Division of Psychiatry, University of Manchester
School of Psychological Sciences, University of Manchester
Division of Psychiatry, University of Manchester, UK
Correspondence: Professor Shôn W. Lewis, Division of Psychiatry, University of Manchester, Second Floor, Education and Research Centre, Wythenshaw Hospital, Manchester M23 9LT. E-mail: shon.lewis{at}man.ac.uk
Declaration of interest S.L. has received fees for talks and consultancies from AstraZeneca, BMS, Pfizer, Wyeth, Lilly, Janssen and Novartis. He is an associate director of the UK Mental Health Research Network and a member of the MRC Neuroscience Board.
*Paper presented at the Third International Early Psychosis Conference, Copenhagen, Denmark, September 2002.
![]() |
ABSTRACT |
---|
![]() |
INTRODUCTION |
---|
|
In general, individual psychological treatments have been evaluated in established schizophrenia, where they have been delivered alongside routine care, in particular, drug treatment. There are particular issues in early schizophrenia, some of which parallel drug treatment issues. Are potential longer-term gains greater in first-episode schizophrenia possibly preventing the emergence of more chronic functional deficits? Might they be effective in preventing or postponing first relapse? Are they only effective during the treatment period or do they confer lasting benefit: how long should they be continued? How is it best to integrate drug and psychological treatments? Can psychological treatments ever be an alternative to drug treatments, rather than an adjunct?
![]() |
FAMILY ENVIRONMENT AND FAMILY INTERVENTIONS |
---|
There is now considerable evidence of efficacy for family intervention, including a Cochrane meta-analytical review (Pharoah et al, 2003) and other systematic meta-analyses meta-analyses (e.g. Pitschel-Walz et al, 2001). The main measure of outcome used in family intervention studies has been reduction in relapse rates. The overall effective size in the Cochrane review of randomised, controlled trials (0.2) was smaller than that in interventions of the type described above but it included less effective designs in the analysis. Studies sharing the features described tend to reduce relapse rate by up to 40% compared with controls over follow-up periods of 918 months, representing an effect size of about 0.4. Those who benefit show improved adherence to medication and their families have reduction in expressed emotion. The benefits in some studies (Tarrier et al, 1993) have continued up to 8 years, but diminished over time.
Family interventions in the first episode have not been widely evaluated, although there is good reason to expect that they should be effective (Goldstein, 1996). The most informative trial was that of Lenior et al (2001) who randomised 64 patients with early schizophrenia, 55% in their first episode, to receive family intervention or routine care alone. Relapse rates were reduced during the actual 12-month experimental treatment period, but did not differ significantly between the two groups at 5-year follow-up, although the total time spent in in-patient care was reduced in the family intervention group.
![]() |
SUBSTANCE MISUSE AND MOTIVATIONAL INTERVENTIONS |
---|
The only therapeutic trial of an effective patient-level intervention is that of Barrowclough et al (2001). Here, patients (not first-episode) with dual diagnosis were randomised to routine care or to a psychological treatment package of motivational interviewing directed at reducing the substance misuse, cognitive therapy aimed at psychotic symptom control and family intervention. Motivational interviewing has been used to treat uncomplicated substance dependence. Patients are encouraged to explore the problems their substance misuse causes and the ways in which it prevents them achieving their goals. They are also encouraged to explore how they could address these problems, including reduction in substance misuse, strategies for relapse prevention and possibly engagement with services and use of drugs to reduce craving or block the effects of illicit drugs. The results of the trial showed at 12 months a significant increase in global functioning, and a halving in relapse rates from 56% to 28% in the experimental group (Haddock et al, 2003).
Drake & Mueser (2001) have argued that the most successful programmes share an integrated approach, so that substance misuse interventions, case management, assessment, family education, medication management and social and rehabilitation aspects are related, and all have features that reflect awareness of the special needs of this group. They also involve active monitoring, outreach and gradual engagement.
