Relapse and frequency of injection of monthly paliperidone palmitate—A retrospective case–control study

BackgroundOutcomes with long-acting injections (LAIs) are generally better than with oral antipsychotic therapy. However, the use of LAIs does not assure compliance with treatment and in clinical practice patients often miss injections or receive their injections later than intended.MethodWe conducted a case–control study to identify demographic and treatment associations with relapse (cases) on paliperidone 1-monthly injection (PP1M) compared with age-, gender-, and ethnicity-matched controls.ResultsWe identified 16 cases and matched 43 controls. Baseline variables did not differ except that cases had received significantly more antipsychotic drugs before initiation with PP1M (3.94 vs. 2.12; p < 0.001). Cases had fewer PP1M injections administered compared with the control group (9.69 vs. 11.37; p < 0.001) and this group had a longer interval between injections than the control group (37 vs. 33 days; p < 0.001).ConclusionsRelapse on PP1M is associated with reduced frequency of injection and a longer interval between doses.     

Clinical improvement,relapse and treatment adherence with paliperidone palmitate 1-month formulation: 1-year treatment in a naturalistic outpatient setting

Purpose: To evaluate paliperidone palmitate 1-month formulation (PP1M) effectiveness in a naturalistic outpatient psychiatric setting.

Materials and methods: We collected data from 50 outpatients affected by schizophrenia disorders treated with PP1M for 12 months in an Italian Mental Health Department. After analyzing selected demographic, clinical and pharmacological variables, we performed mirror analysis to compare psychiatric hospitalizations and urgent consultations required by the same patient 6 and 12 months before and after PP1M implementation (primary outcome). We analyzed clinical improvement in symptom (Clinical Global Impression-severity and improvement) and functioning (Global Assessment of Functioning) scales and drop-out rate during the 12-month PP1M treatment (secondary outcome). Data were statistically analyzed.

Results: The mean PP1M dose was 93.5?mg (±27.7 SD) with a mean interval between each injection of 27.1 d (±4.5 SD). Twenty-three patients (46%) reported adverse effects (sexual dysfunctions, weight gain and extrapyramidal symptoms).Fifteen patients (30%) dropped out after 137.2 d (±103.1 SD) on average: six due to the lack of therapeutic adherence, six due to inefficacy and three due to adverse events. The drop-out patients presented more severe clinical profile in CGI-S and GAF scores at T0 in comparison with others. At mirror analysis, 12-month but not 6-month PP1M treatment statistically significantly reduced psychiatric hospitalizations (t?=?2.3, p?t?=?2.1, p?Conclusions: This naturalistic study indicates that long-term PP1M treatment was safe and effective in preventing hospitalizations and urgent consultations as well as in improving clinical course.     

Factors affecting treatment discontinuation and treatment outcome in patients with schizophrenia in Korea: 10-year follow-up study

Objective

There have been few long-term studies that have assessed factors influencing treatment discontinuation and long-term outcome of schizophrenia in Korea. The present study aimed to evaluate factors affecting treatment discontinuation and treatment outcome, after 10 years, in patients with schizophrenia.

Methods

Among hospitalized patients between 1997 and 1999, 191 patients were given continuous follow-up service. We examined the clinical characteristics and outcome of patients who remained in treatment. Regression analyses were used to find any clinical factors affecting treatment discontinuation.

Results

One hundred thirty-three patients (71.12%) discontinued the treatment. The treatment retention group contained more female patients, paranoid-type patients, patients who had shown self-harming behavior, patients receiving clozapine, and patients with good medication compliance. The recovery rate was 25%. However, 42.3% did not have gainful employment. Further, most patients couldn''t live independently.

Conclusion

The results show the importance of gender, patient behavior, medication, and medication compliance in predicting treatment discontinuation in patients with schizophrenia.     

