Schizophrenia is a chronic disease that requires lifelong medical care and supervision. There is a high rate of relapse, mostly caused by poor adherence to oral antipsychotics. Long-acting injectable (LAI) antipsychotics have proved effective in schizophrenia and other severe psychotic disorders due to the stable blood levels, leading to a reduction of the risk of relapse. LAIs are associated with better functioning, quality of life, and patient satisfaction. In Treatment-resistant schizophrenia the combination of antipsychotics is a common practice. Nevertheless, the combination of two different long-acting injectable antipsychotics is not frequent.

A case of a 34-year-old man is presented, previously diagnosed of Schizophrenia, with highly disabling chronic positive symptoms. With no in-sight and no will in receiving treatment. Has been stable for a year while being in treatment with paliperidone 525mg LAI/ 10 weeks, and aripiprazole 400mg LAI/28 days.

The patient was closely observed and given oral paliperidone, after 5 days long-acting paliperidone was introduced. He was discharged with mild improvement of his psychiatric symptoms. While being in treatment with Paliperidone 525mg, he kept vivid delusions and hallucinations. The patient still refused to take any oral medications. Long-acting aripiprazole 300mg was added to the treatment.

He showed clinical improvement after a month. He has been stabilized for one year.

Treating resistant schizophrenia is among the most challenging clinical endeavors. A very helpful approach to improve adherence in schizophrenia is the use of long-acting injectable (LAI) antipsychotics. A major effort on scientific research of combination of LAI is needed.

No significant relationships.

Long-acting injectable antipsychotics (LAIs) have emerged as a new therapeutic option to treat patients suffering a psychotic disorder. To date, there is a lack of studies regarding safety and clinical use pattern of LAIs in pregnant women.

Provide evidence and real world clinical data of pregnant women with schizophrenia who have been treated with long-acting aripiprazole monohydrate (aripiprazole once monthly [AOM] condition) during their pregnancy.

Descriptive real-world clinical experiences of pregnant women in treatment with AOM. The information was obtained by reviewing electronic medical records and by direct clinical observation management.

The first six case-series describing the pregnancy course of women with schizophrenia treated with AOM. All of them remained psychopathologically stable through pregnancy, and their infants became healthy with normal developmental milestones (Table 1).

Table 1.

Clinical characteristics of six case-reports.

The favorable results in this case-series suggest that despite the lack of evidence on reproductive safety and treatment with AOM during pregnancy, this therapeutic option should be considered in pregnant women with schizophrenia. However, further research on the use of long-acting antipsychotics in pregnant women is needed.

No significant relationships.

Maintaining remission, preventing from future episodes, better treatment adherence and improving the quality of life are main aims of long-term treatment in bipolar disorders (BD). In recent years, new generation long-acting injectable (LAI) antipsychotics have been frequently used in maintenance treatment for bipolar disorders.

We aimed to review socio-demographic and clinical characteristics of bipolar patients taking LAI treatment for maintenance treatment.

Clinical records of 44 bipolar patients who are on LAI treatment and followed in Mazhar Osman Mood Clinic (MOMC) of Selcuk University Medical Faculty were evaluated.

Nearly half of the patients were male (n:24, 54%). 43,2% of the patients were married. The mean age was 36.6±11.9 years and the mean duration of education was 11.5±3.9 years. All of the patients were diagnosed with bipolar 1 disorder. Most of the patients (65.9%) was on aripiprazole LAI while remaining was receiving paliperidone LAI for maintenance treatment. Ten of the patients discontinued the treatment due to the side effects and extrapyramidal side effects was the most common side effect. Relapse was observed in 25% of the patients and there was no difference between aripiprazole and paliperidone in terms of relapse rate.

LAI new generation antipsychotics are taking place in long-term treatment of bipolar disorder via improving treatment adherence. Side effect profile of aripiprazole and paliperidone are different. However, we could not find any difference between two drugs in terms of side effects and relapse rates. Small sample size and shorter duration of follow-up should be considered as limitations.

No significant relationships.

Despite the widespread use of long-acting injectable (LAI) antipsychotics in schizophrenia and other disorders, there is a lack of longitudinal studies evaluating prescription trends and the usefulness of therapeutic drug monitoring (TDM) to inform dosing. Indeed, LAI prescription varies greatly among different areas of the world and over the years.

