Expert Review of Neurotherapeutics
December 4, 2018
Kai Zhang, Kenji Hashimoto
133 citations
Ketamine and its enantiomers show rapid-acting and sustained antidepressant effects in treatment-resistant patients with major depressive disorder and bipolar disorder. Clinical studies demonstrate that (R,S)-ketamine has rapid and sustained antidepressant activity in these populations. Preclinical data suggest that (R)-ketamine may exert longer-lasting antidepressant effects than (S)-ketamine in animal models, with potentially fewer side effects. (S)-norketamine also exhibits rapid and sustained antidepressant effects similar to (S)-ketamine but without causing behavioral and biochemical abnormalities, making it a potentially safer alternative.
Expert Review of Neurotherapeutics
August 10, 2016
Bas T.h. de Veen, Arnt Schellekens, Michel M. M. Verheij et al.
102 citations
Existing treatments for substance use disorders (SUD) are only partially effective. Psilocybin, a hallucinogen with a chemical structure similar to serotonin, may offer a new treatment option. Psilocybin administration spikes cortisol levels and activates the executive control network, increasing control over emotional processes and relieving negative thinking and persistent negative emotions. Preliminary data from ongoing human studies on alcohol and smoking addiction show promising effects on substance use. Psilocybin has low risk of toxicity and dependence and can be used safely under controlled conditions. Recent positive findings need confirmation in well-designed placebo-controlled randomized trials with large sample sizes.
Expert Review of Neurotherapeutics
January 14, 2020
Rebecca Erwin Wells, Elizabeth K. Seng, Robert R Edwards et al.
74 citations
Migraine is a leading cause of disability, and many patients cannot use or afford medications. Mindfulness-based interventions (MBI), such as mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT), offer a potential non-pharmacological treatment. Most research to date consists of small pilot trials with limited rigor, but initial evidence suggests improvements in headache-related disability and psychological well-being. Many questions remain about optimal dosage, duration, delivery, and which patients benefit most. Mindfulness will not cure migraine but may help patients engage in valued activities as part of a comprehensive treatment approach.
Expert Review of Neurotherapeutics
September 21, 2020
Hartej Gill, Barjot Gill, David C J Chen-Li et al.
62 citations
Psychedelics like psilocybin and MDMA show promise as a new type of therapy for mental health disorders. Evidence suggests they may work with just one dose, produce rapid effects, and be effective for treatment-resistant conditions, possibly serving as a standalone treatment. More clinical trials are needed to test their safety, tolerability, and effectiveness in real-world patient populations.
Expert Review of Neurotherapeutics
June 1, 2023
Harry A Fagan, David S Baldwin
55 citations
Generalized Anxiety Disorder (GAD) is common and characterized by excessive worry. Current treatments include pharmacological and psychological options, but many patients do not respond to first-line drugs. This review covers diagnostic criteria, epidemiology, and effective medications such as duloxetine, escitalopram, pregabalin, quetiapine, and venlafaxine. It also discusses treatment guidelines, management of treatment resistance, and special considerations for older adults and children. Evidence for further pharmacological management after initial treatment failure is limited. Many novel anxiolytics have entered clinical trials, but translation from animal models has mostly been unsuccessful. Compounds including certain psychedelics, ketamine, oxytocin, and agents modulating the orexin, endocannabinoid, and immune systems show potential for further study.
Expert Review of Neurotherapeutics
January 1, 2022
Manaswini Pillai, Simon Erridge, Lara Bapir et al.
27 citations
Patients prescribed cannabis-based medicinal products for post-traumatic stress disorder showed significant improvements in PTSD symptoms, sleep, and anxiety at 1, 3, and 6 months, based on an analysis of 162 patients from the UK Medical Cannabis Registry. Most patients (88.89%) had previously or currently used cannabis. Median daily doses were 5.00 mg of cannabidiol and 145.00 mg of Δ9-tetrahydrocannabinol. Adverse events occurred in 20.37% of patients, with 135.8% of the total events reported; most were mild or moderate, and insomnia and fatigue were most common. The findings suggest acceptability and safety up to 6 months, but randomized placebo-controlled trials are needed to confirm causality and optimal dosing.
Expert Review of Neurotherapeutics
April 1, 2025
Stefania Chiappini, Gaia Sampogna, Antonio Ventriglio et al.
17 citations
Depression involves a wide range of emotional, cognitive, and physical symptoms that disrupt daily life. Societal changes such as technological advances, economic pressures, climate change, and shifting cultural norms have altered how depression appears and is understood, leading to the identification of new depression subtypes. These include depression in adolescents and young adults, depression with social disconnection, depression with alcohol or substance use disorder, depression with gender dysphoria, and depression linked to stressful events and environmental factors. Managing these subtypes requires individualized treatment approaches. While SSRIs and SNRIs remain standard, atypical antidepressants like trazodone, ketamine, neuromodulation, and personalized psychotherapy offer hope for complex or treatment-resistant cases.
