Current Psychopharmacology - Volume 7, Issue 1, 2018

Background: Common childhood neuropsychiatric disorders are treated with multiple categories of psycho-active agents. Adverse side effects of psychotropic pharmacotherapeutics range from expected neuro-psychiatric changes to allergic reactions and immunologic abnormalities. Objective: This review focuses on the immune system effects of common categories of medications used to treat neuro-psychiatric and behavioral disorders. Method: Narrative review of literature using PubMed database up to May 10, 2017. Results: Multiple neuro- and psycho-tropic medication classes are found to influence the function of the immune system in various ways, both in the direction of immune suppression and immune stimulation. Conclusion: Immunologic activity of these medications in the frame-work of now wellestablished role of inflammation in neuro-psychiatric diseases should continue to be defined. At the same time, clinicians are advised to pay attention to potentially detrimental immune suppression that may be associated with some of these medications, and consider iatrogenic etiology in patients presenting with undue susceptibility to infection.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a widespread diagnosis that affects many children and adolescents' ability to function and succeed in academics, socially, or other situations. Non-stimulant medications have become widely utilized in this population, especially in stimulant-resistant individuals, whether due to poor efficacy or intolerance of side effects. However, these, too, harbor their own side effect profiles, including cardiovascular and sleep or energy level disturbances. Objectives: We review the literature in discussion of the presentation and management of these adverse events for non-stimulant medications for ADHD, with a particular focus on atomoxetine and alpha agonists guanfacine and clonidine. Conclusion: Non-stimulants are for the most part well tolerated but monitoring for cardiac and sleep difficulty is warranted.

Background: Selective serotonin reuptake inhibitors are the recommended and most commonly used antidepressant medications for children and adolescents. This class of medications has been considered generally safe with few significant treatment emergent adverse reactions that generally abate over time. All antidepressants carry the precautionary warning for potential increase in suicidal ideation and close monitoring is recommended. Management of side effects of this widely used class of drugs is an important aspect of any medical practice that cares for children and adolescents. Objective: To provide a succinct and clinically relevant review of side effects of SSRIs and their management in clinical practice. Method: A literature search was done of relevant published articles in English language in the Medline database. Results and Conclusion: Gastrointestinal side effects are most common with the use of SSRIs and generally are tolerable and do not need discontinuation of the medication. Cardiovascular side effects are uncommon; however, prolonged QT syndrome has been reported. In utero exposure results in a constellation of signs and symptoms in the newborn called poor neonatal adaptation syndrome. In utero exposure also is associated with teratogenicity. Although less frequent, symptoms suggesting behavioral activation, switching, serotonin syndrome and discontinuation or withdrawal syndrome need careful evaluation and management.

The use of antipsychotic medications presents a trade-off for the treating physician. On the one hand, there is enough literature regarding the efficacy of these medications to support their judicial use, while on the other, chronic and at time impairing side effects are troubling to both physicians and the patients. Extrapyramidal side effects are the hallmark of first-generation antipsychotics, while metabolic side effects including weight gain, diabetes mellitus, and lipid abnormalities are more common with second-generation antipsychotics. This article presents a concise overview of the current literature on antipsychotic-related side effects and treatment options.

Background: There are no published guidelines for the pharmacological management of insomnia in the pediatric population, and there are no Food and Drug Administration (FDA) approved medications for this purpose. Yet, many classes of psychopharmacological medications are used off-label in children and adolescents. Objective: To describe the side effects of different classes of medications used as sleep aids in the pediatric population, and management of those side effects. Method: Literature review and summary of existing evidence. Results: Several medications used as pediatric sleep aids have side effects that range from inconvenient constitutional symptoms, major systemic cardiac, endocrinological and neurological symptoms to potentially fatal syndromes. Conclusion: Clinicians need to be vigilant for adverse effects of these medications and to implement strategies to mitigate some of the effects, while educating patients and families about the pros and cons of medication use for insomnia.

Background: Substance use disorders (SUDs) are an increasing problem worldwide. In the United States, there is currently an “opioid epidemic,” primarily initiated by the over-prescription of opioid medications, barriers to continued access to those same medications, and the eventual procurement of illegal opioids to prevent withdrawal. In addition to the diversion of prescription opioids (especially oxycodone and fentanyl), other, more powerful opioids (e.g., carfentanil) have found their way to the street. Of especial concern is the number of adolescents who have access to legal- but diverted- or illegal drugs, as they are at risk for developing SUDs. Clinicians in various treatment settings (such as primary care offices, emergency departments, and mental health clinics) may lack the knowledge and training to safely and effectively treat patients who have SUDs. Fortunately, there are several pharmacologic agents that are approved for the treatment of opioid, alcohol and nicotine use disorders in adults and several agents have been explored to treat cannabis use disorder. To date, none of these medications have been approved for those indications in adolescents, although they can be-and are- used off-label in that patient population. All medications can be associated with adverse events, which are of particular concern in younger patients. Objective: To address the most common adverse effects from medications used to treat substance use disorders, and to offer suggestions regarding management of those unwanted effects. Method: The method utilized was PubMed search, from January 1, 2002 through November 1, 2017, with cross-referencing medications used to treat SUDs, adverse events and their treatment. Results: The substances addressed in this article (opioids, alcohol, tobacco and cannabis) are the most commonly abused in the general population, and are the most likely to be associated with adverse medical, psychiatric, social, financial and legal consequences. Medications used to treat opioid, alcohol, tobacco and cannabis use disorders are described, along with important adverse effects and their treatment. Conclusion: Given that there is no “drug of choice” to treat any given SUD, the selection of agent will depend on the patient's personal characteristics (e.g., age, gender, medical status, degree of social support, etc.) and preferences, and the prescriber's knowledge, comfort, and experience regarding the available medications. The pharmacotherapy of SUDs should always be accompanied by psychosocial therapies.