![]() |
DRUG TREATMENT NON-ADHERENCE AND COMPLIANCE THERAPY |
---|
Kemp et al (1998) used a form of therapy derived from motivational interviewing to enhance adherence to medication. In a clinical trial, patients admitted for acute relapse (not in the first episode) were randomised to receive routine care or routine care plus a brief package of motivational interviewing, adapted for those with schizophrenia and concentrating on ways to treat symptoms, reduce problems and prevent relapse using antipsychotic medication. The experimental group showed clinically and statistically significant reduction in readmission rates and improvements in compliance over 18 months, and improvements in symptoms at the end of therapy but not after 18 months.
![]() |
NEUROCOGNITIVE DEFICITS AND COGNITIVE REMEDIATION |
---|
Cognitive remediation centres on direct remediation of the cognitive deficits that are presumed to lead to symptoms and difficulty in social function (Brenner et al, 1994). For some years this approach has demonstrated limited success, with a failure of any benefits in cognitive function to feed through into improved social function, but recently more refined models of cognitive deficits and improvements in tailoring training to those with schizophrenia have suggested greater benefits may be realised. In a small sample, Wykes et al (1999, 2003) used techniques, such as errorless learning (in which tasks are taught taking care to avoid the subject being confused by making mistakes), scaffolding (where strategies are demonstrated to subjects initially but gradually support is reduced) and massed practice (repeated exercises at least 35 times per week) to produce persistent gains in executive function, memory and self-esteem.
Patterns of cognitive deficit relate to a greater or lesser extent to symptomatology and an extension of cognitive remediation to early schizophrenia may be the targeting of individual deficits that relate to core, emerging symptoms. Poor insight is one important clinical example, where there is mounting evidence of an association with a specific executive neurocognitive task set-shifting. Drake & Lewis (2003) found set-shifting errors involving perseveration to be strongly linked to the core component of poor insight, the inability to relabel symptoms, in a sample with predominantly first-episode psychosis, leading to the proposal that defective self-monitoring contributes both to perseveration and poor insight. Koren and colleagues (Viksman et al, 2002) similarly confirmed that good insight in the first episode was linked to the ability to act appropriately on the basis of self-monitoring. Correction of this deficit might improve insight.
![]() |
EARLY INTERVENTION AND COGNITIVE BEHAVIOURAL THERAPY |
---|
Individual CBT has generated a sizeable body of evidence, although the first trials in this area were undertaken only 10 years ago. The accepted findings are that CBT, if delivered over a period of at least 6 months, will reduce positive and to some extent negative symptoms in otherwise treatment-resistant schizophrenia. In these trials, as with all others so far, CBT has been delivered as an adjunct to drug treatment as usual. A convergence between independent randomised controlled trials in this patient group is striking. Four good quality trials (Tarrier et al, 1993, 1998; Kuipers et al, 1997; Sensky et al, 2000) have used similar inclusion criteria with similar experimental treatments in terms of content and duration. The trials have differed in other respects, particularly the selection and rationale of control interventions and the use or otherwise of blinded assessments of outcome. The effect size for improvement of positive symptoms in these trials is about 0.6. The effect of the intervention extends to improvement in negative symptoms and, in some circumstances, social functioning. In addition, the effect appears to be durable at 69 months post-treatment and beyond. The patient population identified for these trials is closely similar to that used in the earlier clozapine efficacy studies and the effect size, according to systematic review, is not dissimilar (Wahlbeck et al, 2000). An important statistical issue here is that the population and the samples for these trials are selected on the basis of having persistent and stable positive symptoms, so maximising the power of a trial to test the efficacy of an add-on treatment. This statistical advantage may not be present when other patient populations are targeted, such as those with first-episode psychosis or acutely ill patients, or those in remission open to relapse.
The effectiveness of CBT in addition to routine care in first-episode schizophrenia has been evaluated in the SoCRATES trial (Lewis et al, 2002; Tarrier et al, 2004). Taking as its starting point the demonstrated effectiveness of CBT in schizophrenia patients with persistent, treatment-resistant symptoms, the hypotheses of this trial were that CBT, in addition to routine care (drugs), would accelerate resolution of acute symptoms in first-episode schizophrenia, improve 18-month outcomes and delay future relapse. Consecutive first- or second-episode acute inpatient or day patient admissions with DSMIV (American Psychiatric Assocation, 1994) schizophrenia-spectrum psychoses were randomised into the trial from 11 centres. Consenting subjects were randomised within 14 days to one of three treatment arms. The experimental treatment was a 5-week package of CBT, plus three boosters over 3 months, in addition to routine care. A second psychological treatment arm aimed to control for non-specific therapist effects and involved supportive counselling over a similar period plus routine care. The third arm was routine care alone. Outcome assessments were made blind to treatment group and were performed weekly over the first 6 weeks, then at 9 and 18 months.
