Hallucinations as a risk marker for suicidal behaviour in individuals with a history of sexual assault: a general population study with instant replication.

BACKGROUND: Research has shown a strong relationship between hallucinations and suicidal behaviour in general population samples. Whether hallucinations also index suicidal behaviour risk in groups at elevated risk of suicidal behaviour, namely in individuals with a sexual assault history, remains to be seen. AIMS: We assessed whether hallucinations were markers of risk for suicidal behaviour among individuals with a sexual assault history. METHODS: Using the cross-sectional 2007 (N = 7403) and 2014 (N = 7546) Adult Psychiatric Morbidity Surveys, we assessed for an interaction between sexual assault and hallucinations in terms of the odds of suicide attempt, as well as directly comparing the prevalence of suicide attempt in individuals with a sexual assault history with v. without hallucinations. RESULTS: Individuals with a sexual assault history had increased odds of hallucinations and suicide attempt compared to individuals without a sexual assault history in both samples. There was a significant interaction between sexual assault and hallucinations in terms of the odds of suicide attempt. In total, 14-19% of individuals with a sexual assault history who did not report hallucinations had one or more suicide attempt. This increased to 33-52% of individuals with a sexual assault history who did report hallucinations (2007, aOR = 2.85, 1.71-4.75; 2014, aOR = 4.52, 2.78-7.35). CONCLUSIONS: Hallucinations are a risk marker for suicide attempt even among individuals with an elevated risk of suicidal behaviour, specifically individuals with a sexual assault history. This finding highlights the clinical significance of hallucinations with regard to suicidal behaviour risk, even among high-risk populations.

Using polygenic risk scores to investigate the evolution of smoking and mental health outcomes in UK biobank participants.

OBJECTIVE: Mendelian randomization studies report a bi-directional relation between cigarette smoking and mental disorders, yet from a clinical standpoint, mental disorders are the focus of treatment. Here, we used an event history framework to understand their evolution in the life course. Our objective was to estimate the relative contribution of genetic predispositions and self-reported smoking status (never, former, and present smoker) to hospitalizations for major depression, bipolar disorder, and schizophrenia. METHODS: We calculated polygenic risk scores (PRS) for ever smoking, pack-years of smoking as a proportion of adult life, and neuroticism in 337,140 UK Biobank participants of white British ancestry. These PRS and self-reported smoking status were entered as explanatory variables in survival models for hospitalization. RESULTS: The estimated single nucleotide polymorphisms heritabilities (h2 ) were 23%, 5.7%, and 5.7% for pack-years, ever smoking, and neuroticism respectively. PRS pack-years and PRS neuroticism were associated with higher hospitalization risk for mental disorders in all smoking status groups. The hazard for mental health hospitalization was higher in both previous (HR: 1.50, CI: 1.35-1.67) and current (HR: 3.58, 2.97-4.31) compared to never smokers, after adjusting for confounders. CONCLUSION: Since genetic liabilities for smoking and neuroticism are fixed at conception and smoking initiation generally started before age 20, our results show that preventing smoking in adolescents probably prevents the development of mental disorders.

Understanding the inverse relationship between age and psychotic symptoms: The role of borderline personality traits.

OBJECTIVE: There is a well-established inverse relationship between age and positive psychotic symptoms, both in patients with psychotic disorders and in general population samples with psychotic experiences. The reason for this inverse relationship is unclear. We hypothesized that life-course developmental changes in borderline personality traits, which also typically decline with age, might explain the inverse relationship between age and positive psychotic symptoms. METHODS: We tested this hypothesis with data from 19,980 adults who completed 2000, 2007, and 2014 UK Adult Psychiatric Morbidity Survey studies. Hallucinations and delusions were assessed with the Psychosis Screening Questionnaire. Borderline features were assessed with the Structured Clinical Interview for DSM-IV Axis II Personality Disorders Screening Questionnaire. Logistic regression models with effect decompositions were used to conduct the analyses. RESULTS: As expected, age was negatively associated with hallucinations and delusions. These effects were wholly or mostly reduced after controlling for borderline features. Similar results were found in a subgroup of participants with a probable psychotic disorder. Repeating the analysis with a broad index of psychopathology severity instead of borderline features did not produce comparable results. Borderline factor scores reflecting identity/relationship disturbance, mood instability/anger, and self-harm/suicidality were created, all of which appeared to explain part of the inverse relationship between age and psychotic experiences. CONCLUSION: Declining borderline traits throughout adulthood may account for the reduced prevalence of positive psychotic symptoms in both clinical and non-clinical populations. Future research might evaluate the impact of treatments that target borderline traits on positive psychotic symptoms.

