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Violeta Perez-Rodriguez,1 Claudia Aymerich,2,3 Ana Catalan,1,3 Sameer Jauhar,4 Gonzalo Salazar de Pablo2,5,6 1Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK; 2Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK; 3Biobizkaia Health Research Institute. Basque Country University. Basurto University Hospital, OSI Bilbao-Basurto. Centro de Investigación En Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Barakaldo, Bizkaia, Spain; 4Centre for Affective Disorders, Psychological Medicine, Ioppn, King’s College, London, UK; 5Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, UK; 6Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Iisgm, CIBERSAM, Madrid, SpainCorrespondence: Dr Gonzalo Salazar de Pablo, Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London, Room D1.14, Child Psychiatry Building 16 De Crespigny Park, London, SE5 8AB, United Kingdom, Tel +44 0207 848 0002, Email gonzalo.salazar_de_pablo@kcl.ac.ukAbstract: Despite being associated with increased illness severity and suicidality compared to non-psychotic depression, psychotic depression remains under-researched, particularly in adolescents. With this article, we aim to review treatment options for psychotic depression in adolescents. We performed a multi-step narrative review, first identifying studies on adolescents with psychotic depression evaluating any intervention and with any methodological design. We subsequently complemented our search with systematic reviews and meta-analysis evaluating treatment interventions in adults with psychotic depression and adolescents with bipolar depression. Finally, we reviewed clinical guidelines to complement the evidence found and provided recommendations for clinical practice. Based on the findings, we recommend a stepped approach to the treatment of psychotic depression in adolescents. For mild cases with predominance of depressive symptoms, antidepressant monotherapy with a serotonin selective reuptake inhibitor (eg fluoxetine, sertraline or citalopram) could be trialed first. In severe presentations, antidepressant-antipsychotic combination would be the treatment of choice. The antidepressant-antipsychotic combination has been recommended by several clinical guidelines, systematic reviews and meta-analysis in this population, adolescents with bipolar depression and adults with psychotic depression. Another combination of antidepressant-antipsychotic with evidence from a case report is the fluoxetine-quetiapine combination. For those adolescents not responding to the antidepressant-antipsychotic combination, or those requiring a rapid response or unable to take medication, electroconvulsive therapy could be considered. Psychological interventions (eg cognitive behavioral therapy, family therapy or interpersonal psychotherapy training for adolescents) are recommended by clinical guidelines but require further research. Overall, literature on the field is scarce and limited, with most evidence coming from adults and other populations. Further research into effective and safe treatment of psychotic depression in adolescent population is needed.Keywords: treatment, psychosis, mood, teenager

Background Psychedelic drugs are a focus of interest in the treatment of depression and other disorders but there are longstanding concerns about possible adverse psychiatric consequences. Because the relevant literature is largely informal, the seriousness of these risks is difficult to evaluate. Methods Searches were made for case reports of schizophrenia-spectrum, affective or other psychiatric disorders after use of psychedelic drugs. Case reports of flashbacks were also searched for. Individuals with recent use of other drugs (apart from cannabis and alcohol) and/or a previous history of major psychiatric disorder were excluded. Symptoms were tabulated using the Syndrome Check List of the Present State Examination (PSE-9). Results We found 17 case reports of schizophrenia spectrum disorder, 17 of affective disorder (depression, mania, or both), 3 cases of anxiety, 1 of depersonalization, and 1 of unclassifiable illness. The states could develop after a single use of the drug (5/17 schizophrenia; 6/17 affective disorder), and duration was highly variable. Recovery was the rule in cases of affective disorder but not in schizophrenia spectrum disorder. Twelve of 29 cases of flashbacks showed psychiatric symptomatology definitely outlasting the attacks, mainly anxiety (5 cases) and depression (8 cases). Flashback symptoms resolved within twelve months in approximately half of the cases but in a few persisted for years. Conclusions Reliable descriptions of schizophrenia spectrum disorder and major affective disorder after psychedelic drug use disorder exist but are relatively uncommon. Flashbacks are sometimes but not always associated with psychiatric symptomatology, mainly anxiety or depression. [ABSTRACT FROM AUTHOR]

