed. Guidelines for neuroleptic relapse prevention in schizophrenia. New York: Springer-Verlag; 1991. p. 85-93. Kane JM, Rifkin A, Quitkin F, Naya D, Ramos-Lorenzi J. Fluphenazine versus placebo in patients with remitted acute first episode schizophrenia. Arch Gen Psychiatry 1982 ; 39 : 70-3. Kane JM, Woerner M, Borenstein M, Wegner J, Lieberman J. Integrating incidence and prevalence of tardive dyskinesia. Psychopharmacol Bull 1986 ; 22 : 254-8.
98
J.D. Bergiannaki et al.
35 Kissling W. Depot neuroleptics – a step forward? Consensus regarding indication for prophylactic neuroleptic treatment – necessary, but unattainable? In: Barnes TRE, Ed. Depot neuroleptics: a consensus. London: Mediscript; 1988. p. 41-6. 36 Kissling W, Ed. Guidelines for neuroleptic relapse prevention in schizophrenia. Berlin: Springer-Verlag; 1991. 37 Kissling W. Compliance, quality assurance and standards for relapse prevention in schizophrenia. Acta Psychiatr Scand 1994 ; 89 (Suppl 382) : 16-24. 38 Kissling W, Kane JM, Barnes TRE, Dencker SJ, Fleischhacker WW, Goldstein MJ, et al. Guidelines for neuroleptic relapse prevention in schizophrenia: towards a consensus view. In: Kissling W, Ed. Guidelines for neuroleptic relapse prevention in schizophrenia. New York: Springer-Verlag; 1991. p. 15563. 39 Lehman AF, Steinwachs DM. Survey Co-Investigators of the PORT Project. Patterns of usual care for schizophrenia: initial results from the schizophrenia patient outcomes research team (PORT) client survey. Schizophr Bull 1998 ; 24 : 11-20. 40 Lewandowski L, Buchkremer G. Therapeutische Gruppenarbeit mit Angehörigen schizophrener Patienten. Z Klin Psychol 1988 ; 17 : 210-24. 41 Mantonakis J, Markidis M, Kontaxakis V, Liakos A. A scale for detection of negative attitude towards medication among relatives of schizophrenic patients. Acta Psychiatr Scand 1985 ; 2 : 186-9. 42 Marsden CD. Is tardive dyskinesia a unique disorder? In: Casey DE, Chase TN, Christensen AV, Gerlach J, Eds. Dyskinesia – research and treatment. (Psychopharmacology series, vol. 2.). Berlin: Springer; 1985. 43 Marder SR. The role of dosage and plasma levels in neuroleptic relapse prevention. Acta Psychiatr Scand 1994 ; 89 (Suppl 382) : 25-7. 44 Marder SR. Pharmacological treatment strategies in acute schizophrenia. Int Clin Psychopharmacol 1996 ; 11 (Suppl 2) : 29-34. 45 Maurer K, Biehl H. Klinikaufenthalte und produktive Rückfalle bei ersterkrankten Schizophrenen. Nervenheilkunde 1988 ; 7 : 279-90.
46 McEnvoy JP, Hogerty GE, Steingard S. Optimal dose of neuroleptics in acute schizophrenia: a controlled study of the neuroleptic threshold and higher haloperidol dose. Arch Gen Psychiatry 1991 ; 48 : 739-45. 47 McGlashan TH. A selective review of recent North America long-term follow-up studies of schizophrenia. Schizophr Bull 1988 ; 14 : 515-42. 48 Meise U, Fleischhacker WW. Perspectives on treatment needs in schizophrenia. Br J Psychiatry 1996 ; 168 (Suppl 29) : 9-16. 49 Müller P, Ed. Zur Rezidivprophylaxe Schizophrener Psychosen. Stuttgart: Enke; 1982. 50 Pietzcker A. Neuroleptische Langzeit-Medikation in der ambulanten Behandlung schizophren Kranker. Hamburg: Promonta Schriften; 1987. 51 Rabiner CJ, Wegner JT, Kane JM. Outcome study of first episode psychosis: I. Relapse rates after one year. Am J Psychiatry 1986 ; 143 : 1155-8. 52 Rice DP, Kelman S, Miller LS. The economic burden of mental illness. Hosp Community Psychiatry 1992 ; 43 : 1227-32. 53 Rifkin A. A historical review of the adverse reactions to neuroleptic agents. J Clin Psychiatry 1987 ; 3 (Suppl 48) : 6. 54 Sheitman BB, Lee H, Strauss R, Lieberman JA. The evaluation and treatment of first-episode psychosis. Schizophr Bull 1997 ; 23 : 653-61. 55 Shepherd M, Watt D, Falloon I, Smeeton N. The natural history of schizophrenia: a five-year follow-up study of outcome and prediction in a representative sample of schizophrenia. Psychol Med Monogr Suppl 15. Cambridge: Cambridge University Press; 1989. 56 Tegeler J. Maintenance neuroleptic treatment in schizophrenia. In: Kissling W, Ed. Guidelines for neuroleptic relapse prevention in schizophrenia. New York: Springer-Verlag; 1991. p. 34-7. 57 Van Putten T. Why do schizophrenic patients refuse to take their drugs? Arch Gen Psychiatry 1974 ; 31 : 67-72.
