The relation between sleep and violent aggression

Good sleep is important for our emotional stability and aggression control. Although most people do not become violent after a period of poor sleep, this may be different for certain vulnerable individuals. Forensic psychiatric patients may represent a group of such individuals. We studied patients who committed a crime, often violent in nature, but are not completely held accountable for this due to a mental disorder. They usually get sentenced by the court to follow treatment. A novel finding in this thesis is that poor sleep quality is highly prevalent among these forensic populations. The more sleep difficulties these patients experience, the more impulsive and aggressive they are. Individuals with violent traits appear particularly poor sleepers. The causal relationship between sleep quality and violence was studied in an animal model of violence. We found some indications that also violent rats differ slightly from non-violent rats in their sleep patterns as measured by brain activity after exposure to challenging conditions. Moreover, lack of sleep in rats causes increased impulsive behavior. The effect of sleep loss on the prefrontal cortex, a brain area which serves as the “brake” for our behavior, is likely to be responsible for the negative effects of sleep debt on our behavioral inhibitory capabilities. More work needs to be done to understand the neurobiological mechanisms underlying the relation between sleep and violent aggression. Treatment of sleep disorders may open new avenues for the development of aggression control in forensic patients

Insomnia disorder and its reciprocal relation with psychopathology

Sleep is crucial for daytime functioning. In populations with psychiatric conditions, many people suffer from insomnia symptoms or an insomnia disorder. Emerging evidence suggests a bidirectional relationship between insomnia and various psychopathologies, implying that insomnia not only may be a consequence of mental disorders but also may contribute to new development, symptom severity, and reoccurrence of diverse mental disorders. Research on potential mechanisms underlying the insomnia psychopathology association is important, both from the preventive and treatment perspective. Most hypotheses concern the influence of insomnia on emotion regulation and on shared pathophysiological pathways, ranging from gut microbiome composition to genetic and specific neurotransmitter system aberrations

Oral S-ketamine effective after deep brain stimulation in severe treatment-resistant depression and extensive comorbidities

This case report describes successful maintenance treatment with oral S-ketamine in a patient with severe depression, who previously was resistant to electroconvulsive therapy and deep brain stimulation, and who also had comorbid psychotic and obsessive compulsive symptoms

Maintenance ketamine treatment for depression:a systematic review of efficacy, safety, and tolerability

Ketamine has rapid yet often transient antidepressant effects in patients with treatment-resistant depression. Different strategies have been proposed to prolong these effects. Maintenance ketamine treatment appears promising, but little is known about its efficacy, safety, and tolerability in depression. We searched Pubmed, Embase, and the Cochrane Library and identified three randomised controlled trials, eight open-label trials, and 30 case series and reports on maintenance ketamine treatment. We found intravenous, intranasal, oral, and possibly intramuscular and subcutaneous maintenance ketamine treatment to be effective in sustaining antidepressant effect in treatment-resistant depression. Tachyphylaxis, cognitive impairment, addiction, and serious renal and urinary problems seem uncommon. Despite the methodological limitations, we conclude that from a clinical view, maintenance ketamine treatment seems to be of therapeutic potential. We recommend both controlled and naturalistic studies with long-term follow-up and sufficient power to determine the position of maintenance ketamine treatment within routine clinical practice.</p

Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? A systematic review:A systematic review

OBJECTIVE: Ketamine has repeatedly shown to have rapid and robust antidepressant effects in patients with treatment resistant depression (TRD). An important question is whether ketamine is as effective and safe as the current gold standard electroconvulsive therapy (ECT). METHODS: The literature was searched for trials comparing ketamine treatment with ECT for depression in the Pubmed/MEDLINE database and Cochrane Trials Library. RESULTS: A total of 137 manuscripts were identified, 6 articles were included in this review. Overall quality of the included studies was diverse with relevant risk of bias for some of the studies. Results suggest that ketamine treatment might give faster but perhaps less durable antidepressant effects. Side effects differed from ECT, in particular less cognitive impairment was apparent in ketamine treatment. LIMITATIONS: The included studies have limited sample sizes, use different treatment protocols and in most trials, longer term follow up is lacking. Furthermore, allocation bias appears likely in the non-randomized trials. CONCLUSIONS: Current available literature does not yet provide convincing evidence to consider ketamine as an equally effective treatment alternative to ECT in patients with TRD. There are indications for a more favourable short term cognitive side effect profile after ketamine treatment. Methodologically well-designed studies with larger sample sizes and longer follow up duration are warranted

Adverse events in clinical treatments with serotonergic psychedelics and MDMA:A mixed-methods systematic review

Introduction: Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions. Objective: To systematically review the presence of AEs during and after administration of serotonergic psychedelics and 3,4-methyenedioxymethamphetamine (MDMA) in clinical studies. Methods: We systematically searched PubMed, PsycINFO, Embase, and ClinicalTrials.gov for clinical trials with psychedelics since 2000 describing the results of quantitative and qualitative studies. Results: We included 44 articles (34 quantitative + 10 qualitative), describing treatments with MDMA and serotonergic psychedelics (psilocybin, lysergic acid diethylamide, and ayahuasca) in 598 unique patients. In many studies, AEs were not systematically assessed. Despite this limitation, treatments seemed to be overall well tolerated. Nausea, headaches, and anxiety were commonly reported acute AEs across diagnoses and compounds. Late AEs included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious AE occurred during MDMA administration (increase in premature ventricular contractions requiring brief hospitalization); no other AEs required medical intervention. Qualitative studies suggested that psychologically challenging experiences may also be therapeutically beneficial. Except for ayahuasca, a large proportion of patients had prior experience with psychedelic drugs before entering studies. Conclusions: AEs are poorly defined in the context of psychedelic treatments and are probably underreported in the literature due to study design (lack of systematic assessment of AEs) and sample selection. Acute challenging experiences may be therapeutically meaningful, but a better understanding of AEs in the context of psychedelic treatments requires systematic and detailed reporting

The antidepressant effect and safety of non-intranasal esketamine:A systematic review

BACKGROUND: The introduction of esketamine into the field of psychiatry comes on the heels of excitement from studies on racemic ketamine. While the intranasal route has been the most studied to date, other modes of administration of esketamine may also be of interest in the management of depression. AIMS: To systematically review the literature on non-intranasal esketamine for depression in terms of its antidepressant effect and safety. METHODS: We searched PubMed, Embase, the Cochrane Library, and Google Scholar from inception up to February 2021. Search terms included a combination of Medical Subject Headings and text words indicative of esketamine and depression. We selected both controlled and uncontrolled studies examining non-intranasal esketamine for the treatment of depression. RESULTS: We identified four randomized controlled trials (RCTs) on intravenous esketamine and 15 open-label studies on intravenous (n = 80), subcutaneous (n = 73), and oral (n = 5) esketamine. We found intravenous, subcutaneous, and possibly oral administration of esketamine to be effective in reducing depressive symptoms in most patients with major depressive disorder, bipolar depression, and (severe) treatment-resistant depression. Clinical response to repeated administration of esketamine persisted over the course of treatment. Esketamine was well tolerated by most patients, but open-label data indicate marked psychotomimetic symptoms in exceptional cases. The overall quality of the controlled studies was considered high, the overall quality of the uncontrolled studies low to moderate. CONCLUSIONS: Intravenous, subcutaneous, and possibly oral esketamine may offer an effective and safe addition to the depression treatment armamentarium. However, as most included studies lacked a control group and had small sample sizes, the quality of our results is limited. Different types and formulations of ketamine remain to be compared directly