Interventions were commenced within 3 days of randomisation and in the case of the CBT and supportive counselling were manual-based and supervised. In addition, psychological treatment sessions were audiotaped and rated masked to evaluate and confirm treatment fidelity. The randomised sample for analysis was 309 patients: 101 patients received CBT, 106 received supportive counselling and 102 received routine care alone. The median age of the sample was 27.4 years, 70% were male and 83% were in their first admission. Mean total score on the Positive and Negative Syndrome Scale (PANSS; Kay et al, 1987) at baseline was 87, confirming that this was a severely ill sample. Blind assessments over the first 6 weeks showed a trend towards more rapid resolution of acute symptoms in the CBT groups.
Post hoc analyses confirmed that the CBT group was significantly more improved than the routine care group at 4 weeks on PANSS positive symptom and delusion scale scores, but that this effect had disappeared by 6 weeks (Lewis et al, 2002). Follow-up at 18 months showed that the group who had received CBT in the first 5 weeks had a significantly lower PANSS total score (P=0.03; effect size 0.44) and lower PANSS positive score (P=0.01; effect size 0.43) than the routine care group, after adjusting for baseline score, time to assessment, clinical centre, sex, in-patient v. day patient status, first-v. second-episode psychosis and duration of untreated psychosis at baseline. On the primary outcome measures at 18 months, the supportive counselling group showed symptom scores intermediate between the CBT and routine care groups (Tarrier et al, 2004). Analysis of relapse and readmission rates showed that the experimental treatment had no affect on this measure.
The overall conclusions from this trial were that a brief package of CBT in acute early schizophrenia accelerated improvement in target symptoms but that these gains were lost by 6 weeks, perhaps due to the powerful main effect of routine care, i.e. drug treatment. The intervention also led to improved symptomatic outcomes at 18 months compared with routine care alone. However, these effects were small, although measurable and durable, and there is no effect on time to relapse.
![]() |
THE INTERFACE BETWEEN DRUG AND PSYCHOLOGICAL TREATMENTS |
---|
The generally desirable features of a clinical trial are shown in the Appendix. In general, it can be argued that the ground rules for establishing the effectiveness of psychological treatment should be no different from those used to establish the effectiveness of pharmacological therapy. However, there are a number of challenges in evaluating psychological treatments that are not present in drug trials. Cognitivebehavioural therapy, unlike drug treatment, involves modifying behavioural contingencies and the cognitive architecture.
Looking at specific issues, the use of a double-blind design, as is the benchmark approach in phase III clinical trials of a drug treatment, is not possible with psychological treatments. This makes it more, rather than less, important that when a masked parameter is possible, it is used. There have been debates about whether or not it is possible to maintain masking to treatment allocation when assessing outcome. Because of the known potency of the use of open assessments in introducing bias, it is vital to attempt to use independent, masked assessments of outcome, with assessment of the quality of the masking if possible. In addition, the choice of outcomes should include those which are relatively impervious to the effects of masking, such as relapse, hospitalisation and instrumental outcomes, such as employment status.
The choice of control group in these studies is also important. The choice should be based on the hypothesis of the study and take into account that, in general, psychological treatments are used in addition to treatment as usual, rather than an alternative. The hypothesis in this area is usually that CBT has a specific effect over and above a supportive counselling approach. Ideally, this means the use of two control groups, one controlling for non-specific effects of talking treatments (Lewis et al, 2002).
