A systematic review of instruments to measure depressive symptoms in patients with schizophrenia.

BACKGROUND: Depressive symptoms require accurate recognition and monitoring in clinical practice of patients with schizophrenia. Depression instruments developed for use in depressed patients may not discriminate depressive symptoms from negative psychotic symptoms. OBJECTIVE: We reviewed depression instruments on their reliability and validity in patients with schizophrenia. METHODOLOGY: A systematic literature search was carried out in three electronic databases. Psychometric properties were extracted for those instruments of which reliability, divergent, concurrent and predictive validity were reported in one or more publications. RESULTS: Forty-eight publications described the reliability and validity of six depression instruments in patients with schizophrenia. The only self-report was the Beck Depression Inventory (BDI). The Brief Psychiatric Rating Scale-Depression subscale (BPRS-D), Positive and Negative Syndrome Scale-Depression subscale (PANSS-D), Hamilton Rating Scale for Depression (HAMD), Montgomery Asberg Depression Rating Scale (MADRS) and Calgary Depression Scale for Schizophrenia (CDSS) were clinician rated. All instruments were reliable for the measurement of depressive symptoms in patients with schizophrenia. The CDSS most accurately differentiated depressive symptoms from other symptoms of schizophrenia (divergent validity), correlated well with other depression instruments (concurrent validity), and was least likely to miss cases of depression or misdiagnose depression (predictive validity). CONCLUSIONS: We would recommend to use the CDSS for the measurement of depressive symptoms in research and in daily clinical practice of patients with schizophrenia. A valid self-report instrument is to be developed for the use in clinical practice.

The course of depressive symptoms and prescribing patterns of antidepressants in schizophrenia in a one-year follow-up study.

BACKGROUND: Antidepressants are frequently prescribed in patients with psychotic disorders, but little is known about their effects in routine clinical practice. The objective was to investigate the prescribing patterns of antidepressants in relation to the course of depressive symptoms in patients with psychotic disorders. METHODS: A cohort of 214 Dutch patients with psychotic disorders received two assessments of somatic and psychiatric health, including a clinician-rated screening for depressive symptoms, as part of annual routine outcome monitoring. RESULTS: Depressive symptoms were prevalent among 43% (93) of the patients. Antidepressants were prescribed for 40% (86) of the patients and the majority 83% (71) continued this therapy after one year. Multivariable analysis showed that patients with more severe psychopathology had a higher risk to develop depressive symptoms the following year (OR [95% CI]=0.953 [0.912-0.995]). For patients with depressive symptoms at baseline, polypharmacy was a potential risk factor to keep having depressive symptoms (OR [95% CI]=1.593 [1.123-2.261]). Antidepressant use was not an independent predictor in both analyses. CONCLUSIONS: Routine outcome monitoring in patients with psychotic disorders revealed a high prevalence of depressive symptoms. Antidepressants were frequently prescribed and continued in routine clinical practice.

[Pharmacological treatment of negative symptoms in schizophrenia; research and practice]. / Medicamenteuze interventie bij negatieve symptomen bij patiënten met schizofrenie.

BACKGROUND: Negative symptoms in patients with schizophrenia predict a worse social outcome. The treatment options for negative symptoms are extremely limited. Various treatment strategies have been studied in which several types of medication were added to antipsychotics in order to alleviate negative symptoms. AIM: To review the types of medication that have been used to supplement antipsychotic treatment in order to alleviate negative symptoms in patients with schizophrenia. METHOD: By means of PubMed we were able to perform a systematic review of all randomised controlled trials and relevant meta-analyses published up to and including May 2009. RESULTS: The pharmacological mechanisms that were studied in connection with the treatment of negative symptoms were as follows: the modulation of the glutamate system, the modulation of the serotonergic system, the histaminergic system and the dopaminergic system and the influencing by means of antioxidants and hormones. Despite all the methodological problems the modulation of the glutamate system and the blocking of serotonin 5-HT-3/2a receptors may be able to bring about a limited reduction of negative symptoms. The therapeutic results of the pharmacological treatments studied which may be effective is only moderate. CONCLUSION: For the time being the pharmacological addition strategies do not lead us to recommend their use in current clinical practice but they can certainly serve as a basis for further research. medication, negative symptoms, schizophrenia.

