Esketamine nasal spray in patients with treatment-resistant depression: the real-world experience in the French cohort early-access programme.

OBJECTIVE: To present the first real-world data of patients with treatment-resistant depression (TRD) treated with esketamine through a French cohort Temporary Authorisation for Use (ATUc) programme. METHODS: In 2019, the French Health Authorities exceptionally granted the first ATUc in psychiatry for TRD patients. Clinical characteristics, safety and efficacy data were reported by physicians. The ATUc ended ∼6 months after initiation. RESULTS: The cohort (n = 66; median age 53.0 years; 62.1% female; 78.8% with severe major depressive episodes; resistance to a mean of 4.2 previous antidepressants) received esketamine treatment for a median of 30 days. Among 46 analysed patients, 22 (47.8%) achieved response (Montgomery-Åsberg Depression Rating Scale [MADRS] total score reduction ≥50.0%) and 17 (37.0%) achieved remission (MADRS total score of ≤12) at least once at a median of 18.5 (2.0-77.0) and 21.0 (2.0-46.0) days after initiation, respectively. By Week 4, patients had a 31.6% probability of achieving remission (Kaplan-Meier method). Sedation, somnolence, dizziness, hypertension, anxiety and dissociation were the most frequently reported (>10.0%) adverse events. No new safety signals were identified. CONCLUSIONS: Patient characteristics of this cohort demonstrate high-level treatment resistance. The safety and efficacy of esketamine in patients with TRD in real-world clinical practice were consistent with Phase 3 trials.Key pointsPatients with treatment-resistant depression (TRD) exceptionally received esketamine nasal spray ahead of its launch through a French cohort Temporary Authorisation for Use (ATUc) programme.The clinical characteristics of 66 adult patients with TRD included in this cohort demonstrated a high-level of resistance to conventional treatments at the time of treatment request prior to esketamine initiation.No new safety signals were observed with esketamine initiation during the ATUc period compared with the Phase 3 clinical trials.The safety and efficacy of esketamine in the real world remain consistent with that established in Phase 3 clinical trials.The data collected during this ATUc also provide the first real-world data on the management and practical use of esketamine in a hospital setting in France.

Initiation of quarterly palmitate paliperidone in French clinical practice: Results from the observational, cross-sectional OPTIMUS study.

PURPOSE: Long-term antipsychotic treatment is key to a positive clinical outcome in schizophrenia. Recent guidelines recommend the prescription of long-acting antipsychotic formulations (LAIs) as early as the first episode in patients with schizophrenia. The OPTIMUS study evaluated real-world use of a new three-monthly paliperidone palmitate formulation (PP3M) in France. METHODS: For this observational cross-sectional study, all French psychiatrists were invited to enrol patients who had initiated PP3M in the previous 4 months. Snapshot data were collected at a routine consultation, without any modification of clinical practice. RESULTS: This population of 350 patients with schizophrenia started on PP3M predominantly included single men, living independently with a diagnosis of schizophrenia for a median of 9.3 years. Demographic characteristics were broadly comparable to those reported in other studies on LAIs. Investigators cited treatment simplification (96.9%) and patient comfort (93.3%) as the most common reasons for switching to PP3M; enhancing adherence was mentioned less often (61.1%) with most patients previously considered as adherent, and a majority of them expressing a positive attitude to their treatment. One-third of patients accepted the psychiatrist's proposal to initiate PP3M treatment without any discussion, and relatives were involved in the therapeutic decision-making process in only 23.7% of cases. After initiation, few changes were seen in professional follow-up frequency or concomitant pharmacological and non-pharmacological treatment modalities except for a decrease in antipsychotic polytherapy. CONCLUSIONS: PP3M is mostly prescribed in adherent patients with fairly stable schizophrenia, and the longer dosing interval does not substantially affect patient care.

Predictive factors of functional remission in patients with early to mid-stage schizophrenia treated by long acting antipsychotics and the specific role of clinical remission.