There has been a trend of late to focus on pragmatic trials in healthcare evaluations generally. These are trials which tend to be large with simple outcomes that solely address the question of effectiveness. It can be argued that in an area such as psychological treatments of psychosis it is vital to derive treatments from a sound theoretical base and build into the trial design an explanatory component to test whether this hypothesised mechanism is actually that which mediates any effect. One example of an alternative explanation would be that the clinical effect of a psychological treatment is actually mediated inadvertently through another therapeutic mechanism, such as improved adherence to drug treatments. Another important issue specific to this area is replicability. With CBT, this typically involves a range of psychological techniques focusing on different aspects of psychopathology. The emphasis, particularly in Europe, is for the approach to be individually tailored according to individual clinical priorities and case formulation (Tarrier & Calam, 2002). In North America, the approach tends to be more a standardised, less flexible, manualised approach. Issues of replicability are important, given this situation. At the very least, the semi-objective demonstration of treatment fidelity, i.e. that the treatment given adheres to a written procedural protocol, is measured and reported.
The prediction of response to the most suitable interventions is one obvious area of further study. Further development of therapies like individual CBT and family intervention in the light of this, and investigation of the processes of therapy are others. Development of cognitive remediation and integration into other methods of social rehabilitation offers some promise. Investigation of compliance therapy and other interventions delivered by other less highly trained staff is important and potentially problematic because of the complex skills needed. Turkington et al (2002) found a CBT programme delivered by trained community nurses to patients and families was effective in a randomised controlled trial. Development of model programmes integrating different approaches is also a current area of research, although the weakness of many of these studies is that it remains unclear which elements of complex programmes, sometimes given to heterogeneous samples, are effective.
Results of trials of psychodynamic therapy have been discouraging (Mueser & Berenbaum, 1990) but a form of psychotherapy designed to address interpersonal and social difficulties without overstimulating patients had mixed success (Hogarty et al, 1997a,b). Relapse rates were reduced for patients living with families, but increased for the remainder. There was some evidence of improved social function over 3 years (although this was not rated with masking) and almost none of symptomatic benefit.
Do drug and psychological treatments enhance each other?
It has been suggested that the effect of family intervention is independent
of medication (Kuipers et al,
1999), but it may be that optimal antipsychotic treatment can
benefit non-drug therapy. Examples exist in the literature of how
psychological treatments can enhance the effect of drug treatments, or vice
versa. A good example of how a psychological treatment can enhance the effect
of a drug treatment in schizophrenia is the compliance therapy trial of Kemp
et al (1998). The
observed reduction in relapse rates in the experimental treatment group was
not due to any direct effect of psychological treatment but rather an improved
efficiency of the pharmacological treatment. Conversely, a good example of how
an antipsychotic drug treatment can enhance the effect of a psychosocial
treatment can be found in the double-blind randomised controlled comparison
between clozapine and haloperidol in treatment-resistant patients
(Rosenheck et al,
1998). This trial confirmed the effectiveness of clozapine
compared with haloperidol using a design where the identity of the drugs was
double-blind and patients allocated to haloperidol treatment received blood
tests to mimic the monitoring system for clozapine. The clinical trial was run
in the context of a mental health service setting where a range of
psychosocial treatments were on offer of varying degrees of complexity. A
post hoc analysis (Rosenheck
et al, 1998) showed that not only were the
clozapine-treated patients more likely to show an improvement in symptoms, but
over the first 12 months of the trial they were progressively more likely to
be able to take up psychosocial treatments of greater complexity. This
represents an example of an effective drug treatment allowing individuals to
use psychological treatments more efficiently. There may be different
expectations after termination of treatment. Relapse after discontinuing drug
treatment implies efficacy of the drug and the need for continual treatment,
whereas release after stopping a psychological treatment implies a failure to
maintain treatment gains.
Can psychological treatments work in the absence of drug treatments?
Psychological interventions have always been investigated as adjuncts to
antipsychotic medication. The evidence for the efficacy of drug treatment is
so well established that it may be ethically dubious to attempt to test
empirically whether psychological treatments on their own are effective. One
new area may throw light on this. A small number of studies have examined the
possibility of detecting individuals in the prodromal stage, prior to the
development of full psychosis. Yung et al
(1998) have developed
operational criteria to identify four subgroups at ultra-high risk of
incipient psychosis. The improved ability to define high risk accurately has
led to the possibility of intervention to prevent psychosis in this group.