Dubiety exists over whether clinical symptoms of schizophrenia can be distinguished from affective psychosis, the assumption being that absence of a "point of rarity" indicates lack of nosological distinction, based on prior group-level analyses. Advanced machine learning techniques, using unsupervised (hierarchical clustering) and supervised (regularized logistic regression algorithm and nested-cross-validation) were applied to a dataset of 202 patients with functional psychosis (schizophrenia n = 120, affective psychosis, n = 82). Patients were initially assessed with the Present State Examination (PSE), and followed up 2.5 years later, when DSM III diagnoses were applied (independent of initial PSE). Based on PSE syndromes, unsupervised learning discriminated depressive (approximately unbiased probability, AUP = 0.92) and mania/psychosis (AUP = 0.94) clusters. The mania/psychosis cluster further split into two groups - a mania (AUP = 0.84) and a psychosis cluster (AUP = 0.88). Supervised machine learning classified schizophrenia or affective psychosis with 83.66% (95% CI = 77.83% to 88.48%) accuracy. Area under the ROC curve (AUROC) was 89.14%. True positive rate for schizophrenia was 88.24% (95%CI = 81.05-93.42%) and affective psychosis 77.11% (95%CI = 66.58-85.62). Classification accuracy and AUROC remained high when PSE syndromes corresponding to affective symptoms (those that corresponded to the depressive and mania clusters) were removed. PSE syndromes, based on clinical symptoms, therefore discriminated between schizophrenia and affective psychosis, suggesting validity to these diagnostic constructs. [ABSTRACT FROM AUTHOR]

Background. The association between cigarette smoking and psychosis remains unexplained, but could relate to causal effects in both directions, confounding by socioeconomic factors, such as ethnicity, or use of other substances, including cannabis. Few studies have evaluated the association between cigarettes and psychotic experiences (PEs) in diverse, inner-city populations, or relationships with number of cigarettes consumed. Methods. We assessed associations and dose-response relationships between cigarette smoking and PEs in a cross-sectional survey of household residents (n = 1680) in South East London, using logistic regression to adjust for cannabis use, other illicit substances, and socioeconomic factors, including ethnicity. Results. We found association between any PEs and daily cigarette smoking, which remained following adjustment for age, gender, ethnicity, cannabis and use of illicit stimulant drugs (fully adjusted odds ratio 1.47, 95% confidence interval 1.01-2.15). Fully adjusted estimates for the association, and with number of PEs, increased with number of cigarettes smoked daily, implying a dose-response effect (p = 0.001 and <0.001, respectively). Odds of reporting any PEs in ex-smokers were similar to never-smokers. Conclusions. In this diverse epidemiological sample, association between smoking and PEs was not explained by confounders such as cannabis or illicit drugs. Daily cigarette consumption showed a dose-response relationship with the odds of reporting PEs, and of reporting a greater number of PEs. There was no difference in odds of reporting PEs between ex-smokers and never-smokers, raising the possibility that the increase in PEs associated with smoking may be reversible. [ABSTRACT FROM AUTHOR]

Objective Treatment resistance is a challenge for the management of schizophrenia. It is not always clear whether inadequate response is secondary to medication ineffectiveness, as opposed to medication underexposure due to non-adherence or pharmacokinetic factors. We investigated the prevalence of subtherapeutic antipsychotic plasma levels in patients identified as treatment-resistant by their treating clinician. Method Between January 2012 and April 2017, antipsychotic plasma levels were measured in 99 individuals provisionally diagnosed with treatment-resistant schizophrenia by their treating clinicians, but not prescribed clozapine. Patients were followed up to determine whether they were subsequently admitted to hospital. Results Thirty-five per cent of plasma levels were subtherapeutic, and of these, 34% were undetectable. Black ethnicity ( P = 0.006) and lower dose ( P < 0.001) were significantly associated with subtherapeutic/undetectable plasma levels. Individuals with subtherapeutic/undetectable levels were significantly more likely to be admitted to hospital ( P = 0.02). Conclusion A significant proportion of patients considered treatment-resistant have subtherapeutic antipsychotic plasma levels, and this is associated with subsequent admission. The presence of subtherapeutic plasma levels may suggest a need to address adherence or pharmacokinetic factors as opposed to commencing clozapine treatment. While antipsychotic levels are not recommended for the routine adjustment of dosing, they may assist with the assessment of potential treatment resistance in schizophrenia. [ABSTRACT FROM AUTHOR]