Differentiating the third generation of antipsychotics: a focus on lumateperone's similarities and differences.

The development of atypical antipsychotics has evolved to include newer pharmacodynamic properties. Lumateperone, aripiprazole, brexpiprazole, and cariprazine are all dopamine-2 receptor partial agonists with varying receptor affinities. This review aims to compare the clinical and pharmacodynamic differences among these four atypical antipsychotics, all of which are unique when compared to first- and second-generation antipsychotics.

Ketamine as treatment for post-traumatic stress disorder: a review.

Post-traumatic stress disorder (PTSD) continues to make headlines given multiple military engagements across the world and civilian traumas, and resultant PTSD development continues at an even pace. Currently, antidepressant and cognitive-behavioral therapy have the greatest evidence base but still do not yield a remission of PTSD symptoms in many patients. Off-label and novel treatments continue to be considered for more refractory and disabling cases of PTSD.

Brexpiprazole and cariprazine: distinguishing two new atypical antipsychotics from the original dopamine stabilizer aripiprazole.

Background: Brexpiprazole and cariprazine are the latest US Food and Drug Administration approved atypical antipsychotics available in the United States. Both function as partial agonists of the dopamine-2 receptor (DR), a mechanism of action shared with aripiprazole. However, all three differ in their affinities for the DR as well as for serotonin receptors (5-HTRs).

Neural Implications of Psychotherapy, Pharmacotherapy, and Combined Treatment in Major Depressive Disorder.

Numerous clinical trials have been conducted to determine the utility of antidepressant treatment (ADT), psychotherapy, and combined psycho-pharmaco-psychotherapy (PPPT) in treating major depressive disorder (MDD). While all approaches have shown benefit over placebo to varying degrees, the parallel neurophysiological mechanisms that underlie their efficacy have received little attention. The authors will review and discuss a growing body of literature that relates the factors of treatment selection and response to the principles of neuromodulation, with emphasis regarding how neuroimaging and other experimental data reinforce the need for personalized MDD treatment.

Why is mechanism of action important in antidepressant treatment?

Antidepressants are one of the most common treatment strategies for patients diagnosed with major depressive disorder (MDD). However, antidepressant medications have different mechanisms of action that can theoretically and in practice affect how patients respond. Clinicians should assess their patients' symptoms and response to medication at every visit to determine whether or not the treatment is fully effective.

Effectiveness, tolerability and practical application of the newer generation anti-obesity medications.

Objective: Comparison of the efficacy and tolerability of five newer anti-obesity medications to guide clinical decision making, examining bupropion-naltrexone combination, liraglutide, lorcaserin, orlistat, and phentermine-topiramate combination.

Methods: A brief literature review and internet search for high-powered, randomized and placebo-controlled drug trials was conducted. Drug trial information was established for five currently approved anti-obesity medications.

Antidepressant efficacy and side-effect burden: a quick guide for clinicians.

Prescribing of antidepressant treatment (ADT) for major depressive disorder (MDD) has increased in quantity and popularity over the last two decades. This is likely due to the approval of safer medications, better education of clinicians and their patients, direct-to-consumer marketing practices, and less stigma associated with those taking ADT. This trend has also been met with some controversy, however, as the ongoing safety and effectiveness of these treatments have at times been called into question.

Using mechanism of action to choose medications for treatment-resistant depression.

Remission rates for depression continue to be low, and for many patients, complex treatment regimens are needed for optimal response. Many physicians do not fully understand how and why depression medications work or which ones will complement each other. This CME Webcast covers the different mechanisms of action of current pharmacotherapeutic options for depression, both monotherapy and adjunctive medications, and shows clinicians how to use their understanding of mechanisms of action to choose the most effective treatment strategy for their patients, especially those with treatment-resistant or difficult-to-treat depression.

A critical appraisal of the selegiline transdermal system for major depressive disorder.

The selegiline transdermal system (STS) is the first antidepressant transdermal medication approved by the US FDA for the treatment of major depressive disorder. Its unique antidepressant delivery system allows for steady release of selegiline over 24 h with minimal fluctuation in drug serum levels. It is able to deliver high enough central nervous system concentrations required for an antidepressant effect without substantially inhibiting Monoamine oxidase-A in the gastrointestinal and hepatic system, thereby reducing the risk of tyramine hypertensive crises especially at the lowest doses.

Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder.

Clonidine and guanfacine are alpha-2 receptor agonists that decrease sympathetic outflow from the central nervous system. Posttraumatic stress disorder (PTSD) is an anxiety disorder that is theorized to be related to a hyperactive sympathetic nervous system. Currently, the only US Food and Drug Administration (FDA)-approved medications for PTSD are the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine.

Tramadol for the treatment of fibromyalgia.