帕利哌酮缓释片与齐拉西酮治疗精神分裂症对照研究

目的：比较帕利哌酮缓释片与齐拉西酮治疗精神分裂症的疗效与安全性。方法：99例精神分裂症患者随机分为帕利哌酮组48例和齐拉西酮组51例,分别给予帕利哌酮缓释片和齐拉西酮治疗6周。采用阳性与阴性症状量表（PANSS）、个人与社会功能量表（PSP）和治疗中出现的症状量表（TESS）作为评价指标。结果：治疗2周及6周后,两组PANSS评分均低于治疗前（P均〈0．05）;组间比较,以帕利哌酮组PANSS评分显著低于对照组（P均〈0．05）。与治疗前比较,帕利哌酮组个人与社会功能改善显著[PSP评分治疗前和治疗后分别平均（49．85±7．64）分和（60．32±8．24）分];而齐拉西酮组改善不明显[PSP评分分别平均（48．92±5．40）分和（（53．38±6．90）分],组间比较,差异有显著性（P〈0．001）。帕利哌酮缓释片的主要不良反应为锥体外系不良反应、失眠、便秘、泌乳素升高,齐拉西酮主要为心电图QTc间期延长、失眠、头痛、恶心等。结论：帕利哌酮缓释片治疗精神分裂症的疗效和改善社会功能方面均优于齐拉西酮。     

A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia

This 13-week double-blind study was designed to assess noninferiority of the recently approved (in the U.S.) injectable atypical antipsychotic paliperidone palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult patients with schizophrenia. Patients (N = 1220) were randomized (1:1) to either a) PP: deltoid injections on day 1 (150 mg eq.), day 8 (100 mg eq.), and once-monthly flexible dosing as deltoid or gluteal injections on day 36 (50 mg eq. or 100 mg eq.) and day 64 (50 mg eq. or 100 mg eq. or 150 mg eq.) or b) RIS-LAI: gluteal injections days 8 and 22 (25 mg), days 36, 50 (25 or 37.5 mg) and days 64, 78 (25, 37.5 or 50 mg). RIS-LAI-treated patients received oral supplementation with RIS 1-6 mg/day (days 1 to 28), and PP-treated patients received oral placebo. The safety analysis set (n = 1214) included 58% men, 78% white, with mean (SD) baseline PANSS total score: PP, 84.1 (12.09); and RIS-LAI, 83.6 (11.28). Mean (SD) change from baseline to endpoint in PANSS total score decreased similarly in both groups; PP (−18.6 [15.45]) and RIS-LAI (−17.9 [14.24]). PP treatment was noninferior to RIS-LAI (point estimate [95% CI]: 0.4 [−1.62;2.38], per-protocol analysis set [primary analysis]). The tolerability and safety of PP was generally similar to RIS-LAI with no new safety or tolerability findings.     

Patient satisfaction and treatment environment: A 20-year follow-up study from an acute psychiatric ward

The aim of this study was to examine to what extent the different subscales of the Ward Atmosphere Scale (WAS) are related to patient satisfaction on wards for psychotic patients. We wanted to examine if it was possible to replicate previous findings from cross-sectional studies and improve the understanding of which of the WAS subscales that should be considered the most important for patient satisfaction. From 1981 through 2000, the ward atmosphere, in an acute psychiatric ward, was evaluated 11 times with the Ward Atmosphere Scale (WAS). A total of 129 patients completed the WAS as well as a General Satisfaction Index (GSI) comprising three items. Z-scores were calculated to describe the fluctuations in the GSI and the WAS subscales. Four of the WAS subscales, Involvement, Practical orientation, Angry and aggressive behavior and Staff control, strongly co-varied with patient satisfaction. Unexpectedly, the Support and Order and organization subscales correlated only moderately with patient satisfaction. The remaining five WAS subscales (Spontaneous behavior, Autonomy, Personal problem orientation, Program clarity and Staff attitude to expressed feelings) were only weakly correlated with patient satisfaction. This study confirms that four of the six assumedly most important WAS subscales are strongly related to patient satisfaction on wards for psychotic patients. Changes in these WAS subscales seems to be paralleled by changes in patient satisfaction in the expected direction.     

Long-term outcome of pharmacological and psychological treatment for panic disorder with agoraphobia: a 2-year naturalistic follow-up

Two years after completion of a controlled outcome study of treatments for panic disorder with agoraphobia, patients were revisited and interviewed about their complaints. In the initial study, four treatments had been compared: (i) fluvoxamine combined with exposure; (ii) placebo medication plus exposure; (iii) psychological panic management plus exposure; and (iv) exposure alone. Comparison of the results at post-test had revealed superior efficacy of fluvoxamine combined with exposure over the other three treatments in reducing agoraphobic avoidance. The current naturalistic follow-up study investigated the long-term efficacy of the treatments with regard to abatement of complaints and reduced demand for further treatment. In addition, we examined whether patients were able to taper off the study medication without a recurrence of complaints. In total, 71 of the 76 patients of the original trial (93%) were interviewed. Comparison of the mean level of psychopathology at follow-up revealed no difference between the original treatment groups. The effect in the fluvoxamine plus exposure group was maintained, but was no longer superior, due to further improvements in the other treatment groups. Most patients received additional treatment during the follow-up period, usually because the 12 treatment sessions in the controlled study had yielded insufficient improvement. There was a trend for patients who received the fluvoxamine plus exposure treatment to require less aftercare than those who received the other treatments. Finally, almost 50% of the patients who had received medication in the original trial were able to taper off the use of fluvoxamine without a recurrence of complaints.     