Assess trends in LAI prescription in 2013-2020 at the Psychiatry Department of Bozen, Italy, and (2) analyze the correlation between dose of prescribed LAIs and blood levels measured via TDM.

Parametric statistics.

LAIs were administered to 471 patients (x̅ age±SD=47.2±16.3 years; 56.3% men). The pie chart shows LAI treatment duration, i.e., from 1 to 7 consecutive years. The most used LAIs were haloperidol in 2013-2104 (26.5-31.8%) and paliperidone in 2015-2020 (22.5-25.7%). Dose adjustments were rather frequent, whereas the switch between LAI, due to moderate-to-side effects or unsatisfactory improvement of clinical status, was infrequent (41 cases/8 years). LAI interruption for the same reasons or non-compliance was even more infrequent (10 cases), but in 8 cases it happened for opposite reasons, i.e., achievement of patients’ stabilization and good compliance. The Table shows doses and plasma levels of LAIs. Correlations between doses and plasma levels were: haloperidol: r=-0.037, p=0.620; paliperidone: r=0.290; p=0.000; risperidone: r=0.219, p=0.006; fluphenazine r=0.358, p=0.000; aripiprazole: r=-0.051, p=0.610; olanzapine: r=-0.090, p=0.634.

Haloperidol and paliperidone were the most used LAIs. Drug prescription trends and doses were stable over time. A significant positive correlation between dose and plasma level was found for paliperidone, fluphenazine, and aripiprazole.

No significant relationships.

Long-acting injectable (LAI) antipsychotics are related to proven compliance to treatment and more constant medication levels (hence the apparent lower side-effect burden).

To highlight the experience with LAI antipsychotic treatment during pregnancy.

Literature review.

Seven cases are reported. A 35year old with schizophrenia received zuclopenthixole LAI (mostly 200mg/monthly) during both her pregnancies (of healthy girls born at weeks 39 and 40). A 35year old with schizophrenia was under risperidone LAI (25mg/2 weeks) and gave birth to a healthy girl at week 37. Another 35year old (probably with schizophrenia) was on olanzapine LAI (300mg/month during the last quarter of her pregnancy) that led to the birth of a healthy girl at week 40. A 37year old with schizophrenia received paliperidone LAI (100mg/monthly, last injection at week 28) and gave birth to a healthy boy at week 39. Paliperidone LAI (50mg/monthly) was the treatment of another 34year old with schizoaffective disorder that gave birth to a healthy boy at week 40, as well as of a 26year old (263mg/3-monthly), mother of a healthy boy as well (born at an unspecified week of pregnancy). Finally, a 43year old with bipolar disorder was on aripiprazole LAI (300mg/monthly) during her pregnancy that led to the birth of a healthy girl at week 40.

All pregnant women on LAI antipsychotic treatment gave birth to (apparently) healthy babies. LAI doses were mostly low. Long-term follow-up could clarify eventual delayed aftereffects. Based on the literature, LAI antipsychotic treatment could be considered as an option for selected pregnant patients.

No significant relationships.

To evaluate the effectiveness of long-acting injectable antipsychotics (LAI-a) in reducing the 90-day and annual readmission rates in schizophrenia inpatients.

We conducted a cross-sectional study and included 180 adult patients with psychotic disorders discharged from 2018 to 2019 at a state psychiatric hospital. Descriptive statistics were used to measure the differences between the readmit and nonreadmit cohorts. Logistic regression model was used to measure the odds ratio (OR) for 90-day and annual readmission and was controlled for potential readmission risk factors.

A lower proportion of patients receiving LAI-a were readmitted within 90-day (28.6%) and 1-year (32.4%) periods. Patients receiving LAI-a had lower odds of association for 90-day (OR 0.36, 95% confidence intervals [CI] 0.139-0.921) and annual (OR 0.35, 95% CI 0.131-0.954) readmissions compared to those discharged on oral antipsychotics. A higher proportion of inpatients who received fluphenazine LAI had 90-day (25%) and annual (18.2%) readmissions compared to other LAI-a.

Utilization of LAI-a in patients with psychotic disorders can decrease both 90-day and annual psychiatric readmissions by 64% to 65%. Physicians should prefer LAI-a to reduce the readmission rate and improve the quality of life, and decrease the healthcare-related financial burden.

Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders.

We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed.

Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004).

This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients.

Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination.