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Objectives: Clinicians are often hesitant to prescribe psychostimulants in bipolar disorder (BD) due to concerns of inducing (hypo)mania, despite limited published evidence on associations between prescribed psychostimulant use and recurrence of mood episodes in BD. The current systematic review and meta‐analysis evaluated the emergence of (hypo)manic symptoms in patients with BD receiving prescribed psychostimulants or other pro‐cognitive medications in euthymic or depressive states. Methods: A systematic search was performed of MEDLINE, Embase, and PsychINFO from inception to April 5, 2023 and search of Clinicaltrials.gov and Clinicaltrialsregister.eu for unpublished data. References of included studies were hand‐searched. Randomized trials and prospective longitudinal studies that evaluated psychostimulants and non‐stimulant medications recommended for the treatment of ADHD by the Canadian ADHD practice guidelines were included. The review was reported in line with PRISMA guidelines and was preregistered on PROSPERO (CRD42022358588). Results: After screening 414 unique records, we included 27 studies, of which five reported data that was quantitatively synthesized (n = 1653). The use of psychostimulants in BD was not associated with increased scores on the Young Mania Rating Scale in patients who were in a euthymic or depressed state (SMD IV −0.17; 95% CI, −0.40 to 0.06) compared to placebo. There was a high degree of study‐level heterogeneity (I2 = 80%). A qualitative synthesis of studies revealed a limited risk of medication‐induced manic symptoms. Conclusions: Our review provides preliminary evidence to suggest psychostimulants and non‐stimulant ADHD medications have a limited risk of precipitating (hypo)mania symptoms. More extensive studies evaluating the safety and efficacy of these medications are warranted. [ABSTRACT FROM AUTHOR]

Background: Clinical trials have demonstrated rapid antidepressant effects with intravenous (IV) ketamine for major depressive disorder, with relatively less research specifically for bipolar depression. Herein, we describe the real‐world effectiveness of repeated ketamine infusions for treatment‐resistant bipolar depression. Methods: This study was conducted in a community clinic in Mississauga, Ontario (Canadian Rapid Treatment Centre of Excellence; Braxia Health). In this observational study (NCT04209296), patients with treatment‐resistant bipolar I/II depression (n = 66) received four sub‐anesthetic doses of IV ketamine (0.5–0.75 mg/kg) over a two‐week period. Symptoms of depression, suicidality, anxiety, and functioning were assessed with validated self‐report measures. Results: Statistically and clinically significant antidepressant effects were observed in the overall sample, as measured by the Quick Inventory for Depression Symptomatology‐Self Report‐16 (QIDS‐SR16) with further reductions in depressive symptoms observed after each subsequent infusion (n = 66; mean QIDS‐SR16 reduction of 6.08+/−1.39; p < 0.0001). Significant reductions of suicidal thoughts (QIDS‐SR16‐Suicide Item) and anxiety (Generalized Anxiety Disorder‐7) were also observed with functional improvements on the Sheehan Disability Scale (p < 0.0001 on all measures). Moreover, the response rate (QIDS‐SR16 total score decrease ≥50% from baseline) was 35% and remission rate (QIDS‐SR16 total score ≤5) was 20% after four infusions. Infusions were generally well tolerated with treatment‐emergent hypomania observed in only three patients (4.5%) with zero cases of mania or psychosis. Conclusions: Real‐world effectiveness of IV ketamine for bipolar depression was observed. Repeated doses were associated with greater symptom reduction and adequate tolerability. [ABSTRACT FROM AUTHOR]

Background: The association between impaired social cognition and bipolar disorder (BD) is well established. However, to our knowledge, there has not been a recent systematic review that characterizes disparate dimensions of social cognition in BD. Herein, this systematic review and meta‐analysis aimed to synthesize the literature on core aspects of social cognition (i.e., Theory of Mind, emotion recognition, and social judgment) to identify potential areas of impairment. Methods: Online databases (i.e., PubMed, Cochrane Libraries, PsycINFO) and Google Scholar were searched from inception to May 2021. Studies with populations ages ≥16 with DSM‐IV or DSM‐5 defined BD (I or II) either in a euthymic or symptomatic state were included. The risk of bias was measured using the ROBINS‐1 tool, and the quality of the sources was evaluated using GRADE criteria. The results of the studies were quantitatively measured by synthesizing Hedge's g effect sizes through a random effects meta‐analytic approach. Results: A total of 29 studies were included in the final review (i.e., 12 studies on the Theory of Mind, 11 on emotion recognition, and 6 on social judgment). Overall, results demonstrated social cognition to be moderately impaired in individuals with BD (d = 0.59). The individual domains ranged in effect size (0.38 < d < 0.70), providing evidence for variation in impairment within social cognition. Discussion: Individuals with BD exhibit clinically significant deficits in social cognition during euthymic and symptomatic states. Social cognition impairments in individuals with BD are an important therapeutic target for treatment discovery and development. [ABSTRACT FROM AUTHOR]

Summary: Sleep disturbances are commonly reported in patients with treatment‐resistant depression (TRD). Available data have shown that intravenous (IV) ketamine is an effective treatment for patients with TRD and growing data suggest ketamine may improve overall sleep architecture. In the present study, we evaluated whether changes in sleep symptoms mediated the anti‐depressive and/or anti‐suicidal effects of IV ketamine and whether improvement in sleep correlated with a higher likelihood of achieving response or remission. Adults with TRD received four infusions of IV ketamine at a community‐based clinic. Total depressive symptom severity was measured with the Quick Inventory Depressive Symptoms Self‐Report 16‐Item (QIDS‐SR16) at baseline and was repeated across four infusions. Suicidal ideation (SI) and four sleep symptoms were measured using the SI item and the five sleep items on the QIDS‐SR16. A total of 323 patients with TRD received IV ketamine. Self‐reported improvements in insomnia, night‐time restlessness, hypersomnia, early morning waking, and total sleep were significant partial mediators to the improvements observed in depression severity. Similarly, insomnia, night‐time restlessness, early morning waking and total sleep improvements mediated the reduction of IV ketamine on SI. All sleep items, except for hypersomnia, were associated with an increased likelihood of achieving response or remission. Notably, each point improvement in total sleep score was significantly associated with achieving responder/remitter status (odds ratio 3.29, 95% confidence interval 2.00–5.41). Insomnia, sleep restlessness, early morning waking and total sleep improvements were significant mediators of antidepressant and anti‐suicidal improvements in patients with TRD receiving IV ketamine. [ABSTRACT FROM AUTHOR]

Keywords: assisted dying; cancer; capacity; depression; Euthanasia; ketamine; medical assistance in dying; palliative care; psycho-oncology EN assisted dying cancer capacity depression Euthanasia ketamine medical assistance in dying palliative care psycho-oncology 417 420 4 03/17/21 20210301 NES 210301 INTRODUCTION Amid the ongoing ethical and societal debate, there has been a growing global movement toward the legalization of medical assistance in dying (MAiD).1,2 In patients with terminal cancer and comorbid depression, the contributing role of depression in the decision-making process to pursue MAiD can be challenging to determine. Changes in depression severity are shown in Figure 1, with three flexibly dosed intranasal (IN) ketamine treatments (escalating doses of 50-150 mg administered every 3 days), and day 8 Montgomery-Åsberg Depression Rating Scale (MADRS) as the primary study outcome. Patients received three escalating flexible doses of intranasal ketamine dosed every three days. [Extracted from the article]

Objective: To determine the effectiveness of intravenous (IV) ketamine on anxiety, irritability, agitation, and suicidality, in adults with treatment‐resistant major depressive disorder (MDD) or bipolar disorder (BD). Method: Adults (N = 201) with treatment‐resistant MDD or BD received repeat‐dose IV ketamine treatment at a community‐based clinic. Mixed features were measured using symptoms of anxiety, irritability, and agitation (AIA), as measured by the Generalized Anxiety Disorder‐7 (GAD‐7) scale. The Quick Inventory for Depressive Symptomatology Self‐Report‐16 (QIDS‐SR16) was used to measure overall treatment response, and the QIDS‐SR16 suicidal ideation (SI) item was used to measure change in SI symptoms with ketamine treatment. The anxiety, irritability, and agitation items on the GAD‐7 were used to assess effectiveness of IV ketamine in treating symptoms of mixed features. Results: In this retrospective analysis, 113 participants met AIA criteria. Participants with AIA experienced a significantly greater reduction in overall depressive symptoms (F(1, 558) = 9.49, P =.002), SI (F(1, 558) = 3.103, P =.079), anxiety (F(1, 198) = 5.52, P =.007), irritability (F(1, 198) = 28.35, P <.001), and agitation as measured by "trouble relaxing" (F(1, 198) = 6.70, P =.010) from baseline compared to the non‐AIA group, regardless of number of treatments received. Conclusions: Our preliminary results suggest that IV ketamine is effective in rapidly treating AIA and SI in adults with treatment‐resistant mood disorders. This observation suggests that IV ketamine could be considered a treatment alternative for adults with MDD or BD presenting with mixed features. [ABSTRACT FROM AUTHOR]

Aim: We sought to compare alterations in serum bioenergetic markers within a well‐characterized sample of adults with schizophrenia at baseline and after 8 weeks of pharmacological treatment with the hypothesis that treatment would be associated with significant changes in bioenergetic markers given the role of bioenergetic dysfunction in schizophrenia. Methods: We recruited adults with schizophrenia (n = 122) who had not received pharmacological treatment for at least 1 month prior to enrollment, including drug‐naïve (i.e., first‐episode) participants and treatment non‐adherent participants. Pre‐ and post‐treatment serum samples were analyzed using liquid chromatography–tandem mass spectrometry. Results: Metabolites with the greatest change, when comparing pre‐ and post‐treatment levels, were identified revealing 14 water‐soluble metabolites of interest. The composition of these metabolites was: amino acids (n = 6), carnitines (n = 4), polar lipids (n = 3), and organic acid (n = 1). All amino acids and lysophosphatidylcholines (LysoPC) were increased, while the four carnitines – oleoylcarnitine, L‐palmitoylcarnitine, linoleyl carnitine, and L‐acetylcarnitine – were decreased post‐treatment. Of these metabolite biomarkers, six – oleoylcarnitine, linoleyl carnitine, L‐acetylcarnitine, LysoPC(15:0), D‐glutamic acid, and L‐arginine – were identified as having most consistently and predictably changed after 8 weeks of treatment. Conclusion: The current study identified several bioenergetic markers that consistently change with pharmacological treatment. These bioenergetic changes may provide further insights into the pathophysiology of schizophrenia along with furthering our understanding of the mechanisms subserving both the effects (e.g., antipsychotic effects) and side‐effects (e.g., metabolic syndrome) of antipsychotics. [ABSTRACT FROM AUTHOR]

This study (registered with PROSPERO, CRD42018085967) compares the efficacy (i.e. pro‐cognitive effects) and acceptability of antidiabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials comparing antidiabetic agents with placebo and/or another active antidiabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4855) evaluating the effects of 6 different antidiabetic drugs (i.e. intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with antidiabetic agents compared with placebo. Pioglitazone 15 to 30 mg demonstrated the greatest efficacy compared to placebo in network meta‐analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro‐cognitive class effect of antidiabetic agents in AD/MCI. Other antidiabetic agents should also be investigated in future studies. [ABSTRACT FROM AUTHOR]

Objective Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder ( BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. Methods Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, Psych INFO, and Clinicaltrials.gov databases. Data from randomized controlled trials ( RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences ( SMDs) compared with standard therapy alone. Results Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was −0.40 (95% confidence interval −0.14 to −0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low ( I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. Conclusions Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis. [ABSTRACT FROM AUTHOR]