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Tampere School of Public Health, University of Tampere and Department of Psychiatry, Tampere University Hospital, Tampere
National Public Health Institute, Helsinki
Social Insurance Institution, Helsinki
National Research and Development Centre for Welfare and Health, Helsinki, Finland
Correspondence: Dr Matti Joukamaa, Department of Social Psychiatry, Tampere School of Public Health, University of Tampere, FIN-33014, Finland. E-mail: matti.joukamaa{at}uta.fi
See invited commentary, p.
128, this issue. 
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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Aims Schizophrenia and its treatment with neuroleptics were studied
for their prediction of mortality in a representative population sample of
7217 Finns aged 
30 years.
Method A comprehensive health examination was carried out at baseline. Schizophrenia was determined using the Present State Examination and previous medical records.
Results During a 17-year follow-up, 39 of the 99 people with schizophrenia died. Adjusted for age and gender, the relative mortality risk between those with schizophrenia and others was 2.84 (95% CI 2.06–3.90), and was 2.25 (95% CI1.61–3.15) after further adjusting for somatic diseases, bloodpressure, cholesterol, body mass index, smoking, exercise, alcohol intake and education. The number of neuroleptics used at the time of the baseline survey showed a graded relation to mortality. Adjusted for age, gender, somatic diseases and other potential risk factors for premature death, the relative risk was 2.50 (95% CI1.46–4.30) per increment of one neuroleptic.
Conclusions There is an urgent need to ascertain whether the high mortality in schizophrenia is attributable to the disorder itself or the antipsychotic medication.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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METHOD |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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The participants were first interviewed at home by local public health nurses and examined 1–6 weeks later by the Mobile Clinic of the Social Insurance Institution (SII) in two phases: a screening phase and a diagnostic (clinical) phase. The measurements of the screening phase, the methods used for studying chronic diseases and the basic results of the Mini-Finland Health Survey have been previously described in detail (Aromaa et al, 1989; Mäkelä et al, 1993). People with a disease history, symptoms or findings suggestive of chronic diseases were asked to participate in the diagnostic (clinical) phase, which was on average 3.5 months after the screening examination. Cardiovascular and respiratory diseases, diabetes and other somatic conditions were diagnosed on the basis of medical history, symptoms, physical examination and findings of the screening phase (Aromaa et al, 1989; Mäkelä et al, 1993).
Screening procedure
The methods used and the basic findings concerning mental disorders in the
Mini-Finland Health Survey have been described in detail elsewhere (Lehtinen
et al,
1990a,b).
The screening for mental disorders comprised several parts. We tried to make
the screen as sensitive as possible in order to minimise the number of
false-negative cases, as no screen-negative people were invited to participate
in the clinical phase of the study. The most important part of the screen was
the 36-item version of the General Health Questionnaire
(Goldberg, 1972). People were
also invited to participate in the clinical phase if the records in the SII
indicated that they were receiving a disability pension because of a mental
disorder or were entitled to reimbursement for medication for such disorders
(according to the National Health Insurance Scheme in Finland, all psychoses
entitle the individual to free medication for their treatment). People were
also selected if they reported having used health services (including those
provided by a general practitioner) for a mental disorder or there was a
self-perceived mental disorder. A total of 35% of those who participated in
the screening phase were identified by various screening instruments; 95% of
these agreed to participate in the clinical phase of the health
examination.
Case-finding procedure
The most important method of psychiatric case identification in the
clinical phase was use of the short version of the ninth edition of the
Present State Examination (PSE; Wing
et al, 1974), which was administered by a psychiatric
nurse. Training in the use of the PSE was provided by those who developed the
method. The diagnoses were obtained via the computer program CATEGO–ID
(Wing et al, 1978).