Eur Psychiatry 2001 ; 16 : 90–8
ORIGINAL ARTICLE
Relapse prevention in schizophrenia: attitudes of neurologists-psychiatrists J.D. Bergiannaki*, J. Hatzimanolis, J. Liappas, P.N. Sakkas, C.N. Stefanis University Mental Health Research Institute, Eginition Hospital, Vas. Sophias Ave. 72-74, GR115 28 Athens, Greece (Received 28 January 1999; accepted 14 September 1999)
Summary – The overall high relapse rates observed in schizophrenia are attributed to several causes. One important factor influencing satisfactory prevention of relapse is the lack of consistent treatment strategies among medical doctors, especially neurologists-psychiatrists. Nearly one-third of the members of the Hellenic Society of Neurology and Psychiatry were asked to fill in anonymously a structured questionnaire on their treatment attitudes and prescribing tactics regarding schizophrenic patients both after the first schizophrenic episode and after multiple episodes. The majority of Greek neurologists-psychiatrists seem to adopt prescribing habits that approximate the current international standards for prevention of schizophrenic relapse. Their attitudes regarding the treatment and prevention of relapse for the first schizophrenic episode and first relapse are determined from multiple factors. These are: the expected relapse rates after the first episode, the expected prevalence of extrapyramidal side effects following a long-term neuroleptic treatment, the patient’s expected treatment compliance after the first episode, the doctor’s experience with treating schizophrenics, and lastly the knowledge of current literature on the topic. These results point to the need for continuing education, especially of the younger mental health professionals and those working in the private sector, addressing the issue of the actual risk of developing side effects from the treatment. In due course, benefits could result for everyday psychiatric practice and the patients’ compliance with treatment. © 2001 Éditions scientifiques et médicales Elsevier SAS neurologists-psychiatrists / prevention / relapse / schizophrenia / treatment attitudes
INTRODUCTION The relapse rate for schizophrenic psychoses still remains high [27], exceeding 50% within the first year [15] and approximating 85% within 5 years after the first episode [19, 45, 55]. Following a successful treatment, every relapse of the schizophrenic psychosis is accompanied by an immense burden on the patient himself, as well as for his family and society at large [20-22, 47, 50, 52]. The actual percentage of relapse is
*Correspondence and reprints. E-mail address: [email protected] (J.D. Bergiannaki).
still unsatisfactory, in contrast to the great progress achieved by the introduction of neuroleptic treatment [7-9, 31] and the application of several psychosocial strategies. According to Kissling [37], this percentage is three times higher than it ought to be. The undertreatment seems to be one major cause for the current high relapse rates in schizophrenia and could be reduced through more consistent relapse prevention [37]. The compliance with neuroleptic treatment is influenced, apart from factors intrinsic to the schizophrenic
Relapse prevention in schizophrenia
process per se, by multiple other determinants as well. The organization of psychiatric services, factors related to medication, the extent of psychosocial education of patients and their relatives [1, 3, 25, 40, 41] and the layman’s prejudice toward treating mental disorders with medication [18] considerably affect compliance. Furthermore, another important factor influencing the success of relapse prevention in schizophrenia is the lack of consistency on treatment strategies among medical doctors [18]. General practitioners and psychiatrists as well often fail to recommend a prophylactic treatment to their schizophrenic patients, or discontinue such a treatment too early [13]. Thus, for many schizophrenic patients the duration of preventive treatment is inadequate or absent [37]. More specifically, only 40–50% of all schizophrenic patients for whom neuroleptic relapse prevention is indicated is prescribed a prophylactic treatment [30, 35], and barely 25% of the patients with a first schizophrenic episode adhere to prevention [14]. This happens more often with patients after the first episode [14], and leads to detrimental effects, because for these patients early prevention of relapse can hamper a long-term poor outcome [6, 16, 26, 27]. The present study aimed at documenting the treatment attitudes and prescribing tactics of neurologistspsychiatrists regarding the prevention of schizophrenic relapse, and checking to what extent these factors relate to their experience, knowledge and personal fears. SUBJECTS AND METHODS The study sample comprised 203 neurologistspsychiatrists (30.6%) out of a total of 673 members of the Hellenic Society of Neurology and Psychiatry, who were asked to fill in anonymously a structured questionnaire. This questionnaire, similar to Kissling’s [37], consisted of a pair of well-defined case histories of schizophrenic patients: one following a first schizophrenic episode and the other after multiple episodes. Respondents were asked to recommend a treatment for both situations. Likewise, they had to note the treatment duration they would usually consider, and the optimal pertinent dose of a classic neuroleptic like haloperidol. They were also asked their opinion about the lower effective neuroleptic dose for prevention of relapse. Additional information was obtained on the patient’s expected compliance after the first and after multiple schizophrenic episodes, the expected prevalence of development of mild and severe tardive dyskiEur Psychiatry 2001 ; 16 : 90–8
91