Hallucinations in the general population across the adult lifespan: prevalence and psychopathologic significance.

BACKGROUND: Community studies have found a relatively high prevalence of hallucinations, which are associated with a range of (psychotic and non-psychotic) mental disorders, as well as with suicidal ideation and behaviour. The literature on hallucinations in the general population has largely focused on adolescents and young adults. AIMS: We aimed to explore the prevalence and psychopathologic significance of hallucinations across the adult lifespan. METHOD: Using the 1993, 2000, 2007 and 2014 cross-sectional Adult Psychiatric Morbidity Survey series (N = 33 637), we calculated the prevalence of past-year hallucinations in the general population ages 16 to ≥90 years. We used logistic regression to examine the relationship between hallucinations and a range of mental disorders, suicidal ideation and suicide attempts. RESULTS: The prevalence of past-year hallucinations varied across the adult lifespan, from a high of 7% in individuals aged 16-19 years, to a low of 3% in individuals aged ≥70 years. In all age groups, hallucinations were associated with increased risk for mental disorders, suicidal ideation and suicide attempts, but there was also evidence of significant age-related variation. In particular, hallucinations in older adults were less likely to be associated with a cooccurring mental disorder, suicidal ideation or suicide attempt compared with early adulthood and middle age. CONCLUSIONS: Our findings highlight important life-course developmental features of hallucinations from early adulthood to old age.

Melancholic Features in Bipolar Depression and Response to Lamotrigine: A Pooled Analysis of Five Randomized Placebo-Controlled Trials.

BACKGROUND: A pilot study suggested lamotrigine may be more effective for bipolar depression with melancholic features. We tested this hypothesis in a pooled analysis of 5 randomized double-blind placebo-controlled trials of lamotrigine for acute bipolar depression. METHODS: The pooled sample consisted of 1072 adult outpatients. Depressive symptoms were assessed for 7 to 10 weeks with the Hamilton Depression Rating Scale and the Montgomery-Åsberg Depression Rating Scale. The outcome measure was end-trial response (score reduction ≥ 50%). Melancholic features were assessed with both the Structured Clinical Interview for DSM-IV and baseline depression scale items, according to DSM criteria. RESULTS: The item-based melancholic specifier was associated with numerically larger treatment effects, although subgroup-treatment interactions in logistic regression models did not reach statistical significance. The small subgroup of patients with severe psychomotor retardation also appeared to benefit from lamotrigine. However, the Structured Clinical Interview for DSM-IV melancholic specifier was not associated with larger treatment effects. Baseline depression severity was inconsistently associated with response, depending on which scale was used to define severity. The 2 melancholia variables had poor agreement despite having similar prevalences. CONCLUSIONS: Our results do not clearly support the original hypothesis but do reinforce the importance of replicating secondary analyses of clinical trials with additional data.

Mood Instability and Trait Anxiety as Distinct Components of Eysenckian Neuroticism With Differential Relations to Impulsivity and Risk Taking.

