Synergistic interaction of guanfacine or dexmedetomidine coadministered with lidocaine for cutaneous analgesia in rats.

BACKGROUND: This study examined the cutaneous analgesic effects of lidocaine co-injected with guanfacine and its comparison with dexmedetomidine. METHODS: Cutaneous analgesic effects are quantified through the blocking effects of the cutaneous trunci muscle reflex against skin pinpricks in rats. The dose-response curves of guanfacine, dexmedetomidine, and lidocaine were constructed and drug-drug interactions were analyzed by the ED50 isobologram. RESULTS: Subcutaneous injections of guanfacine, dexmedetomidine, and lidocaine produced dose-dependently nociceptive/sensory blockade. On the ED50 (50% effective dose) basis, the potency rankings of the drug are dexmedetomidine (0.09 [0.08-0.11] µmol/kg) > guanfacine (3.98 [2.96-5.34] µmol/kg) > lidocaine (25.40 [23.51-27.44] µmol/kg) (p < 0.01). On their equipotent doses (ED25, ED50, and ED75), the duration of sensory blockade induced by guanfacine or dexmedetomidine was longer than lidocaine's (p < 0.01). Both guanfacine and dexmedetomidine showed synergistic effects with lidocaine. CONCLUSIONS: We showed that guanfacine elicits dose-dependent cutaneous analgesia when administered subcutaneously. Lidocaine is less potent than guanfacine or dexmedetomidine. Both guanfacine and dexmedetomidine enhance the potency and duration of lidocaine. Better synergistic responses we are getting with guanfacine plus lidocaine.

Combined Use of Guanfacine and N-Acetylcysteine for the Treatment of Cognitive Deficits After Traumatic Brain Injury.

Traumatic Brain Injury (TBI) is a significant contributor to disability across the world. TBIs vary in severity, and most cases are designated mild TBI (mTBI), involving only brief loss of consciousness and no intracranial findings on imaging. Despite this categorization, many persons continue to report persistent cognitive changes in the months to years after injury, with particular impairment in the cognitive and executive functions of the pre-frontal cortex. For these persons, there are no currently approved medications, and treatment is limited to symptom management and cognitive or behavioral therapy. The current case studies explored the use of the alpha-2A adrenoreceptor agonist, guanfacine, combined with the antioxidant, N-acetylcysteine (NAC), in the treatment of post-TBI cognitive symptoms, based on guanfacine's ability to strengthen pre-frontal cortical function, and the open-label use of NAC in treating TBI. Two persons from our TBI clinic were treated with this combined regimen, with neuropsychological testing performed pre- and post-treatment. Guanfacine + NAC improved attention, processing speed, memory, and executive functioning with minimal side effects in both persons. These results encourage future placebo-controlled trials to more firmly establish the efficacy of guanfacine and NAC for the treatment of cognitive deficits caused by TBI.

Attention-deficit/hyperactivity disorder in pregnancy and the postpartum period.

Attention-deficit/hyperactivity disorder is a childhood-onset neurodevelopmental disorder that frequently persists into adulthood with 3% of adult women having a diagnosis of attention-deficit/hyperactivity disorder. Many women are diagnosed and treated during their reproductive years, which leads to management implications during pregnancy and the postpartum period. We know from clinical practice that attention-deficit/hyperactivity disorder symptoms frequently become challenging to manage during the perinatal period and require additional support and attention. There is often uncertainty among healthcare providers about the management of attention-deficit/hyperactivity disorder in the perinatal period, particularly the safety of pharmacotherapy for the developing fetus. This guideline is focused on best practices in managing attention-deficit/hyperactivity disorder in the perinatal period. We recommend (1) mitigating the risks associated with attention-deficit/hyperactivity disorder that worsen during the perinatal period via individualized treatment planning; (2) providing psychoeducation, self-management strategies or coaching, and psychotherapies; and, for those with moderate or severe attention-deficit/hyperactivity disorder, (3) considering pharmacotherapy for attention-deficit/hyperactivity disorder, which largely has reassuring safety data. Specifically, providers should work collaboratively with patients and their support networks to balance the risks of perinatal attention-deficit/hyperactivity disorder medication with the risks of inadequately treated attention-deficit/hyperactivity disorder during pregnancy. The risks and impacts of attention-deficit/hyperactivity disorder in pregnancy can be successfully managed through preconception counselling and appropriate perinatal planning, management, and support.