Mental health service use by patients with dysthymic disorder: treatment use and dropout in a 7 1/2-year naturalistic follow-up study

Little is known about long-term treatment use among patients with dysthymia. This paper describes patterns of treatment use by 85 outpatients with dysthymic disorder and a comparison group of 36 outpatients with nonchronic (episodic) major depression in a naturalistic follow-up. Patients with dysthymia had higher rates of treatment use across 7 1/2 years compared with patients with episodic major depression. Baseline variables that predicted which patients with dysthymia dropped out of treatment before recovering from dysthymic disorder included age, ethnicity, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition Axis II pathology as obtained from informant reports, higher self-reported autonomy, and receiving psychotherapy alone as compared to receiving a combination of psychotherapy and medication. Dysthymic disorder places a significant burden on the mental health services system, yet many outpatients with dysthymia may be receiving inadequate treatment. Younger patients, ethnic minority patients, and patients with personality disorders may be at increased risk of dropping out from treatment for depression. Combination treatments may increase treatment retention.     

Pattern of health service utilization and predictors of readmission after a first admission for psychosis: a 2-year follow-up study

OBJECTIVE: To explore the pattern of health service utilization over 2 years following a first admission for psychosis and the baseline characteristics predicting readmission. METHOD: Patients included in a cohort of first-admitted subjects with psychosis (n = 84) were assessed at the end of a 2-year follow-up using multiple sources of information. RESULTS: At the end of the follow-up, one of three subjects had no contact with any mental health professional, and 38% of subjects had no contact with a psychiatrist. Half of the patients were readmitted over the 2-year follow-up. The baseline characteristics independently predicting psychiatric readmission were a high number of helping contacts before first admission and persistence of psychotic symptoms at discharge. CONCLUSION: Decreasing the frequency of readmission in the early course of psychosis is a public health priority. Development of psychotherapeutic programs for subjects with early psychosis who have enduring psychotic symptoms at first discharge should be promoted.     

A 6-year clinical and MRI follow-up study of patients with relapsing–remitting multiple sclerosis treated with Interferon-beta

There are few long-term clinical and magnetic resonance imaging (MRI) data on patients treated with interferon-beta (IFN-beta) for relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to provide clinical and MRI data on 68 patients with RRMS treated over a 6-year period and to investigate whether a baseline MRI predicts their long-term clinical and MRI outcome. Six MRI scans were performed monthly before treatment and a further 13 scans were performed during treatment with IFN-beta, the last of which 6 years after commencement of treatment. The relapse rate, disability as measured by the Expanded Disability Status Scale (EDSS), and MRI parameters, including Gd-enhancing lesion load (Gd-LL), T2 hyperintense lesion load (T2-LL) T1 hypointense lesion load (T1-LL) and supratentorial brain volume (SBV) were measured throughout the study. The mean annual relapse rate over the 6 years was 0.52 (SD 0.67), which is significantly lower (68.6%) than the mean annual relapse rate of 1.6 observed during the 2-year period before the commencement of treatment (P < 0.01). The median EDSS score increased from 2 to 2.5, remaining stable in 60% of the patients. From the baseline scan to the final scan, there was a median increase of 7% in the T2-LL and 23.9% in the T1-LL, whilst SBV decreased by 2.7%. The increase in the EDSS over the course of the study was significantly correlated with a reduction in brain volume (r = 0.46, P = 0.001). Greater brain damage at baseline, as measured by both T2-LL and T1-LL, was significantly associated with an increase in disability over the 6 years (r = 0.44, P = 0.0009; r = 0.50, P = 0.0007, respectively). This study shows a sustained effect of IFN-beta on the relapse rate, which is lower than during the 2 years before treatment commencement. More than half the patients showed an improvement or stabilization in the EDSS score. The increment in disability was correlated with the development of brain atrophy but not with increases in lesion burden. Finally, the finding that the extent of lesion burden at the baseline was a strong predictor of increasing disability suggests that IFN-beta treatment might have a moderate effect in modifying the multiple sclerosis (MS) disease course over 6 years unless preventive treatment is started early.     

