Many children with autism spectrum disorder (ASD) also have attention-deficit/hyperactivity disorder (ADHD). ADHD in children is associated with increased risk of negative outcomes, and early intervention is critical. Current guidelines recommend psychosocial interventions such as behavioral training as the first line of therapy in managing ADHD symptoms in children with or without ASD. Where symptoms are refractory to these interventions, medications such as stimulants, α2-adrenergic agonist inhibitors, selective norepinephrine reuptake inhibitors, and second-generation antipsychotics are recommended. However, these pharmacotherapies do not have regulatory approval for use in children of preschool age, and evidence on their safety and efficacy in this population has historically been very limited. Since publication of the current guidelines in 2020, several new randomized controlled trials and real-world studies have been published that have investigated the efficacy and tolerability of these medications in preschool children with ADHD, with or without comorbid ASD. Here, we provide a review of the key findings of these studies, which suggest that there is growing evidence to support the use of pharmacological interventions in the management of ADHD in preschool children with comorbid ASD.

Hallucinogen-persisting perception disorder (HPPD), also known as acute hallucinogen-induced psychosis or informally known as \"flashbacks,\" is an unusual condition experienced by patients due to the use of different hallucinogenic substances. Hallucinogen-persisting perception disorder causes many symptoms, predominantly persistent visual perception distortion instead of intermittent distortion. Although different hallucinogens could cause HPPD, lysergic acid diethylamide (LSD) and LSD-like properties seem to be the most common hallucinogens causing the symptoms. In our case report, the patient is a 28-year-old Caucasian male with a long psychiatric and social history of polysubstance use using LSD and cannabis. He started experiencing many of the classic symptoms of HPPD seven months after stopping LSD. The diagnosis is suspected by ruling out all other possible underlying causes with the help of several laboratory and imaging tests. Despite having an extensive psychiatric history of illnesses, the patient\'s symptoms failed to improve with antipsychotics, confirming that the symptoms were not only due to mental illness. Although supposedly the first-line treatment for HPPD is the use of alpha-2 adrenergic drugs such as clonidine and benzodiazepines, we started to witness improvement in patient\'s symptoms with the use of lamotrigine, which is the gold standard in treating perceptual disturbance in time and space.

UNASSIGNED: Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent condition that causes persistent problems with attention and/or hyperactivity-impulsivity and often results in significant impairment when left untreated. Medications for this disorder continue to evolve and provide new treatment options. Ongoing review of related medication safety and tolerability remains an important task for prescribers.
UNASSIGNED: This manuscript provides an updated safety review of medications used to treat ADHD in children and adolescents. PubMed and OneSearch online databases were utilized to search for literature relevant to the topic of ADHD medications and safety. Clinical trials of medications used to treat ADHD, systematic reviews and meta-analyses, and articles covering specific safety issues (adverse or unfavorable events) such as cardiovascular effects, seizures, impact on growth, depression, suicidal ideation, substance use disorders, psychosis, and tics are described.
UNASSIGNED: Available pharmacologic treatments for ADHD have favorable efficacy, safety and tolerability and allow many patients to achieve significant improvement of their symptoms. Despite the availability of multiple stimulant and non-stimulant formulations, some individuals with ADHD may not tolerate available medications or attain satisfactory improvement. To satisfy unmet clinical needs, ADHD pharmaceutical research with stimulant and nonstimulant formulations targeting dopamine, norepinephrine, and novel receptors is ongoing.

Background There is a need for improved strategies for managing abrupt opioid withdrawal when transitioning patients with opioid use disorder to comprehensive longitudinal care strategies such as naltrexone maintenance treatment. In addition, alpha-2 adrenergic agonists are used to ameliorate withdrawal symptoms, but current data characterizing real-world treatment are lacking. Methods A retrospective chart review was conducted in outpatients undergoing abrupt opioid withdrawal managed with lofexidine (0.18 mg, 1-4 tablets 4x daily for 7 days, pro re nata [PRN or as needed]) or clonidine (0.2 mg, 1 tablet 3x daily for 10 days, PRN). Withdrawal outcomes were characterized at 30 days of follow-up. Binomial logistic regression was used to assess a potential association of the two treatments with different likelihoods of opioid cessation success in this real-world outpatient practice. Results In cases treated with lofexidine (n=166) and clonidine (n=432), respectively, 40% and 10% were opioid-free, 6% and 2% continued long-term buprenorphine or methadone, 17% and 36% relapsed, and 37% and 52% were lost to follow-up at 30 days post-withdrawal. Among patients returning for follow-up care, 63% of patients treated with lofexidine and 21% treated with clonidine were opioid-free. Lofexidine was associated with a higher likelihood of opioid cessation success relative to clonidine (OR=6.47; Wald Chi-square=53.79, p<0.001). Conclusion Among outpatients returning for follow-up care, nearly two-thirds of those managed with lofexidine reached opioid-free status at 30 days post-withdrawal, which was a higher likelihood than those managed with clonidine, thus allowing their transition to comprehensive care, including naltrexone.