Guanfacine for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents with Down Syndrome: A Retrospective Chart Review.

Study Design: Retrospective case series. Objectives: The objective of this study was to provide naturalistic data on the use of guanfacine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in a clinically referred sample of youth with Down syndrome (DS). Methods: The medical records of children and adolescents with DS who received guanfacine for the treatment of ADHD from a multidisciplinary neurodevelopmental disorder clinic between September 1, 2011, and September 10, 2021, were reviewed. Demographic and clinical characteristics, guanfacine dose and treatment duration, and adverse effects were recorded. Clinical Global Impression Scale (CGI) scores for ADHD symptom severity (S) and improvement (I) were retrospectively assigned by a child and adolescent psychiatrist based on review of the clinic notes. Response to guanfacine was defined as completion of at least 12 weeks of treatment and a Clinical Global Impression Improvement subscale rating ≤2 (1 = "very much improved" or 2 = "much improved"). Results: Twenty-one patients were eligible for inclusion, of whom 17 (81%) completed at least 12 weeks of guanfacine. Ten of the 21 patients (48%; 95% confidence interval [CI]: 28%-68%) responded to treatment. The median time on guanfacine treatment covered by the clinic notes was 50.4 weeks, with a range of 0.3 weeks to 7.5 years. Thirteen patients (62%) remained on guanfacine at the time of their most recent clinic note. Nine patients had adverse events documented in their clinic notes (43%; 95% CI: 24%-63%), most commonly sleepiness (n = 7) and constipation (n = 2). Conclusion: About half of patients with DS responded to guanfacine for the treatment of ADHD and many tolerated long-term use. Study limitations primarily relate to the retrospective nature of the study and small sample size.

Alpha-2 Agonists in Children and Adolescents With Post-traumatic Stress Disorder: A Systematic Review.

Exposure to traumatic stress is common among children. Post-traumatic stress disorder (PTSD) is a debilitating chronic mental disorder that can develop following exposure to a traumatic event. Psychopharmacological research in pediatric PTSD is limited. There is some evidence supporting the use of alpha-2 (α2) agonists for symptoms associated with PTSD. This systematic review identified published studies evaluating the effectiveness of α2 agonists in treating PTSD symptoms in children and adolescents. We conducted an extensive literature search on PubMed, MEDLINE, EMBASE, Cochrane Collaboration, and PsycINFO databases for published articles that evaluated the use of α2 agonists (clonidine and guanfacine) for treating symptoms of PTSD in children and adolescents. The study protocol was registered in Prospero (ID: CRD42021273692) and followed the PRISMA guidelines. A total of 10 published articles about clonidine or guanfacine use in PTSD in children and adolescents were identified. Studies found clonidine effective in reducing PTSD symptoms; however, the effects were variable. Clonidine and guanfacine showed effectiveness in treating nightmares, hyperarousal, aggression, and sleep disturbances and reducing re-experiencing, avoidant, and hyperarousal symptom clusters. No randomized, double-blind, placebo-controlled trials were found during the literature search. α2 agonists' effectiveness in treating symptoms associated with PTSD in children and adolescents is preliminary. Future placebo-controlled trials are needed to assess the efficacy and safety of α2 agonists.

Guanfacine treatment for a patient with delusional parasitosis causing dermatillomania presenting with shared psychiatric disorders.