This article presents the results of 2 studies that investigated mood instability in the Eysenck neuroticism scales and its relationship to trait impulsivity and risk taking. In Study 1 we examined the relationship between a mood instability factor in the Eysenck Personality Inventory and impulsivity (i.e., rapid unplanned behavior) in a general population sample of 6,066 adults. The mood instability factor was positively correlated with impulsivity. The remaining factors, largely reflecting trait anxiety, were also positively correlated with impulsivity, although these correlations disappeared when mood instability was included in the same regression model. In Study 2 we factor analyzed the short form of the revised Eysenck Personality Questionnaire to isolate mood instability and trait anxiety factors and explore their associations with risk taking in a general population sample of 394,170 adults 40 to 69 years old. The mood instability factor was positively associated with risk taking, whereas the association for the trait anxiety factor was negative. Taken together, the results suggest that mood instability and trait anxiety are separable components of Eysenckian neuroticism and that mood instability is the main component that is positively associated with trait impulsivity and risk taking. Further research is needed to clarify the factor structure of Eysenckian neuroticism.

A randomized placebo-controlled trial examining the effects of escitalopram on neuroticism and state anxiety in a nonclinical sample.

OBJECTIVE: This study reanalyzed data from a randomized placebo-controlled trial that failed to find an effect of the selective serotonin reuptake inhibitor escitalopram on neuroticism and state anxiety in a nonclinical sample. The purpose was to test for unique effects on two neuroticism factors, trait anxiety and mood instability, and to explore whether neuroticism moderated the effect of escitalopram on state anxiety. METHODS: The sample included 80 adults who had a first-degree relative with major depression but without any psychiatric disorders themselves. Participants were randomized to escitalopram 10 mg/day or placebo for 4 weeks. Neuroticism was assessed with the Eysenck Personality Questionnaire (EPQ) and state anxiety with the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: The main effects on the neuroticism factors were not statistically significant, although there was a significant interaction such that the effect of escitalopram compared with placebo on HAM-A scores was statistically significant in participants with higher levels of EPQ trait anxiety, even after controlling for baseline HAM-A scores. A similar interaction with EPQ mood instability was nonsignificant. CONCLUSION: A potential beneficial effect of escitalopram on neuroticism may be driven by reductions in anxiety.

Melancholic Symptoms in Bipolar II Depression and Responsiveness to Lamotrigine in an Exploratory Pilot Study.

BACKGROUND: In this exploratory pilot study we reanalyzed data from a previous randomized, double-blind, placebo-controlled trial of lamotrigine for bipolar II depression in which lamotrigine was not superior to placebo to determine if splitting the sample into melancholic and nonmelancholic subgroups revealed a significant treatment effect. METHODS: Adult outpatients (n = 150) in an acute bipolar II depressive episode completed 8 weeks of treatment with lamotrigine (titrated to 200 mg/d) or placebo. Depressive symptoms were assessed at baseline and weekly with the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS). The presence of melancholic depression was determined by baseline responses to the HAMD-17 and MADRS according to the Diagnostic and Statistical Manual of Mental Disorders criteria. Cox regression models stratified by melancholic status were used to predict HAMD-17 and MADRS treatment response. Analysis-of-variance models were used to compare HAMD-17 and MADRS change scores between lamotrigine and placebo groups while testing for interactions by melancholic status. RESULTS: Lamotrigine was associated with higher odds of treatment response compared with placebo in the melancholic subgroup but not in the nonmelancholic subgroup. However, the melancholic subgroup-treatment interactions from the analysis-of-variance models were nonsignificant. CONCLUSIONS: Further research is warranted to test the hypothesis that bipolar depression with melancholic symptoms is more responsive to lamotrigine over placebo than nonmelancholic bipolar depression.

Examining the role of borderline personality traits in the relationship between major depression and nonsuicidal self-injury.

