Catatonia is a syndrome that has been associated with several mental illness disorders but that has also presented as a result of other medical conditions. Schizophrenia and other psychiatric disorders such as mania and depression are known to be associated with catatonia; however, several case reports have been published of certain medical conditions inducing catatonia, including hyponatremia, cerebral venous sinus thrombosis, and liver transplantation. Neuroleptic Malignant Syndrome and anti-NMDA receptor encephalitis are also prominent causes of catatonia. Patients taking benzodiazepines or clozapine are also at risk of developing catatonia following the withdrawal of these medications—it is speculated that the prolonged use of these medications increases gamma-aminobutyric acid (GABA) activity and that discontinuation may increase excitatory neurotransmission, leading to catatonia. The treatment of catatonia often involves the use of benzodiazepines, such as lorazepam, that can be used in combination therapy with antipsychotics. Definitive treatment may be found with electroconvulsive therapy (ECT). Aberrant neuronal activity in different motor pathways, defective neurotransmitter regulation, and impaired oligodendrocyte function have all been proposed as the pathophysiology behind catatonia. There are many clinical challenges that come with catatonia and, as early treatment is associated with better outcomes, it becomes imperative to understand these challenges. The purpose of this manuscript is to provide an overview of these challenges and to look at clinical studies regarding the pathophysiology, diagnosis, and treatment of as well as the complications and risk factors associated with catatonia.

: Opioids are mu receptor agonists and have been an important part of pain treatment for thousands of years. In order to use these drugs appropriately and successfully in patients, whether to control pain, to treat opiate-induced side effects, or opiate withdrawal syndromes, a solid understanding of the pharmacology of such drugs is crucial. The most recognized full agonist opioids are heroin, morphine, codeine, oxycodone, meperidine, and fentanyl. Phenanthrenes refer to a naturally occurring plant-based compound that includes three or more fused rings. The opioids derived from the opium plant are phenanthrene derivatives, whereas most synthetic opioids are simpler molecules that do not have multiple rings. Methadone acts as a synthetic opioid analgesic similar to morphine in both quality and quantity; however, methadone lasts longer and in oral form, has higher efficacy, and is considered a diphenylheptane. Fentanyl is a strong synthetic phenylpiperdine derivative that exhibits activity as a mu-selective opioid agonist approximately 50 to 100 times more potent than morphine. Meperidine is another medication which is a phenylpiperdine. Tramadol is considered a mixed-mechanism opioid drug, as it is a centrally acting analgesic that exerts its effects via binding mu receptors and blocking the reuptake of monoamines. Some of the most common adverse effects shared among all opioids are nausea, vomiting, pruritus, addiction, respiratory depression, constipation, sphincter of Oddi spasm, and miosis (except in the case of meperidine). Chronic opioid usage has also established a relationship to opioid-induced hypogonadism and adrenal suppression. Physicians must be stewards of opioid use and use opioids only when necessary.

Postpartum depression (PPD) is one of the three major categories on the spectrum of postpartum psychiatric syndromes. Postpartum psychiatric syndromes are classified as either postpartum blues, postpartum depression, or postpartum psychosis. Postpartum depression is important to recognize clinically because of the effect it can have on the mother-child bond. The neurosteroid allopregnanolone, a progesterone derivative, is important for its role in positively modulating GABA_A receptors. GABA-mediated signaling has been previously implicated in major depressive disorder. Allopregnanolone-mediated signaling has been identified as an important therapeutic target. Treatment with an allopregnanolone-analog, brexanolone, has been shown to improve depression scores in trials for the treatment of PPD. Brexanolone is a positive allosteric modulator of GABA_A and is the first drug approved by the FDA to treat postpartum depression. Brexanolone enhances the inhibitory effects of GABA_A, restores dysfunctional GABA_A transmembrane channels, and mimics a naturally produced progesterone metabolite that fluctuates during pregnancy and postpartum. One open-label study and two phase two studies have some significant reduction in HAM-D scores after treatment and that the effect was still there 30 days post-treatment. Per the data reported, intravenous infusion of brexanolone could be efficacious and safe for the treatment of women suffering from postpartum depression.

Chronic pain is a common source of morbidity in many patient populations worldwide. There are growing concerns about the potential side effects of currently prescribed medications and a continued need for effective treatment. Related to these concerns, peripheral nerve stimulation has been regaining popularity as a potential treatment modality. Peripheral nerve stimulation components include helically coiled electrical leads, which direct an applied current to afferent neurons providing sensory innervation to the painful area. In theory, the applied current to the peripheral nerve will alter the large-diameter myelinated afferent nerve fibers, which interfere with the central processing of pain signals through small-diameter afferent fibers at the level of the spinal cord. Multiple studies have shown success in the use of peripheral nerve stimulation for acute post-surgical pain for orthopedic surgery, including post total knee arthroplasty and anterior cruciate ligament surgery, and chronic knee pain. Many studies have investigated the utility of peripheral nerve stimulation for the management of chronic shoulder pain. Peripheral nerve stimulation also serves as one of the potential non-pharmacologic therapies to treat back pain along with physical therapy, application of transcutaneous electrical neurostimulation unit, radiofrequency ablation, epidural steroid injections, permanently implanted neurostimulators, and surgery. Studies regarding back pain treatment have shown that peripheral nerve stimulation led to significant improvement in all pain and quality-of-life measures and a reduction in the use of opioids. Further studies are needed as the long-term risks and benefits of peripheral nerve stimulation have not been well studied as most information available on the effectiveness of peripheral nerve stimulation is based on shorter-term improvements in chronic pain.

