Emotional distress has been rising since before the COVID-19 pandemic and the public is told that depression is a major public health problem. For example, in 2017 depressive disorders were ranked as the third leading cause of \"years lost to disability\" and the World Health Organization now ranks depression as the single largest contributor to global disability. Although critical appraisals of the epidemiological data raise questions about the accuracy of population-based depression estimates, the dominance of the medical model and the marketing of psychotropics as \"magic bullets,\" have contributed to a dramatic rise in the prescription of psychiatric drugs. Unfortunately, the pharmaceutical industry\'s influence on psychiatric research and practice has resulted in over-estimates of the effectiveness of psychotropic medications and an under-reporting of harms. This is because the principles that govern commercial entities are incongruent with the principles that guide public health research and interventions. In order to conduct mental health research and develop interventions that are in the public\'s best interest, we need non-reductionist epistemological and empirical approaches that incorporate a biopsychosocial perspective. Taking depression as a case example, we argue that the socio-political factors associated with emotional distress must be identified and addressed. We describe the harms of industry influence on mental health research and show how the emphasis on \"scaling up\" the diagnosis and treatment of depression is an insufficient response from a public health perspective. Solutions for reform are offered.

Depression is among the most common mental health disorders worldwide and treatment resistant depression (TRD) represents a major challenge for both patients and clinicians. In recent years ketamine has received attention as an antidepressant agent, demonstrating promising results in TRD in adults. To date, few attempts have been made in treating adolescent TRD with ketamine and none have used intranasal application. This paper discusses a case of a 17-year-old female adolescent suffering from TRD who underwent treatment with intranasal esketamine application (Spravato 28 mg). As symptoms showed clinically insignificant improvement despite modest gains in objective assessments (GAF, CGI, MADRS), treatment was prematurely discontinued. However, the treatment was tolerable and side effects were scarce and mild. Although this case report does not demonstrate clinical effectiveness, ketamine may nonetheless be a promising substance in treating TRD in other adolescents. Questions regarding the safety of ketamine use in the rapidly developing brains of adolescents still remain unanswered. To further explore the potential benefits of this treatment method a short term RCTs for adolescents with TRD is recommended.

BACKGROUND: Major depressive disorder (MDD) patients not responding to two or more different antidepressant treatments are currently considered to suffer from treatment resistant depression (TRD). Recently, intranasal esketamine has been approved by both the American Food and Drug Administration and European Medicines Agency for TRD and, more recently, in moderate to severe episode of MDD, as acute short-term treatment for the rapid reduction of depressive symptoms, which, according to clinical judgement, constitute a psychiatric emergency. There is currently no indication for obsessive-compulsive disorder (OCD) although recently published studies have already shown a rapid and significant reduction of OCD-like symptoms following ketamine administration. The etiology of OCD has not yet been fully elucidated but there is a growing evidence that glutamate signaling dysfunction in the cortico-striatal-thalamo-cortical circuitry plays an essential role. This case report exemplifies possible clinical effects of esketamine on both depressive and OCD symptoms.
METHODS: We present the case of a 39-year-old man suffering from TRD. During the first evaluation at our clinic, he also reported the presence of OCD spectrum symptoms, causing him to perform time-consuming mental rituals due to pathological doubts regarding the relationship with his wife as well as intrusive thoughts regarding his mental conditions. He underwent psychometric evaluations, therapeutic drug monitoring analysis, and pharmacogenomic tests. The overall results helped to explain patient\'s treatment-resistance. Moreover, we observed a significant reduction in both depressive and OCD symptoms after administration of esketamine.
CONCLUSIONS: This case underlines the importance of pharmacogenomic tests in profiling TRD patients and confirms the possible use of esketamine in the treatment of comorbid OCD.

Functional neurological disorder (FND) is a complex neuropsychiatric condition characterized by the presence of neurological symptoms and signs (either motor or sensory) that cannot be explained by any known medical or mental disease. It is frequently presented with psychiatric comorbidities, such as major depression. Its prognosis is poor, with low improvement or recovery rates at 1 year after their onset, and no particular treatment has demonstrated significant efficacy in this regard. Here, we describe the management of a patient affected by treatment-resistant depression (TRD) and FND characterized by mixed paralysis (sensory and motor) in the left arm, and who was successfully treated with esketamine nasal spray, achieving remission in both disorders. The US Food and Drug Administration and the European Medicines Agency recently approved esketamine, the S-enantiomer of ketamine, for treatment of TRD. It is a fast-acting drug that provides a rapid-onset improvement of depressive symptoms. We have presented the first case, to our knowledge, of functional neurological symptoms being successfully treated with esketamine in a patient with comorbid TRD. While the novelty of this data implies a clear need for further research, it is suggested that esketamine might be a useful tool for the treatment of FND, acting through different theorized mechanisms that are in tune with recent advances in knowledge of the etiopathology of FND.

Limited though promising evidence exists on the efficacy of Deep Brain Stimulation (DBS) of the Medial Forebrain Bundle (MFB) in otherwise intractable patients with Major Depression and Obsessive-Compulsive Disorder (OCD). Herein, we present acute and follow-up results (up to 5 years) of a 42 year old man with a diagnosis of treatment-resistant Bipolar Depression (BD) and comorbid OCD, successfully treated with DBS of the MFB. Regular follow-up visits with psychometric evaluations highlighted a considerable improvement of patient\'s depressive and OC symptoms at 5 years from implant. According to the limited, reported experience, we support the efficacy and tolerability of DBS of the MFB as a promising intervention in patients with treatment-resistant BD and comorbid OCD, with specific emphasis on the long-term outcome.

