Neuropsychiatric Disease and Treatment
January 1, 2020
Daphne Voineskos, Zafiris J Daskalakis, Daniel M. Blumberger
430 citations
Treatment-resistant depression (TRD) is a form of major depressive disorder that does not respond to standard first-line treatments. Although no consensus definition exists, all models require an inadequate response to at least two trials of antidepressant medication. This review compiles meta-analyses, trials, and reviews on TRD challenges and management. It discusses confounds in definitions and staging, difficulties in assessment, and pharmacological augmentation strategies (lithium, triiodothyronine, second-generation antipsychotics, switching antidepressant class). Somatic therapies (electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, deep brain stimulation), psychotherapeutic approaches, and novel treatments (ketamine, psilocybin, anti-inflammatories) are reviewed. The evidence indicates that further large-scale work is needed to understand appropriate treatment pathways and prescribe effective options.
Neuropsychiatric Disease and Treatment
August 1, 2021
A. Wilkowska, A. Włodarczyk, M. Gałuszko-węgielnik et al.
33 citations
In an open-label observational study, 13 patients with treatment-resistant bipolar depression received eight intravenous infusions of 0.5 mg/kg ketamine over four weeks. After the seventh infusion, 61.5% responded and 46.2% achieved remission. Responders also showed a significant antisuicidal effect. Ketamine caused a transient rise in blood pressure and increased dissociative symptoms, but no manic switch or serious adverse events occurred. The findings suggest ketamine is a safe and feasible add-on treatment for this population.
Neuropsychiatric Disease and Treatment
November 1, 2020
Alina Wilkowska, Łukasz P. Szałach, Wiesław Jerzy Cubała
31 citations
Bipolar disorder is a psychiatric illness with high morbidity, mortality, and suicide rates, a neuroprogressive course, and frequent treatment resistance, creating a need for new treatment strategies. Ketamine appears to have rapid antidepressive and antisuicidal effects. Because most available studies concern unipolar depression, this article presents a novel argument that ketamine might be a promising treatment for bipolar disorder.
Neuropsychiatric Disease and Treatment
January 1, 2023
Kwonmok Ko, Ben Carter, Anthony J. Cleare et al.
26 citations
In psychedelic therapy, both mystical and challenging experiences may affect treatment outcomes, but what predicts their intensity is not well understood. Analyzing data from a randomized, double-blind, placebo-controlled trial, 89 healthy volunteers received a placebo, 10 mg, or 25 mg of psilocybin. Higher dosage strongly predicted greater intensity of both mystical and challenging experiences. Older age was linked to less intense challenging experiences. Personality traits showed little correlation, except that neuroticism correlated with more intense challenging experiences at the higher dose. Positive or negative mood before dosing did not predict experience intensity. The analysis was exploratory and post hoc.
Neuropsychiatric Disease and Treatment
May 1, 2015
Wendian Shi, Xiaoli He, Xiangxiang Han et al.
22 citations
A four-week loving-kindness meditation program, practiced three times a week for about 30 minutes each session, improved positive emotions, interpersonal interactions, and complex understanding of others among college freshmen. The meditation group showed strong effects, with effect sizes above 0.8 for both interpersonal interaction and complex understanding of others, compared to a control group that received no meditation training. The findings suggest that loving-kindness meditation can effectively enhance social and emotional functioning in college students.
Neuropsychiatric Disease and Treatment
January 1, 2024
Nadav Liam Modlin, Michael Creed, Maria Sarang et al.
18 citations
Patients with post-traumatic stress disorder (PTSD) often find standard psychotherapies burdensome and drop out. Psychedelic therapy (PT) shows promise for difficult-to-treat conditions, but trials of classical psychedelics for PTSD are lacking. This systematic review of 40 qualitative studies (26 on evidence-based psychotherapies for PTSD, 14 on PT for various conditions) found overlapping themes: both therapies involve key mechanisms of change, require psychological safety and readiness, and can burden patients. In PT, indirect trauma processing and reorganization of self-narratives emerged as unique themes. Trauma-informed care may improve safety and acceptability of PT research.
Neuropsychiatric Disease and Treatment
October 1, 2018
Wallace C. Duncan, Elizabeth E. Slonena, Nadia S. Hejazi et al.
