Dextromethorphan/Bupropion: A Novel Treatment for Patients With Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) affects millions of people and is the leading cause of disability worldwide. Patients report decreased quality of life and ability to perform activities of daily living. It is estimated that the current standard of care, which includes pharmacologic therapy with a selective serotonin reuptake inhibitor, is effective in 40%-60%. Additional treatment options are warranted. The combination of dextromethorphan (DEX) and bupropion (BUP) (Auveulty) was approved for treatment in 2022. This unique combination offers an interesting mechanism of action and favorable onset of action for patients with MDD. PHARMACODYNAMICS AND PHARMACOKINETICS: The mechanism of action of DEX-BUP when used in combination is unique. DEX is a noncompetitive N-methyl-d-aspartate receptor antagonist rapidly metabolized through the CYP450 2D6. BUP is an aminoketone and CYP2D6 inhibitor, which results in increased plasma levels of DEX through competitive CYP2D6 inhibition. CLINICAL TRIALS: In a phase 2 clinical study, the efficacy of DEX-BUP was compared with BUP alone in patients with clinically diagnosed MDD. At baseline, participants had moderate-to-severe depression using the Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impressions Severity (CGI-S) scales. There was a significant overall reduction in MADRS and CGI-S scores in the treatment group compared with the BUP monotherapy with improvement observed as early as week 1 of treatment. Later, a phase 3 study was conducted comparing DEX-BUP 45 mg/105 mg with placebo in patients with moderate-to-severe MDD. Similarly, MADRS and CGI-S scores were significantly reduced in the treatment group. Adverse effects were similar in all groups. THERAPEUTIC ADVANCE: Clinical response to first line treatment options for MDD are reported to be 40%-60%. Availability of additional treatment options, particularly those with reduced time to efficacy, may improve overall treatment and patient quality of life. DEX-BUP is a combination option that has been shown to improve depression symptoms as early as 1 week after initiation.

Clozapine for Treatment-Refractory Aggressive Behavior.

Emergency psychiatry has the main role of resolving suicidal behavior and aggression. These severe psychiatric symptoms can be found in many psychiatric disorders such as schizophrenia, bipolar disorder, major depression, personality disorders, cognitive disorders, intellectual disability and substance abuse. Although indications for the use of antipsychotics are limited to a specific group of diseases, they are frequently used as rescue medication in high-risk or nonresponsive cases. Clozapine, the gold standard for TRS (treatment resistant schizophrenia) is effective in controlling aggression. The aim of the research was to identify the use of clozapine for treatment-refractory aggressive behavior in psychiatric emergency. A retrospective study based on the paper files of patients admitted between 2010 and 2019 in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania. Were included all the patients admitted as a psychiatric emergency and treated with clozapine for aggressive behavior. The hospital is an academic institution with 150 beds for acute patients, serving an area of over 600,000 inhabitants. It is the main public institution where patients with psychiatric emergencies are hospitalized. Off 19,000 patients admitted during the study period, 504 patients (2,4%) with a diagnosis other than schizophrenia or schizoaffective disorder received clozapine for aggressiveness (89.5%). The first four diagnoses identified were bipolar disorder (n = 172), intellectual disability (n = 128), cognitive impairment (n = 112), and personality disorder (n = 92). Other disorders identified but with a smaller number of cases were major depressive disorder (n = 3), adjustment disorders (n = 2), delusional disorder (n = 2), obsessive compulsive disorder (n = 2) and postpartum psychosis (n = 1). Clozapine was used as 3rd or 4th choice. The dose was greater for manic patients (350.29 ± 98.01 mg/day) compared with all the other diagnoses. Clozapine was effective and safe in cases of patients with treatment-refractory aggressive behavior.