Randomized controlled trials have reported psychoanalytic psychotherapy to improve longer-term post-treatment outcomes in patients with treatment-resistant depression. In this case study, we examine the therapy process of a female trial participant diagnosed with treatment-resistant depression. Structured clinical assessments indicated that the patient\'s level of depression remained unchanged during and after treatment. Over the course of the therapy, she repeatedly broke away from important others and finally also from the therapy itself, which we linked to the impact of earlier experiences of abandonment on her internal world. In the discussion, we present a variety of reflections that were put forward by the authors during a series of case discussion meetings. Some of these reflections relate to how the inner world of this patient might have triggered a negative therapeutic reaction and a destructive pattern of repetition. The interpretative stance, in which the therapist interpreted this reaction as indicative of a psychic conflict and linked this conflict to the therapeutic relationship, seemed to be experienced by the patient as unhelpful and persecutory. Other elements that were brought up include basic distrust, lack of symbolization and trauma in the patient, as well as the constraints of the research context.

Major depressive disorder is a mental disorder affecting millions of people worldwide. A considerable proportion of patients demonstrate a lack of response to conventional treatment. With the recent introduction of esketamine, a new treatment option has been approved for treatment-resistant depression. Although the medication is efficacious in a substantial portion of cases, rare, but possibly serious, adverse effects may occur. This case series shows two cases of rhabdomyolysis, a destruction of muscle tissue with elevated creatine kinase levels, after administration of esketamine. The first case presented is about a 33 year old male patient who suffered from a severe episode of a depressive disorder. He got nasal esketamine as an emergency treatment. While there was an initial improvement regarding the depressive symptoms, the patient developed muscle pain and fatigue after the administration of the fourth dose, with creatine kinase (CK) levels above 22,000 U/L, indicating rhabdomyolysis. Following the discontinuation of esketamine and the implementation of supportive care, the CK levels returned to normal and the depressive symptoms abated. The second case is about a 22-year-old male patient who also suffered from a severe depressive episode and got eketamine as an emergency treatment. Following the tenth dose, the patient exhibited muscle weakness and elevated CK levels (8,032 U/L), which persisted even after dose reduction. Esketamine administration was stopped, and the following monitoring demonstrated a slow return to normal levels of CK and liver enzymes. In both cases, there was no known medical history and both patients developed rhabdomyolysis after administration of esketamine. The temporal connection suggests a possible causal relationship. We found no literature on esketamine-induced rhabdomyolysis following the administration of nasal esketamine. However, these two cases emphasize the need of monitoring for laboratory changes like elevated CK-levels in patients receiving esketamine, especially considering its growing use in treatment-resistant depression.

Background: The psychiatric needs of those with cancer and other advanced illnesses are becoming increasingly recognized. Ketamine is emerging as a promising treatment option for depressive disorders in psychiatric and palliative care. In the palliative care setting, its study has been hindered by lack of consistent administration routes and dosing. Intranasal (IN) esketamine (Spravato®) has recently received U.S. Food and Drug Administration (FDA) approval as an adjunctive agent for treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation (SI). Objective: We sought to offer IN esketamine to patients suffering from TRD and SI at a comprehensive cancer center. Methods: We designed and implemented a protocol to administer IN esketamine and describe three cases in which it was provided to patients with TRD and SI at a palliative care clinic in the United States. Results: Following treatment, all three patients had substantial reduction in depression severity and no further suicidalideation. These improvements were maintained for up to a year. No serious adverse events occurred. Conclusions: These cases illustrate the potential utility of IN esketamine in the palliative care setting.

