Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Of the many behavioral disturbances associated with severe mental and neurocognitive disorders, impulsive behaviors, including agitation and aggression, present unique challenges. Frontal inhibition, cognitive impairments, and executive dysfunction commonly combine to promote behavioral disturbances in severe mental and neurocognitive disorders, and the interplay between structures and circuits may explain a mechanism for the impulsive behaviors, agitation, and aggression. A circuit of periaqueductal gray matter, hippocampus, amygdala, and hypothalamus mediates threat response, a bottom-up impulse. Prefrontal cortex (PFC) serves a top-down role to inhibit those bottom-up impulses, and PFC dysfunction impairs a person’s ability to recognize social cues and increases the risk of impulsive aggressive responses by a person failing to make appropriate risk/reward assessments for inhibiting responses. Added sensory deficits in hearing, vision, or pain together with sensory processing and appraisal deficits in cognition combine to foster behavioral disturbances of agitation, aggression, and impulsive acts [1]. Of the PFC, specifically the ventromedial PFC and its connections to lower structures, such as the amygdala, serve this top-down inhibitory function [1, 2]. PFC-amygdala circuit connectivity is disrupted by dysfunction in associated serotonin and dopamine systems in several mental conditions. Enhancing serotonergic and dopaminergic signaling in and around this circuit provides a theoretical approach to pharmacologic agent selection for many of these behavioral disturbances. Severe mental and neurocognitive disorders, including traumatic brain injury (TBI), often show pathology in the brain regions associated with top-down and bottom-up structures, as described above [3].

Schizophrenia-spectrum and other psychotic disorders afflict the bulk of chronically mentally ill individuals [1]. Thus, antipsychotic medications form the core of pharmacological treatment in complex treatment-resistant populations [2].

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Large studies and meta-analyses have noted that anxiety symptoms can occur in up to 65% of patients with schizophrenia, and the prevalence of any anxiety disorder (at the syndromal level) is estimated to be up to 38% [1, 2]. Anxiety symptoms are thus commonly encountered when treating patients with chronic psychotic disorders; however, of equal importance is the conclusion that more than 40% of schizophrenia spectrum patients who report an anxiety symptom are suffering from a cause other than a primary anxiety disorder or depression with anxiety. The differential diagnosis of anxiety symptoms is quite broad among patients with chronic psychotic disorders, but the correct action depends greatly on the underlying etiology. Reflexive use of a benzodiazepine or a selective serotonin reuptake inhibitor (SSRI) to treat anxiety is not appropriate in many instances and can be associated with deleterious outcomes such as increased mortality (benzodiazepines), or antidepressant-induced destabilization of patients with a bipolar diathesis (i.e. patients with a diagnosis of schizoaffective disorder, bipolar type). The issues to consider in documenting a treatment rationale are outlined in Table 8.1. A thoughtful review of the anxiety symptom evolution in relationship to medication changes or other factors should enable the clinician to arrive at a testable hypothesis and plot a course of action.