The role of fetal therapy in the management of mirror syndrome: a narrative review.

OBJECTIVES: Mirror syndrome (MS) is a condition characterized by the presence of maternal, fetal, and placental edema and is reversible through delivery or pregnancy termination. As fetal hydrops itself may be amenable to treatment, we sought to determine outcomes for MS primarily managed by fetal therapy through a narrative review of the literature and cases managed at our fetal center. STUDY DESIGN: PubMed, Embase, Web of Science, Scopus, and Google Scholar databases were searched through January 2024 using key words: mirror syndrome, Ballantyne's syndrome, fetal hydrops, maternal hydrops, pseudotoxemia, triple edema, maternal recovery, fetal therapy, and resolution. Manuscripts describing primary management by fetal therapy that included maternal and fetal outcomes were identified. Clinical details of MS patients managed with fetal therapy at our center were also included for descriptive analysis. RESULTS: 16 of 517 manuscripts (3.1%) described fetal therapy as the primary intended treatment in 17 patients. 3 patients managed at our center were included in the analysis. Among 20 patients undergoing primary fetal therapy for management of mirror syndrome, median gestational age of presentation was 24 weeks and 5 days gestation; predominant clinical findings were maternal edema (15/20), proteinuria (10/20), pulmonary edema (8/20), and hypertension (8/20); the primary laboratory abnormalities were anemia (8/20) and elevated creatinine or transaminases (5/20). Condition-specific fetal therapies led to resolution of hydrops in 17 (85%) cases and MS in 19 (95%) cases. The median time to hydrops resolution was 7.5 days and to resolution of mirror syndrome was 10 days. Fetal therapy prolonged pregnancy by a median of 10 weeks with a median gestational age of 35 weeks and 5 days at delivery. All women delivered for indications other than mirror syndrome and 19/20 fetuses survived. CONCLUSION: In appropriately selected cases, MS often resolves after fetal therapy of hydrops allowing for safe pregnancy prolongation with good maternal and infant outcomes.

Characterization of the maternal serum inflammatory profile during pregnancy according to socioeconomic status.

PROBLEM: In pregnancy, lower socioeconomic status (SES) is associated with adverse outcomes, which is partly attributed to chronic inflammation. Our study compared the maternal serum cytokine profiles in patients with low and high SES. METHOD OF STUDY: This retrospective cohort study compared maternal serum cytokine profiles between Medicaid-insured patients who delivered at an urban safety-net hospital (low SES) and privately-insured patients who delivered at a community-based academic hospital (high SES) in Atlanta, GA (n = 32-33/group). Serum samples were obtained during prenatal venipuncture from 13 to 38 weeks' gestation and the cohorts were matched by gestational age. Interferon (IFN)-γ, Interleukin (IL)-10, IL-1ß, IL-4, IL-6, IL-8, and Tumor Necrosis Factor (TNF)-α were assayed from maternal serum samples using a standard ELISA assay. RESULTS: Median concentrations of IL-6, a promotor of chronic inflammation, were higher in the low SES group (0.85 vs. 0.49 pg/mL, p < .001), while median levels of IL-1ß, a potent monocyte activator, and TNF-α, a master regulator of acute inflammation, were lower in the low SES group (0.09 vs. 0.46 pg/mL, p < .001, and 1.23 vs. 1.58 pg/mL, p = .002, respectively) as compared to the high SES group. After adjusting for maternal age, obesity, hypertensive disorders, and gestational age at delivery, the differences in IL-6 and IL-1ß by SES persisted (p = .0002 and p < .0001, respectively). CONCLUSIONS: In this retrospective cohort study, there were significant differences in levels of pro-inflammatory cytokines during pregnancy for groups defined by SES, even after adjustment for confounding variables. Our data are foundational for further research to investigate SES-associated inflammation that may contribute to adverse pregnancy outcomes.

Characterization of the inflammatory response to COVID-19 illness in pregnancy.