17 citations
Patients with major depressive disorder who had a brief antidepressant response to ketamine (lasting 24-48 hours) showed blunted 24-hour wrist activity amplitude from baseline through three days post-infusion and a phase advance of activity on day one that returned to baseline by day three. Those with a continued response (over 72 hours) had phase-advanced activity at baseline and day one, plus increased amplitude on days one and three. Nonresponders did not show these patterns. The time course of antidepressant response to ketamine appears linked to underlying biological differences in motor activity timekeeping, which may involve circadian system mechanisms.
Neuropsychiatric Disease and Treatment
January 1, 2016
Yuan-Yuan Lu, Chieh-Hsin Lin, Hsien-Yuan Lane
17 citations
A 26-year-old man who abused ketamine by inhalation for 12 months developed manic-like symptoms after using the drug. This case suggests a possible relationship between manic symptoms and ketamine abuse, and may be the first report of mania following recreational ketamine use.
Neuropsychiatric Disease and Treatment
December 1, 2022
Peng Liu, Shanshan Zhang, Yun Liang et al.
16 citations
Adding esketamine to an antidepressant improves outcomes for people with treatment-resistant depression more than placebo plus antidepressant. Across seven randomized controlled trials involving 701 patients receiving esketamine plus antidepressant and 551 receiving placebo plus antidepressant, the combination led to greater reductions in depression severity scores (Montgomery-Asberg Depression Rating Scale and self-rating depression scale), higher response and remission rates at the end of the double-blind induction period, and better quality of life and health status ratings. Minor adverse reactions occurred with esketamine.
Neuropsychiatric Disease and Treatment
October 1, 2020
Joanna Szarmach, Wiesław Jerzy Cubała, Adam Włodarczyk et al.
15 citations
In patients with treatment-resistant depression, intravenous ketamine is generally safe and well-tolerated when added to existing psychiatric medications. Blood pressure and heart rate returned to baseline within 90 minutes after each infusion, with no lasting complications. However, larger temporary increases in blood pressure occurred in patients also taking SSRIs, and heart rate decreases were greater in those not taking mood stabilizers. Risks were more pronounced in patients with coexisting high blood pressure or diabetes. The study included 35 people with major depressive disorder and 14 with bipolar disorder.
Neuropsychiatric Disease and Treatment
January 1, 2025
Daniel A Kinderlehrer
13 citations
Mental health disorders are rising worldwide, and neuroinflammation contributes to many cases, especially depression and anxiety. Anti-inflammatory treatments help these conditions. Psilocin, the active compound in Psilocybe mushrooms, acts as a serotonin agonist and anti-inflammatory agent, enhances neuroplasticity, and reduces overactivity in the default mode network. Studies using hallucinogenic doses under therapist supervision consistently benefit depression and end-of-life anxiety. Microdosing psilocybin in sub-hallucinogenic doses also improves mood disorders and may offer a safer, cheaper, more accessible alternative to full doses for mood disorders and other inflammation-driven conditions.
Neuropsychiatric Disease and Treatment
January 1, 2023
Allan H. Young, Mohamed Abdelghani, Mario F Juruena et al.
10 citations
Treatment-resistant depression (TRD) imposes severe burdens on patients, health services, and society, yet has lacked viable treatment options. An advisory panel of psychiatrists and clinical researchers experienced in managing TRD developed best practice statements on using esketamine nasal spray, one of the first TRD treatments licensed in 30 years. The panel agreed on recommendations for setting up and running an efficient esketamine clinic, emphasizing logistical planning, patient education to prevent discontinuation, and checklists for safe appointments. Expanding treatment options like esketamine nasal spray is likely key to improving long-term outcomes for this underserved population.
Neuropsychiatric Disease and Treatment
January 1, 2025
Ahmed Asad Raza, Ghazi Uddin Ahmed, Habiba Zafar et al.
6 citations
Intranasal esketamine (Spravato) rapidly relieves depression symptoms—often within hours—and improves remission and response rates in treatment-resistant depression (TRD) and severe major depressive disorder. Unlike conventional antidepressants, it works by blocking NMDA receptors to promote synaptogenesis and neuroplasticity. Its use is associated with a very low incidence of treatment-emergent sexual dysfunction (less than 1% of patients), a common side effect of SSRIs and SNRIs. However, esketamine can cause dissociative symptoms and blood pressure changes, and its administration requires in-clinic monitoring under a REMS program. Despite these limitations, it offers a valuable option for patients who do not respond to standard therapies.
Neuropsychiatric Disease and Treatment
January 1, 2023
Iman Khan, Taimoor Asif Jaura, Alaa Tukruna et al.