nesia (TD) and the percentage of relapse rates according to their knowledge of the current literature and their personal experience. The respondents were either in private practice or in the public sector for at least five years. Four groups were formed according to age: group 1 (up to 30 years), group 2 (31–40 years), group 3 (41–50 years) and group 4 (above 51 years). The student t-test (paired and unpaired) was used for comparisons between means (± SEM) and the χ2 was applied for non-parametric variables. To estimate the distribution of frequencies, the mean, median, skewness and kurtosis of the variables, the normality test (Kolmogorow-Smirnof) was used. Multiple linear regression analysis was applied to detect the potential relationship between various dependent and independent variables. RESULTS The majority of subjects were males (males: 135 vs females: 65, P < 0.05). Females were younger than males (in age group 2: females: 55.4% vs males: 47.0%, P < 0.01) and were in psychiatric practice significantly fewer years than males (7.67 ± 0.79 vs 10.34 ± 0.77, P < 0.05). The rate of working hours in private practice/ mental health institutions, the percentage of the neurologic and psychiatric patients’ ratio, and the percentage of schizophrenic patients treated, did not differ between genders. The majority of their practice was psychiatric patients (91.43%), mostly schizophrenics (35%) (table I). Treatment of the first schizophrenic episode During the acute phase of the first paranoid-type schizophrenic episode, with hallucinations but no agitation or disrupting behavior and insomnia, the recommended mean haloperidol dosage was 19.8 ± 11.21 mg/daily, the median 17.50 mg/daily, and the mode 15 mg/daily. The distribution curve exhibited a skewness of 1.41 ± 0.171 and had a kurtosis of 2.769 ± 0.341. Linear regression analysis showed that the recommended haloperidol dosage for the treatment of the first schizophrenic episode related positively to the expected relapse rates and ratio of schizophrenics among patients, and negatively to the percentage of psychiatric patients treated by the respondent (table II). In the event that the psychotic symptoms proved resistant to haloperidol treatment, the majority of the respondents turned to another neuroleptic after 30
92
J.D. Bergiannaki et al.
Table I. Demographic and occupational characteristics of respondents. Number Age group 30–40 years No of years in psychiatric practice Occupation in psychiatric institutions (% of time) Occupation in private practice (% of time) Turnout of psychiatric patients (%) Prevalence of schizophrenic patients (%)
Total
Males
Females
200 100 9.54 ± 0.58 60.84 ± 2.55 37.95 ± 2.52 91.43 ± 1.12 34.83 ± 1.50
135 (67.5%) 64 (47.0%) 10.34 ± 0.77 59.22 ± 3.0 39.04 ± 2.93 91.11 ± 1.4 33.85 ± 1.83
65 (32.5%) 36 (55.4%) 7.67 ± 0.79 65.39 ± 4.77 34.27 ± 4.91 92.03 ± 1.92 37.40 ± 2.65
days. The frequency distribution of the number of days for a change of neuroleptic medication exhibited a normal curve (mean 29.34 ± 1.09 days, median = 30.00, mode = 30, skewness = 1.42 ± 0.171, and kurtosis = 2.77 ± 0.341). Two months after the first schizophrenic episode with paranoid and hallucinatory symptoms and while in remission, the maintenance of neuroleptic treatment for several months, the majority of psychiatrists (85.7%) recommended the maintenance of neuroleptic treatment for several months (figure 1). The gradual tapering of the neuroleptic medication after 2–3 months was proposed by 11.7% of the respondents; only 2.6% would consider discontinuation over a period of 2–3 weeks (figure 1). More precisely, 39.9% of neurologistspsychiatrists would recommend maintenance treatment for up to seven months, 42.9% for up to one year, and 17.35% for a period longer than one year and a half (figure 2). The last group comprised professionals over 40 years of age, who had been active for more than 10 years in the field of psychiatry, worked mostly in mental health institutions (80%), who had treated plenty of schizophrenic patients (75%) and believed that the
Significance P < 0.05 P < 0.01 P < 0.01 Non-significant Non-significant Non-significant Non-significant
patient’s cooperation increases after multiple relapses. Eighty to 90 percent of them were aware of the risk for development of mild or serious tardive dyskinesia (TD) under long-term neuroleptic treatment and used a moderate dose of haloperidol for relapse prevention (mean dose: 22.03 ± 1.89 mg/d). Multiple linear regression analysis showed a positive relationship between the duration of the recommended treatment (in months) and the age group in which the respondent belonged; furthermore, a negative relationship was observed with the expected prevalence of mild reversible tardive dyskinesia five years after initiation of neuroleptic treatment (table III). Almost all respondents (94.9%) prescribed more than one neuroleptic for the prevention of relapse. In case haloperidol was selected for prevention, a minimal dose of 5 mg/daily was prescribed by 46.7% of neurologistspsychiatrists; 37.4% would administer 6–10 mg of haloperidol per day and the remaining 15.9% would prescribe a higher dosage. Linear regression analysis showed that the recommended dosage (in mg/d) of haloperidol used for long-term prevention related negatively to the percentage of expected compliance with
Table II. Treatment of the acute phase of the first schizophrenic episode of paranoid-hallucinatory schizophrenia: linear regression analysis of the recommended haloperidol dosage (mg/day) in relation to several independent variables. Dependent variable: recommended dose of haloperidol (mg/day) Independent variables Sex: (Female: 0 – Male: 1) Age group (1, 2, 3, 4) No of years in psychiatric practice Occupation in private practice (% of time) % of psychiatric patients in treatment % of schizophrenics among patients % of estimated relapse rate after the first schizophrenic episode (according to experience) % of anticipated mild reversible tardive dyskinesia after 5 years of neuroleptic treatment % of expected patient’s cooperation after the first schizophrenic episode Satisfied by present state of relapse prevention in schizophrenia
Regression’s coef. Beta
Significance P
–0.014 –0.036 0.148 0.042 –0.160 0.165 0.176 –0.436 –0.087 –0.076
0.84 0.76 0.21 0.60 0.03 0.04 0.03 0.56 0.25 0.32
Eur Psychiatry 2001 ; 16 : 90–8
Relapse prevention in schizophrenia
93
Figure 1. Percentages of neurologists-psychiatrists (vertical axis) and time elapsed before recommendation of neuroleptic treatment discontinuation (horizontal axis), a), after the first schizophrenic episode and b) after the first relapse.
