New‐generation, non‐SSRI antidepressants: Drug‐drug interactions and therapeutic drug monitoring. Part 2: NaSSAs, NRIs, SNDRIs, MASSAs, NDRIs, and others
Abstract
After the development of “classical” tricyclic antidepressants and monoamine oxidase inhibitors, numerous other classes of antidepressant drugs have been introduced onto the market. The selective serotonin reuptake inhibitor class is the best‐known one, but many others exist, usually identified by their mechanism of activity. In this second part of the review, focused on new‐generation antidepressants not included among selective serotonin reuptake inhibitors, the following classes are considered: noradrenergic and selective serotonergic antidepressants; norepinephrine reuptake inhibitors; serotonin, norepinephrine and dopamine reuptake inhibitors; melatonergic agonists and selective serotonergic antagonists; norepinephrine and dopamine reuptake inhibitors; and so forth. These different mechanisms underlie tolerability and safety profiles that can be very different among the classes, with each one providing significant advantages and disadvantages in comparison with others. The main characteristics of the following antidepressants are described: mianserin, mirtazapine, setiptiline, reboxetine, viloxazine, teniloxazine, atomoxetine, nefazodone, agomelatine, bupropion, esketamine, and tianeptine. The paper is focused on their metabolism and interactions, but also includes brief notes on analytical methods useful for their therapeutic drug monitoring.
After the development of “classical” tricyclic antidepressants and monoamine oxidase inhibitors, numerous other classes of antidepressant drugs have been introduced onto the market. The selective serotonin reuptake inhibitor class is the best‐known one, but many others exist, usually identified by their mechanism of activity. In this second part of the review, focused on new‐generation antidepressants not included among selective serotonin reuptake inhibitors, the following classes are considered: noradrenergic and selective serotonergic antidepressants; norepinephrine reuptake inhibitors; serotonin, norepinephrine and dopamine reuptake inhibitors; melatonergic agonists and selective serotonergic antagonists; norepinephrine and dopamine reuptake inhibitors; and so forth. These different mechanisms underlie tolerability and safety profiles that can be very different among the classes, with each one providing significant advantages and disadvantages in comparison with others. The main characteristics of the following antidepressants are described: mianserin, mirtazapine, setiptiline, reboxetine, viloxazine, teniloxazine, atomoxetine, nefazodone, agomelatine, bupropion, esketamine, and tianeptine. The paper is focused on their metabolism and interactions, but also includes brief notes on analytical methods useful for their therapeutic drug monitoring.
The effect of freeze‐thaw cycles on determination of immunoreactive plasma adrenocorticotrophic hormone concentrations in horses
Abstract
Background
Determination of plasma adrenocotrophic hormone (ACTH) concentration (endogenous or thyrotropin‐releasing hormone [TRH] stimulation test) is the most commonly used diagnostic test for pituitary pars intermedia dysfunction (PPID) in horses. Because ACTH is unstable, samples often are frozen to be shipped to laboratories or to allow for batch analysis of research samples. However, the effect of multiple freeze‐thaw cycles on equine ACTH is unknown.
Objective
To determine the effects of multiple freeze‐thaw cycles on immunoreactive ACTH concentration.
Animals
Twenty‐eight horses ranging from 10 to 27 years of age were used.
Methods
Prospective study. Horses were divided into 4 groups: group 1, PPID‐negative, without TRH stimulation; group 2, PPID‐negative, with TRH stimulation; group 3, PPID‐positive, without TRH stimulation; and group 4, PPID‐positive, with TRH stimulation. Whole blood was collected from each horse at baseline or 30 minutes after TRH stimulation. Immunoreactive plasma ACTH concentration was determined using a chemiluminescence assay. Plasma samples then were frozen at −80°C >24 hours, thawed at 4°C and reanalyzed for 5 freeze‐thaw cycles. Changes in plasma ACTH concentration were analyzed using a linear mixed‐effect model.
Results
Significant effects of freeze‐thaw cycles (P = .001) and PPID status (P = .04) on plasma ACTH concentration were observed, but no significant effect of TRH stimulation was identified.