Three clinical trials have reported interim or final results. McGorry et al (2002) in Melbourne found that specific pharmacotherapy (low-dose risperidone) plus CBT, in comparison with supportive therapy and case management, reduced the risk of early transition to psychosis in an open, randomised trial of 59 young people at ultra-high risk. There was reduction in progression to psychosis at end of the 6-month treatment, but not at follow-up after a further 6-month period of no treatment. However, the relative contribution of psychotherapy could not be determined since theirs was a combined treatment. Woods et al (2003) at Yale compared olanzapine with placebo double-blind in 60 individuals at ultra-high risk. Interim data at 1 year showed that olanzapine was more effective than placebo in reducing the prodromal symptoms themselves, with a trend towards reduction in transition to psychosis. The Morrison et al (2002) trial in Manchester, UK is an open randomised trial of CBT over 6 months v. monitoring in 58 individuals from the same group at ultra-high risk. Participants were assessed for suitability and monitored on a monthly basis using the PANSS, which was also used to determine transition. Full details regarding entry criteria, study design and treatment protocol have been reported (Morrison et al, 2002). An interim analysis of the rate of transition to psychosis suggested an effect of CBT in reducing transmission and reducing severity of subclinical symptoms (Morrison et al, 2002). This will be, to our knowledge, the first study to attempt to evaluate whether CBT alone is effective in any stage of the psychotic disorder (in this case, preventing the progression of subclinical symptoms in the absence of drug treatment). Combining data from these trials will provide information about the relative acceptability, safety and efficacy of drug and non-drug treatments in this emerging area.
![]() |
CONCLUSIONS |
---|
![]() |
APPENDIX |
---|
![]() |
Clinical Implications and Limitations |
---|
LIMITATIONS
![]() |
REFERENCES |
---|
Amminger, G. P., Edwards, J., Brewer, W. J., et al (2002) Duration of untreated psychosis and cognitive deterioration in first-episode schizophrenia. Schizophrenia Research, 54, 223 230.[CrossRef][Medline]
Arseneault, L., Cannon, M., Poulton, R., et al (2002) Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ, 23, 212 213.[CrossRef]
Barrowclough, C., Tarrier, N., Lewis, S., et al (1999) Randomised controlled effectiveness trial of a needs-based psychosocial intervention service for carers of people with schizophrenia. British Journal of Psychiatry, 174, 505 511.[Abstract]
Barrowclough, C., Haddock, G., Tarrier, N., et al (2001) Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders. American Journal of Psychiatry, 158, 706 713.
Bilder, R. M., Lipschutz, L. B., Reiter, G., et al (1992) Intellectual deficits in first episode schizophrenia: evidence for progressive deterioration. Schizophrenia Bulletin, 18, 437 448.[Medline]
Bilder, R. M., Goldman, R. S., Robinson, D., et al
(2000) Neuropsychology of first episode schizophrenia:
initial characterization and clinical correlates. American Journal
of Psychiatry, 157, 549
559.
Brenner, H., Roder, V., Hodel, B., et al (1994) Integrated Personal Therapy for Schizophrenia Patients. Toronto, Canada: Hogrefe & Huber.
Buckley, P. F., Noffsinger, S. G., Smith, D. A., et al (2003) Treatment of the psychotic patient who is violent. Psychiatric Clinics of North America, 26, 231 272.[CrossRef][Medline]
Byrne, M., Hodges, A., Grant, E., et al (2000) Neuropsychological assessment of young people at high genetic risk for schizophrenia compared with controls: results preliminary findings from the Edinburgh High Risk Study. Psychological Medicine, 29, 1161 1173.[CrossRef]
Butzlaff, R. L. & Hooley, J. M. (1998)
Expressed emotion and psychiatric relapse: a meta-analysis.
Archives of General Psychiatry,
55, 547
552.
Cosway, R., Byrne, M., Clafferty, R., et al (2000) Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study. Psychological Medicine, 30, 1111 1121.[CrossRef][Medline]
Drake, R. E. & Mueser, K. T. (2001) Substance abuse comorbidity. In Comprehensive Care of Schizophrenia. A Textbook of Clinical Management (eds J. A. Lieberman & R. M. Murray). London: Martin Dunitz.