Objectives: To determine whether conditions coexisting with attention-deficit/hyperactivity disorder (ADHD) in preschool-age children are associated with choice of stimulants or alpha-2 adrenergic agonists (A2As) and/or likelihood of improvement in ADHD symptoms. Methods: A retrospective electronic health record review of 497 children from 7 Developmental Behavioral Pediatrics Research Network (DBPNet) sites. Children were <72 months when treated with medication for ADHD from January 1, 2013 to July 1, 2017. We abstracted coexisting conditions, initial medication prescribed, and whether the medication was associated with improvement in symptoms. Analysis of improvement was adjusted for clustering by clinician and site. Results: The median (interquartile range) child age at the time of initiation of ADHD medication was 62 (54-67) months. The most common coexisting conditions included language disorders (40%), sleep disorders (28%), disruptive behavior disorders (22.7%), autism spectrum disorder (ASD; 21.8%), and motor disorders (19.9%). No coexisting conditions were present in 17.1%; 1 in 36.8%, 2 in 26.8%, and ≥3 in 19.3%. Stimulants were initially prescribed for 322 (64.8%) and A2A for 175 (35.2%) children. Children prescribed stimulants were more likely to have no coexisting conditions than those prescribed A2A (22.3% vs. 7.4%; p < 0.001). Coexisting ASD and sleep disorder were associated with increased likelihood of starting A2As versus stimulants (p < 0.0005; p = 0.002). The association between medication treatment and improvement varied by number of coexisting conditions for 0, 1, 2, or ≥3, respectively (84.7%, 73.8%, 72.9%, 64.6%; p = 0.031). Children with ≥3 coexisting conditions were less likely to respond to stimulants than children with no coexisting conditions (67.4% vs. 79.9%; p = 0.037). Conclusions: Among preschool-age children with ADHD, those with ≥3 coexisting conditions were less likely to respond to stimulants than those with no coexisting conditions. This was not found for A2A, but further research is needed as very few children with no coexisting conditions were treated with A2A.

BACKGROUND: We report a case of lorazepam-induced agitated delirium treated with haloperidol, which in turn triggered the onset of neuroleptic malignant syndrome (NMS). The latter condition, a medical emergency, was effectively treated with medical treatment and dexmedetomidine, a versatile and highly selective short-acting alpha-2 adrenergic agonist with sedative-hypnotic and anxiolytic effects.
METHODS: A 65-year-old man with a history of bipolar disorder presented to the emergency department with severe abdominal discomfort after binge eating. During his hospital stay, he received intravenous lorazepam for insomnia. On the next day, he became delirious and was thus treated with seven doses (5 mg each) of haloperidol over a 48 h period. Signs of NMS (hyperthermia, rigidity, myoclonus of upper limbs, impaired consciousness, tachypnea, and dark urine) became apparent and haloperidol was immediately suspended and brisk diuresis was initiated. On intensive care unit admission, he was confused, disoriented, and markedly agitated. Dexmedetomidine infusion was started with the goal of achieving a Richmond Agitation-Sedation Scale score of -1 or 0. NMS was resolved gradually and the patient stabilized, permitting discontinuation of dexmedetomidine after 3 d.
CONCLUSIONS: Dexmedetomidine may be clinically helpful for the management of NMS, most likely because of its sympatholytic activity.

The high number of patients infected with the SARS-CoV-2 virus requiring care for ARDS puts sedation in the critical care unit (CCU) to the edge. Depth of sedation has evolved over the last 40 years (no-sedation, deep sedation, daily emergence, minimal sedation, etc.). Most guidelines now recommend determining the depth of sedation and minimizing the use of benzodiazepines and opioids. The broader use of alpha-2 adrenergic agonists (\'alpha-2 agonists\') led to sedation regimens beginning at admission to the CCU that contrast with hypnotics+opioids (\"conventional\" sedation), with major consequences for cognition, ventilation and circulatory performance. The same doses of alpha-2 agonists used for \'cooperative\' sedation (ataraxia, analgognosia) elicit no respiratory depression but modify the autonomic nervous system (cardiac parasympathetic activation, attenuation of excessive cardiac and vasomotor sympathetic activity). Alpha-2 agonists should be selected only in patients who benefit from their effects (\'personalized\' indications, as opposed to a \'one size fits all\' approach). Then, titration to effect is required, especially in the setting of systemic hypotension and/or hypovolemia. Since no general guidelines exist for the use of alpha-2 agonists for CCU sedation, our clinical experience is summarized for the benefit of physicians in clinical situations in which a recommendation might never exist (refractory delirium tremens; unstable, hypovolemic, hypotensive patients, etc.). Because the physiology of alpha-2 receptors and the pharmacology of alpha-2 agonists lead to personalized indications, some details are offered. Since interactions between conventional sedatives and alpha-2 agonists have received little attention, these interactions are addressed. Within the existing guidelines for CCU sedation, this article could facilitate the use of alpha-2 agonists as effective and safe sedation while awaiting large, multicentre trials and more evidence-based medicine.