Conclusions and Clinical Importance
The plasma ACTH concentration is altered by freeze‐thaw cycles, and the effect is observed sooner in horses with PPID. To diagnose PPID, multiple freeze‐thaw cycles should be avoided when measuring plasma ACTH concentration.
Psychotropic drugs in dermatology: A dermatologist’s approach and choice of medications
Abstract
Psychiatric symptoms in dermatology practice are increasingly being recognized. The use of psychiatric medications by dermatologist is dealt with caution and uncertainty in several psychodermatological conditions. Several skin conditions are associated with anxiety, depression, and obsessive‐compulsive symptoms. Some conditions such as delusion of parasitosis require antipsychotic medication treatment. Keeping in mind the importance of psychotropic medications and its use in dermatology, following brief review will familiarize dermatologists about the ease of understanding and prescribing psychotropic medications to help their patients with psychiatric symptoms and increase the compliance in treatment.
Psychiatric symptoms in dermatology practice are increasingly being recognized. The use of psychiatric medications by dermatologist is dealt with caution and uncertainty in several psychodermatological conditions. Several skin conditions are associated with anxiety, depression, and obsessive‐compulsive symptoms. Some conditions such as delusion of parasitosis require antipsychotic medication treatment. Keeping in mind the importance of psychotropic medications and its use in dermatology, following brief review will familiarize dermatologists about the ease of understanding and prescribing psychotropic medications to help their patients with psychiatric symptoms and increase the compliance in treatment.
Ventricular arrhythmia suppression with ivabradine in a patient with catecholaminergic polymorphic ventricular tachycardia refractory to nadolol, flecainide, and sympathectomy
Abstract
Conventional treatment strategies for catecholaminergic polymorphic ventricular tachycardia (CPVT) include avoidance of strenuous exercise and competitive sports, drugs such as ß‐blockers and flecainide and, cervical sympathectomy. An implantable cardioverter‐defibrillator (ICD) has been utilized if the response to these strategies is inadequate; however, ICD use in CPVT patients, in addition to usual complications, is associated with an increased risk of life‐threatening electrical storm. Ivabradine is a selective inhibitor of hyperpolarization‐activated cyclic nucleotide‐gated potassium channel 4 generated funny current (If), which has been shown to be efficacious in suppression of inappropriate sinus tachycardia, junctional tachycardia, atrial tachycardia, and ventricular ectopy in humans. We report an 18‐year‐old male with a severe CPVT phenotype refractory to flecainide, nadolol, and sympathectomy who exhibited suppression of ventricular arrhythmias after initiation of ivabradine. These findings are of importance as ivabradine could be an important add‐on therapy in CPVT patients who are drug refractory or are unable to continue conventional therapies at the recommended doses.
Conventional treatment strategies for catecholaminergic polymorphic ventricular tachycardia (CPVT) include avoidance of strenuous exercise and competitive sports, drugs such as ß‐blockers and flecainide and, cervical sympathectomy. An implantable cardioverter‐defibrillator (ICD) has been utilized if the response to these strategies is inadequate; however, ICD use in CPVT patients, in addition to usual complications, is associated with an increased risk of life‐threatening electrical storm. Ivabradine is a selective inhibitor of hyperpolarization‐activated cyclic nucleotide‐gated potassium channel 4 generated funny current (If), which has been shown to be efficacious in suppression of inappropriate sinus tachycardia, junctional tachycardia, atrial tachycardia, and ventricular ectopy in humans. We report an 18‐year‐old male with a severe CPVT phenotype refractory to flecainide, nadolol, and sympathectomy who exhibited suppression of ventricular arrhythmias after initiation of ivabradine. These findings are of importance as ivabradine could be an important add‐on therapy in CPVT patients who are drug refractory or are unable to continue conventional therapies at the recommended doses.
H syndrome with a possibly new immunological phenotype
Successful treatment of Pachyonychia congenita with Rosuvastatin
Abstract
Pachyonychia congenita (PC) is a rare genetic disorder affecting nails, skin, oral mucosae, larynx, hair and teeth. Patients with PC present with nail thickening and painful plantar keratoderma. Additional features include hyperhidrosis, oral leukokeratosis, follicular keratosis, palmar keratoderma, cutaneous cysts, hoarseness or laryngeal involvement, coarse or twisted hair and abnormalities of the teeth 1. Current treatment focuses on symptom relief 2. Several experimental therapies (including siRNA, mTOR‐inhibition) have been developed but did not reach clinical use 3, 4. We herein report on the effective therapy of a 9‐year‐old female with PC due to a heterozygous KRT6A mutation. After failed efficacy of common available therapies, our patient was successfully treated with Rosuvastatin.