[Routine Outcome Monitoring for patients with severe mental illness: a consensus document]. / Routine outcome monitoring voor patiënten met ernstige psychiatrische aandoeningen; een consensusdocument.

BACKGROUND: Routine outcome monitoring (ROM) means the assessment of the patient's condition on a routine basis using instruments. So far there is no consensus about which instruments should be used for ROM with severely mentally ill patients (ROM-SMI). AIM: To reach a consensus about instruments for ROM-SMI in the Netherlands and Belgium and to create possibilities for comparison of ROM data. METHOD: This article discusses the consensus document of the National Remission Working Group for ROM in patients with smi and covers the following topics: reasons for ROM-SMI, domains for ROM-SMI and appropriate instruments, logistics and analyses of the data. RESULTS: Patients with SMI have problems in several domains. These can be assessed by collecting information about psychiatric symptoms, addiction, somatic problems, general functioning, needs, quality of life and care satisfaction. Potential instruments for ROM-SMI are short, valid, reliable and assess several domains, taking the patient's perspective into account, and have been used in national and international research. The working group advises institutions to choose from a limited set of instruments. After the scores have been aggregated and standardised, comparisons can be drawn. ROM-SMI data can be interpreted more meaningfully, if outcome data are supplemented with data regarding patient characteristics and the treatment interventions already applied. CONCLUSION: It should be possible to reach a consensus about instruments for ROM-SMI and the way in which they should be used. The use of identical instruments will lead to improvements in mental health care and create possibilities for comparison (benchmarking) and research.

Incidence and persistence of tardive dyskinesia and extrapyramidal symptoms in schizophrenia.

Although it has been suggested that second-generation antipsychotics (SGA) may reduce the rate of prevalent tardive dyskinesia (TD), little is known about the incidence and outcome of TD in those exposed exclusively to SGA. The incidence and subsequent persistence of TD and extrapyramidal symptoms (EPS) was calculated in a cohort of patients with schizophrenia treated predominantly with SGA. This cohort of more than 10,000 patients with schizophrenia was seen six times over a period of two years. Dichotomous measures of EPS and TD were used to calculate the yearly incidence rates of TD and EPS as well as their subsequent cumulative persistence rate in a subset of 9104 and 6285 patients at risk for TD and EPS, respectively. Of 9104 individuals who did not present with TD at baseline, 138 developed TD, yielding a TD incidence rate of 0.74% (95% CI: 0.62, 0.87) and a subsequent cumulative persistence rate of 80%. Of 6285 individuals without EPS at baseline, 464 developed EPS yielding an incidence rate of 3.7% (95% CI: 3.4, 4.0) and a subsequent cumulative persistence rate of 82%. Incidence rates of TD and EPS may be low in the SGA era. However, once emerged, these disorders prove persistent, suggesting strong moderators effects of underlying predisposing factors.

The incidence of metabolic syndrome and its reversal in a cohort of schizophrenic patients followed for one year.