失匹配负波与情感性精神障碍临床相及

目的 探讨情感性精神障碍患者的夫匹配负波（ＭＭＮ）变异与临床相及治疗的关系。方法应用美国ＮｉｃｏｌｅｔＳｐｉｒｉｔ脑诱发电位仪,记录３９例抑郁症患者（末服药者１８例,服药者２１例）、２２例躁狂症患者和３３名健康有的ＭＭＮ,同时记录Ｐ３００电位比较。对其中１８例末服药抑郁症患者于治疗１周和６周时进行ＭＭＮ和Ｐ３００记录。结果 与健康人组比较,抑郁症组和躁狂症组的ＭＭＮ潜伏期和波幅变化的差异无显著性（     

Effect of smoking habits and concomitant valproic acid use on relapse in patients with treatment-resistant schizophrenia receiving clozapine: A 1-year retrospective cohort study

Introduction

No study has investigated the impact of smoking habits and concomitant valproic acid (VPA) use on clinical outcomes in maintenance treatment with clozapine. Thus, we aimed to examine the effect of smoking habits and concomitant VPA use on relapse during the first year after discharge in patients with treatment-resistant schizophrenia (TRS) receiving clozapine.

Methods

This retrospective cohort study included patients with TRS who were initiated on clozapine during hospitalization and discharged between April 2012 and January 2021 in two tertiary psychiatric hospitals in Japan. Relapse was defined as rehospitalization due to psychiatric exacerbation during the first year after discharge. A multivariable Cox proportional hazards regression analysis was performed to analyze the effect of smoking habits and concomitant VPA use on relapse. Subgroup analyses were also conducted to examine potential interactions between smoking habits and concomitant VPA use.

Results

Among the included 192 patients, 69 (35.9%) met the criteria of relapse. While smoking habits (adjusted hazard ratio [aHR], 2.27; 95% confidence interval [CI], 1.28–4.01; p < 0.01) independently increased the risk of relapse, a significant interaction for relapse risk was found between smoking habits and concomitant VPA use (p-interaction = 0.015). Concomitant VPA use may be an effective modifier of the increased relapse risk associated with smoking habits. Among patients who smoked, those using VPA concomitantly exhibited a higher risk of relapse (aHR, 5.32; 95% CI, 1.68–16.9; p < 0.01) than those not using VPA (aHR, 1.41; 95% CI, 0.73–2.70; p = 0.30).

Conclusion

The findings suggest that the combination of smoking habits and concomitant VPA use may increase the risk of relapse after discharge. Future studies are required to elucidate the mechanisms underlying these findings, such as a decrease in clozapine blood levels.     

Risks of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder treated with long-acting injectable or oral antipsychotics: A population-based retrospective cohort study in Taiwan

BackgroundLong-acting injectable (LAI) antipsychotics improve medication adherence in patients with schizophrenia and extend the duration of therapeutic drug levels but with administration of an increased dose. Real-world mortality data in patients prescribed LAIs are lacking. We conducted a population-based cohort study to estimate and compare the incidence rates of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder exposed to LAIs and oral antipsychotics.MethodsPatients with a diagnosis of schizophrenia/schizoaffective disorder between January 1, 2015 and November 30, 2019 were enrolled from the Taiwan National Health Insurance Research Database and linked to Death Registry records. Eligible patients were new antipsychotic users. Relative risks of death for each antipsychotic compared with oral paliperidone were evaluated using a Cox proportional hazard model adjusted for age, sex, Charlson Comorbidity Index, index year, bipolar or major depressive or other mood disorders, mental disorders due to drug use, and baseline hospitalization frequency.ResultsThere were 228,791.08 person-years of follow-up (mean 2.48 years). The incidence rates of all-cause death in users of LAI paliperidone administered monthly (PP1M) and every 3 months (PP3M) were 7.40/1,000 person-years (95% confidence interval 5.94–9.11) and 9.93 (5.88–15.79), respectively. The incidences of completed suicide were 2.03/1,000 person-years (1.32–2.99) and 3.10 (1.14–6.88), respectively. No significant associations were observed between PP1M and PP3M compared to oral paliperidone in incidences of all-cause death or for completed suicide.DiscussionNo increased risk of all-cause death or completed suicide was observed in users of antipsychotic LAIs, including PP1M and PP3M.     

