Children exposed to potentially traumatic events are at risk of developing posttraumatic stress disorder (PTSD). However, the subsequent developmental course of posttraumatic stress symptoms appears to vary considerably. In this regard, some PTSD symptoms resolve without significant interventions, while for many children and adolescents, they persist until the patient receives appropriate treatment specifically designed to address PTSD and other trauma related symptoms. Evidence-based psychotherapies represent the standard of care for children with PTSD and, while psychopharmacologic interventions are utilized for many youth with posttraumatic stress symptoms and PTSD, there is little data available to guide the use of these medications in this population. However, given the structural challenges involved in disseminating and delivering evidence-based psychotherapies in all settings, prescribing clinicians should be aware of the medications whose use in children with pediatric PTSD has been studied. Herein, we review the PTSD assessment modalities, as well as the use of pharmacologic interventions in PTSD, including antiadrenergic agents, selective serotonin reuptake inhibitors and other medications.
Adolescent* ; Adrenergic Antagonists ; Child ; Humans ; Psychotherapy ; Serotonin Uptake Inhibitors ; Standard of Care ; Stress Disorders, Post-Traumatic*

Adolescent ; Adrenergic Uptake Inhibitors ; therapeutic use ; Atomoxetine Hydrochloride ; Child ; Female ; Humans ; Male ; Propylamines ; adverse effects ; therapeutic use ; Tourette Syndrome ; drug therapy

BACKGROUNDDuloxetine, a selective serotonin and noradrenaline reuptake inhibitor, has been shown to be effective in treatment of diabetic peripheral neuropathic pain and approved for the management of patients with diabetic peripheral neuropathic pain (DPNP) in the United States, European Union, and many other countries. This study assessed the efficacy and safety of duloxetine in Chinese patients with diabetic peripheral neuropathic pain.

METHODSThis double-blind, randomized, placebo-controlled, flexible-dose study treated adult patients with diabetic peripheral neuropathic pain and baseline Brief Pain Inventory (BPI) 24-hour average pain severity ratings ≥ 4 with duloxetine 60 mg to 120 mg once daily or placebo for 12 weeks. Dose adjustments of duloxetine or matching placebo were based upon investigator's judgment of clinical response. Change from baseline to endpoint in BPI average pain was the primary efficacy outcome. Secondary outcome measures included BPI-severity and -Interference, Patient Global Impression of Improvement, Clinical Global Impressions of Severity, EuroQol: 5 Dimensions, Athens Insomnia Scale, and safety measures.

RESULTSOf 215 patients randomized, 88.4% and 82.1% of patients in placebo and duloxetine groups, respectively, completed the study. Mean change from baseline to endpoint in BPI average pain was not statistically different between the treatment groups (P = 0.124). Duloxetine- treated patients showed significantly greater pain reduction compared with those in placebo group at weeks 1, 2, and 4 (P = 0.004, P = 0.009, and P = 0.006, respectively), but not at weeks 8 (P = 0.125) and 12 (P = 0.107). Duloxetine-treated patients experienced statistically significant improvement in Patient Global Impression of Improvement, Clinical Global Impression of Severity, area under the curve for pain relief, BPI-severity pain right now, and BPI-interference walking ability. Patients treated with duloxetine 120 mg once daily showed significantly greater pain reduction on the Brief Pain Inventory average pain score relative to placebo. Duloxetine-treated patients reported nausea, somnolence, anorexia, and dysuria significantly more than placebo.

CONCLUSIONSAlthough the primary study endpoint was not achieved, the overall observed response pattern suggests the efficacy of duloxetine in the treatment of Chinese patients with diabetic peripheral neuropathic pain. The safety profile for duloxetine is similar to that reported in other global trials.

Adrenergic Uptake Inhibitors ; therapeutic use ; Aged ; Diabetic Neuropathies ; drug therapy ; Double-Blind Method ; Duloxetine Hydrochloride ; Female ; Humans ; Male ; Middle Aged ; Placebos ; Thiophenes ; therapeutic use ; Treatment Outcome

BACKGROUND: One of the most common side effects of antidepressant medication is orthostatic hypotension, which can be caused by impaired vasoconstriction. This study was designed to compare the inhibitory effects of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), on the contractile responses to alpha1-adrenergic receptor activation and depolarization in isolated rat aorta. METHODS: Vascular rings were suspended for the measurement of isometric tension in a water-jacketed bath filled with Tyrode solution. After pretreatment with antidepressant for 20 min, vasoconstriction induced by norepinephrine (NE) or 35 mM K+ was measured and compared to the control response. RESULTS: Whereas trazodone and tricyclic antidepressants (TCAs) selectively inhibited NE-induced vasoconstriction, SSRIs inhibited depolarization-induced vasoconstriction more potently. The IC50 value of fluoxetine on depolarization- induced vasoconstriction was 3.29 microM, which is consistent with the previous results on L-type Ca2+ currents of cardiac myocyte. Moclobemide, a monoamine oxidase inhibitor, had no effect on vasoconstriction induced by either alpha- adrenergic receptor activation, or depolarization. CONCLUSION: These results suggest that SSRIs, different from TCAs and trazodone, have potent inhibitory actions to depolarization-induced contraction that may be due to blocking Ca2+ entry through L-type Ca2+ channel.
Animals ; Antidepressive Agents ; Antidepressive Agents, Tricyclic ; Aorta* ; Baths ; Fluoxetine ; Hypotension, Orthostatic ; Inhibitory Concentration 50 ; Moclobemide ; Monoamine Oxidase Inhibitors ; Myocytes, Cardiac ; Norepinephrine ; Rats* ; Receptors, Adrenergic ; Serotonin Uptake Inhibitors* ; Trazodone ; Vasoconstriction*

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.
Adult ; Child ; Humans ; Adrenergic Uptake Inhibitors/therapeutic use* ; Atomoxetine Hydrochloride/therapeutic use* ; Attention Deficit Disorder with Hyperactivity/genetics* ; Cytochrome P-450 CYP2D6/therapeutic use* ; Drug Monitoring ; Genetic Testing ; Propylamines/therapeutic use* ; Treatment Outcome