Background: Many of the adverse effects of psychopharmacologic agents are dermatologic in nature, ranging from relatively benign rashes to severe, potentially lifethreatening conditions. For the pediatric population, many case reports describe cutaneous reactions, however large-scale studies in the pediatric population are nonexistent. Objective: To review common dermatologic reactions to psychopharmacologic agents in pediatric population. Method: Narrative review of current literature using PubMed database was conducted. Results: Adverse cutaneous reactions that have been reported for these drugs include exanthematous rash, urticaria, lichenoid drug eruption, livedo reticularis, vitiligo, drug-induced hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms syndrome, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis. Conclusion: Many of the serious conditions are rare but likely under-diagnosed in the pediatric population, despite being particularly vulnerable to certain agents. Specific risk factors unique to the pediatric population, such as differential drug metabolism compared to adults, must be considered in the management of psychotropic medications. This should influence the pediatrician's judicious use of psychotropic agents to ensure maximal safety and efficacy for their patients.

Objective: The aim of this study was to develop a colon targeted press coated tablet of venlafaxine hydrochloride (VH) for the chronotherapy of depression. The press coating technique for colon targeting can overcome the limitations associated with the solvent coating technique. Methodology: The core tablets were prepared by direct compression using different ratios of VH:HPMC K100M (1:1, 1:2, 1:3). Core tablets were evaluated for various parameters such as average weight, thickness, hardness, friability, swelling index and in vitro drug release. A coating layer of guar gum and ethylcellulose in different ratio (1:0.25, 1:0.5, 1:1, 0.5:1, 0.25:1) was applied on the core tablet by press coating technique. Press coated tablets were evaluated for various parameters such as average weight, thickness, hardness, friability and in vitro drug release. Results: The drug release from the core tablets decreased with increased amount of HPMC K100M. F3 was selected as an optimized formulation for core tablets due to sustained drug release upto 3 hours. The drug release from optimized formulation followed Higuchi matrix kinetics and mechanism of release was found to be Fickian diffusion. The coating layer was soft and friable with formulation containing a higher proportion of guar gum as compared to ethylcellulose. The in vitro release from optimized press coated tablet PC3 followed the first order kinetics. Conclusion: The formulation (PC3) coated with granules containing guar gum and ethylcellulose (1:1) showed the desired average lag time of 5 h for the chronotherapy of depression by colon targeting.

Background: Given that the rat mesocorticolimbic system contains dopamine neurons, and enkephalin receptors modulate the inhibitory input to these neurons (i.e., originating in ventral tegmental area) and its terminals in the striatum, the interaction between these systems imply functional overlap. Indeed, dopamine denervation in the striatum augments opioid receptor number and sensitivity as well as motor response to morphine administration. Further research is needed to understand how dopamine denervation impacts opioid-related reward behavior. Objective: The following study was conducted to investigate the effects of dopamine depletion in the nucleus accumbens on morphine-induced responding for conditioned reward. Method: Two weeks following 6-hydroxydopamine (6-OHDA) double-drop lesions of the mesolimbic dopamine system, apomorphine (0.1 mg/kg, i.p.) and amphetamine (1.5 mg/kg, i.p.) were administered directly into the nucleus accumbens and activity levels were monitored. Results: Apomorphine increased locomotion in lesioned rats, whereas amphetamine enhanced sham-lesioned activity. Lesioned rats and controls received intra-accumbens morphine (0.05, 0.5 and 2.5 μg/0.5 μl, i.c.) and were tested for total bar pressing for conditioned reward. Morphine infusion in intact rats did not alter bar pressing but in lesioned rats, intra-accumbens morphine did increase reward-related responding. Conclusion: Our findings indicate that 6-OHDA lesions of the NAc may lead to a shift in opiate involvement in conditioned reward. This shift suggests that opiate involvement in dopaminerelated behaviors may be differentially impacted by the integrity of the dopamine system. Results are discussed in terms of alterations in the opiate system following dopamine depletion, which may have implications for pharmacotherapies for psychiatric disorders such as substance use disorders, depression, and neurodegenerative disorders such as Lesch-Nyhan Syndrome.