Dermatillomania often coexists with delusional parasitosis (DP) and can cause extreme patient morbidity. The standard treatment for DP has been conventional antipsychotic drugs; however, their use is limited by potential adverse effects and monitoring requirements. Guanfacine, an alpha-2 adrenergic receptor agonist, has emerged as a promising alternative for patients with attention deficit hyperactivity disorder with concurrent tics. Although no current research supports guanfacine's efficacy in managing DP or dermatillomania, its pharmacological profile hints at potential benefits. A 58-year-old woman presented to our clinic for DP causing dermatillomania and was started on guanfacine. She reported fewer beliefs about parasites infesting her body and had fewer excoriating lesions on this medication. Additionally, her Patient Health Questionnaire-9 score peaked with a score of 23 at diagnosis and significantly decreased to 13 three months after starting guanfacine. However, further research is needed to ascertain if guanfacine is an effective treatment for DP.

QT-Interval Prolongation Associated with Supratherapeutic Guanfacine Concentration: A Case Report.

INTRODUCTION: Guanfacine, an alpha-2 adrenergic agonist, is used to treat attention deficit hyperactivity disorder (ADHD). Although cardiovascular effects including hypotension and bradycardia are common adverse effects of guanfacine, the effect of guanfacine on QT intervals remains unclear. The association between the serum concentration of guanfacine and its toxicity has also not been fully investigated. CASE REPORT: This is a case of a 21-year-old woman with ADHD who developed repeated presyncope 1 day before admission. She was taking 3 mg of extended-release guanfacine and 50 mg of sertraline. On admission, she had bradycardia and hypotension. An electrocardiogram (ECG) showed a QT interval of 0.68 s and a QTcF interval of 0.648 s. The QT intervals were manually measured and corrected by the Fridericia formula (QTcF = QT/RR1/3). Although she denied taking an overdose of guanfacine and other drugs, we suspected guanfacine toxicity. The serum guanfacine concentration was 13.0 ng/mL on admission and decreased to 3.2 ng/mL on day 1 and 0.4 ng/mL on day 2. Changes in QTcF intervals and her vital signs correlated with serum guanfacine concentrations. CONCLUSION: Supratherapeutic serum guanfacine concentrations may induce QT prolongation.

Effect of ion pair strategy on transdermal delivery of guanfacine: Which factor dominates drug permeation?

Ion pair is an effective chemical approach to promoting drug transdermal permeation, and the traditional interpretation for its enhanced permeation effect is mainly attributed to counterions altering the physicochemical properties of the drug (lipophilicity, melting point, etc.). In this work, guanfacine (GFC), a non-stimulant for anti-attention deficit and hyperactivity disorder (ADHD), was used as a model drug, and several organic or inorganic acids were designed thereby successfully constructing ion pairs. The transdermal permeation ability of ion pairs through isolated porcine skin was observed and ranked as follows: guanfacine caprylate (GFC-CA) > GFC > guanfacine laurate (GFC-LA) > guanfacine fumarate (GFC-FA) > guanfacine hydrochloride (GFC-HA) > guanfacine palmitate (GFC-PA). The effect of key physicochemical properties (octanol-water partition coefficient, molecular volume, melting point) on the transdermal permeation rate of the model drug was analyzed in detail. In addition, GFC-CA was observed to alter the lipid structure of the skin, suggesting the traditional explanation of the action of ion pair may be inadequate and underrated, and ion pair may also enhance permeation by disrupting skin structure. The intriguing phenomenon is expected to provide a novel approach to achieving precise transdermal drug delivery.

Practical clinical guidelines and pharmacological treatment for attention-deficit hyperactivity disorder in Asia.

Attention-deficit hyperactivity disorder (ADHD) is characterized by persistent symptoms of inattention, hyperactivity, and impulsivity. Both, stimulant and nonstimulant medications have been approved for the treatment of this disorder. Several Western guidelines recommend the use of prescribed Food and Drug Administration (FDA)-approved medications for ADHD along with parental training in behavior management and behavioral classroom intervention. In 2022, new Japanese guidelines for ADHD were issued, which recommended school environment management and psychosocial treatment as the first-line treatment, with pharmacological treatment added as the second-line treatment. Although Japanese guidelines, including pharmacological treatments, have been established, the guidelines and utilization of ADHD medications across Asian regions are unclear. Therefore, to appropriately evaluate the strategy of pharmacological treatments for ADHD, we investigated Asian regional guidelines for ADHD medication in children. We also reviewed the guidelines in Malaysia, Singapore, India, and the Republic of Korea and found that these guidelines differ from Western guidelines.

A case of pulmonary edema due to guanfacine intoxication with measurement of serum guanfacine concentrations.

Guanfacine hydrochloride extended-release (GXR) is used to treat attention deficit hyperactivity disorder. It is a selective α2A-adrenorecepor agonist that was reported to cause QT prolongation and hypotension in the event of overdosing. We report the case of a 17-year-old man who took 226 tablets of GXR 3 mg for attempted suicide. He was found complaining of dyspnea, and emergency medical services were called. When the patient was transferred to our hospital, his Glasgow coma scale was 12 (E4V3M5). He was agitated and hypoxemic. He was intubated for invasive mechanical ventilation under sedation. His chest X-ray and computed tomography scan showed pulmonary edema. Transthoracic echocardiography showed markedly reduced cardiac function. His serum guanfacine concentration peaked on day 3 after admission. His pulmonary edema improved quickly after a decrease in serum guanfacine concentration, but cardiac decompensation persisted for about 1 month. This case reveals that the decline in cardiac function after guanfacine intoxication is prolonged even after its serum concentration has decreased.

Anxiety and dysautonomia symptoms in patients with a NaV1.7 mutation and the potential benefits of low-dose short-acting guanfacine.

PURPOSE: Guanfacine is an α2A-adrenergic receptor agonist, FDA-approved to treat attention-deficit hyperactivity disorder and high blood pressure, typically as an extended-release formulation up to 7 mg/day. In our dysautonomia clinic, we observed that off-label use of short-acting guanfacine at 1 mg/day facilitated symptom relief in two families with multiple members presenting with severe generalized anxiety. We also noted anecdotal improvements in associated dysautonomia symptoms such as hyperhidrosis, cognitive impairment, and palpitations. We postulated that a genetic deficit existed in these patients that might augment guanfacine susceptibility. METHODS: We used whole-exome sequencing to identify mutations in patients with shared generalized anxiety and dysautonomia symptoms. Guanfacine-induced changes in the function of voltage-gated Na+ channels were investigated using voltage-clamp electrophysiology. RESULTS: Whole-exome sequencing uncovered the p.I739V mutation in SCN9A in the proband of two nonrelated families. Moreover, guanfacine inhibited ionic currents evoked by wild-type and mutant NaV1.7 encoded by SCN9A, as well as other NaV channel subtypes to a varying degree. CONCLUSION: Our study provides further evidence for a possible pathophysiological role of NaV1.7 in anxiety and dysautonomia. Combined with off-target effects on NaV channel function, daily administration of 1 mg short-acting guanfacine may be sufficient to normalize NaV channel mutation-induced changes in sympathetic activity, perhaps aided by partial inhibition of NaV1.7 or other channel subtypes. In a broader context, expanding genetic and functional data about ion channel aberrations may enable the prospect of stratifying patients in which mutation-induced increased sympathetic tone normalization by guanfacine can support treatment strategies for anxiety and dysautonomia symptoms.

Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Studies and Biological Assays.