Drake, R. J. & Lewis, S. W. (2003) Insight and neurocognition in acute schizophrenia and related disorders. Schizophrenia Research, 62, 165 173.[CrossRef][Medline]
Drake, R. J., Haley, C. J., Akhtar, S., et al
(2000) Causes and consequences of duration of untreated
psychosis in schizophrenia. British Journal of
Psychiatry, 177, 511
515.
Drake, R. E., Xie, H., McHugo, G. J., et al (2000) The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophrenia Bulletin, 26, 441 449.[Medline]
Erlenmeyer-Kimling, L., Rock, D., Roberts, S. A., et al
(2000) Attention, memory and motor skills as childhood
predictors of schizophrenia related psychoses: the New York High Risk Project.
American Journal of Psychiatry,
157, 1416
1422.
Gaebel, W., Janner, M., Frommann, N., et al (2002) First vs multiple episode schizophrenia: two-year outcome of intermittent and maintenance medication strategies. Schizophrenia Research, 53, 145 159.[CrossRef][Medline]
Goldstein, M. J. (1996) Psycho-education and family treatment related to the phase of psychiatric disorder. International Clinical Psychopharmacology, 11 (suppl. 2), s77 s83.
Green, M. F. (1996) What are the functional consequences of the neurocognitive deficits in schizophrenia? American Journal of Psychiatry, 153, 321 330.[Abstract]
Gumley, A., OGrady, M., McNay, L., et al (2003) Early intervention for relapse in schizophrenia: results of a 12 month randomised controlled trial of CBT. Psychological Medicine, 33, 419 431.[CrossRef][Medline]
Haddock, G., Barrowclough, C., Tarrier, N., et al
(2003) Cognitivebehavioural therapy and motivational
intervention for schizophrenia and substance misuse: 18-month outcomes of a
randomised controlled trial. British Journal of
Psychiatry, 183, 418
426.
Hans, S. L., Marcus, J., Nuechterlein, K. H., et al
(1999) Neurobehavioural deficits at adolescence in children
at risk for schizophrenia. The Jerusalem infant development study.
Archives of General Psychiatry,
56, 741
748.
Harrigan, S. M., McGorry, P. D. & Krstev, H. (2003) Does treatment delay in first-episode psychosis really matter? Psychological Medicine, 33, 97 110.[CrossRef][Medline]
Ho, B. C., Alicata, D., Ward, J., et al
(2003) Untreated initial psychosis: relation to cognitive
deficits and brain morphology in first-episode schizophrenia.
American Journal of Psychiatry,
160, 142
148.
Hogarty, G. E., Greenwald, D., Ulrich, R. F., et al
(1997a) Three-year trials of personal therapy among
schizophrenic patients living with or independent of family, II: effects on
adjustment of patients. American Journal of
Psychiatry, 154, 1514
1524.
Hogarty, G. E., Kornblith, S. J., Greenwald, D., et al
(1997b) Three-year trials of personal therapy among
schizophrenic patients living with or independent of family: I, description of
study and effects on relapse rates. American Journal of
Psychiatry, 154, 1504
1513.
Hutton, S. B., Puri, B. K., Duncan, L. J., et al (1998) Executive function in first episode schizophrenia. Psychological Medicine, 28, 463 473.[CrossRef][Medline]
Joyce, E., Hutton, S., Mutsatsa, S., et al
(2002) Executive dysfunction in first-episode schizophrenia
and relationship to duration of untreated psychosis: the West London Study.
British Journal of Psychiatry,
181 (suppl. 43), s38
s44.
Kay, S. R., Fiszbein, A. & Opler, L. A. (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13, 261 267.[Medline]
Kemp, R., Hayward, P., Applethwaite, G., et al
(1996) Compliance therapy in psychotic patients: randomised
controlled trial. BMJ,
312, 345
349.