Cross-sectional studies showed a high prevalence of metabolic syndrome in patients with schizophrenia.This study aimed to identify the incidence of metabolic syndrome and its reversal in a non-preselected cohort of chronic psychotic patients in routine practice in one year follow-up and to find variables to describe development and reversal of metabolic syndrome. This cohort study was conducted as part of a disease management program and patients were included if they had two complete assessments in a one year follow-up. We conducted two logistic regressions to find variables to describe the development of metabolic syndrome and the reversal of metabolic syndrome. At the time of the first assessment 35% (n=92) of the 260 included patients had metabolic syndrome. Within one year 21 patients developed metabolic syndrome and 30 patients had it reversed. This was an incidence of 13% (21/168) and a reversal of 33% (30/92). Smoking, family history of cardiovascular diseases, and duration of disease >6 years was associated with a higher risk of developing metabolic syndrome as well as abdominal obesity and dyslipidemia. Patients with abdominal obesity had a smaller chance of reversing metabolic syndrome. Other variables included in the logistic regression such as receiving cardiovascular/antidiabetic drug treatment or duration of disease >6 years did not alter the risk of reversing the metabolic syndrome. Our study showed that the natural course of metabolic syndrome is dynamic. A considerable number of patients developed or reversed the metabolic syndrome in one year follow-up.

[Prevention and treatment of somatic complications arising from the use of antipsychotics]. / Preventie en behandeling van somatische complicaties bij antipsychoticagebruik.

BACKGROUND: Antipsychotics are effective drugs that are prescribed frequently for a large group of patients. However, they also have many side-effects which can lead ultimately to serious somatic complications. These complications fall into various categories: metabolic, cardiovascular, neurobiological, haematological, gastro-intestinal and urogenital. AIM: To make an inventory of the side-effects and advise on ways of monitoring and preventing them. method The multidisciplinary working group on somatic complications arising from the use of antipsychotics (Werkgroep Somatische Complicaties) has collected literature on the subject and has discussed it at a number of consensus meetings. results The most frequent somatic complications are described on the basis of specific risk profiles and advice is given on how to identify these complications and on how to treat them when necessary. It is essential to monitor, systematically and regularly, somatic complications arising from the use of antipsychotics; furthermore, polypharmacy should be avoided. The person ultimately responsible for this is the doctor who has prescribed the antipsychotics. In addition, it is important to draw patients' attention to the general rules for a healthy lifestyle: no smoking, a balanced diet and adequate exercise. CONCLUSION: It is very important that somatic complications should be monitored carefully and accurately. So far, the Netherlands has no official guidelines on ways to identify and treat somatic complications.

A 12-month follow-up study of treating overweight schizophrenic patients with aripiprazole.

OBJECTIVE: To investigate the feasibility of switching overweight schizophrenic patients to aripiprazole and to assess the impact of 12 months of aripiprazole treatment on weight in routine practice. METHOD: This was a non-controlled cohort study in overweight schizophrenic patients. Data were collected before treatment with aripiprazole was started and at 12-month follow-up. RESULTS: A total of 53 patients were included; of these 55% continued using aripiprazole for 12 months. Aripiprazole treatment for 12 months (P = 0.027) and stopping clozapine or olanzapine treatment (P = 0.038) predicted weight loss (> or =3 kg). Patients receiving aripiprazole monotherapy (n = 16, mean -3.0 kg) had similar weight loss than patients receiving aripiprazole in addition to another antipsychotic drug (n = 13, mean -4.4 kg). CONCLUSION: In routine practice once aripiprazole treatment was started, more than half of the patients remained on aripiprazole and most of them lost weight. Adding aripiprazole to clozapine gave similar weight loss as monotherapy with aripiprazole.

Novel antipsychotics in bipolar and schizoaffective mania.

OBJECTIVE: Novel antipsychotics are increasingly used in the treatment of bipolar and schizoaffective mania. This paper presents an overview of the controlled studies in this field. METHOD: Using cross-references, a computerized search was performed on MEDLINE and EMBASE psychiatry covering the period 1990-2002. RESULTS: Olanzapine and risperidone, added to mood stabilizers, and olanzapine as monotherapy enjoy the most evidential support in terms of efficacy and side-effect profile for their use in acute bipolar mania. The use of modern antipsychotics in bipolar prophylaxis and in both the short- and long-term treatment of schizomania has not been widely studied yet. CONCLUSION: More controlled trials are still needed comparing modern antipsychotics as monotherapy and adjunctive to mood stabilizers with conventional antipsychotics, lithium, anticonvulsants and with each other in short-term and, especially, maintenance treatment of (schizo)mania. Partly based on controlled studies, olanzapine, risperidone and other modern antipsychotics could become preferable for these indications.