medication of the schizophrenic patients after the first episode (table IV). First post-relapse period Mental health professionals significantly modified their attitudes towards neuroleptic relapse prevention as soon as a relapse occurred after a one-year remission of the first schizophrenic episode. In this event, the majority of psychiatrists (87.5%) increased the period of neuroleptics (figures 1 and 2) from 10.70 ± 0.60 months after the first episode, to 19.37 ± 1.10 months after the first relapse (P < 0.01). The number of psychiatristsneurologists who did not recommend neuroleptic relapse prevention following both the first schizophrenic episode and the first relapse did not change significantly (33 vs 29) (figure 1). This particular group comprised private practitioners who had few schizophrenics among their clients. They also underestimated the relapse rates both after the first episode and after multiple relapses and were not informed on the relapse rates reported in the literature. Furthermore, they usually administered lower doses of haloperidol during the acute phase of the first schizophrenic episode, and turned earlier to another Eur Psychiatry 2001 ; 16 : 90–8
neuroleptic when no immediate improvement was achieved (table V). According to their personal experience, psychiatristsneurologists reported that the rate of relapse after the first schizophrenic episode was significantly lower than that 5 years after illness onset and multiple relapses (paired t-test 53.33 ± 1.52 vs 60.17 ± 1.70, P < 0.000). No divergence was observed between the relapse rates noted as derived from their personal experience and those actually reported in the literature, either after the first schizophrenic episode (53.06 ± 1.60 vs 53.89 ± 1.33, NS), or after five years of illness and multiple relapses (59.99 ± 1.80 vs 58.66 ± 1.62, NS). The percentage of expected occurrence of mild and reversible tardive dyskinesia after 5 years of continuous neuroleptic administration was significantly higher than that expected for severe and irreversible tardive dyskinesia (14.39 ± 1.026 vs 6.33 ± 0.748, P < 0.000). Concerning the patient’s cooperation after multiple relapses, respondents’ estimations, in mean percentages, were significantly higher than those after the first episode (54.18 ± 1.57 vs 44.97 ± 1.83, P < 0.05). Finally, the majority of neurologists-psychiatrists (54.5%) were not satisfied with the present state of relapse prevention in
94
J.D. Bergiannaki et al.
Figure 2. Percentages of neurologists-psychiatrists (vertical axis), and duration of maintenance neuroleptic treatment (horizontal axis), a) after the first schizophrenic episode, and b) after the first relapse.
schizophrenia. All of them (97.5%) believe that compliance with treatment may improve by way of educational actions. DISCUSSION The aim of the present study was to assess the attitudes of neurologists-psychiatrists pertaining to the treatment of schizophrenic patients, with a specific focus on the recommended dosage and maintenance treatment with neuroleptics for prevention of relapse. First, it is
difficult to form a clear opinion about treatment attitudes towards the schizophrenic patient, because psychiatrists adjust their treatment to the particularities of any individual case. The presentation of identical case reports to all interviewed neurologists-psychiatrists allowed differences in prescribing tactics to be more adequately identified [37], and permitted reliable comparisons with the questionnaires administered by other investigators [12, 36]. In our sample males were overrepresented, reflecting the composition of the enlisted members of the Hel-
Table III. Two months after full remission of the first schizophrenic episode with paranoid and hallucinatory symptoms: linear regression analysis of the duration (in months) of the recommended neuroleptic preventive treatment in relation to several independent variables. Dependent variable: duration (in months) of recommended neuroleptic preventive treatment after the first schizophrenic episode Independent variables Regression’s coef. Significance Beta P Sex: (Female: 0 – Male: 1) Age group (1, 2, 3, 4) No of years in psychiatric practice Occupation in psychiatric institutions (% of time) % of schizophrenics among patients % of estimated relapse rate after the first schizophrenic episode (according to experience) % of expected patient’s cooperation after the first schizophrenic episode % of anticipated mild reversible tardive dyskinesia (TD) after 5 years of neuroleptic treatment