5 citations
About 40% of people with obsessive-compulsive disorder do not benefit from existing treatments, which also carry side effects. This systematic review evaluated alternative drugs for OCD. Searching databases up to March 2022, 16 studies examined psilocybin, cannabis, nicotine, and morphine. Most studies showed reduced Y-BOCS scores, though some nicotine or cannabis users reported no change or worsening symptoms. All psilocybin and morphine users, 88.2% of nicotine users, and 74.1% of cannabis users reported positive effects, suggesting these drugs have potential for OCD management. Further research is needed on mechanisms, and policies to destigmatize and encourage clinical trials are crucial.
Neuropsychiatric Disease and Treatment
January 1, 2024
Chan Li, Chen Zhu, Genghong Tu et al.
4 citations
Repeated ketamine administration (20 mg/kg) induces conditioned place preference (CPP) in mice, a model of addiction, and significantly alters gut microbiota diversity and composition. Compared to controls, ketamine exposure increased the relative abundance of four microbial families (Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae, Family-XIII) and decreased one (Prevotellaceae). At the genus level, five genera increased and one decreased. Ketamine dependence reduced levels of tight junction proteins, GABA, and GABRA1, while increasing BDNF and 5-HT. However, an oral antibiotic cocktail that created pseudo-germ-free mice did not enhance ketamine-induced addictive behavior, suggesting the gut microbiota mediates ketamine-induced CPP.
Neuropsychiatric Disease and Treatment
January 1, 2024
Xuemeng Chen, Rui Zhou, Lan Lan et al.
4 citations
Electroconvulsive therapy (ECT) is effective for treatment-resistant major depressive disorder. Combining esketamine with propofol anesthesia during ECT may improve outcomes. In a randomized, double-blind trial, 111 patients were assigned to receive propofol alone (1 mg/kg), low-dose esketamine (0.25 mg/kg) with propofol (0.75 mg/kg), or higher-dose esketamine (0.5 mg/kg) with propofol (0.5 mg/kg). Outcomes included depression scales, suicide risk, cognitive function, hospital stay, readmission, and side effects. The results may guide better ECT anesthesia choices.
Neuropsychiatric Disease and Treatment
January 1, 2025
Ying Zhang, Zhaojuan Ke, Jie Luo et al.
3 citations
Major depressive disorder (MDD) is common and carries a high suicide risk. Electroconvulsive therapy (ECT) is highly effective but limited by adverse effects; ketamine/esketamine can boost ECT's efficacy and safety but have their own side effects. Binaural beat music (BBM), a non-invasive therapy, may improve mood and assist (es)ketamine. This 2×2 factorial, randomized, blinded clinical trial recruits 476 MDD patients requiring ECT, randomly assigned to four groups: blank sound with saline, blank sound with esketamine, BBM with saline, or BBM with esketamine. The primary outcome is response rate measured by the Hamilton depression scale; secondary outcomes include remission, suicidal ideation, cognitive function, and side effects. The data are expected to show BBM's potential for optimizing ECT strategies and improving patient outcomes.
Neuropsychiatric Disease and Treatment
January 1, 2025
Yitong Ding, Zhengye Wang, Jing Huang et al.
3 citations
Adding esketamine to dexmedetomidine improves sleep and depression in people with both insomnia and depression. In a randomized trial with 84 patients, those receiving both drugs after three days showed longer total sleep time, more deep (N3) sleep, less light (N2) and REM sleep, and lower depression and sleep rating scores compared to those given dexmedetomidine alone. Sleep improvements were linked to better depression scores and higher brain-derived neurotrophic factor levels. Dry mouth was the most common side effect. The combination extended sleep, deepened sleep continuity, and reduced depression with few adverse events.
Neuropsychiatric Disease and Treatment
January 1, 2025
Zhaojuan Ke, Ying Zhang, Binyang Cai et al.
1 citation
Miscarriage and the subsequent curettage procedure increase risks of depression, anxiety, and insomnia. Ketamine and its derivative esketamine can prevent postpartum depression and treat depressive symptoms after miscarriage curettage, but side effects limit their use. Ascorbic acid (vitamin C) may enhance esketamine's antidepressant effects while reducing its dosage and adverse effects. This 2×2 factorial, double-blinded, randomized controlled trial will recruit 424 women with miscarriage undergoing painless curettage, allocating them equally to four groups: placebo, esketamine alone, vitamin C alone, or vitamin C plus esketamine.