Off-label use of antipsychotics in the community pharmacy: the sex differences.

Antipsychotic drugs are generally registered for treating schizophrenia, psychosis, mania, and conditions of severe (locomotor) agitation. In common practice, however, they are prescribed in a wide range of different psychiatric disorders. We conducted a retrospective, exploratory study to examine off-label use of antipsychotics and possibly sex differences. We defined antipsychotic use as quasi-label when used in non-registered disorders that have psychosis as an inherent co-morbidity. When antipsychotics were prescribed in disorders that are generally not known with psychosis, we defined this as off-label use. In this study, we combined pharmacy records with data from general practitioners in order to evaluate the range of diagnoses for which antipsychotic drugs are used. We focused on sex differences in type of disorder and in prescribed dosages of antipsychotic drugs. Among 97 male and 95 female antipsychotic users, we could classify women significantly more often as on-label antipsychotic drug users compared with men. Most often, this occurred with typical antipsychotic drug treatment. While female patients used equal dosages for on-label and quasi-/off-label indications, we found that male patients used significantly lower dosages in quasi-/off-label indications compared with on-label indications. We suggest elaborate future research on the characteristics of quasi- and off-label antipsychotic drug use in order to define effective and safe use of antipsychotic drugs among off-label indications.

Do integrated mental healthcare organisations facilitate process quality in the treatment of people with schizophrenia and related psychoses?

OBJECTIVE: The objective of this study is to investigate the influence of mergers of ambulatory and mental healthcare organisations on the process quality of care for persons suffering from schizophrenia or related psychoses. THEORY: On the basis of the theory of Donabedian we assume the relationships between three types of quality in healthcare: structure quality, process quality and outcome quality. This study focuses on the influences of structure quality, i.e. years since merger and catchment area size upon process quality. METHODS: Criteria according to Tugwell for evaluating healthcare were used to describe the process quality of schizophrenia care, resulting in a process quality questionnaire with 6 subscales and 21 items. Leading psychiatrists of 31 Dutch mental healthcare organisations, covering 89% of the country, answered the questionnaire. Both programmes and documents from the responding institutions and schizophrenia projects were analysed. Correlations of two determinants, age of the merged organisation and catchment area size, were made with total scale scores and the sub scores of the questionnaire. RESULTS: The response rate was 97% (31/32). Twenty-two organisations (71%) had a score of more than 50% on the used scale, 8 (29%) scored less. Two evidence-based interventions were implemented in more than 50% of the organisations, three in less than 50%. A low degree of implementation occurs in establishing care for people with schizophrenia from ethnic minorities, standardising diagnostic procedures and continuity of care. No significant relationship between the age of the merged organisation ('age') and the total process quality of schizophrenia care was found, however, the relationships between age and the subscales availability of interventions and integrated treatment were significant. No association was found between the size of the MHO's catchment area and any of the used subscales. CONCLUSIONS: The age of integration of residential and ambulatory mental health institutions correlates significantly with two subscales of process quality of schizophrenia care, i.e. availability of interventions and treatment. Catchment area size is not significantly associated with process quality or any of the subscales. Despite the mentioned positive effects, the overall picture of schizophrenia care is not very positive. Additional forces other than merely integration of ambulatory and residential services are needed for the further implementation of evidence-based interventions, diagnostic standards and continuity of care. The development of a national 'schizophrenia standard' (like in other countries) in relation with implementation plans and strategies to evaluate care on a regional level is recommended as well as further research on patient outcomes in relation to mergers of mental healthcare organisations.

Reasoning about the optimal duration of prophylactic antipsychotic medication in schizophrenia: evidence and arguments.