0.067 0.274 0.063 0.160 0.036 0.047 –0.021 –0.164
0.43 0.01 0.52 0.64 0.67 0.58 0.80 0.04
Eur Psychiatry 2001 ; 16 : 90–8
95
Relapse prevention in schizophrenia
Table IV. Post-remission phase after the first schizophrenic episode: linear regression analysis of the recommended minimal dosage of haloperidol (mg/day) for relapse prevention in relation to several independent variables. Dependent variable: recommended minimal dose of haloperidol (mg/day) Independent variables
Regression’s coef. Beta
Significance P
0.004 0.137 0.029 0.184 0.063 –0.066 –0.192 –0.068
0.95 0.16 0.75 0.50 0.46 0.42 0.01 0.39
Sex: (Female: 0 – Male: 1) Age group (1, 2, 3, 4) No of years in psychiatric practice Occupation in psychiatric institutions (% of time) % of schizophrenics among patients % of estimated relapse rate after the first schizophrenic episode (according to experience) % of expected patient’s cooperation after the first schizophrenic episode % of anticipated mild reversible tardive dyskinesia (TD) after 5 years of neuroleptic treatment
lenic Society for Neurology and Psychiatry up to 1994 (males: 75.9% vs females: 24.1%). Males were older than females on the average, a difference reflecting the predilection of Greek female medical doctors for the psychiatric specialty during the last two decades. However, according to our results, age and gender did not influence significantly the treatment attitudes of respondents (tables II-IV). The decision on the optimal dosage of an antipsychotic agent for treatment of the acute schizophrenic episode is quite difficult [26]. More than half of the respondents would recommend for management of the first schizophrenic episode with paranoid and hallucinatory symptoms a mean dose of 20 mg/d of a classic neuroleptic like haloperidol. This dosage is within the range proposed by the PORT treatment recommenda-
tion [39], but it is somewhat higher than the one reported by Baldessarini et al. [2]. However, the frequencies distribution curve of haloperidol dosage in our sample was normal, suggesting a considerable agreement in the prescribing tactics. The choice of unusually high doses of haloperidol was characteristic of neurologists-psychiatrists who did not attend to many psychiatric patients. This observation illustrates the difficulty of medical doctors lacking adequate experience to appropriately treat the schizophrenic patient. Whenever the psychotic symptoms proved to be resistant to haloperidol, the majority of professionals turned to another medication within 30 days, a practice that is in accordance with the established norm [44]. Although Greek respondents maintained the preventive treatment for numerous months following the first
Table V. Characteristics of psychiatrists who do not modify their treatment attitudes (no modification), compared to psychiatrists who modify/extend their preventive treatment (modification), following the first relapse after a year of full and stable remission of a first episode of paranoid-hallucinatory schizophrenia.
% of relapse after the first schizophrenic episode (according to experience) % of relapse after the first schizophrenic episode (according to literature) % of relapse after multiple episodes (according to experience) % of relapse after multiple episodes (according to literature) % of expected mild–reversible tardive dyskinesia after 5 years of neuroleptic treatment % of expected severe tardive dyskinesia after 5 years of neuroleptic treatment Recommended dosage of haloperidol (mg/day) during the acute phase of the first schizophrenic episode Days elapsed before turning to another neuroleptic No of years in psychiatric practice Occupation in private practice (% of time) Occupation in psychiatric institutions (% of time) Turnout of psychiatric patients (%) Prevalence of schizophrenic patients (%) Eur Psychiatry 2001 ; 16 : 90–8
No modification N = 29
Modification N = 174
Significance P
26.33 ± 5.31 39.64 ± 4.27 31.88 ± 6.34 43.67 ± 5.51 12.94 ± 3.88 6.00 ± 1.49 11.35 ± 2.13
55.38 ± 1.48 55.22 ± 1.35 62.20 ± 1.66 60.66 ± 1.66 15.20 ± 1.14 6.36 ± 0.81 20.52 ± 0.82
P < 0.01 P < 0.01 P < 0.01 P < 0.01 Non-significant Non-significant P < 0.01
20.65 ± 3.60 10.59 ± 1.73 66.47 ± 8.18 30.81 ± 7.47 89.59 ± 4.15 25.94 ± 4.43
30.14 ± 1.12 9.44 ± 0.61 35.22 ± 2.57 34.39 ± 2.57 91.61 ± 1.16 35.65 ± 1.57
P < 0.01 P < 0.01 P < 0.01 Non-significant P < 0.01 P < 0.01
96
J.D. Bergiannaki et al.