BACKGROUND: Depression and borderline personality disorder (BPD) are highly comorbid conditions that are both associated with nonsuicidal self-injury (NSSI). AIMS: The purpose of this study was to determine if depression is associated with NSSI after controlling for BPD traits. A distinction was made between NSSI for emotional regulation and NSSI for interpersonal motives. METHOD: Logistic regression analyses were conducted on cross-sectional data from a general population sample of 7370 adults who completed the 2007 Adult Psychiatric Morbidity Survey. Depressive symptoms were assessed with the revised Clinical Interview Schedule. NSSI and motives for NSSI were also assessed during clinical interviews. BPD traits were assessed with the participant-completed Structured Clinical Interview for DSM-IV Axis II Personality Disorders. RESULTS: Participants in a major depressive episode were more likely to have engaged in emotional-regulation NSSI and interpersonal NSSI than participants without depression. After controlling for BPD traits depression remained associated with emotional-regulation NSSI, whereas the association with interpersonal NSSI became nonsignificant. There were statistically significant relationships between depression and both types of NSSI occurring indirectly through BPD traits. CONCLUSIONS: BPD traits account for a significant portion of the cross-sectional relationship between depression and past NSSI that varies in size depending on the motive for NSSI. People with depression are more likely to have engaged in NSSI for emotional regulation even in the absence of prominent BPD traits. In contrast, BPD traits may be more prominent in people with depression who have engaged in interpersonal NSSI.

The Efficacy of Psychostimulants in Major Depressive Episodes: A Systematic Review and Meta-Analysis.

BACKGROUND: Psychostimulants are frequently prescribed off-label for adults with major depressive disorder or bipolar disorder. The frequent and increasing usage of stimulants in mood disorders warrants a careful appraisal of the efficacy of this class of agents. Herein, we aim to estimate the efficacy of psychostimulants in adults with unipolar or bipolar depression. METHODS: The PubMed/Medline database was searched from inception to January 16, 2016 for randomized, placebo-controlled clinical trials investigating the antidepressant efficacy of psychostimulants in the treatment of adults with unipolar or bipolar depression. RESULTS: Psychostimulants were associated with statistically significant improvement in depressive symptoms in major depressive disorder (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.13-1.78; P = 0.003) and bipolar disorder (OR, 1.42; 95% CI, 1.13-1.78; P = 0.003). Efficacy outcomes differed across the psychostimulants evaluated as a function of response rates: ar/modafinil (OR, 1.47; 95% CI, 1.20-1.81; P = 0.0002); dextroamphetamine (OR, 7.11; 95% CI, 1.09-46.44; P = 0.04); lisdexamfetamine dimesylate (OR, 1.21; 95% CI, 0.94-1.56; P = ns); methylphenidate (OR, 1.49; 95% CI, 0.88-2.54; P = ns). Efficacy outcomes also differed between agents used as adjunctive therapy (OR, 1.39; 95% CI, 1.19-1.64) or monotherapy (OR, 2.25; 95% CI, 0.67-7.52). CONCLUSIONS: Psychostimulants are insufficiently studied as adjunctive or monotherapy in adults with mood disorders. Most published studies have significant methodological limitations (eg, heterogeneous samples, dependent measures, type/dose of agent). In addition to improvements in methodological factors, a testable hypothesis is that psychostimulants may be more appropriately tested in select domains of psychopathology (eg, cognitive emotional processing), rather than as "broad-spectrum" antidepressants.

Interpersonal sensitivity and response to selective serotonin reuptake inhibitors in patients with acute major depressive disorder.

BACKGROUND: Patients with major depression often suffer from excessive interpersonal sensitivity, although it is not typically measured in antidepressant clinical trials. Preliminary evidence suggests selective serotonin reuptake inhibitors have the capacity to reduce interpersonal sensitivity. METHODS: This was a pooled analysis of data from 1709 patients in three randomized, double-blind, placebo-controlled trials of fluoxetine and paroxetine for acute major depressive disorder. Depressive symptoms were assessed with the Hamilton Depression Rating Scale. A factor from the Symptom Checklist was used to assess interpersonal sensitivity. Our outcome of interest was change from baseline scores at the last assessment (up to 8 or 12 weeks, depending on the trial). RESULTS: Both medications produced significantly greater reductions in interpersonal sensitivity relative to placebo. The effect of medication remained significant after controlling for depression improvement, which explained 18.5% of the variation in interpersonal sensitivity improvement among those treated with active medication. The effect of medication on depressive symptoms, relative to placebo, was not influenced by baseline interpersonal sensitivity. LIMITATIONS: The outcome measured interpersonal sensitivity over the last week, and the results do not necessarily reflect changes in long-standing, trait-like patterns of interpersonal sensitivity. Only two medications were studied. CONCLUSIONS: Selective serotonin reuptake inhibitors are effective at treating interpersonal sensitivity in acutely depressed patients. This appears to be a unique drug effect that is not only the result of depression improvement. Future clinical trials might benefit from assessing interpersonal sensitivity more routinely.

