brexpiprazole and Depressive-Disorder

The substantive delay (often 4-6 weeks) between the commencement of an antidepressant and any discernible improvement in depressive symptoms is an ongoing concern in the management of depressive disorders. This delay incurs the risk of cessation of medication, self-harm/suicide and ongoing 'damage' to the brain caused by the illness. Both historically and now, off-label polypharmacy has been used in clinical practice in an attempt to facilitate both immediate- and long-term relief from symptoms. While somewhat effective, this strategy was unregulated and associated with severe adverse side effects for patients. In this article we proffer an alternative paradigm to achieve a more rapid antidepressant response by conceptualising the gap in terms of windows of response. The Windows of Antidepressant Response Paradigm (WARP) frames treatment response as windows of time in which a clinical response can be expected following initiation of an antidepressant. The paradigm defines three distinct windows-the immediate-response window (1-2 days), fast-response window (up to 1 week) and slow-response window (from 1 week onwards). Newer agents such as rapid-acting antidepressants are considered to act within the immediate-response window, whereas atypical antipsychotic augmentation strategies are captured within the fast-response window. The slow-response window represents the delay experienced with conventional antidepressant monotherapy. Novel agents such as esketamine and brexpiprazole are discussed as examples to better understand the clinical utility of WARP. This framework can be used to guide research in this field and aide the development of newer, more effective antidepressant agents as well as providing a strategy to guide the prescription of multiple agents in clinical practice.

Topics: Antidepressive Agents; Depressive Disorder; Humans; Ketamine; Quinolones; Thiophenes

Brexpiprazole (Rexulti®) is an atypical antipsychotic that has been developed by Otsuka Pharmaceutical Co. Ltd and H. Lundbeck A/S as an oral treatment for several psychiatric disorders. Brexpiprazole is a novel serotonin-dopamine activity modulator that acts as a partial agonist of serotonin 1A (5-HT1A) and dopamine D2 receptors, as well as a potent antagonist of 5-HT2A receptors and noradrenergic α1B and α2C receptors. In July 2015, brexpiprazole received its first approval in the USA for use as an adjunctive treatment of major depressive disorder (MDD) and the treatment of schizophrenia. In several countries, brexpiprazole is in development for MDDs, schizophrenia, post-traumatic stress disorder and agitation in patients with dementia of the Alzheimer's type. This article summarizes the milestones in the development of brexpiprazole leading to its first global approval in MDD and schizophrenia.

Topics: Depressive Disorder; Drug Approval; Humans; Internationality; Molecular Structure; Quinolones; Schizophrenia; Thiophenes

Copulatory or pelvic thrusting dyskinesia is a subtype of tardive dyskinesia (TD) which is caused by exposure to dopamine blocking agents.. A man exhibiting rhythmic, stereotypical pelvic thrusting movements.. Recognition of copulatory dyskinesia as a distinctive iatrogenic disorder helps prevent unnecessary investigations and guides the implementation of corrective strategies.

Topics: Adrenergic beta-Antagonists; Aged; Aripiprazole; Clonazepam; Deprescriptions; Depressive Disorder; Drug Substitution; GABA Modulators; Humans; Male; Parkinsonian Disorders; Pelvis; Propranolol; Quinolones; Serotonin Agents; Tardive Dyskinesia; Tetrabenazine; Thiophenes; Treatment Failure; Valine