schizophrenic episode, they did not meet the standards of the consensus of Bruges [38] and the PORT treatment recommendations [39], which propose treatment maintenance for 1–2 years after the first episode, and for at least 5 years after multiple episodes [56]. According to our results, the more experienced professionals, who worked at psychiatric institutions and had attended to a large number of schizophrenics, were in tune to the above international standards. The recommended duration of treatment was in negative relation to the expected prevalence of moderate tardive dyskinesia and in positive relation to the age of the respondent. This finding points out that the worry of emergence of side effects was greater among younger psychiatrists who curtail the duration of preventive treatment. This is in agreement with a previous study that holds that the main reason for the widespread nonconforming of doctors to the above standards is due to underestimation of the relapse risk for untreated schizophrenics and overestimation of the potential risks of side effects [37]. It is well known that side effects, i.e., heavy sedation, anticholinergic effects and dystonias [29, 53, 57] need to be minimized to enhance compliance and prevent relapse [5, 48]. Therefore, our findings imply that systematic information on the actual prevalence of TD could improve prophylactic treatment. Inasmuch as atypical neuroleptics have been recently introduced to medical practice, apt information of young psychiatrists and professionals in private practice with limited schizophrenic clientele could be a promising policy for reducing relapse rates. The dosage of haloperidol proposed for prevention subsequent to the first schizophrenic episode was higher than the one reported in American studies [46], but conformed with that reported in European studies [10, 12]. Certain divergences observed within small subgroups of our sample have also been noted by others [12, 32, 37]. These differences obviously reflect the lack of common consent on the relapse risk, as well as the controversies concerning the treatment guidelines for the first schizophrenic episode [4, 6, 24, 28, 43] and the duration of maintenance on neuroleptics [18]. The recommended haloperidol dosage for relapse prevention following remission of the first schizophrenic episode was in negative relation to the expected compliance from the patient. A likely reason for this phenomenon is that the doctor’s urge for a rapid and efficient therapeutic outcome is coupled to poor expectations for adequate compliance and therefore to a precocious treatment discontinuation. This finding is discordant
with the standing treatment guidelines that regard the optimal neuroleptic threshold dosage to be generally fairly adequate for an effective antipsychotic treatment without causing extrapyramidal side effects [46]. Consequently, this practice may be attributed to a sort of ‘reaction formation’ that contributes to the establishment of a ‘vicious circle’ between the expected poor compliance of the patient, the administration of an unexpectedly high dosage of neuroleptics, the development of side effects, and the incitement/sustenance of poor compliance. This phenomenon should be made explicit in any future educational program for psychiatrists, because of the obvious importance for the enhancement of the doctor-patient relationship [11]. It is well known that the optimal dosage and duration of treatment cannot be easily established and that patients at low risk for relapse following neuroleptic withdrawal cannot be safely identified [54]. The fact that the first schizophrenic relapse modified the attitudes of the majority of the psychiatrists-neurologists with respect to neuroleptic relapse prevention indicates that this is a potentially self-resolved problem. According to our results the respondents who did not change their treatment attitudes after the first relapse consisted of a minority with limited experience with schizophrenic patients and poor knowledge of the relevant treatment and relapse risk (table V). Moreover, the majority of respondents were well informed on the actual relapse rates for the first schizophrenic episode, which were in accordance with those reported by previous studies [6, 33, 49]. Conversely, they underestimated the relapse rates after multiple episodes compared to those accounted for in the literature [23, 49]. The reason apparently was lack of adequate information. Besides, the respondents were aware of the actual prevalence rates of mild and severe tardive dyskinesia as reported elsewhere [17, 31, 34, 42]. Finally, the estimated percentage of cooperation and compliance of patients after the first schizophrenic episode was similar to that reported by other investigators [51]; the reported increase of these percentages after multiple relapses was in partial agreement with previous studies [15]. CONCLUSION The majority of Greek neurologists-psychiatrists seem to hold views and take up attitudes towards relapse prevention that approximate the current international standards. Divergences were identified in particular subgroups composed of respondents oriented to private Eur Psychiatry 2001 ; 16 : 90–8
Relapse prevention in schizophrenia
practice, active both in the fields of neurology and psychiatry, and less informed on the current scientific literature. The attitudes of medical doctors regarding the treatment and prevention of relapse of the first schizophrenic episode were determined by the anticipated rate of relapse and treatment compliance after the first episode; the expected prevalence of extrapyramidal side effects after long-term neuroleptic prevention; the knowledge of current literature on the topic; and personal experience of attending to schizophrenic patients. In this context, continuing educational programs addressing the issue of the actual risk of side effects, especially designed for young professionals and those working in private practice, could prove to be particularly useful in improving everyday psychiatric practice and patient compliance.