Intranasal racemic ketamine for patients hospitalized with treatment-resistant depression: A retrospective analysis.

Most research describing ketamine as a treatment for depression has relied on intravenous dosing. There remains a need for more research to support this treatment with other routes of administration. This was a retrospective chart review of 30 patients hospitalized with unipolar or bipolar treatment-resistant depression who were treated with up to four doses of compounded intranasal racemic ketamine (50 mg or 75 mg). Treatment courses lasted up to 7 days. Symptom improvement was measured with either the Hamilton Depression Rating Scale or the Montgomery-Åsberg Depression Rating Scale. Ketamine was well tolerated with no severe adverse events or treatment discontinuations due to adverse effects. Blood pressures increased by 4-6 mmHg on average with no patients requiring medication to lower blood pressure. Twenty patients (66.7%) were classified as treatment responders based on depression scores decreasing by more than 50%. Among the 27 patients with moderate to severe suicidal ideation scores at baseline, these decreased by 68.5% on average. Overall, the results suggest that compounded intranasal racemic ketamine was safe and effective in the treatment of depressive symptoms and suicidal ideation in a real-world sample of patients hospitalized with treatment-resistant depression. Additional research comparing intranasal ketamine to esketamine and intravenous racemic ketamine is warranted. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Intranasal ketamine as a treatment for psychiatric complications of long COVID: A case report.

Background: Neuropsychiatric symptoms associated with long COVID are a growing concern. A proposed pathophysiology is increased inflammatory mediators. There is evidence that typical serotonergic antidepressants have limited efficacy in the presence of inflammation. Although ketamine has shown promise in MDD, there is limited evidence supporting the use of ketamine to treat depressive symptoms associated with long COVID. Case Report: This case took place on an inpatient psychiatry unit in a Canadian hospital. The patient was admitted with a 10-month history of worsening depression and suicidality following infection with COVID-19. Depressive symptoms and suicidal ideation were assessed throughout treatment using the Montgomery-Asberg Depression Rating Scale (MADRS). Written informed consent was obtained prior to data collection. This patient received 4 doses of intranasal ketamine which resulted in rapid improvement of depressive symptoms and complete resolution of suicidality with no major adverse events. Discussion: There is evidence to support long COVID symptoms result from dysregulated inflammatory processes. The presence of inflammation in patients with MDD has correlated to poor outcomes with first-line antidepressants. It has been demonstrated that IV ketamine is associated with decreased inflammatory mediators and proportional decrease in depressive symptoms. Conclusions: Intranasal ketamine in this case was effective at treating depressive symptoms and suicidal ideation associated with long COVID. This is consistent with available data that demonstrates ketamine's efficacy in reducing inflammatory mediators associated with neuropsychiatric symptoms. Therefore, ketamine may be a potential therapeutic option to treat long COVID and persistent depressive symptoms.

Emotional blunting with bupropion and serotonin reuptake inhibitors in three randomized controlled trials for acute major depressive disorder.