BACKGROUND: Anorexia nervosa is a life-threatening psychiatric illness with a high mortality rate and limited treatment options. This illness is frequently comorbid with major depressive disorder, leading to additional obstacles in patient quality of life, and increasing the mortality rate further due to risk of suicide. Ketamine, a competitive N-methyl-D-aspartate receptor antagonist, has been shown to be beneficial in depression given its effects on neuroplasticity. There are few cases in the literature describing ketamine use in patients with eating disorders, and even fewer that describe psychotherapy-assisted ketamine use in this patient population. We present the case of a 33-year-old woman with a history of severe and enduring anorexia nervosa and comorbid major depressive disorder who we treated safely with ketamine-assisted psychotherapy using intravenous ketamine in a general hospital setting.
METHODS: Our patient is a 33-year-old woman with past psychiatric history of severe and enduring anorexia nervosa and major depressive disorder with comorbid psychiatric and medical conditions who presented to the hospital due to malnutrition. She had an extensive psychiatric history as well as multiple medical hospitalizations due to her eating disorder. She had tried numerous psychiatric treatments, including antidepressants, mood stabilizers, antipsychotics, electroconvulsive therapy, and multiple types of therapies without significant improvement in symptoms. She agreed to try ketamine for treatment-resistant depression and received it intravenously for seven sessions in a closely monitored setting, and simultaneously engaged in acceptance and commitment therapy during sessions. She demonstrated increased cognitive flexibility, disappearance of suicidal ideation, and reduction in Beck Depression Inventory Scores.
CONCLUSIONS: Our case is unique in that it demonstrates the successful usage of ketamine-assisted psychotherapy in a hospital setting with severe and enduring anorexia nervosa and comorbid major depressive disorder. Her body mass index was profoundly low at 13, whereas the lowest documented in the literature was 16.9. This case shows that ketamine-assisted psychotherapy may be a promising treatment modality for patients with anorexia nervosa with co-morbid depression who have failed other interventions.

Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a transient increase in glutamate release, leading to increases in neurotrophic signaling and restoration of synaptic function in brain regions involved in mood regulation and emotional behavior. Several randomized clinical trials have shown its effectiveness in reducing the symptoms of depression in some people, despite its short-term side effects that include mainly disorientation, dizziness, nausea, and increased blood pressure. In 2019, the United States Food and Drug Administration (FDA) as well as the European Medicines Agency approved the use of esketamine nasal spray in combination with an oral antidepressant for treatment-resistant depression in adults. Our study aimed to evaluate the effectiveness of this new therapeutic proposal in a case series of five Greek patients with treatment- resistant depression. Intranasal esketamine was administered under medical supervision in combination with an oral antidepressant. Depressive symptoms were evaluated at three time points (baseline, end of treatment, and one-year post-treatment) using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Patient Health Questionnaire (PHQ-9), the CGI Clinical Global Impression Scale, and the Perceived Deficits Questionnaire for Depression (PDQ-D). Possible side effects were assessed using the Richmond Suppression Agitation Scale (RASS), the Sheehan Disability Scale (SDS), the CADSS Disruptive States Scale, and a predefined list of adverse events (AEs) and serious adverse events (SAEs). Patients followed an individualized treatment plan for seven to twelve months depending on the achievement of an adequate response. Statistical analysis of the results revealed a significant improvement (p<0.05) on all scales used. All participants maintained their level of improvement at follow-up after twelve months. Adverse effects were found to be mild and tolerable. It is worth noting that significant side effects were reported only by the two patients with comorbid personality disorder. The results, despite limited to a small sample, indicate the positive effect of esketamine on the stable reduction of depressive symptoms among patients with resistant depression, even after the completion of treatment.

OBJECTIVE: Treatment and management for difficult-to-treat depression are challenging, especially in a subset of patients who are at high risk for relapse and recurrence. The conditions that represent this subset are recurrent depressive disorder (RDD) and bipolar disorder (BD). In this context, we aimed to examine the effectiveness of maintenance transcranial magnetic stimulation (TMS) on a real-world clinical basis by retrospectively extracting data from the TMS registry data in Tokyo, Japan.
METHODS: Data on patients diagnosed with treatment-resistant RDD and BD who received maintenance intermittent theta burst stimulation (iTBS) weekly after successful treatment with acute iTBS between March 2020 and October 2023 were extracted from the registry.
RESULTS: All patients (21 cases: 10 cases with RDD and 11 cases with BD) could sustain response, and 19 of them further maintained remission. In this study, maintenance iTBS did not exacerbate depressive symptoms in any of the cases, but may rather have the effect of stabilizing the mental condition and preventing recurrence.
CONCLUSIONS: This case series is of great clinical significance because it is the first study to report on the effectiveness of maintenance iTBS for RDD and BD, with a follow-up of more than 2 years. Further validation with a randomized controlled trial design with a larger sample size is warranted.