13 14 15 16 17 18 19 20
ACKNOWLEDGEMENTS This study was partly supported by a grant by Lundbeck Hellas SA (1995). REFERENCES 1 Angermeyer MC, Siara CS. Effects on assassination attempts on Lafontaine and Schauble on public opinion about psychiatric patients. Part 2: 1991 development. Nervenarzt 1994 ; 65 (Suppl 382) : 49-56. 2 Baldessarini RJ, Cohen BM, Teicher MH. Significance of neuroleptic dose and plasma levels in the pharmacological treatment of psychoses. Arch Gen Psychiatry 1988 ; 45 : 79-91. 3 Baüml J, Kissling W, Meurer C, Wais A, Lauter H. Informationszentrierte Angehörigengruppen zur Complianceverbesserung bei schizophrenen Patienten. Psychiat Prax 1991 ; 18 : 48-54. 4 Bleuler M. The schizophrenic disorders–long-term patient and family studies. New Haven: Yale University Press; 1978. 5 Citrome L. New antipsychotic medications: what advantages do they offer? Postgrad Med 1997 ; 101 : 207-10. 6 Crow TJ, McMillan JF, Johnson AL, Johnstone EC. The Northwick Park study of first episodes of schizophrenia: II. A randomized controlled trial of prophylactic neuroleptic treatment. Br J Psychiatry 1986 ; 148 : 120-7. 7 Davis JM. Overview: maintenance of therapy in psychiatry. Am J Psychiatry 1975 ; 132 : 1237-45. 8 Davis JM. Antipsychotic drugs. In: Kaplan HI, Freedman AM, Sadock BJ, Eds. Comprehensive textbook of psychiatry. 3rd ed. Baltimore: Williams and Wilkins; 1980. p. 2257-89. 9 Davis J. Maintenance medication. In: Barnes TRE, Ed. Depot neuroleptics: a consensus. London: Mediscript; 1988. p. 47-52. 10 Denker SJ, May PRA. The treatment of acute psychosis. Copenhagen: Lundbeck; 1986. 11 Fenton WS, Blyler CR, Heinssen RK. Determinants of medication compliance in schizophrenia: empirical and clinical findings. Schizophr Bull 1997 ; 23 : 637-51. 12 Fleischhacker WW, Meise U. The current status of maintenance treatment in schizophrenia. In: Kissling W, Ed. GuideEur Psychiatry 2001 ; 16 : 90–8
21 22 23 24
25
26 27
28 29 30 31 32
33 34
97
lines for neuroleptic relapse prevention in schizophrenia. New York: Springer-Verlag; 1991. p. 13-5. Gäbel W. Towards the improvement of compliance: the significance of psycho-education and new antipsychotic drugs. Int Clin Psychopharmacol 1997 ; 12 (Suppl 1) : S37-S42. Gäbel W, Pietzcker A. Indikation zur neuroleptischen Langzeitmedikation – standardverfahren oder individualprognostisch geleitete Intervention? Nervenarzt 1983 ; 54 : 467-76. Gäbel W, Pietzcker A. One-year outcome of schizophrenic patients – the interaction of chronicity and neuroleptic treatment. Pharmacopsychiatry 1985 ; 18 : 235-9. Gäbel W, Marder S. Conclusions and treatment recommendations for the acute episode in schizophrenia. Int Clin Psychopharmacol 1996 ; 11 (Suppl 2) : 93-100. Gerlach J, Casey DE. Tardive dyskinesia. Acta Psychiatr Scand 1988 ; 77 : 369-78. Gjerris A, Kissling W. Concluding remarks. Acta Psychiatr Scand 1994 ; 89 (Suppl 382) : 93. Gmür M, Tschopp A. Die Behandlungskontinuität bei schizophrenen Patienten in der Ambulanz. Eine Fünfjahresnachuntersuchung. Nervenarzt 1988 ; 59 : 727-30. Guenther V, Meise U. Compliance – Ein Komplexes Problem. Wien Med Wochenschr 1990 ; 140 : 265-9. Gunderson JG, Mosher LR. The cost of schizophrenia. Am J Psychiatry 1975 ; 132 : 901-6. Hall W, Goldstein G, Andrews G, Lapsley H, Bartels R, Silove D. Estimating the economic costs of schizophrenia. Schizophr Bull 1985 ; 11 : 598-610. Hogarty GE, Goldberg SC, Collaborative Study Group. Drug and sociotherapy in the aftercare of schizophrenic patients: one year relapse rates. Arch Gen Psychiatry 1974 ; 28 : 54-64. Hogarty GE. Resistance of schizophrenic patients to social and vocational rehabilitation. In: Dencker SJ, Kulhanek F, Eds. Treatment resistance in schizophrenia. Wiesbaden: Braunschweig; 1988. Hornung WP, Kieserg A, Feldmann R, Buchkremer G. Psychoeducational training for schizophrenic patients: background, procedure and empirical findings. Patient Educ Couns 1996 ; 29 : 257-68. Janicak PG, Davis JM. Antipsychotic dosing strategies in acute schizophrenia. Int Clin Psychopharmacol 1996 ; 11 (Suppl 2) : 35-40. Johnstone EC, Crow TJ, Johnson AL, Macmillan JF. The Northwick Park study of first episodes of schizophrenia. I. Presentation of the illness and problems relating to admission. Br J Psychiatry 1986 ; 148 : 115-20. Johnstone EC, Geddes J. How high is the relapse rate in schizophrenia? Acta Psychiatr Scand 1994 ; 89 (Suppl 382) : 6-10. Kane JM. Problems of compliance in the outpatient treatment of schizophrenia. J Clin Psychiatry 1983 ; 1 : 3-6. Kane JM. Compliance issues in outpatient treatment. J Clin Psychopharmacol 1985 ; 5 : 225-75. Kane JM. Treatment of schizophrenia. Schizophr Bull 1987 ; 13 : 133-56. Kane JM. Dosage and route of administration of neuroleptic drugs during different phases of a schizophrenic illness. In: Kissling W, Ed. Guidelines for neuroleptic relapse prevention in schizophrenia. New York: Springer-Verlag; 1991. p. 85-93. Kane JM, Rifkin A, Quitkin F, Naya D, Ramos-Lorenzi J. Fluphenazine versus placebo in patients with remitted acute first episode schizophrenia. Arch Gen Psychiatry 1982 ; 39 : 70-3. Kane JM, Woerner M, Borenstein M, Wegner J, Lieberman J. Integrating incidence and prevalence of tardive dyskinesia. Psychopharmacol Bull 1986 ; 22 : 254-8.