OBJECTIVE: To review evidence-based literature regarding the necessary duration of antipsychotic relapse prevention in schizophrenia and related psychoses. METHOD: A computerized search was performed on Medline, Embase Psychiatry and PsycLIT which covered the period 1974-99. We also used cross-references. RESULTS: Although schizophrenia refers mainly to an intrinsic biological vulnerability, only maintenance studies with a follow-up of 2 years at most are available. Relapses appear unpredictable and occur even after long-term successful remission during antipsychotic treatment. CONCLUSION: Since rehabilitation efforts have effects only after long-term endeavours, antipsychotic relapse prevention should be maintained for long periods. It is reasonable to treat patients suffering from schizophrenia and related psychoses for longer periods than indicated by the current guidelines.

Efficacy of risperidone, olanzapine and clozapine in the treatment of therapy resistant schizophrenia.

Therapy-resistance for positive symptoms is one of the most important problems that occurs with the medical treatment of schizophrenia. In the past years, clozapine has proven its effectiveness in this area and has been included in the treatment protocols and guidelines. Because of the risk of agranulocytosis with this compound and the intensive laboratory controls to be done, several studies have been performed with the new antipsychotics risperidone and olanzapine as alternative treatments. A review of the literature suggests that both drugs are as effective as the classic antipsychotics for therapy-resistant patients. A switch to risperidone or olanzapine possibly would be a alternative for those patients who have favourable effects on a low dose of clozapine. Furthermore the new antipsychotics have less side effects and ameliorating effects on negative and cognitive symptoms, so contributing to overall improvement in chronic schizophrenic disorders. However, in case of persistent positive symptopathology, clozapine remains the golden standard. The new antipsychotics should be included in treatment protocols before clozapine.

Stability and change in needs of patients with schizophrenic disorders: a 15- and 17-year follow-up from first onset of psychosis, and a comparison between 'objective' and 'subjective' assessments of needs for care.

Need for care was studied in a Dutch incidence cohort of patients with schizophrenic disorders 15 and 17 years from first onset of psychosis. Long-term course of the disorders varied from complete remission and full community participation to chronic psychosis and long-term hospital stay. Fifty patients were assessed twice with the Needs For Care Assessment Schedule (NFCAS, Brewin and Wing 1989); at the latter follow-up an assessment was also made using the Camberwell Assessment of Need (CAN, Phelan et al. 1995). The NFCAS is an investigator- or professional-based instrument which provides an 'objective' assessment of needs. Need for care was recorded in 22 areas of clinical and social functioning. Comparison of the two assessments over a 2-year period demonstrated a high stability on the individual items (mean 88%, mostly concerning the absence of a problem twice), but did not show the expected stability of need status among this group of patients with chronic disorders. One in five patients (22%) had no needs at all on both occasions and 56% of the patients showed a change in needs. There was more negative than positive change: 28% suffered from new unmet needs at the 17-year follow-up, while only 12% had improved their status to no needs. About one-third (36%) had at least one unmet need, mostly regarding psychotic symptoms, dyskinesia or underactivity. The CAN provides a 'subjective' assessment of needs according to the view of patients themselves. The problems patients reported most commonly were in the areas of day-time activities, social relationships and information on their condition and treatment, for all which they asked for more help than they received. This patient-based instrument produces slightly higher numbers of problems and unmet needs, and a lower ratio between met and unmet needs. There is an overall percentage of 21% of disagreement between patient and investigator view regarding the unmet need status. Agreement between the two instruments on the nature of the problems with unmet needs was lacking altogether.

Natural course of schizophrenic disorders: a 15-year followup of a Dutch incidence cohort.