Trace amine-associated receptor 1 (TAAR1) is an attractive target for the design of innovative drugs to be applied in diverse pharmacological settings. Due to a non-negligible structural similarity with endogenous ligands, most of the agonists developed so far resulted in being affected by a low selectivity for TAAR1 with respect to other monoaminergic G protein-coupled receptors, like the adrenoreceptors. This study utilized comparative molecular docking studies and quantitative-structure activity relationship (QSAR) analyses to unveil key structural differences between TAAR1 and alpha2-adrenoreceptor (α2-ADR), with the aim to design novel TAAR1 agonists characterized by a higher selectivity profile and reduced off-target effects. While the presence of hydrophobic motives is encouraged towards both the two receptors, the introduction of polar/positively charged groups and the ligand conformation deeply affect the TAAR1 or α2-ADR putative selectivity. These computational methods allowed the identification of the α2A-ADR agonist guanfacine as an attractive TAAR1-targeting lead compound, demonstrating nanomolar activity in vitro. In vivo exploration of the efficacy of guanfacine showed that it is able to decrease the locomotor activity of dopamine transporter knockout (DAT-KO) rats. Therefore, guanfacine can be considered as an interesting template molecule worthy of structural optimization. The dual activity of guanfacine on both α2-ADR and TAAR1 signaling and the related crosstalk between the two pathways will deserve more in-depth investigation.

An adolescent boy with kleptomania and attention-deficit hyperactivity disorder treated with methylphenidate and guanfacine: A case report.

We present the case of a patient, a boy of 16 years of age at initial presentation, with kleptomania, an impulse disorder characterized by an impulse to steal unneeded items, and attention-deficit hyperactivity disorder (ADHD). The patient's parents reported that he would frequently impulsively steal items and money that he did not need. Cognitive and physical assessments revealed no abnormalities, and the patient had no history of substance abuse. The patient was diagnosed with kleptomania and ADHD. The patient was started on Osmotic Release Oral System Methylphenidate (OROS-MPH), a medication commonly used to treat ADHD, and experienced improvement in ADHD symptoms and stealing behavior. At 19 years of age, it was discovered that the patient's behavioral symptoms were uncontrolled during times of the day when the blood concentration of MPH was likely to have waned. After starting an additional dose of guanfacine at night, his symptoms during these times of day improved. While existing research is not definitive, there may be a connection between ADHD and kleptomania. Further, there are some reports that treatment of ADHD with MPH also reduced stealing behavior, aligning with our present findings. We discuss the potential mechanisms behind these improvements and further present the first evidence of the efficacy of guanfacine in the treatment of kleptomania.

Case Report: Guanfacine and methylphenidate improved chronic lower back pain in autosomal dominant polycystic kidney disease with comorbid attention deficit hyperactivity disorder and autism spectrum disorder.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by the bilateral development of multiple cysts in the kidneys. Pain management is a clinically important issue, especially because approximately 60% of patients with ADPKD experience chronic pain related to hemorrhage from renal cysts, which significantly reduces their daily life. The cystic fibrosis transmembrane conductance regulator, the molecule responsible for cyst formation in ADPKD, is also the cause of cystic fibrosis. Since attention deficit hyperactivity disorder (ADHD) is known to occur frequently in conjunction with cystic fibrosis, ADPKD may be associated with ADHD. However, to our knowledge, no study has investigated 1) ADHD or autism spectrum disorder (ASD) as comorbidities with ADPKD, 2) the effects of ADHD medications on chronic pain in ADPKD, or 3) cerebral blood flow corresponding to guanfacine (GF) or methylphenidate (MP) treatment for chronic pain. We report the case of a 15-year-old girl with ADPKD, who had chronic back pain associated with ADPKD and had to withdraw from high school because the pain interfered with her daily life. Although she took antihypertensive medications to prevent bleeding, they did not provide adequate blood pressure control. The patient was referred to a child psychiatrist and diagnosed with ASD; however, the pain did not improve. Subsequently, she was referred to our pain center. The diagnosis of ADHD was confirmed and treatment with ADHD medications was initiated. Monotherapy with MP, atomoxetine, and GF resulted in hypertension and hypotension as side effects; however, a combination of MP 18 mg and GF 4 mg provided pain relief and moderate blood pressure control, and the patient was able to go on to college. During the course of treatment, there was an improvement in the distribution of cerebral blood flow in the prefrontal and insular cortices. Confirmation of an ADHD diagnosis comorbid with ASD enabled the use of ADHD medications. The combination of MP and GF improved chronic back pain and high blood pressure due to ADPKD and cerebral blood flow. Screening for ADHD is important in the treatment of ADPKD.