OBJECTIVE: Pregnant patients face greater morbidity and mortality from COVID-19 related illness than their non-pregnant peers. Previous research in non-pregnant patients established that poor clinical outcomes in SARS-CoV-2 positive patients admitted to the ICU were correlated with a significant increase in the proinflammatory markers interleukin (IL)-1ß, IL-6, IL-8, and IL-10. Importantly, high levels of these inflammatory markers have also been associated with adverse pregnancy outcomes, including spontaneous preterm birth, preeclampsia, and severe respiratory disease. STUDY DESIGN: This was a retrospective cohort study that compared the serum inflammatory cytokine profiles of pregnant patients with acute/post-acute SARS-CoV-2 infection to those with previous exposure. All subjects in both cohorts tested positive for SARS-CoV-2 antibodies; however, those in the acute/post-acute infection cohort had a documented positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) result within 30 days of serum sample collection. Serum samples were obtained during prenatal venipuncture from 13 to 39 weeks' gestation and the cohorts were matched by gestational age. The inflammatory cytokines interferon (IFN)-γ, IL-10, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor (TNF)-α were assayed from maternal serum using a standard ELISA assay and median cytokine concentrations were compared using the Mann-Whitney test. RESULTS AND DISCUSSION: We enrolled 50 non-Hispanic Black patients with confirmed COVID-19 infection who received prenatal care at Grady Memorial Hospital in Atlanta, Georgia. Those with acute/post-acute infection (n = 22) had significantly higher concentrations of SARS-CoV-2 antibody, IL-10, IL-1ß, and IL-8, while patients with previous exposure (n = 28) had significantly higher concentrations of IL-4. There were no significant inter-group differences in medical comorbidities. Pregnant patients with acute/post-acute SARS-CoV-2 infection had significantly higher serum concentrations of pro-inflammatory cytokines as compared to those with previous exposure, suggesting that, like in the non-pregnant population, SARS-CoV-2 infection alters the levels of circulating proinflammatory markers during pregnancy. The increased levels of cytokines may contribute to the adverse obstetric outcomes observed with COVID-19 illness.

Antibody response, neutralizing potency, and transplacental antibody transfer following SARS-CoV-2 infection versus mRNA-1273, BNT162b2 COVID-19 vaccination in pregnancy.

OBJECTIVE: To improve our understanding of the immune response, including the neutralization antibody response, following COVID-19 vaccination in pregnancy. METHODS: This was a prospective cohort study comprising patients with PCR-confirmed SARS-CoV-2 infection and patients who received both doses of mRNA COVID-19 vaccine (mRNA-1273, BNT162b2) in pregnancy recruited from two hospitals in Atlanta, GA, USA. Maternal blood and cord blood at delivery were assayed for anti-receptor binding domain (RBD) IgG, IgA and IgM, and neutralizing antibody. The detection of antibodies, titers, and maternal to fetal transfer ratios were compared. RESULTS: Nearly all patients had detectable RBD-binding IgG in maternal and cord samples. The vaccinated versus infected cohort had a significantly greater proportion of cord samples with detectable neutralizing antibody (94% vs. 28%, P < 0.001) and significantly higher transfer ratios for RBD-specific IgG and neutralizing antibodies with a transfer efficiency of 105% (vs. 80%, P < 0.001) and 110% (vs. 90%, P < 0.001), respectively. There was a significant linear decline in maternal and cord blood RBD-specific IgG and neutralizing antibody titers as time from vaccination to delivery increased. CONCLUSIONS: Those who receive the mRNA COVID-19 vaccine mount an immune response that is equivalent to-if not greater than-those naturally infected by SARS-CoV-2 during pregnancy.

Fibrodysplasia Ossificans Progressiva and Pregnancy: A Case Series and Review of the Literature.

Objective: To evaluate maternal and fetal outcomes in pregnant patients with fibrodysplasia ossificans progressiva (FOP; OMIM#135100), an ultrarare genetic disorder characterized by progressive heterotopic ossification of soft tissues and cumulative disability. Methods: This is a retrospective case series of three patients with FOP who were admitted to Grady Memorial Hospital in Atlanta, Georgia, from to February 2011 to July 2021. Results: Three women delivered preterm infants at our institution. These cases posed unique anesthetic and obstetric technical challenges, particularly when securing the airway and performing cesarean delivery. Importantly, each patient received perioperative glucocorticoids for prevention of further heterotopic ossification. Conclusion: FOP is a unique clinical diagnosis encountered by obstetricians and requires multidisciplinary management for optimal outcomes.

Outcomes of pregnant patients treated with REGEN-COV during the COVID-19 pandemic.