OBJECTIVE: To study the effect of clonidine administrated as a co-analgesic during scoliosis surgery, on the neuromonitoring of spinal motor pathways.
METHODS: Using standardized intraoperative monitoring, we compared the time course of peripherally and transcranially electrically evoked motor potentials (TcEMEPs) before and after injection of a single bolus of clonidine in children under total intravenous anesthesia (TIVA). MEP data were obtained from 9 patients and somatosensory evoked potentials (SSEPs) were obtained from 2 patients. The potential effect of clonidine on mean blood pressure (BP) was controlled.
RESULTS: TcEMEPs from upper and lower limbs rapidly showed significant drops in amplitude after the injection of clonidine. Amplitudes reached minimal values within five minutes and remained very weak for at least 10-20minutes during which monitoring of the central motor pathways was severely compromised. SSEPs were not altered during maximal amplitude depression of the TcEMEPS.
CONCLUSIONS: This is the first report showing that clonidine severely interferes with neuromonitoring of the spinal cord motor pathways. The results are discussed in light of the literature describing the effects of dexmedetomidine, another α-2 adrenergic agonist. The experimental and literature data point to central mechanisms taking place at both the spinal and cerebral levels. Therefore, clonidine as well as other α-2 adrenergic agonists should be used with extreme caution in patients for whom neuromonitoring of the motor pathways is required during surgery.

Clonidine, an α2-adrenergic agonist, has a potent sympatholytic effect and augments the pressor effect of ephedrine during general anesthesia. We evaluated whether oral clonidine premedication would alter the hemodynamic changes and enhance the pressor response to intravenous ephedrine during epidural anesthesia in 35 adult patients. They were randomly administered either premedication with clonidine approximately 5 μg·kg-1 po (n=17) or no clonidine medication (n=18). After establishment of epidural anesthesia, the hemodynamic response to ephedrine iv was measured in the awake state at 1-min intervals for 10 min. Then, the same hemodynamic measurement was repeated in the asleep state induced with midazolam iv. There were no differences in blood pressure (BP) and heart rate values between groups during the onset of epidural anesthesia, except that BP before epidural anesthesia was lower in the clonidine group than the control group (P<0.05). The magnitude and duration of pressor responses to ephedrine were comparable between groups in awake and asleep states. In conclusion oral clonidine premedication 5 μg·kg-1 alters neither the hemodynamic changes nor the pressor response to intravenous ephedrine during epidural anesthesia.

The use of sheep in experiments is widespread and is increasing worldwide, and so is the need to develop species-specific anaesthetic techniques to ensure animal safety. Previous studies have mentioned several protocols involving the administration of alpha-2 adrenergic agonists in sheep; however, assessment of the efficacy and safety of these infusion techniques is still relatively new. Thus, the aim of the present study is to assess the effectiveness of detomidine constant rate infusion (CRI) in sheep by measuring the cardiovascular and respiratory parameters, blood gas variables and sedation scores. Eight adult female Santa Inês sheep received 20 µg/kg of detomidine hydrochloride intravenously as a bolus loading dose, followed by an infusion rate of 60 µg/kg/h. The heart rates and respiratory rates changed continuously during the CRI period. No arrhythmias were observed. The reduction in arterial partial pressure of oxygen (PaO2) was not significant, but one animal showed signs of hypoxaemia (minimum PaO2 of 66.9 mmHg). The arterial partial pressure of carbon dioxide (PaCO2) increased, but the animals did not become hypercapnic. The bicarbonate (HCO3-), pH and base excess (BE) tended towards metabolic alkalosis. The cardiac output (CO), stroke volume (SV), cardiac index (CI) and ejection fraction (EF%) showed no significant changes. The fractional shortening (FS%) decreased slightly, starting at T45min. Sedation scores varied between 3 (0/10) after sedation and during recovery and 7 (0/10) during CRI. We concluded that administering detomidine at an infusion rate of 60 µg/kg/h in Santa Inês sheep is a simple technique that produces satisfactory sedation for minimally invasive procedures.