Cees J. Slooff

Effects of bilateral repetitive transcranial magnetic stimulation on treatment resistant auditory-verbal hallucinations in schizophrenia: a randomized controlled trial.

BACKGROUND Neuroimaging findings implicate bilateral superior temporal regions in the genesis of auditory-verbal hallucinations (AVH). This study aimed to investigate whether 1 Hz repetitive transcranial magnetic stimulation (rTMS) of the bilateral temporo-parietal region would lead to increased effectiveness in the management of AVH, compared to left rTMS or placebo. METHODS 38 patients with schizophrenia (DSM-IV) and medication-resistant AVH were randomly assigned to 1 Hz rTMS treatment of the left temporo-parietal region, bilateral temporo-parietal regions, or placebo. Stimulation was conducted over 6 days, twice daily for 20 min, at 90% of the motor threshold. Effect measures included the Auditory Hallucination Rating Scale (AHRS), Positive and Negative Affect Scale (PANAS), and a score for hallucination severity obtained from the Positive and Negative Syndrome Scale (PANSS). RESULTS All groups showed some improvement on the total AHRS. Hallucination frequency was significantly reduced in the left rTMS group only. The bilateral rTMS group demonstrated the most remarkable reduction in self-reported affective responsiveness to AVH. A modest, but significant decrease on the PANSS hallucination item was observed in the combined rTMS treatment group, whereas no change occurred in the placebo group. The left rTMS group showed a significant reduction on the general psychopathology subscale. CONCLUSION Compared to bilateral or sham stimulation, rTMS of the left temporo-parietal region appears most effective in reducing auditory hallucinations, and additionally may have an effect on general psychopathology. Placebo effects should however not be ruled out, since sham stimulation also led to improvement on a number of AVH parameters.

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 effects of lifestyle interventions on (long-term) weight management, cardiometabolic risk and depressive symptoms in people with psychotic disorders: a meta-analysis.

Aims The aim of this study was to estimate the effects of lifestyle interventions on bodyweight and other cardiometabolic risk factors in people with psychotic disorders. Additionally, the long-term effects on body weight and the effects on depressive symptoms were examined. Material and Methods We searched four databases for randomized controlled trials (RCTs) that compared lifestyle interventions to control conditions in patients with psychotic disorders. Lifestyle interventions were aimed at weight loss or weight gain prevention, and the study outcomes included bodyweight or metabolic parameters. Results The search resulted in 25 RCTs -only 4 were considered high quality- showing an overall effect of lifestyle interventions on bodyweight (effect size (ES) = −0.63, p<0.0001). Lifestyle interventions were effective in both weight loss (ES = −0.52, p<0.0001) and weight-gain-prevention (ES = −0.84, p = 0.0002). There were significant long-term effects, two to six months post-intervention, for both weight-gain-prevention interventions (ES = −0.85, p = 0.0002) and weight loss studies (ES = −0.46, p = 0.02). Up to ten studies reported on cardiometabolic risk factors and showed that lifestyle interventions led to significant improvements in waist circumference, triglycerides, fasting glucose and insulin. No significant effects were found for blood pressure and cholesterol levels. Four studies reported on depressive symptoms and showed a significant effect (ES = −0.95, p = 0.05). Conclusion Lifestyle interventions are effective in treating and preventing obesity, and in reducing cardiometabolic risk factors. However, the quality of the studies leaves much to be desired.

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.

Weight change from 3-year observational data: findings from the worldwide schizophrenia outpatient health outcomes database.

BACKGROUND Weight change data from randomized clinical trials are often of limited duration and trials do not always report a full range of clinically relevant categorical end points. METHOD We conducted a post hoc analysis of data from the observational Worldwide Schizophrenia Outpatient Health Outcomes database (2000-2005) on weight change in 4,626 patients completing 3 years of antipsychotic monotherapy with amisulpride, clozapine, olanzapine, quetiapine, risperidone, and oral and depot first-generation antipsychotics (FGAs). Reported outcomes included mean and categorical weight changes and the trajectories of different measures of weight change. RESULTS Mean weight gain was lowest with amisulpride (1.8 kg; 95% CI, 0.2-3.3) and highest with olanzapine (4.2 kg; 95% CI, 3.9-4.5). Weight change for all antipsychotics was most rapid during the first 6 months; subsequent weight change was slower but did not plateau. All drugs showed considerable individual variation in weight change. The proportion losing ≥7% of their baseline bodyweight was highest with quetiapine (10%; 95% CI, 7%-16%) and lowest with depot FGAs (5%; 95% CI, 3%-10%). Between 7% and 15% of patients moved into an overweight or obese body mass index (kg/m2)category (≥25). CONCLUSIONS The degree of weight gain varied between antipsychotics. All antipsychotics were associated with significant (≥7%) weight loss and gain from baseline. The mean rate of weight gain was maximal during the first 6 months but continued over 3 years without a plateau in this specific cohort. Patients should receive regular monitoring of weight throughout treatment.

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.