Diagnostic information was also obtained from: case notes of participants in
in-patient psychiatric care; SII records on disability pensions granted
because of a mental disorder and on reimbursement for medication to treat
psychoses; examination by the physician in the clinical phase of the survey;
and assessment by the psychiatric nurse conducting the PSE interview. A panel
of two psychiatrists reviewed the case notes of in-patients and the
psychiatric records entitling individuals to SII benefits (disability pensions
and reimbursement for medicines) to validate the diagnoses. For the final
diagnostic assessments, a special computer program was designed that combined
information from various sources, taking into account the degree of certainty
and eliminating mutually incompatible assessment combinations. There were 99
people with a diagnosis of schizophrenia, giving an age-adjusted prevalence of
1.3% with no gender difference (Lehtinen
et al, 1990a); this was in accordance with an
earlier population study in Finland
(Vaisanen, 1975).
The mortality of those examined has been systematically monitored since the baseline assessment. This information was obtained from the Central Statistical Office of Finland. The principal causes of death were coded according to ICD–8 (World Health Organization, 1974). During a follow-up from 1978 until 1994 the numbers of deaths (in parentheses deaths of people with schizophrenia) were as follows (see Joukamaa et al, 2001): a total of 1597 (39) deaths occurred; 876 (17) were caused by any cardiovascular disease; 130 (8) by respiratory diseases; 341 (7) by cancers; 72 (2) by injuries; and 20 (2) by suicides.
The definitions and measurement of lifestyle and related factors (level of education, exercise, smoking, alcohol intake, body mass index, systolic and diastolic blood pressure, serum total and high-density lipoprotein (HDL) cholesterol) have been described in more detail elsewhere (Aromaa et al, 1989; Mäkelä et al, 1993). Participants were asked about drugs prescribed by their physician. The use of neuroleptic drugs among people with schizophrenia was also recorded in the screening phase and was categorised according to the number prescribed. At the time of the baseline assessment the following conventional neuroleptics were the only neuroleptic drugs in use in Finland: phenothiazines with an aliphatic side-chain (promazine, chlorpromazine, levomepromazine); phenothiazines with a methylpiperazine side-chain (thioproperazine, trifluoperazine); phenothiazines with a piperazine-ethanol side-chain (perphenazine, fluphenazine, thiopropazate); phenothiazines with a piperidine side-chain (thioridazine, pericyazine, pipotiazine); thioxanthenes (chlorprothixene, clopenthixol, flupenthixol, thiothixene); butyrophenones (haloperidol, melperone, moperone); piperazines (pimozide); benzamides (sulpiride); and indoles (oxyperine).
A number of factors may be associated both with schizophrenia and mortality and could therefore confound the analysis. Age, gender, level of education, smoking, alcohol intake, exercise, body mass index, systolic and diastolic pressure, serum total and HDL cholesterol, diabetes, cardiovascular and respiratory diseases and other somatic diseases were therefore considered potential confounders or effect modifiers in the present study (Brown, 1997; Mortensen, 2003).
Statistical analysis
Logistic regression was used to estimate the associations between the
potential confounding and effect-modifying factors and the prevalence of
schizophrenia. The general linear model was used to compute multiple partial
correlation ratios between those factors and the number of neuroleptic drugs
among participants with schizophrenia. Cox’s proportional hazards
regression model (Cox, 1972)
was used to estimate the strength of the association between schizophrenia and
mortality and between neuroleptic drug use for schizophrenia and mortality.
The number of neuroleptic drugs for schizophrenia was included both as a
categorical variable and as a continuous variable in the model. Potential
confounding and effect-modifying factors were entered into the Cox models.
Adjusted relative risks and their 95% confidence intervals (CIs) were
estimated based on this model. The SAS software package version 6.12
(SAS Institute, 1997) was
used.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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The age- and gender-adjusted relative risk of total mortality between people with schizophrenia and others was 2.84 (95% CI 2.06–3.90). The risk of mortality was increased among people with schizophrenia even after controlling for potential risk factors for premature death (low level of education, smoking, alcohol intake, exercise, body mass index, systolic and diastolic pressure, and total and HDL cholesterol) and coexistent somatic diseases (Table 3). As there was no difference between men and women in the association between schizophrenia and mortality, they were combined in these analyses.