Purpose of Review: Insomnia is a common type of sleep disorder defined by an ongoing difficulty initiating or maintaining sleep or nonrestorative sleep with subsequent daytime impairment. The sleep disturbances in insomnia usually manifest as difficulty in falling asleep, maintaining the continuity of sleep, or waking up too early in the morning well before the desired time, irrespective of the adequate circumstances to sleep every night. Insomnia can significantly impact daytime functioning resulting in decreased workplace productivity, proneness to errors and accidents, inability to concentrate, frequent daytime naps, and poor quality of life. The treatment of insomnia should involve a multi-disciplinary approach, focusing on implementing behavioral interventions, improving sleep hygiene, managing psychological stressors, hypnotic treatment, and pharmacological therapy. The most effective therapies utilize cognitive behavioral therapy in conjunction with pharmacotherapy to minimize the needed dose and any resulting side effects. Non-benzodiazepine hypnotics such as zolpidem, eszopiclone, zaleplon are the most used as adjunctive treatment. One of the most used of these hypnotics is zolpidem. However, zolpidem has a wide variety of adverse effects and has some special considerations noted in the literature. Recent Findings: Zolpidem has been associated with an increased risk of falls in hospitalized patients with an OR of 4.28 (P <0.001) when prescribed short-term for insomnia. The relative risk (RR) for hip fractures in patients taking zolpidem was described as 1.92 (95% CI 1.65-2.24; P<0.001), with hip fractures being the most commonly seen. A case series of 119 inpatients aged 50 or older demonstrated that a majority (80.8%) of ADRs were central nervous system (CNS)-related such as confusion, dizziness, and daytime sleepiness. A systematic review of 24 previous studies of sleepwalking associated with zolpidem demonstrated that the association was not dependent on age, dose, medical history, or even a history of sleepwalking at any time before zolpidem use. Suicide attempts and completion have been successfully linked with zolpidem use (OR 2.08; 95% CI 1.83-2.63) in patients regardless of the presence of comorbid psychiatric illness. There have been multiple cases reported of seizures following the withdrawal of zolpidem. Most cases have demonstrated that withdrawal seizures occurred in patients taking daily dosages of around 450-600mg/day, but some reported them as low as 160mg/day. Rebound insomnia has been a concern to prescribers of zolpidem. Sleep onset latency has been demonstrated to be significantly increased on the first night after stopping zolpidem (13.0 minutes; 95% CI 4.3-21.7; P<0.01). Women had a non-significantly higher mean plasma concentration than men after 8 hours for the 10mg IR (28 vs. 20 ng/mL) and the 12.5mg MR (33 vs. 28ng/mL). The FDA has classified zolpidem as a category C drug based on adverse outcomes seen in animal fetal development. In the mothers exposed to zolpidem, there was an increased incidence of low birth weight (OR = 1.39; P<0.001), preterm delivery (OR 1.49; P<0.001), small for gestational age (SGA) babies (OR = 1.34; P<0.001), and cesarean deliveries (OR =1.74; P<0.001). The rate of congenital abnormalities was not significantly increased with zolpidem (0.48 vs 0.65%; P = 0.329). Summary: Insomnia is linked to fatigue, distractibility, mood instability, decreased satisfaction, and overall decreased quality of life. Optimal therapy can aid patients in returning to baseline and increase their quality of life. Zolpidem is a helpful drug for the treatment of insomnia in conjunction with cognitive-behavioral therapy. When prescribed to elderly patients, the dose should be adjusted to account for their slower drug metabolism. Still, zolpidem is considered a reasonable choice of therapy because it has a lower incidence of residual daytime sleepiness and risk of falls when compared to other drugs. The most concerning adverse effects, which are often the most publicized, include the complex behaviors that have been seen in patients taking Zolpidem, such as sleeping, hallucinations, increased suicidality, driving cars while asleep, and even a few cases of committing homicide. Even so, zolpidem could be a suitable pharmacological treatment for insomnia. Decisions for whether or not to prescribe it and the dosage should be made on a case-by-case basis, considering both the psychical and psychiatric risks posed to the patient with insomnia versus if the patient were to take zolpidem to treat their condition.

Purpose of Review: The opioid epidemic has been responsible for significant morbidity and mortality in the USA and worldwide. As a result, it is essential to recognize the threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as a drug adulterant has been shown to impact overdose rates drastically. In this regard, the Drug Enforcement Agency recently released a public safety alert announcing the new threat of a new adulterant called xylazine. Xylazine is a powerful animal sedative with a different mechanism of action when compared to illicit opioids such as heroin and fentanyl. Xylazine is typically injected intravenously via a syringe, often in combination with multiple other drugs. One of the most common drugs, xylazine, is taken in combination with fentanyl, with users of this drug combination describing xylazine as prolonging the euphoric sensation produced by fentanyl.Recent Findings: Xylazine may cause adverse effects such as bradycardia, brief hypertension followed by hypotension, premature ventricular contractions, ataxia, slurred speech, sedation, and respiratory depression. Much of the recent literature on xylazine use in humans comes from case reports and review articles.Summary: Related to widespread use in veterinary medicine and increasing circulation in illicit drug markets, there is a critical need for public awareness and additional clinical-based studies to further increase understanding of mediated or modulated pharmacological effects of xylazine in humans. Further research is urgently needed to more clearly understand the implications of unregulated xylazine in the illicit drug market, to formulate public health interventions, and to implement harm reduction strategies.