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Psychotropic Drug Therapies and Clinical Considerations in Modern Practice

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A special issue of Neurology International (ISSN 2035-8377).

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 108691

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Dr. Elyse M. Cornett

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Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA, USA
Interests: neuroscience; pharmacology; drug abuse; pain management; opioids
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Prof. Dr. Alan David Kaye

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Department of Anesthesiology, Louisiana State University, Shreveport, LA, USA
Interests: pharmacology; anesthesiology; pain management; pain medicine; opioids
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

The rate of progress in psychotropic drug development has been rapid over the last 15 years. There have also been unprecedented rises in expenditure on prescription medications in general and on psychotropic drugs in particular. Psychotropic drugs play a more central role in therapy. They are also closely watched by health insurers, state budget makers, and ordinary people. Modern psychopharmacology has provided therapeutic advantages that have completely revolutionized modern psychiatry. It has also had a significant effect on nosology and psychological disease theories, on hypotheses for psychiatric study, as well as on the preparation of mental health practitioners and the organization of contemporary mental health services.

Dr. Elyse M. Cornett
Dr. Alan David Kaye
Guest Editors

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Keywords

Opioids
Antidepressants
ADHD
PTSD

Published Papers (12 papers)

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13 pages, 1785 KiB

Open AccessArticle

Evaluating Therapeutic Equivalence of Generic and Original Levetiracetam in Patients with Epilepsy: A Retrospective Study

by Jannapas Tharavichitkun, Tinonkorn Yadee, Poomchai Angkaow and Thanarat Suansanae

Neurol. Int. 2022, 14(1), 271-283; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint14010022 - 15 Mar 2022

Cited by 3 | Viewed by 2726

Abstract

The brand interchangeability of antiepileptic drugs (AEDs) is a topic of debate, especially regarding their therapeutic equivalence. This study evaluates the efficacy and tolerability of generic levetiracetam compared to the brand-name equivalent in a routine clinical setting. We conducted a retrospective study, examining patients with stable seizure frequency who received generic levetiracetam after the brand-name drug. During the six-month substitution period, changes in seizure frequency, hospitalization due to seizure exacerbation, adverse events, composite outcomes related to adjusting the AED dosage, and switching back to original levetiracetam were analyzed. Seventy-five patients were enrolled; the majority (85.3%) had focal onset seizures, and almost half (49.3%) had refractory epilepsy. Six months after the substitution, the mean seizure frequency per month was not significantly different (3.15 ± 14.47 vs. 2.77 ± 11.41; p = 0.970). In patients with controlled seizures before the change, the seizure frequency increased significantly (0.56 ± 1.83 vs. 0.03 ± 0.16; p = 0.012). Adverse events occurred in six patients. We have observed recurrent seizures or adverse events from 14 days after the transition. The original drug return rates due to recurrent seizures and adverse events were 5.3% and 1.3%, respectively. Generic levetiracetam might not show therapeutic equivalence to the original molecule, especially in patients adequately controlled by the brand-name drug. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

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Review

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16 pages, 359 KiB

Open AccessReview

Novel Designer Benzodiazepines: Comprehensive Review of Evolving Clinical and Adverse Effects

by Amber N. Edinoff, Catherine A. Nix, Amira S. Odisho, Caroline P. Babin, Alyssa G. Derouen, Salim C. Lutfallah, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2022, 14(3), 648-663; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint14030053 - 22 Aug 2022

Cited by 18 | Viewed by 5982

Abstract

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazeZpine) is a triazolo-analogue of flubromazepam. The most common effects noted by recreational users include heavy hypnosis and sedation, long-lasting amnesia, and rapid development of tolerance. Other effects included anxiolysis, muscle-relaxing effects, euphoria, loss of control, and severe withdrawals. Clonazolam, or 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-α]-[1,4]-benzodiazepine, is a triazolo-analog of clonazepam. It is reported to be over twice as potent as alprazolam. Deschloroetizolam (2-Ethyl-9-methyl-4-phenyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine) is part of the thienodiazepine drug class, which, like benzodiazepines, stimulates GABA-A receptors. Meclonazepam ((3S)-5-(2-chlorophenyl)-3-methyl-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one) is a designer benzodiazepine with additional anti-parasitic effects. Although it has proven to be an efficacious therapy for schistosomiasis, its sedative side effects have prevented it from being marketed as a therapeutic agent. The use of DBZs has been a subject of multiple recent clinical studies, likely related to increasing presence and availability on the internet drug market and lack of regulation. Many studies have aimed to identify the prevalence of DBZs and their effects on those using them. This review discussed these designer benzodiazepines and the dangers and adverse effects that the clinician should know. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