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There were only four unnatural deaths among those with schizophrenia. Adjusted for age and gender, the relative risk of natural death between people with schizophrenia and others was 2.80 (95% CI 2.00–3.93).
Of the 99 people with schizophrenia, 20 were taking no neuroleptic drug at baseline, 31 one drug, 34 two drugs and 14 three or more drugs. The most commonly used neuroleptic was thioridazine (34%), followed by perphenazine (20%), chlorpromazine (19%), levomepromazine (14%), chlorprothixene (13%) and haloperidol (12%); use of other neuroleptics was less than 10%. Among participants with schizophrenia, there was a strong inverse relationship between serum HDL cholesterol and the number of neuroleptic drugs prescribed (correlation coefficient=–0.41, P<0.001) that remained statistically significant after adjustment for age, gender, all lifestyle-related factors and coexistent somatic diseases (partial correlation=–0.31, P=0.007). Smoking was also associated with the number of neuroleptics prescribed (correlation coefficient=0.35, P=0.007), but the association did not reach statistical significance in the multifactorial analysis (partial correlation=0.27, P=0.14).
The number of neuroleptic drugs prescribed at the time of the baseline survey was related to the subsequent mortality. Of people with schizophrenia taking one, two and three or more neuroleptic drugs, 11 (35%), 15 (44%) and 8 (57%) respectively died during follow-up, whereas the corresponding rate was 5 (20%) among those without neuroleptic medication. Table 4 shows the relative risk of dying among those with schizophrenia per increment of one neuroleptic drug adjusted for age, gender, lifestyle-related factors and chronic somatic diseases. Irrespective of the factors modelled, the relationship between number of neuroleptic drugs and mortality remained strong and statistically significant.
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To assess the combined effect of schizophrenia and the number of neuroleptic drugs in the whole of the study population, the 68 people taking neuroleptics for other psychoses were excluded. Adjusted for age and gender, people with schizophrenia taking no neuroleptic, one, two and three or more neuroleptic drugs had relative risks (95% CI) of 1.29 (0.53–3.11), 2.97 (1.64–5.38), 3.21 (1.93–5.35) and 6.83 (3.40–13.71) respectively compared with those without schizophrenia or any antipsychotic treatment with neuroleptics. The association remained stable throughout the observation period. Even after excluding the first 10 years of follow-up, the corresponding estimates were 1.69 (0.42–6.80), 4.75 (1.95–11.53), 2.53 (0.63–10.21) and 5.35 (1.33–21.55).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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Although the excess mortality of people with schizophrenia was first demonstrated before the Second World War, the causes have varied over the years, especially before the neuroleptic era (see Brown, 1997). It has been claimed that the contemporary high natural mortality in schizophrenia results from a variety of lifestyle factors (Brown, 1997; Mortensen, 2003). Of these factors we were able to consider several (smoking, exercise, body mass index, blood pressure, serum total and HDL cholesterol), but not all (e.g. dietary factors). However, after adjustment for these factors the excess mortality of people with schizophrenia persisted. Similarly, comorbid somatic diseases did not account for the mortality. Obviously there are other factors associated with mortality in schizophrenia and the association with neuroleptic drugs was very clear. This remained after adjustment for many different potentially confounding factors. At the time of the baseline survey only classic neuroleptic drugs were in use in Finland.
It is now well known that most or all classic neuroleptics can cause prolongation of the QT interval of the electrocardiogram which is associated with the potentially fatal arrhythmia torsade de pointes (Witchel et al, 2003). Recently, in a large study Ray et al (2001) showed that prescription of moderate doses of antipsychotics was associated with large relative and absolute increases in the risk of sudden cardiac death. It has been proposed that antipsychotic drugs might also be associated with venous thrombosis, pulmonary embolism (Thomassen et al, 2001) and asthma mortality (Joseph et al, 1996). These associations could explain at least some of the deaths from respiratory diseases in the present study.
Neuroleptic polypharmacy
The risk of dying increased in our study if the participants were taking
more than one neuroleptic drug. This is in line with previous findings.