BACKGROUND: Pregnant patients with SARS-CoV-2 infection are at increased risk for severe disease including hospitalization, intensive care admission, ventilatory support, and death. Although pregnant patients were excluded from investigational trials for pharmacologic treatments for COVID-19 illness, the National Institutes of Health treatment guidelines state that efficacious treatments should not be withheld from pregnant patients. An infusion of casirivimab and imdevimab (REGEN-COV), a monoclonal antibody therapy, was shown to reduce the risk of COVID-19-related hospitalization or death from any cause and resolved symptoms and reduced SARS-CoV-2 viral load more rapidly than placebo. In July of 2021, the Food and Drug Administration released an Emergency Use Authorization for REGEN-COV. Although pregnant persons were not included in the original trials, given the higher risk of morbidity and mortality in the pregnant population, our institution offered REGEN-COV to our pregnant patients beginning in August of 2021. Side effects after REGEN-COV administration are rare and thought to be secondary to COVID-19 rather than REGEN-COV. OBJECTIVE: This study aimed to track safety and clinical outcomes in unvaccinated pregnant patients who received REGEN-COV and to compare these outcomes with those of a contemporary cohort of patients who tested positive for SARS-CoV-2 and were eligible but did not receive REGEN-COV. Our hypothesis was that REGEN-COV administration during pregnancy is safe, and that pregnant persons who received REGEN-COV would experience less severe COVID-19 respiratory illness, with decreased length of hospital stay, rates of intensive care unit admission, and need for oxygen and other COVID-19 therapeutics. STUDY DESIGN: This is a retrospective cohort study of pregnant patients who either tested positive for SARS-CoV-2 or had a known exposure to a COVID-19-positive person, and were therefore eligible for REGEN-COV at our institution. Within this cohort, we compared those who received REGEN-COV with those who did not between March and October of 2021 at Grady Memorial Hospital in Atlanta, Georgia. The main outcomes studied were perinatal outcomes, safety data, and the clinical course of SARS-CoV-2 infection. RESULTS: From March to October of 2021, 86 pregnant people tested positive for SARS-CoV-2 via real-time polymerase chain reaction or had a confirmed exposure. In this group, 36 received REGEN-COV and 50 did not. There were no instances of infusion rate adjustment or discontinuation, anaphylaxis, or death among individuals who received REGEN-COV. One individual experienced worsening shortness of breath >24 hours after administration, which was classified as an infusion-related reaction. There were no significant differences in perinatal outcomes, length of hospitalization, rates of intensive care unit admission, additional pharmacologic treatment for COVID-19, or oxygen requirement between the 2 groups. CONCLUSION: Administration of REGEN-COV is safe in pregnancy and did not increase adverse maternal, neonatal, or obstetrical outcomes. There was not a statistically significant difference in COVID-19-related outcomes in our high-risk population. Given the likely safety of this drug in pregnancy and its known benefits in the nonpregnant population, we advocate for the continued use of this therapy and encourage the development of future studies to enroll a larger and more diverse cohort to explore its efficacy further.

Child Mortality In The US And 19 OECD Comparator Nations: A 50-Year Time-Trend Analysis.

The United States has poorer child health outcomes than other wealthy nations despite greater per capita spending on health care for children. To better understand this phenomenon, we examined mortality trends for the US and nineteen comparator nations in the Organization for Economic Cooperation and Development for children ages 0-19 from 1961 to 2010 using publicly available data. While child mortality progressively declined across all countries, mortality in the US has been higher than in peer nations since the 1980s. From 2001 to 2010 the risk of death in the US was 76 percent greater for infants and 57 percent greater for children ages 1-19. During this decade, children ages 15-19 were eighty-two times more likely to die from gun homicide in the US. Over the fifty-year study period, the lagging US performance amounted to over 600,000 excess deaths. Policy interventions should focus on infants and on children ages 15-19, the two age groups with the greatest disparities, by addressing perinatal causes of death, automobile accidents, and assaults by firearm.

Pyramidal cell-selective GluN1 knockout causes impairments in salience attribution and related EEG activity.

