Sjoerd Sytema

Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy: Long-term Follow-up of a 2-Year Randomized Clinical Trial

IMPORTANCE Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before. OBJECTIVE To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial. DESIGN Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR. SETTING One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission. PARTICIPANTS After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment. INTERVENTION After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician. MAIN OUTCOMES AND MEASURES Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters. RESULTS The DR patients experienced twice the recovery rate of the MT patients (40.4% vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates. CONCLUSIONS AND RELEVANCE Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN16228411.

CLINICAL RECOVERY IN FIRST EPISODE PSYCHOSIS

Introduction: Generally agreed outcome criteria in psychosis are required to evaluate the effectiveness of new treatment strategies. The aim of this study is to explore clinical recovery in first-episode patients, defined by meeting criteria for both symptomatic and functional remission. Method: In a sample of first-episode patients (N = 125), symptomatic and functional remission during the last 9 months of a 2-year follow-up period were examined, as well as recovery and its predictors. Results: Half the patients (52.0%) showed symptomatic remission and a quarter (26.4%) functional remission, while one-fifth (19.2%) met both criteria sets and were considered recovered. Recovery was significantly associated with short duration of untreated psychosis and better baseline functioning. Conclusion: Most functionally remitted patients were also symptomatically remitted, while a minority of symptomatically remitted patients were also functionally remitted. Treatment delay may affect chance of recovery.

Duration of untreated psychosis and negative symptoms ? A systematic review and meta-analysis of individual patient data

BACKGROUND Longer duration of untreated psychosis (DUP) is associated with poorer outcome in terms of positive symptoms, relapse rate, and time to remission. In contrast, the association with negative symptoms is less consistent. AIMS The study had three aims. First, to arrive at a more precise estimate of the correlation between DUP and negative symptoms than previous reviews, by substantially increasing the amount of available data. Second, to see whether the strength of this correlation attenuated over longer follow-up intervals. Third, to determine whether there is a relationship between DUP and changes in negative symptoms. METHOD Relevant databases were searched for studies published between December 1992 and March 2009 that reported data on DUP and negative symptoms. We obtained individual patient data where possible and calculated summary correlations between DUP and negative symptoms for each study at baseline, short and long-term follow-up. We used multilevel regression analysis to examine whether the effect of DUP on negative symptoms was the greatest in the early stages of illness. RESULTS We included 28 non-overlapping studies from the 402 papers detected by the search strategy. After contacting the authors we obtained individual patient data from 16 of these studies involving 3339 participants. The mean DUP was 61.4 weeks (SD=132.7, median DUP=12.0). Shorter DUP was significantly associated with less severe negative symptoms at baseline and also at short (1-2 years) and longer term follow-up (5-8 years) (r=0.117, 0.180 and 0.202 respectively, p<0.001). The relationship between improvement in negative symptoms and DUP was found to be non-linear: people with a DUP shorter than 9 months showed substantially greater negative symptom reduction than those with a DUP of greater than 9 months. CONCLUSIONS Shorter DUP is associated with less severe negative symptoms at short and long-term follow up, especially when the DUP is less than 9 months. Since there is no effective treatment for negative symptoms, reducing DUP to less than 9 months may be the best way to ameliorate them.

Assertive community treatment in the Netherlands: a randomized controlled trial

Objective:  Assertive community treatment is rapidly implemented by many European mental health services, but recently the evidence base has been questioned. Positive results of randomized trials in the USA were not replicated in the UK. The question is whether the UK findings are representative for other European countries with modern mental health services.

Continuity of care for patients with schizophrenia and related disorders : a comparative South-Verona and Groningen case-register study

BACKGROUND It is widely believed that for the severely mentally ill continuity of care is essential to ensure a better outcome and prevent long-term hospitalization. However, not much progress has been made in the operationalization and measurement of this concept. We used two indicators to compare continuity of care of schizophrenic patients in two kinds of mental health systems. One is a community mental health system without the back-up of a mental hospital (South-Verona, Italy). The other is an institution-based system in which mental hospitals are still predominant (Groningen, The Netherlands). METHODS The first indicator of continuity of care, readiness of aftercare, is the time from discharge from hospital to the first day- or out-patient contact. Survival analysis was applied to correct for censored observations. The second indicator, flexibility of care, is the use of combinations of in-, day- and out-patient care during 2-year follow-up. RESULTS More patients in South-Verona received community care within 2 weeks after discharge (71.5%), than in the Groningen register area (54.6%). The survival functions differed significantly. Cox regression analysis revealed that in both systems a contact before admission, the time between this contact and admission and the duration of the admission are predictors for aftercare. A higher percentage of patients made multiple service use (combinations of in-, day- and out-patient care) in South-Verona than in Groningen (62 v. 45%). CONCLUSIONS Both indicators showed a higher continuity of care in the South-Verona system.

