Journal of Clinical Psychopharmacology最新文献

Objectives: The primary objective of this study was to evaluate the efficacy and safety of increasing the dose of lurasidone from 40 mg/d to 80 mg/d in patients with schizophrenia.

Methods: This post hoc analysis focused on patients who completed a 6-week double-blind, placebo-controlled trial of lurasidone and transitioned to a subsequent 12-week open-label extension trial. Patients initially assigned to lurasidone (40 mg/d) or placebo during the double-blind trial (DBT-LUR group or DBT-PLA group, respectively) received lurasidone (40 mg/d) during the extension. Clinicians could increase the dose to 80 mg/d based on clinical judgment. The efficacy outcomes included the change in the Positive and Negative Syndrome Scale (PANSS) total score from the start to the end of the lurasidone (80 mg/d) treatment period. Safety outcome was the rate of newly emergent adverse events.

Results: Of 287 patients in the intention-to-treat population, 153 received an increased dose of lurasidone from 40 mg/d to 80 mg/d. Significant reductions in the PANSS total scores were observed in both groups (all P values, ≤0.001). Additionally, 35.9% of the DBT-LUR group and 40.0% of the DBT-PLA group achieved a ≥20% reduction in the PANSS total score. New adverse events emerged in 47.4% of the DBT-LUR group and 48.0% of the DBT-PLA group during the lurasidone (80 mg/d) treatment period.

Conclusions: Increasing the dose of lurasidone from 40 mg/d to 80 mg/d may be effective and well tolerated in patients with schizophrenia. Because of the lack of a control group and blinding, the results should be interpreted with caution.

Purpose/background: Agitated depression is a specific variant of depressive disorder characterized by marked psychomotor agitation, including prominent restlessness and pacing, intense anxiety, irritability, and insomnia. These symptoms can be severe, and patients might be at increased risk of suicide. Authors have suggested that agitated depression can worsen with the use of antidepressants but can respond to options such as electroconvulsive therapy (ECT), lithium, anticonvulsants, antipsychotics, and benzodiazepines. Appropriate identification of this variant of depressive disorder is essential for proper treatment, as some of these patients might be labeled as resistant to treatment due to the worsening or lack of response to several antidepressant trials.

Methods/procedure: Summary of 2 recent cases and literature review on agitated depression symptoms and treatment.

Finding/results: Our 2 patients presented with symptoms of depressed mood, increased anxiety, irritability, poor sleep, poor appetite, restlessness, rumination, indecisiveness, and psychosis. Both patients had worsening symptoms with the use of various antidepressants but improved with the use of lorazepam and olanzapine. We review literature describing this variant of depressive disorder and its suggested treatment.

Implication/conclusion: Agitated depression has been poorly characterized in the literature. The criteria suggested by Koukopoulos et al (Acta Psychiatr Scand. 2007;115:50-57) and the provisional criteria for melancholia, as indicated by Mahgoub et al (Front Psychiatry. 2024;15:1372136), might help recognize this variant of depressive disorder. These patients might have a poor response or worsen with the use of antidepressants while responding to options like gamma-amino butyric acid (GABA) agonists, antipsychotics, and ECT.

Background: Clozapine has demonstrated efficacy in treating treatment-resistant schizophrenia; however, it has a wide range of side effects. Sialorrhea is a common side effect of clozapine that causes the patient to withdraw from social life. This review aims to evaluate and summarize the prevalence, mechanism, risk factors, and management of clozapine-associated sialorrhea.

Procedures: The literature was explored for the prevalence, the mechanisms, the risk factors, and the management of sialorrhea. The following search strings and terms were used: "clozapine," "sialorrhea," "hypersalivation," "clozapine induced sialorrhea," and "clozapine induced hypersalivation".

Study results: Hypersalivation is one of the most common side effects of clozapine. Over the course of clozapine therapy, hypersalivation has been reported to have an incidence of 30% to -80%. Although different treatment approaches are applied on a case-by-case basis in the clinic, depending on the practitioners' preferences, there is a lack of clear guidelines for managing this common side effect that jeopardizes patients' social life.

Conclusions: It is important for healthcare professionals and patients that some clear treatment options for clozapine-associated sialorrhea are brought to the forefront and widely used, especially based on the research conducted to date.

Purpose/background: Antipsychotic polypharmacy (APP) is controversial yet applied in 20% of patients with psychotic disorders. We investigated indications for initiating and continuing APP, including the contribution of unfinished cross-titrations.

Methods/procedures: This 2-month study was part of a prospective study to reduce inappropriate APP in inpatients. With each new prescription resulting in APP, we asked the prescriber for the indication (eg, switching antipsychotics, sedation for agitation/sleep disorders, treatment refractoriness, other) and repeated this at 30 and 60 days. Secondary outcome was unfinished cross-titration at 60 days.

Findings/results: In a consecutive cohort of 55 patients, 80% diagnosed with schizophrenia, switching antipsychotics was the primary initial indication for APP in 31 of 55 patients (56%), followed by sedation in 12 of 55 patients (22%), and treatment refractoriness in 10 of 55 patients (18%). Overall, APP was discontinued after 30 days in 25 of 55 patients (45%) and after 60 days in 28 of 55 patients (51%). At 60 days, APP initiated for switching antipsychotics was ongoing in 9 of 31 patients (29%), APP initiated for sedation was ongoing in 8 of 12 patients (66%), and APP initiated for refractoriness was ongoing in 9 of 10 patients (90%). The initial indication for APP was maintained at 60 days in 21 of 27 patients (78%). Unfinished cross-titration occurred in 9 of 31 patients (29%) with APP initiated for switching antipsychotics.

Implications/conclusions: APP was initiated primarily because of cross-titration switching of antipsychotics. The reason for APP was generally maintained consistently over time, particularly when initiated for treatment refractoriness. Of all patients with APP initiated to switch antipsychotics, 29% ended in unfinished cross-titration.