Therapeutics for Substance-Using Women: The Need to Elucidate Sex-Specific Targets for Better-Tailored Treatments.

In the last decade, alcohol consumption in the US has risen by 84% in women compared with 35% in men. Furthermore, research has shown that sex- and gender-related differences may disadvantage women in terms of developing a range of psychological, cognitive, and medical problems considerably earlier in their drinking history than men, and despite consuming a similar quantity of substances. While this "telescoping" process has been acknowledged in the literature, a concomitant understanding of the underlying biobehavioral mechanisms, and an increase in the development of specific treatments tailored to women, has not occurred. In the current chapter we focus on understanding why the need for personalized, sex-specific medications is imperative, and highlight some of the potential sex-specific gonadal and stress-related adaptations underpinning the accelerated progress from controlled to compulsive drug and alcohol seeking in women. We additionally discuss the efficacy of these mechanisms as novel targets for medications development, using exogenous progesterone and guanfacine as examples. Finally, we assess some of the challenges faced and progress made in terms of developing innovative medications in women. We suggest that agents such as exogenous progesterone and adrenergic medications, such as guanfacine, may provide some efficacy in terms of attenuating stress-induced craving for several substances, as well as improving the ability to emotionally regulate in the face of stress, preferentially in women. However, to fully leverage the potential of these therapeutics in substance-using women, greater focus needs to the placed on reducing barriers to treatment and research by encouraging women into clinical trials.

The role of sex hormones in targeting stress-induced tobacco craving, stress-reactivity, and smoking with guanfacine among women who smoke.

Women who smoke are particularly vulnerable to tobacco craving, smoking behaviors, and relapse in the context of stress when compared to men who smoke. One factor in this sex difference may be sex hormones, including estradiol and progesterone; however, smoking cessation medication trials often do not explore the impact of sex hormones on drug effects. This secondary analysis of a double-blind, placebo-controlled study explored the impact of levels of actual estradiol and progesterone on guanfacine, a noradrenergic α2a agonist, which attenuates stress-induced smoking behaviors in women. Women who smoke (n = 43) completed a stress induction laboratory paradigm followed by an ad-libitum smoking period. Assessment of tobacco craving, and stress-reactivity (via cortisol response) occurred pre- and post-stress induction. Results indicated that guanfacine attenuated stress-induced tobacco craving (F = 10.94, p = 0.02) and cortisol response (F = 14.23, p < 0.001); however, high levels of estradiol overrode guanfacine's effect on craving (F = 4.00, p = 0.05), cortisol response (F = 14.23, p < 0.001), and smoking during the ad-libitum period (F = 12.23, p = 0.001). Additionally, progesterone proved to be protective against tobacco craving and enhanced guanfacine's medication effect on craving (F = 5.57, p = 0.02). The present study found that sex hormones had a significant impact on medication effects in a smoking cessation trial and thus underscore the importance of examining the role of sex hormones in future medication trials.

Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID.

Sustained cognitive deficits are a common and debilitating feature of "long COVID", but currently there are no FDA-approved treatments. The cognitive functions of the dorsolateral prefrontal cortex (dlPFC) are the most consistently afflicted by long COVID, including deficits in working memory, motivation, and executive functioning. COVID-19 infection greatly increases kynurenic acid (KYNA) and glutamate carboxypeptidase II (GCPII) in brain, both of which can be particularly deleterious to PFC function. KYNA blocks both NMDA and nicotinic-alpha-7 receptors, the two receptors required for dlPFC neurotransmission, and GCPII reduces mGluR3 regulation of cAMP-calcium-potassium channel signaling, which weakens dlPFC network connectivity and reduces dlPFC neuronal firing. Two agents approved for other indications may be helpful in restoring dlPFC physiology: the antioxidant N-acetyl cysteine inhibits the production of KYNA, and the α2A-adrenoceptor agonist guanfacine regulates cAMP-calcium-potassium channel signaling in dlPFC and is also anti-inflammatory. Thus, these agents may be helpful in treating the cognitive symptoms of long COVID.