Kemp, R., Kirov, G., Everitt, B., et al (1998) Randomised controlled trial of compliance therapy: 18-month follow-up. British Journal of Psychiatry, 172, 413 419.[Abstract]
Kuipers, E., Garety, P., Fowler, D., et al (1997) The LondonEast Anglia randomised controlled trial of cognitivebehavioural therapy for psychosis. I: Effects of the treatment phase. British Journal of Psychiatry, 171, 319 327.[Abstract]
Kuipers, E., Bebbington, P., Pilling, S., et al (1999) Family intervention in psychosis: who needs it? Epidemiologia e Psichiatria Sociale, 8, 169 173.[Medline]
Lenior, M. E., Dingemans, P. M., Linszen, D. H., et al
(2001) Social functioning and the course of early-onset
schizophrenia: five year follow-up of a psychosocial intervention.
British Journal of Psychiatry,
179, 53
58.
Lewis, S., Tarrier, N., Haddock, G., et al
(2002) Randomised controlled trial of
cognitivebehavioural therapy in early schizophrenia: acute-phase
outcomes. British Journal of Psychiatry,
181 (suppl. 43), s91
s97.
Linszen, D. H., Dingemans, P. M. & Lenior, M. E. (1994) Cannabis abuse and the course of recent-onset schizophrenic disorders. Archives of General Psychiatry, 51, 273 279.[Abstract]
McFarlane, W. R., Lukens, E., Link, B., et al (1995) Multiple family groups and psychoeducation in the treatment of schizophrenia. Archives of General Psychiatry, 52, 679 687.[Abstract]
McGorry, P. D., Yung, A. R., Phillips, L. J., et al
(2002) Randomised controlled trial of interventions designed
to reduce the risk of progression to first-episode psychosis in a clinical
sample with subthreshold symptoms. Archives of General
Psychiatry, 59, 921
928.
Mohamed, S., Paulsen, J. S., OLeary, D., et al
(1999) Generalized cognitive deficits in schizophrenia. A
study of first episode patients. Archives of General
Psychiatry, 56, 749
754.
Mojtabai, R., Bromet, E. J., Harvey, P. D., et al
(2000) Neuropsychological differences between first-admission
schizophrenia and psychotic affective disorders. American Journal
of Psychiatry, 157, 1453
1460.
Morrison, A. P., Bentall, R. P., French, P., et al
(2002) Randomised controlled trial of early detection and
cognitive therapy for preventing transition to psychosis in high risk
individuals: Study design and interim analysis of transition rate and
psychological risk factors. British Journal of
Psychiatry, 181 (suppl. 43), 78
84.
Mueser, K.T. & Berenbaum, H. (1990) Psychodynamic treatment of schizophrenia: is there a future? Psychological Medicine, 20, 253 262.[Medline]
Norman, R. M. G., Lewis, S.W. & Marshall, M. (2005) Duration of untreated psychosis and its relationship to clinical outcome. British Journal of Psychiatry, 187 (suppl. 48), s19 s23.[CrossRef]
Pharoah, F. M., Mari, J. J. & Streiner, D. (2003) Family intervention for schizophrenia. Cochrane Database of Systematic Reviews, (2), CD000088 .
PilschelWalz, G., Leucht, S., Bauml, J., et al (2001) The effect of family interventions on relapse and rehospitalisation in schizophrenia a meta-analysis. Schizophrenia Bulletin, 27, 73 92.[Medline]
Remington, G., Kapur, S. & Zipursky, R. B. (1998) Pharmacotherapy of first-episode schizophrenia. British Journal of Psychiatry, 172 (suppl. 33), s66 s70.
Riley, E. M., McGovern, D., Mockler, D., et al (2000) Neuropsychological functioning in first episode psychosis evidence of specific deficits. Schizophrenia Research, 43, 47 55.[CrossRef][Medline]
Rosenheck, R., Tekell, J., Peters, J., et al
(1998) Does participation in psychosocial treatment augment
the benefit of clozapine? clozapine? Archives of General
Psychiatry, 55, 618
625.