13 pages, 651 KiB

Open AccessReview

Oxytocin, a Novel Treatment for Methamphetamine Use Disorder

by Amber N. Edinoff, Elliot Thompson, Chandler E. Merriman, Mark R. Alvarez, E. Saunders Alpaugh, Elyse M. Cornett, Kevin S. Murnane, Rachel L. Kozinn, Mila Shah-Bruce, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2022, 14(1), 186-198; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint14010015 - 30 Jan 2022

Cited by 8 | Viewed by 7574

Abstract

The treatment of substance abuse with oxytocin is a novel approach to a challenging public health issue that continues to contribute to a growing economic cost for societies worldwide. Methamphetamine addiction is one of the leading causes of mortality worldwide, and despite advances in understanding the neurobiology of methamphetamine addiction, treatment options are limited. There are no medications that the Food and Drug Administration currently approves for stimulant use disorder. Off-label use of therapies for stimulant misuse include antidepressants, anxiolytics, and milder stimulants as replacement agents. Due to the shortcomings of these attempts to treat a complicated psychiatric disorder, recent attention to oxytocin therapy (OT) has gained momentum in clinical studies as a possible therapy in the context of social stress, social anxiety, social cognition, and psychosis. Oxytocin produces enhanced connectivity between cortical regions. The results from studies in rodents with OT suggest that central neuromodulation of oxytocin may be beneficial across transition states of stimulant dependence and may alleviate intense withdrawal symptoms. Studies of oxytocin in the context of other drugs of abuse, including cocaine, cannabis, and alcohol, also support the potential of oxytocin to treat stimulant use disorder, methamphetamine type. Methamphetamine abuse continues to be a significant cause of distress and dysfunction throughout the world. The effects of oxytocin on methamphetamine use outlined in this review should act as a catalyst for further investigation into the efficacy of treating stimulant use disorder, methamphetamine type with oxytocin in humans. More human-based research should initiate studies involving the long-term efficacy, side effects, and patient selection. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

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14 pages, 308 KiB

Open AccessReview

Bremelanotide for Treatment of Female Hypoactive Sexual Desire

by Amber N. Edinoff, Nicole M. Sanders, Kyle B. Lewis, Tucker L. Apgar, Elyse M. Cornett, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2022, 14(1), 75-88; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint14010006 - 04 Jan 2022

Cited by 12 | Viewed by 4790

Abstract

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

13 pages, 290 KiB

Open AccessReview

Naltrexone Implant for Opioid Use Disorder

by Amber N. Edinoff, Catherine A. Nix, Claudia V. Orellana, Samantha M. StPierre, Erin A. Crane, Blaine T. Bulloch, Elyse M. Cornett, Rachel L. Kozinn, Adam M. Kaye, Kevin S. Murnane and Alan D. Kaye

Neurol. Int. 2022, 14(1), 49-61; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint14010004 - 30 Dec 2021

Cited by 10 | Viewed by 4080

Abstract

The continued rise in the availability of illicit opioids and opioid-related deaths in the United States has left physicians, researchers, and lawmakers desperate for solutions to this ongoing epidemic. The research into therapeutic options for the treatment of opioid use disorder (OUD) began with the introduction of methadone in the 1960s. The approval of oral naltrexone initially showed much promise, as the drug was observed to be highly potent in antagonizing the effects of opioids while producing no opioid agonist effects of its own and having a favorable side effect profile. Patients that routinely take their naltrexone reported fewer days of heroin use and had more negative drug tests than those without treatment. Poor outcomes in OUD patients treated with naltrexone have been directly tied to short treatment time. Studies have shown that naltrexone given orally vs. as an implant at the 6-month interval showed a higher non-compliance rate among those who used oral medications at the 6-month mark and a slower return to use rate. There were concerns that naltrexone could possibly worsen negative symptoms seen in opiate use disorder related to blockade of endogenous opioids that are important for pleasurable stimuli. Studies have shown that naltrexone demonstrated no increase in levels of anxiety, depression and anhedonia in participants and another study found that those treated with naltrexone had a significant reduction in mental health-related hospitalizations. The latter study also concluded that there was no increased risk for mental health-related incidents in patients taking naltrexone via a long-acting implant. Although not yet FDA approved in the United States, naltrexone implant has shown promising results in Europe and Australia and may provide a novel treatment option for opioid addiction. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