BACKGROUND: Functional remission has become a major therapeutic objective in schizophrenia, but the probability of such positive outcome has a large variability, ranging from 15% to 51%. Additionally, how clinical remission constitutes a prerequisite for functional remission also remains unclear. METHODS: A prospective observational study was conducted in French schizophrenic patients who initiated treatment with a long-acting injectable (LAI) after an acute episode. Functional and clinical remissions were assessed using the FROGS and the Andreasen criteria, and the role of clinical remission and predictive factors of functional remission was evaluated. RESULTS: Three hundred three patients with schizophrenia (DSM-IV criteria) were followed for 12 months. At 12 months, 45.1% of the patients reached functional remission while 55.1% obtained clinical remission. Clinical remission facilitated functional remission (OR = 14.74), especially in patients with psychosis for less than 5 years (OR = 23.73). Other predictive factors concerned the family environment, education level, employment status, baseline functioning levels and level of insight. CONCLUSIONS: About half of patients treated with LAI reached functional remission after one year of follow-up. Reduced clinical symptoms and reaching clinical remission largely favored functional remission. These results stress the importance of continuous and appropriate symptomatic treatment to reach functional remission and maximize recovery chances.

Comparison of Paliperidone Palmitate and Risperidone Long-Acting Injection in Schizophrenic Patients: Results From a Multicenter Retrospective Cohort Study in France.

PURPOSE/BACKGROUND: The study objective was to compare the impact of being treated by paliperidone palmitate (PP) or risperidone long-acting injection (RLAI) on the length of stay on initial hospitalization, rehospitalization risk, and treatment duration in schizophrenic patients. METHODS: We conducted an observational retrospective cohort study in 43 centers in France, including schizophrenic patients who initiated a treatment by PP or RLAI during initial hospitalization. The follow-up periods started in September 2012 for the RLAI group (median follow-up duration, 233 days) and in June 2013 for the PP group (259 days). Statistical analyses were based on Cox regression models, with propensity score weighting to account for differences in patients' characteristics. FINDINGS/RESULTS: The analysis included 347 patients: 197 in the PP treatment group and 150 in the RLAI group. Compared with patients on RLAI, patients on PP were significantly more likely to have nonpsychiatric comorbidities, to have been on previous antipsychotic therapy, or to have been hospitalized for psychiatric care in the previous year. With regard to length of stay on initial hospitalization, there was no statistically significant difference between both groups (hazard ratio, 1.13 [0.97; 1.31]). Being on PP was associated with similar times to first rehospitalization compared with RLAI (hazard ratio, 0.92 [0.65; 1.30]). IMPLICATIONS/CONCLUSIONS: We observed nonsignificant differences in initial hospitalization duration and time to rehospitalization between PP and RLAI, potentially due to lack of statistical power. A trend was observed in favor of PP with regard to time to treatment discontinuation, although this result was compromised by patients who switched between RLAI and PP.

Medication adherence in patients with psychotic disorders: an observational survey involving patients before they switch to long-acting injectable risperidone.

BACKGROUND: Maintaining antipsychotic therapy in psychosis is important in preventing relapse. Long-acting depot preparations can prevent covert non-adherence and thus potentially contribute to better patient outcomes. In this observational survey the main objective is to evaluate medication adherence and its determinants for oral treatment in a large sample of patients with psychosis. METHODS: In this cross-sectional survey medication adherence for oral treatment was assessed by patients using the patient-rated Medication Adherence Questionnaire (MAQ). Data were collected by physicians on patients with a recent acute psychotic episode before switching to long-acting injectable risperidone. Other evaluations included disease severity (Clinical Global Impression - Severity), patients' insight (Positive and Negative Syndrome Scale item G12), treatment acceptance (clinician-rated Compliance Rating Scale), and therapeutic alliance (patient-rated 4-Point ordinal Alliance Scale). RESULTS: A total of 399 psychiatrists enrolled 1,887 patients (mean age 36.8±11.9 years; 61.6% had schizophrenia). Adherence to oral medication was "low" in 53.2% of patients, "medium" in 29.5%, and "high" in 17.3%. Of patients with psychiatrist-rated active acceptance of treatment, 70% had "medium" or "high" MAQ scores (P<0.0001). Medication adherence was significantly associated with therapeutic alliance (4-Point ordinal Alliance Scale score; P<0.0001). Patient age was significantly associated with adherence: mean age increased with greater adherence (35.6, 36.7, and 38.6 years for patients with "low", "medium", and "high" levels of adherence, respectively; P=0.0007), while age <40 years was associated with "low" MAQ classification (P=0.0003). Poor adherence was also associated with a diagnosis of schizophrenia (P=0.0083), more severe disease (Clinical Global Impression - Severity ≥4; P<0.0001), and lower insight (Positive and Negative Syndrome Scale-G12 ≥4; P<0.0001). CONCLUSION: Self-reported adherence was low in most patients, with a strong positive association between self-reported adherence and psychiatrists' assessment of treatment acceptance. Understanding factors associated with poor medication adherence may help physicians to better manage their patients, thereby improving outcomes.