The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up

The present study assessed the long-term (i.e., 24 months) efficacy of the ketogenic diet (KD) as an add-on therapy in children with refractory epilepsy, with focus on seizure frequency, seizure severity, and tolerability. Most patients were treated with the MCT-diet.At one and two years, 33% and 23%, respectively, of the 48 included patients were still on the KD. After three months, one year, and two years of treatment, 16.7% of the patients were responders. The highest responder rate (i.e., 22.9%) was seen at six and nine months of treatment. Of the fifteen patients with seizure clusters during baseline, 60% were responders after three months when looking at cluster reduction and most of them were not responders for the total seizure frequency. From three months of treatment onwards, most of the patients had a relevant decrease in seizure severity which was mainly related to the most severe seizure type.Gastrointestinal dysfunction was often reported, especially in the first six weeks of treatment. Growth deceleration was present in 30% of the patients, and weight reduction in 15%.Improved arousal was mentioned in 30% of patients. No patients developed ECG abnormalities or kidney stones. Increase in lipid profile was rare.The KD is an effective therapy for children with therapy-resistant epilepsy. Effectiveness is reflected in the reduction of seizure frequency as well as in the reduction of seizure severity. After 6 months of treatment, it is obvious which patients are responders and tolerate the treatment well. Most of these patients will continue to benefit from the KD for a longer time. Long-term use of the diet was well tolerated.     

Factors associated with recovery and recurrence of depression in older people: A prospective study

The Liverpool Continuing Health in the Community Study has followed up 1070 elderly community subjects over 6 years. In the first year 123 subjects had case-level depression. Three years later 49 (39.8%) of the previously depressed were recovered, 33 (26.8%) were depressed, 16 (13%) were not available for interview and 25 (20.3%) were dead. This study looks at factors associated with the 3-year outcome of patients who were depressed at year 0. Two outcome groups that were compared were a recovered depression group and a recurrent/persistent depression group. The factors that were significantly associated with a recurrence of depression (or persistent depression) at year 3 were bereavement of a close figure in the 6 months before interview, loneliness and life dissatisfaction at year 3. A variety of traditional risk factors for depression (including age, marital status, physical ill-health and incapacity) failed to attain significance in predicting recurrent or persistent depression. When combined, both recovered and recurrently depressed groups at year 3 had significantly higher levels of pain and a higher number of serious upsets in the past 6 months and 6 weeks compared to a compared to a control group. The depressed at year 0 were more likely to have entered more dependent forms of accommodation by year 3.     

A 3-year follow-up study on cardiovascular disease and mortality in older people with intellectual disabilities

BackgroundWith increasing longevity and a similar or increased prevalence of cardiovascular disease risk factors (as compared to the general population), people with intellectual disabilities (IDs) are at risk of developing cardiovascular disease. However, prospective studies on incidence and influencing factors of cardiovascular disease and mortality are lacking.MethodsA three year follow-up study was undertaken to study the incidence and symptoms at presentation of myocardial accident, stroke and heart failure in older people with ID. Furthermore, the predictive value of cardiovascular disease risk factors on myocardial accident, stroke and heart failure and on all-cause mortality were studied. The baseline group consisted of the 1050 participants, aged 50 years and over, in the Dutch Healthy Ageing and Intellectual Disability (HA-ID) study. Baseline measurements were conducted between November 2008 and July 2010. Three years after baseline, medical files of 790 participants were studied.ResultsCardiovascular disease (myocardial infarction, stroke and heart failure) occurred in 5.9% of the population during 3 year follow-up, and 32% of them died due to the condition. Incidence of myocardial infarction is 2.8 per 1000 personyears, for stroke 3.2 per 1000 personyears and for heart failure 12.5 per 1000 personyears. Incidence of these conditions is probably underestimated, due to atypical symptom presentation. The use of atypical antipsychotics and a history of heart failure were predictive for myocardial infarction. Heart failure was predicted by abdominal obesity, chronic kidney disease and a history of heart failure. A total of cardiovascular disease (myocardial infarction, stroke or heart failure) was predicted by abdominal obesity, a history of stroke and a history of heart failure. A low body-mass index, peripheral arterial disease, chronic kidney disease and inflammation were predictive for 3-year all-cause mortality.ConclusionIncidence of cardiovascular disease in older people with ID is similar to that in the general population. A pro-active assessment and treatment of the presented cardiovascular disease risk factors may reduce cardiovascular disease and mortality in older people with ID.