John E. Kraus

Meta-Analysis of Efficacy and Treatment-Emergent Suicidality in Adults by Psychiatric Indication and Age Subgroup Following Initiation of Paroxetine Therapy: A Complete Set of Randomized Placebo-Controlled Trials

OBJECTIVE This meta-analysis of placebo-controlled paroxetine trials examines suicidality incidence in adults, focusing on disorder and age as potential risk factors. The findings are put in context with an efficacy meta-analysis of the same trial datasets. DATA SOURCES GlaxoSmithKline paroxetine clinical trial database(s). STUDY SELECTION All double-blind, randomized, placebo-controlled, parallel-group studies of paroxetine therapy in adults enrolling at least 30 patients total were included in the analysis. The dataset comprised 14,911 patients from 61 trials. DATA EXTRACTION Possible cases of suicidality were identified and blindly categorized by an expert panel, using methodology previously used by the US Food and Drug Administration. Incidences of suicidal behavior (preparatory act, suicide attempt, or completed suicide) and any suicidality (suicidal behavior or ideation) were compared between paroxetine and placebo. Efficacy assessments were based on standard depression rating scales (eg, Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale) and Clinical Global Impressions Improvement scale (CGI-I) scores. RESULTS In the primary dataset, ie, all disorders combined, there were no significant differences between paroxetine and placebo for overall suicidality (suicidal behavior or ideation: n/n = 83/8,958 [0.93%] vs n/n = 65/5,953 [1.09%], respectively; OR = 0.9 [95% CI, 0.7-1.3]; P = .649) or for suicidal behavior specifically (n/n = 50/8,958 [0.56%] vs n/n = 40/5,953 [0.67%], respectively; OR = 1.2 [95% CI, 0.8-1.9]; P = .483). However, in patients with major depressive disorder (MDD), a greater incidence of suicidal behavior occurred in paroxetine-treated patients than in placebo-treated patients (n/n = 11/3,455 [0.32%] vs n/n = 1/1,978 [0.05%], respectively; OR = 6.7 [95% CI, 1.1-149.4]; P = .058). Across all indications, a higher incidence of suicidal behavior occurred in paroxetine-treated versus placebo-treated adults aged 18 to 24 years (n/n = 17/776 [2.19%] vs n/n = 5/542 [0.92%], respectively; OR = 2.4 [95% CI, 0.9-7.3]). In older age groups, no increase in suicidality was observed. Efficacy was demonstrated in all disorders evaluated, including MDD. CONCLUSIONS Across all disorders, overall suicidality incidence was similar between paroxetine and placebo. However, a higher frequency of suicidal behavior occurred with paroxetine in MDD, which was largely explained by the higher incidence in young adults. These data support the efficacy of paroxetine therapy; however, they also highlight the need for careful monitoring of suicidality during antidepressant therapy, particularly in younger adults.

Implementing a smoking ban in an acute psychiatric admissions unit.

In contrast to general medical hospitals, psychiatric hospitals often allow patients to smoke cigarettes. In addition to obvious health concerns, smoking can also interfere with clinical assessments and therapeutic activities, Implementation of a smoking ban on an acute male admissions unit did not result in any increase in aggressive behaviors. In addition, staff attitudes following the ban improved, and most staff members believed the ban was both ethical and beneficial to patients. Our research indicates that banning smoking on an acute admissions unit is feasible and well tolerated by patients and staff, although it may require extra vigilance for smoking-related contraband.

Pathophysiology of Schizophrenia

Epidemiological and genetic studies have provided important clues that guide the study of the neurobiological basis and the cause of schizophrenia. Studies have revealed that schizophrenia is heterogeneous in phenomenology [1 2], age of onset [3], response to treatment [4] and outcome [5–[7] and illness course [8]. Consequently, etiological or pathophysiological theories of schizophrenia must account for this heterogeneity. One explanation is that schizophrenia may arise from multiple etiological and pathophysiological processes; prompting references to “the schizophrenias” rather than “schizophrenia”. Alternatively, this heterogeneity may be due to a common etiological process, and the variable disease expression due to neurobiological differences that act as modifying factors in affected individuals, or to altered disease expression due to environmental factors.