Tramadol is a novel, synthetic opioid receptor agonist with serotonin-norepinephrine reuptake inhibitor properties that is often prescribed acutely for painful conditions. Fibromyalgia (FM) is a chronic painful condition that is difficult to treat and until more recently has had no approved medical treatments. Currently, the only US FDA-approved medications for FM include duloxetine, milnacipran and pregabalin.

Tardive dyskinesia in patients treated with atypical antipsychotics: case series and brief review of etiologic and treatment considerations.

Tardive dyskinesia (TD) is a disfiguring side-effect of antipsychotic medications that is potentially irreversible in affected patients. Newer atypical antipsychotics are felt by many to have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications.

Managing insomnia: an overview of insomnia and pharmacologic treatment strategies in use and on the horizon.

This review explores basic sleep physiology, the mechanism of action for each class of hypnotic agents, their clinical application based on pharmacodynamic and pharmacokinetic factors, and potential pharmacologic sleep-inducing mechanisms of future hypnotics. The paper challenges the reader to understand the neuroscientific basis of insomnia and use this knowledge to guide prescription of hypnotic agents. Currently indicated hypnotic agents are discussed with regard to their mechanism of drug action and clinical application.

A neuroscientific update on monoamine oxidase and its inhibitors.

The goal of this brief review is to explain the role of monoamine oxidase enzymes in the neurobiology, etiology, and presentation of psychiatric illnesses, primarily major depressive disorder. This article will initially focus on the basic science and function of the monoamine oxidase system and some proposed neuropsychiatric symptoms that may arise if this enzyme system is altered by genetic predisposition. These findings and theories will next be translationally discussed in regard to clinical application pertaining to enzyme inhibition and the treatment of major depressive and other psychiatric disorders.

Psychopharmacological Practice: The DSM Versus The Brain.

In 1952, the Diagnostic and Statistical Manual of Mental Disorders (DSM) system of creating, validating, studying and employing a diagnostic system in clinical psychiatric practice was introduced. There have been several updates and revisions to this manual and, regardless of its a theoretical framework, it actually does have a framework and presupposition. Essentially the DSM dictates that all psychiatric disorders are syndromes, or a collection of symptoms that commonly occur together and impair psychosocial functioning.

Glutamate neurocircuitry: theoretical underpinnings in schizophrenia.

The Dopamine Hypothesis of Schizophrenia is actively being challenged by the NMDA Receptor Hypofunctioning Hypothesis of Schizophrenia. The latter hypothesis may actually be the starting point in neuronal pathways that ultimately modifies dopamine pathways involved in generating both positive and negative symptoms of schizophrenia postulated by the former hypothesis. The authors suggest that even this latter, NMDA receptor-based, hypothesis is likely too narrow and offer a review of typical glutamate and dopamine-based neurocircuitry, propose genetic vulnerabilities impacting glutamate neurocircuitry, and provide a broad interpretation of a possible etiology of schizophrenia.

Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: acute and chronic effects.

Background: Major depressive disorder is a prevalent, disabling, and often chronic or recurrent psychiatric condition. About 35% of patients fail to respond to conventional treatment approaches and are considered to have treatment-resistant depression (TRD).

Objective: We compared the safety and effectiveness of different stimulation levels of adjunctive vagus nerve stimulation (VNS) therapy for the treatment of TRD.

Memantine as an augmentation therapy for anxiety disorders.

Objective. Glutamate, an excitatory neurotransmitter in the central nervous system (CNS), may play a role in the development of anxiety. Memantine partially blocks N-methyl-D-aspartate (NMDA) receptors' glutamate channels located in the CNS.

Clinical utility of vilazodone for the treatment of adults with major depressive disorder and theoretical implications for future clinical use.

Background: Vilazodone is the latest approved antidepressant available in the United States. Its dual mechanism of action combines the inhibition of serotonin transporters while simultaneously partially agonizing serotonin-1a (5-HT1A) receptors. This combined activity results in serotonin facilitation across the brain's serotonergic pathways, which has been termed by the authors as that of a serotonin partial agonist and reuptake inhibitor, or SPARI.

Genetic data supporting the NMDA glutamate receptor hypothesis for schizophrenia.

The Dopamine Hypothesis has been the leading theory used to explain the mechanism of the clinical manifestation of schizophrenia symptoms for decades. It is unclear if excess dopaminergic activity is the primary pathophysiology causing psychosis or if this dopamine excess is triggered by upstream, downstream or neurodevelopmental abnormalities. A corollary hypothesis suggests that the glutamatergic system may be involved in the pathogenesis of schizophrenia, and that dysfunction of the glutamate system may actually lead to dopamine excess.

Obesity and psychotropics.

Weight gain is on the rise in the United States as is the diagnosis and treatment of mental disorders. These two phenomena are distinctly separate but tend to overlap in that most psychotropic agents approved for use in the United States are associated with the potential to induce weight gain. Metabolic disorders such as diabetes, hypercholesterolemia, and hypertension are also on the rise and often associated with weight gain and clearly associated with certain psychotropic medications.