Successful Treatment of Tourette Syndrome With a Combination of Guanfacine and Aripiprazole: A Case Series.

Tourette syndrome (TS) is a disorder of the nervous system that causes motor and vocal tics. Tics occur as sudden onset, rapid stereotyped purposeless movements or sounds. Combination therapies can be utilized for adequate control of motor and vocal tics. Patients diagnosed with TS and treated with aripiprazole and guanfacine from 2011-2022 at Saint Louis University Hospital were retrospectively surveyed. Three patients with TS treated with aripiprazole and guanfacine experienced significant improvement or complete resolution of their motor and vocal tics. In our cohort of three patients, the combination of guanfacine and aripiprazole significantly improved or resolved motor and vocal tics that were previously poorly controlled on other traditional medications.

The Role of Alpha-2 Agonists for Attention Deficit Hyperactivity Disorder in Children: A Review.

INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can affect academic, social, and personal functioning in children and adolescents. This review summarizes clinical trials demonstrating the effectiveness of Alpha-2 agonists in reducing symptoms of inattention, hyperactivity, and impulsivity in children with ADHD. Studies were identified through a systematic search of PubMed and Cochrane databases. However, these medications' long-term safety and efficacy remain uncertain, with a lack of data on their effects on growth, cardiovascular function, and other adverse events. Further studies are required to determine these medications' optimal dose and treatment duration. METHODS: Medications that target the noradrenergic system, such as Alpha-2 agonists, have been increasingly used as a treatment option for ADHD, with guanfacine and clonidine being two of the most commonly used medications. They function by selectively targeting Alpha-2 adrenergic receptors in the brain leading to improved attention and reduced hyperactivity and impulsivity symptoms in children with ADHD. RESULTS: Clinical trials have demonstrated the effectiveness of Alpha-2 agonists in treating ADHD in children by reducing symptoms of inattention, hyperactivity, and impulsivity. However, these medications' long-term safety and efficacy still need to be completely understood. Due to a lack of information on the effects of Alpha-2 agonists on growth, cardiovascular function, and other long-term adverse events, more studies must investigate the optimal dose and treatment duration for these medications. CONCLUSIONS: Despite these concerns, Alpha-2 agonists remain a valuable treatment option for ADHD in children, especially those unable to tolerate stimulant medications or who have coexisting conditions such as tic disorders. Future research should continue to explore the safety and efficacy of Alpha-2 agonists in the long term. In conclusion, Alpha-2 agonists show promise as a treatment for ADHD in children; however, the safety and efficacy of these drugs in the long term are not yet completely understood. Additional studies are required to investigate the optimal dose and treatment duration for these medications in their use as a treatment for this debilitating disease.

Advances in Pharmacotherapy for Pediatric Anxiety Disorders.

The evidence base for psychopharmacologic interventions in children and adolescents with anxiety disorders has significantly increased, and our understanding of the relative efficacy and tolerability of interventions has expanded contemporaneously. Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for pediatric anxiety due to their robust efficacy although other agents may have efficacy. This review summarizes the data concerning the use of SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, atypical anxiolytics (eg, 5HT1A agonists, alpha agonists), and benzodiazepines in pediatric anxiety disorder cases (ie, generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, and panic disorder). The extant data suggest that SSRIs and SNRIs are effective and well tolerated. SSRIs as monotherapy and SSRIs + cognitive behavioral therapy reduce symptoms in youth with anxiety disorders. However, randomized controlled trials do not suggest efficacy for benzodiazepines or the 5HT1A agonist, buspirone, in pediatric anxiety disorder cases.