BACKGROUND: Emotional blunting is theorized to be an adverse effect of antidepressants, particularly serotonin reuptake inhibitors, but this has not been firmly established. Another possibility is that emotional blunting represents a residual depressive symptom. METHODS: We analyzed data from adult outpatients with acute major depressive disorder who participated in three 8-week randomized controlled trials. Trials 1 and 2 were pooled (venlafaxine, n = 378; bupropion, n = 389; placebo, n = 383) and Trial 3 (escitalopram, n = 254; bupropion, n = 260) was analyzed separately. Emotional blunting was measured with the "inability to feel" item from the Montgomery-Åsberg Depression Rating Scale. RESULTS: Emotional responsiveness improved, on average, in all treatment groups. Only a minority of participants (≤6 %) experienced more emotional blunting post-treatment, compared to baseline, with no significant differences between treatment groups, although roughly 20-25 % continued to report an inability to feel normal emotions at the final assessment. In Trials 1 and 2, emotional blunting was associated with poorer outcomes in terms of depressive symptoms, suicidal ideation, and sexual function, but these correlations were nearly identical in the placebo group. LIMITATIONS: The trials were short and cannot speak to the possibility of emotional blunting from long-term treatment. Emotional blunting was measured with a single item. CONCLUSIONS: The study medications did not significantly decrease emotional responsiveness, and there was no evidence that emotional blunting mediated treatment response. In acute treatment, emotional blunting may be better conceptualized as a residual symptom than as an adverse drug effect.

Medication Gaps and Antipsychotic Polypharmacy in Previously Hospitalized Schizophrenia Patients: An Electronic Cohort Study in Three Canadian Provinces.

Background: Real world evidence about antipsychotics focuses on rehospitalization. Modeling the time course of pharmacotherapy would show patients' adherence to medications and physicians' adherence to medication guidelines. We aimed to calculate the cumulative time spent in second generation antipsychotics (SGAs), gaps, antipsychotic polypharmacy, and clozapine in discharged schizophrenia patients. Methods: Hospitalization and pharmacy dispensing data from 2008-2018 in Manitoba, Saskatchewan, and British Columbia were linked and an electronic cohort (N = 2,997) was created (mean follow-up: 49 months, SD = 38). Cohort members were required to have a minimum of 6 weeks medicated with aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, or ziprasidone. Results: The multistate model predicted that schizophrenia patients accumulated 44 months in SGA monotherapy, 4 months in polypharmacy, 11 months in medication gaps and 17 days in clozapine over a 5-year period. The majority of transitions were between SGA and medication gap. Accumulated time in medication gaps was seven times as much as in clozapine. Each 10% delay in SGA initiation post-discharge was associated with a 2, 1, and 6% higher risk for polypharmacy (95% CI: 1.01-1.02), gap (95% CI: 1.01-1.01), and clozapine (95% CI: 1.04-1.08), respectively. Interpretation: Schizophrenia patients accumulated more time unmedicated and in polypharmacy compared to clozapine. Either treatment guidelines for schizophrenia are not followed, or real-world challenges hamper their implementation.

Instability of Suicidal Ideation in Patients Hospitalized for Depression: An Exploratory Study Using Smartphone Ecological Momentary Assessment.

This study used ecological momentary assessment (EMA) to explore the correlates of suicidal ideation (SI) instability in patients hospitalized for depression and SI. Thirty-nine adult inpatients were given smartphones with visual analogue scales to rate current depressed mood, anger/irritability, feeling socially connected, and SI three times a day throughout hospitalization. Affective Lability Scales (ALS) were also completed at baseline. SI instability was correlated with SI intensity, depressed mood instability, and social connection instability. Social connection instability was not associated with SI instability after controlling for depressed mood instability. ALS scores were not associated with EMA-derived SI instability. Participants with multiple past suicide attempts experienced greater SI instability. More research examining the clinical significance of SI instability is warranted.

Sexual assault and psychosis in two large general population samples: Is childhood and adolescence a developmental window of sensitivity?