Waddington et al
(1998) found that receiving
more than one antipsychotic concurrently was associated with reduced survival
in a 10-year follow-up of 88 people with schizophrenia. In a French study the
mortality among patients with chronic schizophrenia was associated with the
dosage of neuroleptics (Bralet et
al, 2000). Why is more than one neuroleptic drug prescribed?
We can presume that one reason might be the lack of response to a single
antipsychotic, possibly related to the severity of the illness. Is it also
possible that the most severe forms of schizophrenia carry a higher risk of
dying than less severe schizophrenia. However, it must be borne in mind that
antipsychotic polypharmacy can also lead to increased side-effects because of
the potential influence on many receptors in addition to brain D2
dopamine receptors (Waddington et
al, 1998).
If classic neuroleptics were the cause of premature deaths among people with schizophrenia it could be assumed that the excess mortality would have decreased with the introduction of the newer atypical antipsychotics. However, a Swedish study found an increase in mortality in patients with schizophrenia (Osby et al, 2000). The newer atypical antipsychotic agents can affect somatic health in different ways (Wirshing et al, 2003).
Study strengths and limitations
The strengths of the present study included a long follow-up and a
representative sample with a high participation rate. Because of the
comprehensive nature of the Mini-Finland Health Survey we were able to take
many potential confounding factors into account. The main screening instrument
used, the General Health Questionnaire, is most suitable for screening for
non-psychotic psychiatric illnesses such as anxiety and mood disorders.
However, other aspects of our screening procedure, especially review of the
SII records concerning disability pensions and reimbursement for medicines
used to treat severe mental disorders, identified those with psychotic
disorders. Another limitation was that we were not able to define the total
period of neuroleptic use or total dosage or to assess the impact of prior
treatment. In addition, the number of people with schizophrenia was relatively
low, only 99, of whom 39 died during follow-up. In spite of these limitations
we consider the results valid. The association of the use of neuroleptic drugs
and mortality poses questions which could not be answered in this study. A
careful quantitative analysis of the association of neuroleptic drug dosage
and mortality would be especially interesting.
Conclusions
More attention should be paid to the somatic health of people with
schizophrenia. Our results indicate a need to modify the deleterious lifestyle
factors of patients with schizophrenia previously recommended by Brown et
al (2000). The recognition
and medical management of somatic diseases among people with schizophrenia is
a challenge to psychiatrists. Future research needs to determine whether the
high mortality among those with schizophrenia is mainly attributable to the
disorder per se or to the antipsychotic medication. Study of the association
between the newer antipsychotic drugs and mortality in patients with
schizophrenia will be important after a sufficient period of treatment has
elapsed to allow long-term follow-up.
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Clinical Implications and Limitations |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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LIMITATIONS
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...REFERENCES |
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Bralet, M. C., Yon, V., Loas, G., et al (2000) Causes de la mortalité chez les schizophrènes: étude prospective sur 8 ans d’une cohorte de 150 schizophrènes chroniques. Encéphale, 26, 32 –41.[Medline]
Brown, S. (1997) Excess mortality of
schizophrenia. A meta-analysis. British Journal of
Psychiatry, 171, 502
–508.
Brown, S., Inskip, H. & Barraclough, B.
(2000) Causes of the excess mortality of schizophrenia.
British Journal of Psychiatry,
177, 212
–217.
Cox, D. R. (1972) Regression models and life-tables. Journal of the Royal Statistical Society B, 34, 187 –220.
Goldberg, D. P. (1972) The Detection of Psychiatric Illness by Questionnaire. Maudsley Monograph 21. London: Oxford University Press.
Harris, E. C. & Barraclough, B. (1998)
Excess mortality of mental disorder. British Journal of
Psychiatry, 173, 11
–53.
Heilä, H. & Lönnqvist, J. (2003) The clinical epidemiology of suicide in schizophrenia. In The Epidemiology of Schizophrenia (eds R. Murray, P. Jones, E. Susser, et al), pp. 288–316. Cambridge: Cambridge University Press.