Rund, B. R. (1998) A review of longitudinal studies of cognitive functions in schizophrenia patients. Schizophrenia Bulletin, 24, 425 435.[Medline]
Scully, P. J., Coakley, G., Kinsella, A., et al (1997) Psychopathology, executive (frontal) and general cognitive impairment in relation to duration of initially untreated vs subsequently treated psychosis in chronic schizophrenia. Psychological Medicine, 27, 1303 1310.[CrossRef][Medline]
Sellwood, W., Barrowclough, C., Tarrier, N., et al (2001) Needs-based cognitivebehavioural family intervention for carers of patients suffering from schizophrenia: 12-month follow-up. Acta Psychiatrica Scandinavica, 104, 346 355.[CrossRef][Medline]
Sensky, T., Turkington, T., Kingdon, D., et al (2000) A randomised, controlled trial of cognitive behaviour therapy for persistent positive symptoms in schizophrenia resistant to medication. Archives of Generaly Psychiatry, 57, 165 173.[CrossRef]
Stirling, J., White, C., Lewis, S., et al (2003) Neurocognitive function and outcome in first-episode schizophrenia: a 10-year follow-up of an epidemiological cohort. Schizophrenia Research, 15, 65, 75 86.
Tarrier, N. & Calam, R. (2002) New developments in cognitive behavioural therapy case formulation: epidemiological, systemic and social context: an integrative approach. Behavioural and Cognitive Psychotherapy, 30, 311 328.[CrossRef]
Tarrier, N., Sharpe, L., Beckett, R., et al (1993) Atrial of two cognitive behavioural methods of treating drug-reistant residual psychotic symptoms in schizophrenic patients: II. Treatment-specific changes in coping and problem-solving skills. Social Psychiatry and Psychiatric Epidemiology, 28, 5 10.[CrossRef][Medline]
Tarrier, N., Yusopoff, L., Kinney, C., et al
(1998) Randomised controlled trial of intensive cognitive
behavioural therapy for patients with chronic schizophrenia.
BMJ, 317, 303
307.
Tarrier, N., Lewis, S., Haddock, G., et al
(2004) Cognitive behavioural therapy in first-episode
and early schizophrenia: 18-month follow-up of a randomised controlled trial.
British Journal of Psychiatry,
184, 231
239.
Turkington, D., Kingdon, D., Turner, T., et al
(2002) Effectiveness of a brief cognitivebehavioural
therapy intervention in the treatment of schizophrenia. British
Journal of Psychiatry, 180, 523
527.
Vaughn, C. E. & Leff, J. P. (1976) The influence of family and social factors on the course of psychiatric illness. A comparison of schizophrenic and depressed neurotic patients. British Journal of Psychiatry, 129, 125 137.[Abstract]
Verdoux, H., Lengronne, J., Liraud, F., et al (2000) Medication adherence in psychosis: predictors and impact on outcome. A 2-year follow-up of first-admitted subjects. Acta Psychiatrica Scandinavica, 102, 203 210.[CrossRef][Medline]
Viksman, P., Poyurovsky, M., Balush, V., et al (2002) Metacognition in first episode schizophrenia: its relationship to theory of mind and executive functioning. Schizophrenia Research, 53, 137.[CrossRef]
Wahlbeck, K., Tuunainen, A., Gilbody, S., et al (2000) Influence of methodology on outcomes of randomised clozapine trials. Pharmacopsychiatry, 33, 54 59.[CrossRef][Medline]
Woods, S. W., Breier, A., Zipursky, R. B., et al (2003) Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome. Biological Psychiatry, 54, 453 564.[CrossRef][Medline]
Wykes, T., Reeder, C., Corner, J., et al (1999) The effects of neurocognitive remediation on executive processing in patients with schizophrenia. Schizophrenia Bulletin, 25, 291 307.[Medline]
Wykes, T., Reeder, C., Williams, C., et al (2003) Are the effects of cognitive remediation therapy (CRT) durable? Results from an exploratory trial. Schizophrenia Research, 61, 163 174.[CrossRef][Medline]
Yung, A., Phillips, L. J., McGorry, P. D., et al (1998) Prediction of psychosis. A step towards indicated prevention of schizophrenia. British Journal of Psychiatry, 172 (suppl. 33), s14 s20.
Zammit, S., Allebeck, P., Andreasson, S., et al
(2002) Self reported cannabis use as a risk factor for
schizophrenia in Swedish conscripts of 1969: historical cohort study.
BMJ, 325, 1183
1184.
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Psychiatric Bulletin | Advances in Psychiatric Treatment | All RCPsych Journals |