Despite treating depression with antidepressants, their effectiveness is often insufficient. Comparative effectiveness studies and meta-analyses show the effectiveness of antidepressants; however, they do not provide clear indications as to the choice of a specific antidepressant. The rational choice of antidepressants may be based on matching their mechanisms of action to the symptomatic profiles of depression, reflecting the heterogeneity of symptoms in different patients. The authors presented a series of cases of patients diagnosed with depression in whom at least one previous antidepressant treatment was shown to be ineffective before drug targeted symptom cluster-matching treatment (SCMT). The presented pilot study shows for the first time the effectiveness of SCMT in the different clusters of depressive symptoms. All the described patients obtained recovery from depressive symptoms after introducing drug-targeted SCMT. Once validated in clinical trials, SCMT might become an effective and rational method of selecting an antidepressant according to the individual profile of depressive symptoms, the mechanism of their formation, and the mechanism of drug action. Although the study results are preliminary, SCMT can be a way to personalize treatment, increasing the likelihood of improvement even in patients who meet criteria for treatment-resistant depression.

Treatment-resistant depression (TRD) is a chronic and severe psychiatric illness associated with limited therapeutic options. Deep brain stimulation (DBS) is a promising therapy for TRD patients. However, its safety and efficacy are still unclear. Here we reported the safety and efficacy of lateral habenula (LHb) DBS for a TRD patient who had failed medical, psychological, electroconvulsive, and ketamine therapy. The DBS system is compatible with 3T magnetic resonance imaging along with local field potential (LFP) streaming. Two DBS electrodes were implanted at the bilateral LHb without any complication. The patient showed acute stimulation effects and achieved long-term improvements in his depression, anxiety, and sleep with left LHb 160 Hz frequency stimulation, accompanying the change of LFPs. These results provided clinical evidence toward the safety and efficacy and electrophysiological basis of LHb DBS for TRD.

UNASSIGNED: One year observation and evaluation of the VNS (vagus nerve stimulation) efficacy and safety for patients with treatment resistant depression in Polish conditions.
UNASSIGNED: An open label, uncontrolled and one center retrospective study of VNS therapy was implemented with stable pharmacotherapy in 6 patients with treatment resistant depression (TRD). For the first 3 months, only VNS parameters were altered but the pharmacological treatment was unchanged and in the following 9 months, medication and VNS dosing parameters were altered according to the clinical state of the patients.
UNASSIGNED: The baseline 24-item Hamilton Depression Rating Scale (HAMD-24) score averaged 24. Both response (>50% reduction in baseline scores) and remission rates after 3 months of treatment were only 40%. After 1 year of VNS therapy, the response rates increased to 86%. Most frequent side-effects were voice alteration (86% at 3 months of stimulation) and headaches (40%).
UNASSIGNED: VNS treatment was safe and effective in TRD patients and its efficacy increased with time. Efficacy ratings are similar to the previously reported studies using a congenial protocol.

Studies have demonstrated the effectiveness of deep brain stimulation (DBS) as a treatment modality for psychiatric conditions. We present a case reviewing the longitudinal neuropsychological performance outcomes following bed nucleus of the stria terminalis-area (BNST) DBS in a patient with treatment-resistant depression (TRD). The cognitive safety of DBS is well documented for various targets, however cognitive outcomes of BNST-area DBS have not been extensively reported for patients with TRD. Neuropsychological assessment was conducted pre- and post-DBS. Twelve months following DBS, augmented general cognitive performance was observed with significant changes in specific domains.

OBJECTIVE: Obstructive sleep apnea (OSA) is a common clinical problem that can have serious health consequences and complicate the course of mental disorders. It is estimated that the prevalence of sleep apnea in patients with bipolar disorder can be 21-47.5%. Some symptoms of OSA are the same as the symptoms of depression: daytime drowsiness, cognitive dysfunction, decreased drive, apathy, depressed mood, anhedonia.
METHODS: We present a case of a patient whose depressive symptoms persisted despite repeated changes of pharmacological treatment and were exacerbated by severe sleep disorder. OSA was also the cause of serious respiratory complications and prolonged disorders of consciousness that occurred during ECT treatment.
RESULTS: Based on test results of WatchPAT200 and polysomnography, the diagnosis of severe sleep apnea was established and Continuous Positive Airway Pressure (CPAP) treatment was introduced. Severe OSA led in this patient to almost total absence of REM sleep, a significant reduction of deep sleep as well as the reduction of total sleep time.
CONCLUSIONS: The presence of daytime sleepiness, unremitting despite the modification of treatment, indicates the need for diagnostic screening for OSA, which can mimic some of the symptoms of depression, increase the risk of complications during anesthesia, and can be one of the causes of drug resistance. In addition to the negative impact of obstructive sleep apnea on the course of bipolar disorder, OSA also causes significant cognitive impairment in terms of attention and vigilance, long-term semantic and visual memory as well as visual-spatial and executive functions.