19 pages, 476 KiB

Open AccessReview

Anesthetic Considerations for Patients on Psychotropic Drug Therapies

by Monica W. Harbell, Catalina Dumitrascu, Layne Bettini, Soojie Yu, Cameron M. Thiele and Veerandra Koyyalamudi

Neurol. Int. 2021, 13(4), 640-658; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint13040062 - 29 Nov 2021

Cited by 10 | Viewed by 10781

Abstract

Psychotropic drugs are used in the treatment of psychiatric and non-psychiatric conditions. Many patients who are on psychotropic medications may present for procedures requiring anesthesia. Psychotropic medications can have dangerous interactions with drugs commonly used in anesthesia, some of which can be life-threatening. In this review, we describe the current anesthetic considerations for patients on psychotropic drug therapies, including antidepressants, antipsychotics, mood stabilizers, anxiolytics, and stimulants. The pharmacology, side effects, and potential drug interactions of the commonly prescribed psychotropic drug therapies with anesthetic agents are described. Further, we highlight the current recommendations regarding the cessation and continuation of these medications during the perioperative period. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

14 pages, 318 KiB

Open AccessReview

Benzodiazepines: Uses, Dangers, and Clinical Considerations

by Amber N. Edinoff, Catherine A. Nix, Janice Hollier, Caroline E. Sagrera, Blake M. Delacroix, Tunde Abubakar, Elyse M. Cornett, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2021, 13(4), 594-607; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint13040059 - 10 Nov 2021

Cited by 50 | Viewed by 18005

Abstract

Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous system (CNS). They quickly diffuse through the blood–brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

13 pages, 312 KiB

Open AccessReview

New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations

by David Fanelli, Gregory Weller and Henry Liu

Neurol. Int. 2021, 13(4), 497-509; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint13040049 - 01 Oct 2021

Cited by 10 | Viewed by 7489

Abstract

Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic neuronal uptake of serotonin and norepinephrine and prolong the effects of the monoamines in the synaptic cleft within the central nervous system, leading to increased postsynaptic receptor activation and neuronal activities. Serotonin-norepinephrine reuptake inhibitors can have multiple clinical indications, including as the first-line agents for the management of depression and anxiety, and as analgesics in the treatment of chronic pain. The effects of reuptake inhibition of norepinephrine and serotonin are often dose-dependent and agent-dependent. There are five FDA-approved serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, levomilnacipran, milnacipran and sibutramine) currently being marketed in the United States. As the COVID-19 pandemic significantly increased the incidence and prevalence of anxiety and depression across the country, there are significantly increased prescriptions of these medications perioperatively. Thus, anesthesiologists are more likely than ever to have patients administered with these agents and scheduled for elective or emergency surgical procedures. A thorough understanding of these commonly prescribed serotonin-norepinephrine reuptake inhibitors and their interactions with commonly utilized anesthetic agents is paramount. There are two potentially increased risks related to the continuation of SNRIs through the perioperative period: intraoperative bleeding and serotonin syndrome. SNRIs have some off-label uses, more new indications, and ever-increasing new applications in perioperative practice. This article aims to review the commonly prescribed serotonin-norepinephrine reuptake inhibitors and the current clinical evidence regarding their considerations in perioperative anesthesia and analgesia. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

19 pages, 373 KiB

Open AccessReview

Selective Serotonin Reuptake Inhibitors and Clozapine: Clinically Relevant Interactions and Considerations

by Amber N. Edinoff, Juliana M. Fort, Joshua J. Woo, Christopher D. Causey, Caroline R. Burroughs, Elyse M. Cornett, Adam M. Kaye and Alan D. Kaye

Neurol. Int. 2021, 13(3), 445-463; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint13030044 - 01 Sep 2021

Cited by 12 | Viewed by 6384

Abstract

The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic improvements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, showing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

15 pages, 345 KiB

Open AccessReview

Selective Serotonin Reuptake Inhibitors and Adverse Effects: A Narrative Review

by Amber N. Edinoff, Haseeb A. Akuly, Tony A. Hanna, Carolina O. Ochoa, Shelby J. Patti, Yahya A. Ghaffar, Alan D. Kaye, Omar Viswanath, Ivan Urits, Andrea G. Boyer, Elyse M. Cornett and Adam M. Kaye

