Objective:To review the pharmacology, pharmacokinetics, efficacy, safety, use requirements, and place in therapy of esketamine for treatment-resistant depression (TRD). Data Sources: A comprehensive PubMed search (1966 to October 2019) was conducted using the search terms depression, treatment-resistant, suicide, intranasal, esketamine, and JNJ-54135419. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling, and Clinicaltrials.gov . Study Selection and Data Extraction: All English-language trials evaluating intranasal esketamine for TRD were included and discussed. Data Synthesis: Intranasal esketamine was approved by the US Food and Drug Administration, in conjunction with an oral antidepressant, for treating TRD in adults. Two short-term trials (TRANSFORM-1 and -2) found statistically significant reduction in the Montgomery-Asberg Depression Rating Scale score at day 28 for the fixed 56-mg dose (−4.1; 95% CI = −7.69 to −0.49; P = 0.027 [exploratory]) and flexible-dosed arms (−4.0; 95% CI = −7.31 to −0.64; P = 0.02), though the fixed-dose 84-mg arm (−3.2; 95% CI = −6.88 to 0.45; P = 0.088) of TRANSFORM-1 and TRANSFORM-3 did not (−3.6; 95% CI = −7.2 to 0.07; P = 0.059). Two long-term trials (SUSTAIN-1 and -2) suggested maintenance of response with continued use. Esketamine’s adverse effects include dizziness, dysgeusia, somnolence, dissociation, suicidal thoughts and behaviors, and increased heart rate and blood pressure. Relevance to Patient Care and Clinical Practice: Although providing a novel antidepressant mechanism and formulation for TRD, esketamine’s role in treatment will likely be limited by cost, administration, and diversion concerns. Conclusion: Intranasal esketamine significantly reduced depression symptoms in TRD, though with tolerability issues.
Background:All antipsychotics are associated with extrapyramidal symptoms (EPS). These can present as dysphagia, esophageal dysmotility, or aspiration, all of which may not be recognized as EPS.Case Report:A 62-year-old with schizophrenia, prescribed olanzapine 5 mg daily, presented agitated and endorsed difficulty swallowing. Speech therapy suggested her complaints were related to either reflux or dysmotility. Esophageal manometry showed her lower esophageal sphincter was not fully relaxing, and identified an esophagogastric junction outflow obstruction. Despite therapeutic dilation, oral intake remained poor. Following an increase in olanzapine, she developed EPS, her dysphagia worsened, and she was choking on food. Following a switch to aripiprazole her EPS and appetite improved, and she ceased complaining of dysphagia.Discussion:Dysphagia has been reported with first- and second-generation antipsychotics. A review of the second-generation antipsychotic literature identified case reports of dysphagia with clozapine (n = 5), risperidone (n = 5), olanzapine (n = 2), quetiapine (n = 2), aripiprazole (n = 1), and paliperidone (n = 1). Postulated mechanisms of antipsychotic-induced dysphagia include that it may be an extrapyramidal adverse reaction or related to anticholinergic effects of antipsychotics. Management of dysphagia includes discontinuing the antipsychotic, reducing the dose, dividing the dose, or switching to another antipsychotic. Complications of dysphagia include airway obstruction (eg, choking, asphyxia), aspiration pneumonia, and weight loss. Additional complications include dehydration, malnutrition, and nonadherence to oral medications.Conclusion:It is important to recognize symptoms of dysphagia and esophageal dysmotility in antipsychotic-treated patients. Intervention is necessary to prevent complications.
Pimavanserin is a novel 5-HT inverse agonist that has shown promising results for managing hallucinations and delusions in patients with PDP without worsening motor effects or orthostasis. Yet its high cost and specialty pharmacy access may limit use in clinical practice.
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