Tardive dysphoria (TDp) is a phenomenon characterized by the delayed onset or worsening of depressive symptoms following the discontinuation or alteration of antidepressant medications. TDp is a recently defined, under-recognized, and understudied condition. We present a series of five TDp cases exploring the diverse presentations, management strategies, and associated medical conditions. In all the cases, TDp manifested after prolonged use of selective serotonin reuptake inhibitors (SSRIs). All cases were successfully managed with atypical antidepressants. These cases offer insight into TDp, providing clinicians and researchers with examples of atypical trajectories in depressive symptomatology.

The link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria\'s involvement in many mechanisms identified in depression and the high prevalence of MDD in individuals with mitochondrial disorders. Mitochondrial functions and energy metabolism are increasingly considered to be involved in MDD\'s pathogenesis. This study focused on cellular and mitochondrial (dys)function in two atypical cases: an antidepressant non-responding MDD patient (\"Non-R\") and another with an unexplained mitochondrial disorder (\"Mito\"). Skin biopsies from these patients and controls were used to generate various cell types, including astrocytes and neurons, and cellular and mitochondrial functions were analyzed. Similarities were observed between the Mito patient and a broader MDD cohort, including decreased respiration and mitochondrial function. Conversely, the Non-R patient exhibited increased respiratory rates, mitochondrial calcium, and resting membrane potential. In conclusion, the Non-R patient\'s data offered a new perspective on MDD, suggesting a detrimental imbalance in mitochondrial and cellular processes, rather than simply reduced functions. Meanwhile, the Mito patient\'s data revealed the extensive effects of mitochondrial dysfunctions on cellular functions, potentially highlighting new MDD-associated impairments. Together, these case studies enhance our comprehension of MDD.

Ketamine is a novel and exciting putative antidepressant medication for patients with treatment-resistant depression. A complication commonly seen in frequent and heavy recreational use of ketamine is ulcerative cystitis, which presents with lower urinary tract symptoms (LUTS) and upper renal tract damage and can be seen in over 25% of regular users. Although Ketamine-induced cystitis (KIC) is a recognised complication in recreational use of ketamine, its occurrence in therapeutic use of ketamine in depression has so far not been reported. The exact pathogenesis of KIC is currently unknown, making treatment and prevention advice much more difficult. Early diagnosis of KIC and immediate cessation of ketamine has been shown to improve adverse urinary tract symptoms and prevent further damage.
We present a case of a 28-year-old female who was started on ketamine treatment for depression, and who then developed symptoms of KIC, which was confirmed by urine microscopy, culture and analysis.
To our knowledge, this is the first reported case of KIC in a patient receiving treatment-dose ketamine as part of their antidepressant therapy.

BACKGROUND: Single-time non-invasive brain stimulation was carried out using the two-technique approach on a patient suffering from treatment-resistant depression. Five treatment sessions given at weekly intervals resulted in a significant improvement in the Patient Health Questionnaire-9 score for up to 6 weeks. The findings of this study could pave the way for a more efficient less resource-intensive time- and budget-saving technique of employing non-invasive brain stimulation for patients with treatment-resistant depression by minimizing the number of stimulation sessions.
METHODS: A 67-year-old married non-Latino white American woman suffering from treatment-resistant depression received intermittent tetraburst stimulation in combination with transcranial direct current stimulation weekly for 5 consecutive weeks. Diagnostic transcranial magnetic stimulation showed an observable electrophysiological change. The patient reported a drastic improvement in Patient Health Questionnaire-9 score up until 6-week follow-up and expressed satisfaction with the treatment.
CONCLUSIONS: This case study suggests that a streamlined protocol for using non-invasive brain stimulation could prove more effective for patients and healthcare providers in terms of safety in comparison to the present guidelines.