BACKGROUND: Research has shown a strong relationship between psychosis and sexual assault. Theories on developmental trauma as a causal factor for psychosis suggest that exposure to sexual trauma in childhood would have a stronger association with psychosis than sexual trauma in adulthood. We hypothesized that exposure to sexual trauma earlier in childhood and adolescence would be more strongly associated with hallucinations, delusional beliefs and psychotic disorder than sexual trauma that occurred later in life. METHODS: Using the 2007 and 2014 Adult Psychiatric Morbidity Surveys (N = 14,949) we calculated the prevalence of sexual assault, hallucinations, delusional beliefs, and psychotic disorder. We used logistic regression to examine the relationship between age of exposure to sexual assault (first exposure <16 vs first exposure ≥16) and odds of hallucinations, delusions, and psychotic disorder. RESULTS: Sexual assault at any age was associated with an increased odds of hallucinations (aOR = 2.00, 95%CI = 1.63-2.46), delusional beliefs (aOR = 2.55, 95%CI = 2.24-2.89) and psychotic disorder (aOR = 5.28, 95%CI = 3.59-7.76). There was no significant difference, however, in the prevalence of hallucinations, delusional beliefs or psychotic disorders in individuals first exposed to sexual assault <16 and individuals first exposed ≥16. CONCLUSIONS: Contrary to our hypothesis, we did not find evidence that exposure to sexual assault in childhood and adolescence was more strongly associated with hallucinations, delusional beliefs or psychotic disorder than exposure to sexual assault age >16. Our findings do not support the idea that childhood and adolescence are uniquely sensitive periods for the emergence of psychotic experiences or psychotic disorder in relation to sexual trauma.

Compounded intranasal racemic ketamine for major depressive disorder: A case report.

Ketamine has been safely used as an anesthetic for over 50 years. More recently sub-anesthetic doses have shown benefit for treatment-resistant depression (TRD). The majority of data on ketamine for depression is based on intravenous administration which is resource intensive and logistically challenging. Due to these concerns, novel modes of administration, including intranasal, are being explored. In 2019, the U.S. Food and Drug Administration (FDA) approved a commercially formulated intranasal s-enantiomer ketamine product, esketamine, for TRD. The cost of intranasal esketamine is significant and phase III clinical trials have not consistently demonstrated benefit over placebo. We describe a case of a patient with major depressive disorder (MDD) and acute suicidality who achieved rapid remission following three treatments with intranasal racemic ketamine. The associated drug cost was $42 USD, significantly cheaper than commercially available esketamine, and treatment was administered on an inpatient psychiatry ward with basic hemodynamic monitoring. Intranasal ketamine was not associated with significant adverse drug effects and facilitated a relatively short hospital admission. The case report provides support for the use of intranasal racemic ketamine as adjunctive treatment for MDD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Lamotrigine for acute bipolar depression: An exploratory item-level analysis.

OBJECTIVES: Lamotrigine is used to treat bipolar depression despite inconsistent evidence. Here we present the results of an exploratory item-level analysis of pooled data from five randomized placebo-controlled trials of lamotrigine for acute bipolar depression. The goal was to determine if certain depression scale items were more responsive to lamotrigine treatment. METHODS: The pooled sample contained 1072 adult outpatients treated for up to 7-10 weeks. Depressive symptoms were measured with the Hamilton Depression Rating Scale and the Montgomery-Åsberg Depression Rating Scale. Change scores on individual scale items were compared between treatment groups. RESULTS: There were statistically significant effects on items assessing depressed mood/sadness, lack of interest/anhedonia, pessimism/guilt, and anergia/fatigue, on both scales. However, there was marked variation in the baseline symptom prevalence, and items with higher scores at baseline tended to have larger and statistically significant treatment effects. CONCLUSIONS: The results suggested a significant treatment effect on core symptoms of depression. A floor effect appeared to limit the sensitivity of other scale items. Given the exploratory nature of the analysis, firm conclusions cannot be drawn, although the results were consistent with past research. Relying on total depression scale sum scores over targeted assessments of core depressive symptoms may have impeded signal detection in the original trials.