Care provided by general practitioners to patients with psychotic disorders: a cohort study

BackgroundPatients suffering from psychotic disorders have an increased risk of comorbid somatic diseases such as cardiovascular disorders and diabetes mellitus. Doctor-related factors, such as unfamiliarity with these patients, as well as patient-related factors, such as cognitive disturbance and negative symptoms, contribute to suboptimal health care for these patients.General practitioners (GPs) could play a key role in diagnosing and treating this somatic comorbidity as in the Netherlands, almost all residents are registered at a general practice. This study aims to find out whether there are any differences between the levels of health care provided by GPs to patients with psychotic disorders, compared to other types of patients.MethodsA cohort of patients with an ICPC code of psychosis and two matched control groups, one consisting of patients with other mental problems and the other one of patients without any mental problems, were followed over a period of 5 years.ResultsPatients with psychotic disorders (N = 734) contacted the GP practice more often than patients in the control groups. These patients, both adults (p = 0.051) and the elderly (p < 0.005), received more home visits from their GPs. In the adult group (16 to 65 years old inclusive), the number of consultations was significantly higher among both psychosis patients and the group of patients with other mental problems (p < 0.0005). The number of telephone consultations was significantly higher in both age categories, adult group (p < 0.0005), and > 65 years old (p = 0.007). With regard to chronic illnesses, elderly psychosis patients had fewer contacts related to cardiovascular diseases or chronic lung diseases.ConclusionPatients with psychotic disorders contact the GP practice more frequently than other types of patients. Adult psychosis patients with diabetes mellitus, cardiovascular diseases or chronic lung diseases receive the same amount of health care for these diseases as other primary care patients. The finding that older patients with psychotic disorders are diagnosed with cardiovascular diseases and obstructive lung diseases less frequently than other types of elderly patients requires further study.

Tardive dyskinesia in schizophrenia is associated with prolactin-related sexual disturbances

Tardive dyskinesia (TD) may occur in never-medicated patients with psychotic illness, indicating the existence of non-medication, possibly disease-related, causes. We tested the hypothesis that, independent of the antipsychotic-induced rise in prolactin, the incidence of TD would be associated with the incidence of prolactin-related sexual disturbances (PRSD), which would be suggestive of a common pathology involving multiple dopamine tracts. Simple, global measures of TD and PRSD (loss of libido, amenorrhea, gynaecomastia, impotence, and galactorrhea) were rated in a prospective, observational European Health Outcomes Study (SOHO). New onset of TD and new onset of PRSD at 3, 6, and 12 months was analyzed in a risk set of 4263 patients using a Cox proportional hazard model yielding adjusted hazard ratios (aHR). Incidence of TD was significantly and linearly comorbid with the incidence of PRSD in both men and women. Compared to those with no PRSD, the risk for TD was 2.0 (95% CI: 1.1, 3.7) with one PRSD, 2.4 (95% CI: 1.3, 4.5) with two PRSD, and 3.6 (95% CI: 1.1, 11.8) with three PRSD. Associations were stronger in those who only had received prolactin-sparing medications (aHR per unit PRSD increase=2.0, 95% CI: 1.2, 3.3) than in those who only had received prolactin-raising medications (aHR=1.3, 95% CI: 0.9, 1.9). In people with schizophrenia, TD and PRSD show comorbidities that are independent of antipsychotic-induced alterations in plasma prolactin. This may suggest a shared, pandopaminergic pathological mechanism associated with schizophrenia itself, rather than only a medication effect.

Prognosis and outcome in a cohort of patients with non-affective functional psychosis

SummaryOver a period of 3 years since the first in a lifetime onset of an episode of non-affective functional psychosis a cohort of 82 Dutch patients was studied at set intervals with regard to prognosis and outcome. Prognostic statements on remission, relapse, duration of episode, length of stay in hospital, and occupational, family and overall social adjustment were checked against actual outcome after I year. In general, the research team of three psychiatrists, a psychologist and a sociologist began quite optimistically, but became slightly more pessimistic with time. However, their predictions proved hardly better than chance statements. The team appeared to be more pessimistic about the diagnosis of schizophrenia than about that of reactive psychosis, although they were not correct with one diagnostic category more often than with the other.

Psychometric properties of the self-report version of the Quick Inventory of Depressive Symptoms (QIDS-SR16) questionnaire in patients with schizophrenia

BackgroundSelf-report instruments for the assessment of depressive symptoms in patients with psychotic disorders are scarce. The Quick Inventory of Depressive Symptoms (QIDS-SR16) may be a useful self-report instrument, but has received little attention in this field. This paper aimed to test the psychometric properties of the QIDS-SR16 questionnaire in patients with a psychotic disorder.MethodsPatients diagnosed with a psychotic disorder from health care institutions in The Netherlands were included in the study. Depressive symptoms were assessed with the QIDS-SR16 and the Calgary Depression Scale for Schizophrenia (CDSS). Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) and extrapyramidal symptoms (EPS) with three EPS rating scales. Spearman’s correlation coefficients were used to compare the total score of the QIDS-SR16 with the total scores of the CDSS, PANSS-subscales and EPS rating scales.ResultsIn a sample of 621 patients with psychotic disorders, the QIDS-SR16 showed good internal consistency (α = 0.87). The QIDS-SR16 correlated moderately with the CDSS (r = 0.44) and the PANSS subscale for emotional distress (r = 0.47). The QIDS-SR16 showed weak correlation with the PANSS subscale for negative symptoms (r = 0.28) and minimal correlation with EPS rating scales (r = 0.09-0.16).ConclusionsThe QIDS-SR16 may reliably assess depressive symptoms in patients with psychotic disorders, but its concurrent validity with the CDSS was rather poor in this population. We would recommend developing a new self-report questionnaire for the assessment of depressive symptoms in patients with psychotic disorders.