98
J.D. Bergiannaki et al.
35 Kissling W. Depot neuroleptics – a step forward? Consensus regarding indication for prophylactic neuroleptic treatment – necessary, but unattainable? In: Barnes TRE, Ed. Depot neuroleptics: a consensus. London: Mediscript; 1988. p. 41-6. 36 Kissling W, Ed. Guidelines for neuroleptic relapse prevention in schizophrenia. Berlin: Springer-Verlag; 1991. 37 Kissling W. Compliance, quality assurance and standards for relapse prevention in schizophrenia. Acta Psychiatr Scand 1994 ; 89 (Suppl 382) : 16-24. 38 Kissling W, Kane JM, Barnes TRE, Dencker SJ, Fleischhacker WW, Goldstein MJ, et al. Guidelines for neuroleptic relapse prevention in schizophrenia: towards a consensus view. In: Kissling W, Ed. Guidelines for neuroleptic relapse prevention in schizophrenia. New York: Springer-Verlag; 1991. p. 15563. 39 Lehman AF, Steinwachs DM. Survey Co-Investigators of the PORT Project. Patterns of usual care for schizophrenia: initial results from the schizophrenia patient outcomes research team (PORT) client survey. Schizophr Bull 1998 ; 24 : 11-20. 40 Lewandowski L, Buchkremer G. Therapeutische Gruppenarbeit mit Angehörigen schizophrener Patienten. Z Klin Psychol 1988 ; 17 : 210-24. 41 Mantonakis J, Markidis M, Kontaxakis V, Liakos A. A scale for detection of negative attitude towards medication among relatives of schizophrenic patients. Acta Psychiatr Scand 1985 ; 2 : 186-9. 42 Marsden CD. Is tardive dyskinesia a unique disorder? In: Casey DE, Chase TN, Christensen AV, Gerlach J, Eds. Dyskinesia – research and treatment. (Psychopharmacology series, vol. 2.). Berlin: Springer; 1985. 43 Marder SR. The role of dosage and plasma levels in neuroleptic relapse prevention. Acta Psychiatr Scand 1994 ; 89 (Suppl 382) : 25-7. 44 Marder SR. Pharmacological treatment strategies in acute schizophrenia. Int Clin Psychopharmacol 1996 ; 11 (Suppl 2) : 29-34. 45 Maurer K, Biehl H. Klinikaufenthalte und produktive Rückfalle bei ersterkrankten Schizophrenen. Nervenheilkunde 1988 ; 7 : 279-90.
46 McEnvoy JP, Hogerty GE, Steingard S. Optimal dose of neuroleptics in acute schizophrenia: a controlled study of the neuroleptic threshold and higher haloperidol dose. Arch Gen Psychiatry 1991 ; 48 : 739-45. 47 McGlashan TH. A selective review of recent North America long-term follow-up studies of schizophrenia. Schizophr Bull 1988 ; 14 : 515-42. 48 Meise U, Fleischhacker WW. Perspectives on treatment needs in schizophrenia. Br J Psychiatry 1996 ; 168 (Suppl 29) : 9-16. 49 Müller P, Ed. Zur Rezidivprophylaxe Schizophrener Psychosen. Stuttgart: Enke; 1982. 50 Pietzcker A. Neuroleptische Langzeit-Medikation in der ambulanten Behandlung schizophren Kranker. Hamburg: Promonta Schriften; 1987. 51 Rabiner CJ, Wegner JT, Kane JM. Outcome study of first episode psychosis: I. Relapse rates after one year. Am J Psychiatry 1986 ; 143 : 1155-8. 52 Rice DP, Kelman S, Miller LS. The economic burden of mental illness. Hosp Community Psychiatry 1992 ; 43 : 1227-32. 53 Rifkin A. A historical review of the adverse reactions to neuroleptic agents. J Clin Psychiatry 1987 ; 3 (Suppl 48) : 6. 54 Sheitman BB, Lee H, Strauss R, Lieberman JA. The evaluation and treatment of first-episode psychosis. Schizophr Bull 1997 ; 23 : 653-61. 55 Shepherd M, Watt D, Falloon I, Smeeton N. The natural history of schizophrenia: a five-year follow-up study of outcome and prediction in a representative sample of schizophrenia. Psychol Med Monogr Suppl 15. Cambridge: Cambridge University Press; 1989. 56 Tegeler J. Maintenance neuroleptic treatment in schizophrenia. In: Kissling W, Ed. Guidelines for neuroleptic relapse prevention in schizophrenia. New York: Springer-Verlag; 1991. p. 34-7. 57 Van Putten T. Why do schizophrenic patients refuse to take their drugs? Arch Gen Psychiatry 1974 ; 31 : 67-72.
Eur Psychiatry 2001 ; 16 : 90–8