Pachyonychia congenita (PC) is a rare genetic disorder affecting nails, skin, oral mucosae, larynx, hair and teeth. Patients with PC present with nail thickening and painful plantar keratoderma. Additional features include hyperhidrosis, oral leukokeratosis, follicular keratosis, palmar keratoderma, cutaneous cysts, hoarseness or laryngeal involvement, coarse or twisted hair and abnormalities of the teeth 1. Current treatment focuses on symptom relief 2. Several experimental therapies (including siRNA, mTOR‐inhibition) have been developed but did not reach clinical use 3, 4. We herein report on the effective therapy of a 9‐year‐old female with PC due to a heterozygous KRT6A mutation. After failed efficacy of common available therapies, our patient was successfully treated with Rosuvastatin.
Ischemic ulcers of the toes secondary to Raynaud’s phenomenon in a child successfully treated with botulinum toxin
Abstract
Raynaud’s phenomenon (RP) is an episodic vasospastic response to cold or emotional stress causing color changes and pain. These attacks can lead to digital ischemia, ulcers, and gangrene. Severe and refractory RP in children is a therapeutic challenge for clinicians because there are no standardized treatment protocols for these patients. We present a case of RP involving the toes of a child successfully treated with botulinum toxin A.
Raynaud’s phenomenon (RP) is an episodic vasospastic response to cold or emotional stress causing color changes and pain. These attacks can lead to digital ischemia, ulcers, and gangrene. Severe and refractory RP in children is a therapeutic challenge for clinicians because there are no standardized treatment protocols for these patients. We present a case of RP involving the toes of a child successfully treated with botulinum toxin A.
Transcutaneous Vagus Nerve Stimulation in Patients With Severe Traumatic Brain Injury: A Feasibility Trial
Objectives
Preclinical studies have shown that surgically implanted vagus nerve stimulation (VNS) promotes recovery of consciousness and cognitive function following experimental traumatic brain injury (TBI). The aim of this study is to report the feasibility and safety of a noninvasive transcutaneous vagus nerve stimulation (tVNS) in patients with persistent impairment of consciousness following severe TBI.
Preclinical studies have shown that surgically implanted vagus nerve stimulation (VNS) promotes recovery of consciousness and cognitive function following experimental traumatic brain injury (TBI). The aim of this study is to report the feasibility and safety of a noninvasive transcutaneous vagus nerve stimulation (tVNS) in patients with persistent impairment of consciousness following severe TBI.
Materials and Methods
The feasibility of tVNS was evaluated in five patients presenting with diffuse axonal injury and reduced dominant EEG activity one month following severe TBI. tVNS was applied to the left cymba conchae of the external ear using a skin electrode four hours daily for eight weeks. Possible effects of tVNS on physiological parameters and general side effects were recorded. In addition, we report the rate of recovery using coma recovery scale revised (CRS‐R).
Results
The tVNS regime of four hours daily for eight weeks was feasible and well tolerated with little side effects and no clinically relevant effects on physiological parameters. Three patients showed improvements (>3 points) in the CRS‐R following eight weeks tVNS.
Conclusion
We demonstrated that tVNS is a feasible and safe VNS strategy for patients following severe TBI. Controlled studies are needed to clarify whether tVNS has a potential to promote recovery of consciousness following severe TBI.
A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson’s Disease Dementia
Abstract
Background
IRL752 is a novel small‐molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex.
Objective
The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson’s disease and dementia.
Methods
Patients with Parkinson’s disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients’ regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days.
Results
A total of 32 patients were randomized to treatment, and 29 patients completed the 4‐week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2‐hour postdose plasma concentration of about 4 μM on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa.
Conclusions
IRL752 appears to be safe and well tolerated for a 4‐week treatment in patients with Parkinson’s disease and dementia. © 2020 International Parkinson and Movement Disorder Society