Expert Review of Neurotherapeutics
June 1, 2025
Rosalie Girard Pepin, Fatemeh Seyfzadeh, David Williamson et al.
7 citations
Pharmacological treatment options for disorders of consciousness (DoC), which range from coma to minimally conscious state, remain limited due to the heterogeneity of causes such as traumatic brain injury, stroke, and infections. A lack of rigorous clinical trials has led to off-label use of drugs—including dopaminergic and GABAergic agents, antidepressants, statins, and anticonvulsants—often without clear mechanistic understanding. Robust longitudinal trials are needed, prioritizing early subacute intervention and better-defined outcomes that consider immediate responses and long-term quality of life. A shift toward personalized medicine and unified functional frameworks is advocated, along with increased use of AI tools to predict treatment responses.
Expert Review of Neurotherapeutics
January 1, 2023
Emmanuelle A. D. Schindler, Peter S. Hendricks
5 citations
Most current psychedelic research targets depression and substance use disorders, but reports also indicate benefits for headache disorders and chronic pain. This perspective reviews conventional treatments for these conditions and describes historical, recent, and ongoing investigations of psychedelics' therapeutic effects, including the first two clinical trials of psilocybin in headache disorders and case reports of psilocybin mushroom self-administration in chronic pain patients. It highlights challenges when applying the standard psychedelic-assisted psychotherapy model—featuring larger doses, emphasis on subjective effects, and required adjunctive psychotherapy—to headache and chronic pain disorders. Flexibility in protocols is needed to evaluate different treatment paradigms and mechanisms.
Expert Review of Neurotherapeutics
February 1, 2025
Donatella Marazziti, Francesco Weiss, Riccardo Gurrieri et al.
4 citations
After decades of neglect, psychedelics are again being studied for clinical use, but the current enthusiasm risks overstating their benefits and downplaying their harms. The authors review the literature to give a balanced account of both therapeutic potential and risks. Psychedelics show promise for many conditions and appear to have limited risk of abuse or dependence when given under controlled conditions by trained staff. However, many questions remain, and more research is needed to identify which patients and conditions will benefit and which face greater risk of adverse effects.
Expert Review of Neurotherapeutics
July 1, 2026
Stephen Rush, Henry A Nasrallah
Treatment-resistant depression may stem from impaired neural adaptability rather than a simple chemical imbalance. This expert review synthesizes research showing a shift from monoamine-based models of depression toward frameworks centered on neuroplasticity, synaptic growth, glutamatergic signaling, and brain network dysfunction. The authors describe how treatments such as ketamine, neuromodulation, and psychedelics may work by reopening windows of plasticity and recalibrating dysfunctional neural networks, representing a paradigm shift in antidepressant development. The review is a conceptual synthesis, not treatment guidelines, and prospective studies are needed to validate and apply these mechanistically informed models clinically.
Expert Review of Neurotherapeutics
September 1, 2024
Joseph Blanco, Pamela Quimbaya, Manuel Mena et al.
A review of the neurobiology of major depressive disorder and the pharmacology, efficacy, safety, and tolerability of dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) for adults. The combination is an approved alternative for MDD, usable as a first-line therapy, as a second option after failed remission with a serotonin-targeting agent, and for treatment-resistant depression. Clinicians' familiarity with both drugs may increase acceptability, and further research into other indications, including addiction disorders, may yield additional benefits. The review is based on observational studies, clinical trials, and other secondary studies from systematic literature searches.
Expert Review of Neurotherapeutics
August 1, 2024
Andreas Reis, Marlon Westhoff, Hicham Quintarelli et al.
Mindfulness-based interventions show promise as complementary treatments for obsessive-compulsive disorder (OCD), a condition marked by intrusive thoughts and repetitive behaviors. A meta-analysis of ten randomized controlled trials demonstrated the effectiveness of mindfulness techniques. Integrating these strategies into cognitive-behavioral therapy (CBT) may enhance emotional regulation, cognitive flexibility, and acceptance of intrusive thoughts. However, variability in OCD symptoms and treatment responses requires individualized approaches. Further research is needed to refine mindfulness techniques and optimize their effectiveness for patients with persistent symptoms.
Expert Review of Neurotherapeutics
March 1, 2023
Zamfira Parincu, Dan V. Iosifescu
Major depressive disorder (MDD) is a leading cause of disability, but many patients do not improve with standard monoamine-targeting drugs, and benefits typically take 4-6 weeks. Combinations of dextromethorphan, an oral NMDA receptor antagonist, may offer faster relief. A systematic search of US Clinical Trials, PubMed, press releases, and poster presentations identified two case reports and eight clinical trials on dextromethorphan for MDD or treatment-resistant depression (TRD), plus additional studies in bipolar disorder. Clinical studies show that dextromethorphan combined with quinidine or bupropion effectively reduces depressive symptoms in MDD. However, results in adults with TRD or bipolar depression were mixed. The dextromethorphan-bupropion combination appears well-tolerated, safe, and efficacious for MDD, but more studies on TRD and bipolar depression are needed.