Joseph, K. S., Blais, L., Ernst, P., et al (1996) Increased morbidity and mortality related to asthma among asthmatic patients who use major tranquillisers. BMJ, 31, 79 –82.
Joukamaa, M., Heliövaara, M., Knekt, P., et al
(2001) Mental disorders and cause-specific mortality.
British Journal of Psychiatry,
179, 498
–502.
Lehtinen, V., Joukamaa, M., Jyrkinen, E., et al (1990a) Prevalence of mental disorders among adults in Finland. Basic results from the Mini-Finland Health Survey. Acta Psychiatrica Scandinavica, 81, 418 –425.[Medline]
Lehtinen, V., Joukamaa, M., Jyrkinen, E., et al (1990b) Need for mental health services of the adult population in Finland: results from the Mini-Finland Health Survey. Acta Psychiatrica Scandinavica, 81, 426 –431.[Medline]
Mäkelä M., Heliövaara, M., Sievers, K., et al (1993) Musculoskeletal disorders as determinants of disability in Finns aged 30 years or more. Journal of Clinical Epidemiology, 46, 549 –559.[CrossRef][Medline]
Montout, C., Casadebaig, F., Lagnaoui, R., et al (2002) Neuroleptics and mortality in schizophrenia: prospective analysis of deaths in a French cohort of schizophrenic patients. Schizophrenia Research, 57, 147 –156.[CrossRef][Medline]
Mortensen, P. B. (2003) Mortality and physical illness in schizophrenia. InThe Epidemiology of Schizophrenia (eds R. Murray, P. Jones, E. Susser, et al), pp. 275–287. Cambridge: Cambridge University Press.
Osby, U., Correia, N., Brandt, L., et al (2000) Mortality and causes of death in schizophrenia in Stockholm county, Sweden. Schizophrenia Research, 45, 21 –28.[CrossRef][Medline]
Ray, W. A. & Meador, K. G. (2002)
Antipsychotics and sudden death: is thioridazine the only bad actor?
British Journal of Psychiatry,
180, 483
–484.
Ray, W. A., Meredith, S., Thapa, P. B., et al
(2001) Antipsychotics and the risk of sudden cardiac death.
Archives of General Psychiatry,
58, 1161
–1167.
SAS Institute (1997) SAS/STAT Software: Changes and Enhancements through Release 6.12. Cary, NC: SAS Institute.
Thomassen, R., Vandenbroucke, J. P. & Rosendaal, F. R.
(2001) Antipsychotic medication and venous thrombosis.
British Journal of Psychiatry,
179, 63
–66.
Vaisanen, E. (1975) Psychiatric disorders in Finland. Acta Psychiatrica Scandinavica Supplementum, 263, 22 –33.[Medline]
Waddington, J. L., Youssef, H. A. & Kinsella, A.
(1998) Mortality in schizophrenia. Antipsychotic polypharmacy
and absence of adjunctive anticholinergics over the course of a 10-year
prospective study. British Journal of Psychiatry,
173, 325
–329.
Wing, J. K., Cooper, J. E. & Sartorius, N. (1974) The Measurement and Classification of Psychiatric Symptoms. London: Cambridge University Press.
Wing, J. K., Mann, S. A., Leff, J. P., et al (1978) The concept of a case in psychiatric population surveys. Psychological Medicine, 8, 203 –217.[Medline]
Wirshing, D. A., Pierre, J. M., Erhart, S. M., et al (2003) Understanding the new and evolving profile of adverse drug effects in schizophrenia. Psychiatric Clinics of North America, 26, 165 –190.[CrossRef][Medline]
Witchel, H. J., Hancox, J. C. & Nutt, D. J. (2003) Psychotropic drugs, cardiac arrhythmia, and sudden death. Journal of Clinical Psychopharmacology, 23, 58 –77.[CrossRef][Medline]
World Health Organization (1974) Eighth Revision of the International Classification of Diseases and Related Health Problems (ICD–8). Geneva: WHO.
Received for publication October 28, 2004. Revision received March 15, 2005. Accepted for publication May 18, 2005.
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