Schizophrenia is a disabling psychiatric disease characterized by symptoms including hallucinations, delusions, social withdrawal, loss of pleasure, and inappropriate affect. Although schizophrenia is marked by dysfunction in dopaminergic and glutamatergic signaling, it is not presently clear how these dysfunctions give rise to symptoms. The aberrant salience hypothesis of schizophrenia argues that abnormal attribution of motivational salience to stimuli is one of the main contributors to both positive and negative symptoms of schizophrenia. The proposed mechanisms for this hypothesis are overactive striatal dopaminergic and hypoactive glutamatergic signaling. The current study assessed salience attribution in mice (n = 72) using an oddball paradigm in which an infrequent stimulus either co-occurred with shock (conditioned group) or was presented alone (non-conditioned group). Behavioral response (freezing) and electroencephalogram (whole brain and amygdala) were used to assess salience attribution. Mice with pyramidal cell-selective knockout of ionotropic glutamate receptors (GluN1) were used to reproduce a prominent physiological change involved in schizophrenia. Non-conditioned knockout mice froze significantly more in response to the unpaired stimulus than non-conditioned wild-type mice, suggesting that this irrelevant cue acquired motivational salience for the knockouts. In accordance with this finding, low-frequency event-related spectral perturbation was significantly increased in non-conditioned knockout mice relative to both conditioned knockout and non-conditioned wild-type mice. These results suggest that pyramidal cell-selective GluN1 knockout leads to inappropriate attribution of salience for irrelevant stimuli as characterized by abnormalities in both behavior and brain circuitry functions.

Implementing tools to support evidence-based practice: a survey and brief intervention study of the National Elf Service across Oxford Health NHS Foundation Trust.

BACKGROUND: Technology and the internet has enabled rapid access to research but most mental health professionals do not have time to keep up with the vast and growing scientific literature. Secondary information sources, such as the National Elf Service (NES), aim to summarise the most important and up-to-date research to improve mental health professionals' access to information to support evidence-based medicine (EBM). OBJECTIVE: To explore mental health professionals' attitudes towards evidence-based practice and methods used to keep up-to-date with research. To promote use of a digital evidence-based platform (the National Elf Service), assess its use and explore its potential to impact clinical practice. METHODS: Baseline and follow-up surveys were distributed among staff of 5 adult mental health community teams and 2 early intervention services (n=331) in Oxford Health Foundation Trust (OHFT) prior to and following an intervention raising awareness of the National Elf Service. FINDINGS: Of 133 baseline survey responders, the majority of staff reported their clinical practice was informed by evidence, mostly using existing clinical guidelines and online resources. Few had used the National Elf Service. 122 staff members completed the follow-up survey. Postintervention, 42 staff members indicated they had used the National Elf Service (compared with 13 preintervention) and that it had improved access to research. Lack of time was most often the barrier restricting evidence-based practice. CONCLUSIONS: Mental health professionals are engaged with EBM and those that used the National Elf Service felt it did, or could have the potential to impact on their clinical practice. CLINICAL IMPLICATIONS: Barriers and challenges to implement EBM more widely suggest targeted efforts should be made to embed evidence-based practice into the working culture.

Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis.

INTRODUCTION: Gabapentin has been extensively prescribed off-label for psychiatric indications, with little established evidence of efficacy. Gabapentin and pregabalin, a very similar drug with the same mechanism of action, bind to a subunit of voltage-dependent calcium channels which are implicated in the aetiopathogenesis of bipolar disorder, anxiety and insomnia. This systematic review and meta-analysis aims to collect and critically appraise all the available evidence about the efficacy and tolerability of gabapentin and pregabalin in the treatment of bipolar disorder, insomnia and anxiety. METHODS AND ANALYSIS: We will include all randomised controlled trials (RCTs) reported as double-blind and comparing gabapentin or pregabalin with placebo or any other active pharmacological treatment (any preparation, dose, frequency, route of delivery or setting) in patients with bipolar disorder, anxiety or insomnia. For consideration of adverse effects (tolerability), single-blind or open-label RCTs and non-randomised evidence will also be summarised. The main outcomes will be efficacy (measured as dichotomous and continuous outcome) and acceptability (proportion of patients who dropped out of the allocated treatment). Published and unpublished studies will be sought through relevant database searches, trial registries and websites; all reference selection and data extraction will be conducted by at least 2 independent reviewers. We will conduct a random-effects meta-analysis to synthesise all evidence for each outcome. Heterogeneity between studies will be investigated by the I2 statistic. Data from included studies will be entered into a funnel plot for investigation of small-study effects. No subgroup analysis will be undertaken, but we will carry out sensitivity analyses about combination treatment, psychiatric comorbidity, use of rescue medications and fixed versus random-effects model. ETHICS AND DISSEMINATION: This review does not require ethical approval. This protocol has been registered on PROSPERO (CRD42016041802). The results of the systematic review will be disseminated via publication in a peer-reviewed journal.

Effect of increased compulsion on readmission to hospital or disengagement from community services for patients with psychosis: follow-up of a cohort from the OCTET trial.

BACKGROUND: Community treatment orders (CTOs) have not been shown in randomised trials to reduce readmission to hospital in patients with psychosis, but these trials have been short (11-12 months). We previously investigated the effect of CTOs on readmission rates over 12 months in a randomised trial (OCTET). Here, we present follow-up data for a cohort of individuals recruited to our original trial to examine the long-term effect of CTOs on readmissions and the risk of patients disengaging from mental health services temporarily or enduringly. METHODS: For OCTET, an open-label, parallel, randomised controlled trial, we recruited patients aged 18-65 years involuntarily admitted to mental health hospitals in 32 trusts in England, with a diagnosis of psychosis and deemed suitable for CTOs by their clinicians. Between Nov 10, 2008, and Feb 22, 2011, we recruited and randomly assigned 336 eligible patients (1:1) to be discharged on either a CTO (n=167) or to voluntary status via Section 17 leave (control group; n=169). For the analysis presented in this report, we assessed data at 36 months for 330 of these patients. We tested rates of readmission to hospital, time to first readmission, number of readmissions, and duration of readmission in patients assigned to CTO versus those assigned to control, and in all patients with CTO experience at any time in the 36 months versus those without. We also tested whether duration of CTO affected readmission outcomes in patients with CTO experience. We examined discontinuation (≥60 days between clinical contacts) and disengagement from services (no clinical contact for ≥90 days with no return to contact) in the whole cohort. OCTET is registered with isrctn.com, number ISRCTN73110773. FINDINGS: We obtained data for 330 patients in the relevant period between Nov 10, 2008 and Feb 22, 2014 (36 months after the last patient was randomly assigned to OCTET). We identified no difference between the randomised groups in the numbers of patients readmitted (100 [61%] of 165 CTOs vs 113 [68%] of 165 controls; relative risk 0·88 [95% CI 0·75-1·03]), number of readmissions (mean 2·4 readmissions [SD 1·91] vs 2·2 [1·43]; incident density ratio [IDR] 0·97 [95% CI 0·76-1·24]), duration of readmissions (median 117·5 days [IQR 63-303] vs 139·5 days [63·0-309·5]; IDR 0·84 [95% CI 0·51-1·38]), or time to first readmission (median 601·0 days [95% CI 387·0-777·0] vs 420·0 days [352·0-548·0]; hazard ratio [HR] 0·81 [95% CI 0·62-1·06]). The CTO experience group had significantly more readmissions than the group without (IDR 1·39 [95% CI 1·07-1·79]) and we noted no significant difference between groups in readmission rates, duration of readmission, or time to first readmission. We did not identify a linear relationship between readmission outcomes and duration of CTO. 19 (6%) patients disengaged from services (12 [7%] of 165 CTOs vs 7 [4%] of 165 controls). Longer duration of compulsion was associated with later disengagement (HR 0·946 [95% CI 0·90-0·99, p=0·023). 187 (57%) experienced no discontinuities, and we noted no significant difference between the CTO and control groups for time to disengagement or number of discontinuities. Levels of discontinuity were associated with compulsion (IDR 0·973 [95% CI 0·96-0·99, p<0·0001]. We identified no effect of baseline characteristics on the associations between compulsion and disengagement. INTERPRETATION: We identified no evidence that increased compulsion leads to improved readmission outcomes or to disengagement from services in patients with psychosis over 36 months. The level of persisting clinical follow-up was much higher than expected, irrespective of CTO status, and could partly account for the absence of CTO effect. The findings from our 36-month follow-up support our original findings that CTOs do not provide patient benefits, and the continued high level of their use should be reviewed. FUNDING: National Institute for Health Research.

Oxytocin reduces amygdala activity, increases social interactions, and reduces anxiety-like behavior irrespective of NMDAR antagonism.

Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala, leading to increased fear and social anxiety. Several studies have demonstrated the prosocial effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of subchronic oxytocin on EEG activity in amygdala of mice during performance of the three-chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, whereas oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate prosocial and social anxiety pathways may mediate social preference.

Associations between continuity of care and patient outcomes in mental health care: a systematic review.

OBJECTIVE: Research investigating the association between continuity of care (CoC) and patient outcomes in mental health care is limited. A previous review (1970-2002) concluded that evidence for an association between CoC and outcomes was inconsistent and limited. This systematic review, conducted a decade later, provides an update. METHODS: Searches (1950-2014) were conducted on MEDLINE and PsycINFO. Included studies used a clearly identified measure of CoC and examined its relation to an outcome among adults (ages 18-65). Only English-language publications were included. RESULTS: A total of 984 studies were identified that measured CoC. Eighteen met inclusion criteria, and 13 found an association between CoC and an outcome. As found in the previous review, studies reported conflicting results for the most frequently examined outcomes (hospitalization, symptom severity, social functioning, and service satisfaction). Little consistency was found between studies in choice of CoC measures and outcomes. Studies varied markedly in quality. Two of the three studies rated as good quality reported significant associations between CoC and social functioning. Compared with older studies, studies published since the previous systematic review (2002-2014) found a larger proportion of significant associations. CONCLUSIONS: Little consistency was found in the way CoC was measured, which made it difficult to compare studies. Therefore, clear evidence about the association between CoC and outcomes remains limited. Results in regard to social functioning are encouraging. However, in order for conclusions to be made, researchers need to be more consistent with the measures they choose to allow comparison of studies.

Animal Models of Psychosis: Current State and Future Directions.

Psychosis is an abnormal mental state characterized by disorganization, delusions and hallucinations. Animal models have become an increasingly important research tool in the effort to understand both the underlying pathophysiology and treatment of psychosis. There are multiple animal models for psychosis, with each formed by the coupling of a manipulation and a measurement. In this manuscript we do not address the diseases of which psychosis is a prominent comorbidity. Instead, we summarize the current state of affairs and future directions for animal models of psychosis. To accomplish this, our manuscript will first discuss relevant behavioral and electrophysiological measurements. We then provide an overview of the different manipulations that are combined with these measurements to produce animal models. The strengths and limitations of each model will be addressed in order to evaluate its cross-species comparability.

Effectiveness of financial incentives to improve adherence to maintenance treatment with antipsychotics: cluster randomised controlled trial.

OBJECTIVE: To test whether offering financial incentives to patients with psychotic disorders is effective in improving adherence to maintenance treatment with antipsychotics. DESIGN: Cluster randomised controlled trial. SETTING: Community mental health teams in secondary psychiatric care in the United Kingdom. PARTICIPANTS: Patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder, who were prescribed long acting antipsychotic (depot) injections but had received 75% or less of the prescribed injections. We randomly allocated 73 teams with a total of 141 patients. Primary outcome data were available for 35 intervention teams with 75 patients (96% of randomised) and for 31 control teams with 56 patients (89% of randomised). INTERVENTIONS: Participants in the intervention group were offered £15 (€17; $22) for each depot injection over a 12 month period. Participants in the control condition received treatment as usual. MAIN OUTCOME MEASURE: The primary outcome was the percentage of prescribed depot injections given during the 12 month intervention period. RESULTS: 73 teams with 141 consenting patients were randomised, and outcomes were assessed for 131 patients (93%). Average baseline adherence was 69% in the intervention group and 67% in the control group. During the 12 month trial period adherence was 85% in the intervention group and 71% in the control group. The adjusted effect estimate was 11.5% (95% confidence interval 3.9% to 19.0%, P=0.003). A secondary outcome was an adherence of ≥ 95%, which was achieved in 28% of the intervention group and 5% of the control group (adjusted odds ratio 8.21, 95% confidence interval 2.00 to 33.67, P=0.003). Although differences in clinician rated clinical improvement between the groups failed to reach statistical significance, patients in the intervention group had more favourable subjective quality of life ratings (ß=0.71, 95% confidence interval 0.26 to 1.15, P=0.002). The number of admissions to hospital and adverse events were low in both groups and did not show substantial differences. CONCLUSION: Offering modest financial incentives to patients with psychotic disorders is an effective method for improving adherence to maintenance treatment with antipsychotics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77769281.