Data are presented on the 15-year natural course of schizophrenia and other nonaffective functional psychoses in a cohort of 82 first-contact cases from a circumscribed area in the Netherlands. The subjects were suffering from functional psychosis with International Classification of Diseases-Ninth Revision (ICD-9) diagnoses 295, 297, or 298.3-9 (broad definition of schizophrenia) on entry. Standardized assessments of psychopathology, psychological impairments, negative symptomatology, social disability, and use of mental healthcare were used. The study reveals a pattern of chronicity and relapses with a high risk of suicide: Two-thirds of the subjects had at least one relapse and after each relapse 1 of 6 subjects did not remit from the episode; 1 of 10 committed suicide; and 1 of 7 had at least one episode with affective psychotic symptoms that started on average 6 years after the onset of the schizophrenic disorder. Diagnoses were reclassified in five patients, according to DSM-III-R criteria for a bipolar disorder. The predictive power--in terms of time in psychosis and in partial or full remission--of demographic, illness, and treatment variables at onset of the illness was very limited. Insidious onset and delays in mental health treatment are risk factors that predict a longer duration of first or subsequent episodes. The importance of mental health treatment in regard to outcome is probably subject to change because an early warning and intervention strategy could prevent further damage and deterioration. Our data support the need for an adequate relapse prevention program as a priority for our mental health services.

Expressed emotion on long-stay wards.

We examined the influence of an educational programme on nurses' level of expressed emotion (EE), on ward climate and on social functioning and psychopathology of hospitalized schizophrenic patients. Nurses and patients were from long-stay wards of six Dutch psychiatric hospitals. Despite an increase of nurses' knowledge about schizophrenia we did not find measurable effects on nurses' levels of EE. According to the five minute speech sample method, a third of the nurses participating in this study had a high level of expressed emotion, mainly consisting of criticism. This was a rather stable pattern. Patients, however, were reluctant to give their nurses high EE ratings on the level of expressed emotion scale. Psychopathology was not influenced by the educational programme, but social functioning of patients was related to EE in nurses. Moreover, we found a significant decline in the number of restrictive ward rules at follow-up. We conclude that, while it may be difficult to detect changes in EE level after an educational programme for nurses, there nevertheless appear to be measurable benefits for patients.

Assessment of the need for care 15 years after onset of a Dutch cohort of patients with schizophrenia, and an international comparison.

Assessment of needs for care is crucial in the evaluation of ongoing changes from institutional care to various forms of day- and outpatient treatment. Do patients really do better in the community and are they adequately cared for? The 15-year follow-up of a Dutch incidence cohort of patients with schizophrenia and other functional non-affective psychoses showed that 47 (out of 63) patients had positive ratings of symptoms and disabilities. They were assessed by means of the Needs for Care Assessment Schedule, which articulates the problems and corresponding interventions resulting in a judgement of met or unmet need for treatment or assessment. There was a mean of 2.1 clinical problems and 2.1 social problems per patient. Few problems were considered to generate unmet needs: 14% of the clinical problems and only 7% of the social problems. Nevertheless, 32% of the patients had one or more unmet needs. These results were compared with data from six research centres in the United Kingdom (Camberwell, Oxford and South Glamorgan), Canada (Montreal), Italy (Verona) and Finland (Tampere). Despite differences in health care settings in the four countries, the ratio of met to unmet needs (about 4-5 to 1) among chronic, mostly schizophrenic patients is more or less the same with the exception of an apparently underserved hostel population in Oxford and the Finnish patient population probably due to high expectations with respect to independent community living.

Lithium treatment in affective disorders: The significance of strongly elevated erythrocyte choline levels.

In manic-depressive patients treated with lithium salts the transport of choline over the erythrocyte membrane is strongly inhibited, resulting in dramatically increased erythrocyte choline levels (for review see ref. 1). Whether or not there is a relationship between this effect and treatment response is not clear. Data on this issue are scarce possibly because the measurement of treatment response in lithium prophylaxis is very difficult and time consuming. Also the effect on erythrocyte choline is specific for lithium and not for manic-depressive illness. We will address here the question of a possible relation between erythrocyte choline and clinical effects of lithium.