Behavioral Parent Training as an Adjunct to Routine Care in Children with Attention-Deficit/Hyperactivity Disorder: Moderators of Treatment Response

OBJECTIVE To investigate predictors and moderators of outcome of behavioral parent training (BPT) as adjunct to ongoing routine clinical care (RCC), versus RCC alone. METHODS We randomly assigned 94 referred children (4-12 years) with attention-deficit/hyperactivity disorder (ADHD) to BPT plus RCC or RCC alone. Outcome was based on parent-reported behavioral problems and ADHD symptoms. Predictor/moderator variables included childrens IQ, age, and comorbidity profile, and maternal ADHD, depression, and parenting self-efficacy. RESULTS Superior BPT treatment effects on behavioral problems and ADHD symptoms were present in children with no or single-type comorbidity-anxiety/depression or oppositional defiant disorder (ODD)/conduct disorder (CD)-and when mothers had high parenting self-efficacy, but absent in children with broad comorbidity (anxiety/depression and ODD/CD) and when mothers had low parenting self-efficacy. In older children ADHD symptoms tended to decrease more through BPT than in younger children. CONCLUSIONS Adjunctive BPT is most useful when mothers have high parenting self-efficacy and in children with no or single-type comorbidity.

THE RELIABILITY OF DIAGNOSTIC CODING IN PSYCHIATRIC CASE REGISTERS

In total, 103 cases were randomly selected from the Groningen, Nottingham and South Verona registers. Six raters (two in each of the register areas) were involved in coding these cases according to the ICD-9. In general, interrater agreement was satisfactory when codes were grouped into a limited number of categories. Nevertheless, considerable variation in agreement rates was found. We distinguished three steps in the diagnostic process. The selected logistic model showed that reliability is significantly affected in each step, but only substantial in the first where clinicians formulate a diagnosis.

Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin?

OBJECTIVE To assess the degree to which sexual side effects (SSE) are associated with prolactin-raising antipsychotics, and to what degree such SSE are reducible to serum prolactin levels. METHOD A large sample (n=264) of patients treated for 6 weeks with prolactin-raising and prolactin-sparing antipsychotics was assessed for changes in sexual performance in terms of libido, arousal and orgasm using the Antipsychotics and Sexual Functioning Questionnaire. For men also erection and ejaculation were evaluated. At 6 weeks, prolactin levels were assessed and analyzed in relation to sexual performance. RESULTS Men and women reported SSE (libido and orgasm) with about the same frequency. Prolactin-raising medication induced significantly more SSE than prolactin-sparing medication (adjusted OR=3.4, 95% CI: 1.8, 6.5) with 43% of emerging SSE attributable to prolactin-raising medication. When adjusted for serum prolactin, the association between prolactin-raising medication and SSE was reduced but remained significant (OR=2.1, 95% CI: 1.0, 4.5); 27% of emerging SSE remained attributable to prolactin-raising medication. For erectile and ejaculatory dysfunction in men, the attributable fraction due to prolactin-raising medication was 32% before, and 11% after adjustment for serum prolactin. CONCLUSIONS Around 40% of emerging SSE in schizophrenia are attributable to the prolactin-raising properties of antipsychotic medication. Of this attributable fraction, around one-third to two-thirds is directly reducible to the effects of serum prolactin.

Continuity of care and readmission in two service systems: a comparative Victorian and Groningen case-register study

Sytema S, Burgess P. Continuity of care and readmission in two service systems: a comparative Victorian and Groningen case‐register study. Acta Psychiatr Scand 1999: 100: 212–219.

Treatment delay and response rate in first episode psychosis.

Objective:  There is no consistent evidence of long duration of untreated psychosis (DUP) predicting long time to response (TTR) in first psychosis. This study aims to investigate the predictors of DUP and TTR in a first episode patient population.