Neurol. Int. 2021, 13(3), 387-401; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint13030038 - 05 Aug 2021

Cited by 97 | Viewed by 33037

Abstract

Depression is the most prevalent psychiatric disorder in the world, affecting 4.4% of the global population. Despite an array of treatment modalities, depressive disorders remain difficult to manage due to many factors. Beginning with the introduction of fluoxetine to the United States in 1988, selective serotonin reuptake inhibitors (SSRIs) quickly became a mainstay of treatment for a variety of psychiatric disorders. The primary mechanism of action of SSRIs is to inhibit presynaptic reuptake of serotonin at the serotonin transporter, subsequently increasing serotonin at the postsynaptic membrane in the serotonergic synapse. The six major SSRIs that are marketed in the USA today, fluoxetine, citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine, are a group of structurally unrelated molecules that share a similar mechanism of action. While their primary mechanism of action is similar, each SSRI has unique pharmacokinetics, pharmacodynamics, and side effect profile. One of the more controversial adverse effects of SSRIs is the black box warning for increased risk of suicidality in children and young adults aged 18–24. There is a lack of understanding of the complexities and interactions between SSRIs in the developing brain of a young person with depression. Adults, who do not have certain risk factors, which could be confounding factors, do not seem to carry this increased risk of suicidality. Ultimately, when prescribing SSRIs to any patient, a risk–benefit analysis must factor in the potential treatment effects, adverse effects, and dangers of the illness to be treated. The aim of this review is to educate clinicians on potential adverse effects of SSRIs. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

18 pages, 355 KiB

Open AccessReview

Aripiprazole Lauroxil, a Novel Injectable Long-Acting Antipsychotic Treatment for Adults with Schizophrenia: A Comprehensive Review

by Kunal Maini, Haley Gould, Jessica Hicks, Fatima Iqbal, James Patterson II, Amber N. Edinoff, Elyse M. Cornett, Adam M. Kaye, Omar Viswanath, Ivan Urits and Alan D. Kaye

Neurol. Int. 2021, 13(3), 279-296; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint13030029 - 01 Jul 2021

Cited by 5 | Viewed by 3857

Abstract

Purpose of Review. This is a comprehensive review of the literature regarding the use of Aripiprazole lauroxil for schizophrenia. This review presents the background, evidence, and indications for using aripiprazole lauroxil to treat schizophrenia in the context of current theories on the development of schizophrenia. Recent Findings. Schizophrenia is a chronic mental health disorder that currently affects approximately 3.3 million people in the United States. Its symptoms, which must be present for more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Aripiprazole lauroxil is a long-acting intramuscular injection that works as a combination of partial agonist activity at D₂ and 5-HT_1A receptors combined with antagonist activity at 5-HT_2A receptors. It can be dosed as a 4-, 6-, or 8-week injection, depending on oral dosage. Aripiprazole lauroxil was FDA approved in October of 2015. Summary. Schizophrenia is a severe psychiatric disorder if left untreated. There are multiple medications to help treat schizophrenia. One antipsychotic agent, aripiprazole lauroxil, offers long duration injections that optimize and improve compliance. Known side effects include weight gain, akathisia, neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension. Aripiprazole lauroxil is an FDA-approved drug that can be administered monthly, every six weeks, or every two months and has been shown to be both safe and effective. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

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5 pages, 1445 KiB

Open AccessCase Report

Acute Carbamazepine Intoxication

by María Dolores Calabria Gallego and Mónica Alañá García

Neurol. Int. 2022, 14(3), 614-618; https://0-doi-org.brum.beds.ac.uk/10.3390/neurolint14030049 - 22 Jul 2022

Cited by 1 | Viewed by 2326

Abstract

Carbamazepine is an anticonvulsant drug with multiple mechanisms of action, which condition the presence of a characteristic clinical picture after the overingestion of the drug. We expose a case report about a patient who, in the context of an attempted suicide, presented acute intoxication by benzodiazepines and carbamazepine, presenting the characteristic clinical picture of fluctuations in the level of consciousness, even presenting gaze deconjugation, almost unreactive coma and generalized hypotonia. Full article

(This article belongs to the Special Issue Psychotropic Drug Therapies and Clinical Considerations in Modern Practice)

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