Neuropsychiatric Disease and Treatment
January 1, 2024
Hui Song, Yang Luo, Lingzhi Fang
Esketamine nasal spray provides rapid relief for treatment-resistant depression (TRD) and helps prevent suicidal behavior. It works primarily by blocking NMDA receptors in the brain, with additional effects on AMPA receptors, opioid receptors, monoaminergic receptors, and inflammatory pathways, though the full synergistic mechanisms are not yet understood. Multiple randomized controlled trials show that esketamine reduces depressive symptoms within hours and maintains these benefits over several weeks, with a favorable safety profile and minimal side effects in long-term use. Its approval offers a new therapeutic option for patients with severe depression, impacting healthcare practices and policies.
Neuropsychiatric Disease and Treatment
March 1, 2018
Eva Češková, Petr Šilhán
Current treatment for severe mental disorders remains suboptimal. Improvement comes from both new procedures and optimizing existing ones, including therapeutic drug monitoring. New pharmacological options include more sophisticated monoaminergic drugs, rediscovered older drugs, and agents targeting novel mechanisms. For depression, treatment resistance is a major challenge; switching to multimodal antidepressants or augmenting with atypical antipsychotics like aripiprazole and brexpiprazole shows promise, as do nutraceuticals, ketamine, and opioids. Antipsychotics remain central for schizophrenia; new partial dopamine agonists brexpiprazole and cariprazine join aripiprazole, and long-acting injectable formulations of aripiprazole lauroxil and 3-month paliperidone palmitate are now available. Emerging options include cannabidiol, glutamate modulators, and nicotine receptor agonists.
Neuropsychiatric Disease and Treatment
September 1, 2019
Jia-Yuan Zhang, Xiang-Zi Ji, Li-na Meng et al.
A tailored 8-week mindfulness-based stress reduction (MBSR) program, adapted for adolescents, reduced depression and rumination and increased mindfulness in youngsters with sub-threshold depression. In a double-blind randomized controlled trial with 56 participants, those in the MBSR group showed significantly lower depression scores on the BDI-II and lower rumination scores on the RRS immediately after the intervention and at a three-month follow-up, compared to a control group. Mindfulness, measured by the MAAS, also improved and the effect persisted for three months. The findings suggest that adapted MBSR can benefit the psychological health of adolescents with sub-threshold depression.
Neuropsychiatric Disease and Treatment
November 14, 2016
M. Líšková, Denisa Janečková, Lucie Klůzová Kráčmarová et al.
Sleep paralysis (SP) in Czech university students is most strongly predicted by nightmares, while the intensity of fear during episodes is most strongly predicted by dream occurrences. In a sample of 606 students who had experienced at least one SP episode, 62% reported intense fear and 16% reported pleasant feelings. Women experienced SP more often than men. Higher scores on the Boundary Questionnaire (BQ-18) were associated with more frequent pleasant episodes, and higher scores on the Modified Tellegen Absorption Scale (MODTAS) were associated with hallucinations during SP. The authors suggest that personality variables, alongside rapid eye movement sleep dysregulation, may contribute to the characteristics of SP.
Neuropsychiatric Disease and Treatment
July 19, 2016
B. Sharpless
Sleep paralysis is a frightening event in which a person awakens conscious but temporarily unable to move, due to lingering REM-sleep muscle atonia, often accompanied by vivid hallucinations. When it occurs without narcolepsy or other medical conditions, it is called isolated sleep paralysis. The condition is underrecognized by nonsleep specialists, partly because patients are reluctant to disclose episodes and because medical training lacks coverage. A growing body of research documents its prevalence, risk factors, and clinical impact. Available treatments include pharmacological and psychotherapeutic interventions, but these require more empirical support from larger, well-controlled trials.
Neuropsychiatric Disease and Treatment
June 6, 2012
S. Golzari, Kazem Khodadoust, Farid Alakbarli et al.
Akhawayni's 10th-century Persian medical text, Hidayat al-muta'allemin fi al-tibb, includes a chapter on sleep paralysis (night-mare) placed before the description and treatment of epilepsy. This article reviews Akhawayni's teachings on sleep paralysis alongside descriptions and treatments by Greek, medieval, and Renaissance scholars. The authors contend that Akhawayni's descriptions, together with other early writings, offer insight into sleep paralysis during the Middle Ages in general and in Persia in particular.