The Cal-DSH diversion guidelines.

The Cal-DSH Diversion Guidelines provide 10 general guidelines that jurisdictions should consider when developing diversion programs for individuals with a serious mental illness (SMI) who become involved in the criminal justice system. Screening for SMI in a jail setting is reviewed. In addition, important treatment interventions for SMI and substance use disorders are highlighted with the need to address criminogenic risk factors highlighted.

Dopamine antagonist antipsychotics in diverted forensic populations.

In community settings, negative symptoms and cognitive deficits are the primary barriers to independent living, stable relationships, and employment for individuals suffering from schizophrenia-spectrum disorders. In contrast, however, positive psychotic symptoms (e.g., command hallucinations and persecutory delusions) often drive behavior which serves as the gateway to arrest and criminalization. Historically, the keystone of treatment for positive psychotic symptoms has been antagonism of dopamine D2 receptors in the mesolimbic tract. In this article, we review and explore the principles underlying dopamine antagonism for the treatment of psychosis; optimization of dopamine antagonists in treating positive psychotic symptoms; the advantages of depot dopamine antagonist antipsychotics in forensic settings; the concepts of pharmacokinetic and pharmacodynamic treatment failures; and the role of medication plasma concentrations in optimizing and managing treatment.

Deuterium Tetrabenazine for Tardive Dyskinesia.

Tardive dyskinesia remains a significant, potentially stigmatizing or crippling adverse effect for any patient treated with an antipsychotic medication. While second- and third-generation antipsychotics have exhibited lower annual incidence rates for tardive dyskinesia than classic or first-generation agents, 3.9% versus 5.5%, the estimated incidence rate is only modestly lower. When coupled with the fact that second- and third-generation antipsychotic medications have come to be employed in treating a wider range of disorders (e.g., autism spectrum disorders, mood disorders, personality disorders, etc.), it is clear that the population of patients exposed to the risk of tardive dyskinesia has expanded. On April 3, 2017, the U.S. Food and Drug Administration (FDA) approved a deuterated version of tetrabenazine (Xenozine®) for the treatment of the involuntary choreic movements associated with Huntington's disease. More recent data, however, have indicated that deuterium tetrabenazine or deutetrabenazine (Austedo®) is effective in treating tardive dyskinesia. Moreover, like the other derivative of tetrabenazine, valbenazine (Ingrezza®), deutetrabenazine offers less frequent dosing and a better short-term adverse effect profile than that of tetrabenazine. Longer use in a broader range of patients, however, will be required to identify risks and benefits not found in short-term trials, as well as optimal use parameters for treatment of tardive dyskinesia.

Augmentation of phenelzine with aripiprazole and quetiapine in a treatment-resistant patient with psychotic unipolar depression: case report and literature review.

Irreversible monoamine oxidase inhibitor (MAOI) antidepressants have significant efficacy in treatment-resistant unipolar depression, but in some instances patients may not achieve remission. Among the adjunctive and augmentation strategies, certain second-generation antipsychotics (SGAs) have approval for inadequate responders to antidepressant therapy, including aripiprazole, brexpiprazole, and quetiapine, with lurasidone and the olanzapine/fluoxetine combination indicated for bipolar depression. Clinicians may eschew SGA options in part due to the limited literature on SGA-MAOI combinations, with only one published case involving aripiprazole, and none for olanzapine, lurasidone, or brexpiprazole. In addition to the limited publication history on SGA-MAOI treatment, clinicians may also be deterred by uncertainty regarding SGA mechanisms and the risk of serotonin syndrome or other adverse outcomes. This paper describes the case of a 54-year-old male with a history of psychotic unipolar depression treated with a combination of phenelzine, aripiprazole, and quetiapine, and reviews the 12 published cases of SGA-MAOI combination therapy with a focus on the pharmacological basis for serotonin syndrome, and the SGA mechanisms that should not be associated with a risk for this syndrome.

Ciprofloxacin and Clozapine: A Potentially Fatal but Underappreciated Interaction.

Objective. Clozapine provides a 50%-60% response rate in refractory schizophrenia but has a narrow therapeutic index and is susceptible to pharmacokinetic interactions, particularly with strong inhibitors or inducers of cytochrome P450 (CYP) 1A2. Case Report. We report the case of a 28-year-old nonsmoking female with intellectual disability who was maintained for 3 years on clozapine 100 mg orally twice daily. The patient was treated for presumptive urinary tract infection with ciprofloxacin 500 mg orally twice daily and two days later collapsed and died despite resuscitation efforts. The postmortem femoral clozapine plasma level was dramatically elevated at 2900 ng/mL, and the cause of death was listed as acute clozapine toxicity. Conclusion. Given the potentially fatal pharmacokinetic interaction between clozapine and ciprofloxacin, clinicians are advised to monitor baseline clozapine levels prior to adding strong CYP450 1A2 inhibitors, reduce the clozapine dose by at least two-thirds if adding a 1A2 inhibitor such as ciprofloxacin, check subsequent steady state clozapine levels, and adjust the clozapine dose to maintain levels close to those obtained at baseline.

Psychopharmacology of Persistent Violence and Aggression.

Persistent violence not due to acute psychosis or mania can be managed only after appropriate characterization of the aggressive episodes (psychotic, impulsive, or predatory/planned/instrumental). The type of violence combined with the psychiatric diagnosis dictates the evidence-based pharmacologic approaches for psychotically motivated and impulsive aggression, whereas instrumental violence mandates forensic/behavioral strategies. For nonacute inpatients, schizophrenia spectrum disorders, traumatic brain injury, and dementia comprise the majority of individuals who are persistently aggressive, with impulsive actions the most common form of violence across all diagnoses. Neurobiological considerations combined with empirical data provide a comprehensive framework for systematic medication trials to manage persistently aggressive patients.

Illustrative cases to support the Cal-VAT guidelines.

There is increasing interest in developing more nuanced methods for managing aggression and violence in long-term psychiatric inpatient settings. However, the dearth of controlled studies has, at times, hampered presentation of viable options. Following the publication of guidelines developed in the California State Hospital forensic system, the authors present a group of 7 cases illustrating different approaches to violence management, including pharmacological, psychotherapeutic, and environmental interventions.

California State Hospital Violence Assessment and Treatment (Cal-VAT) guideline.

Here we provide comprehensive guidelines for the assessment and treatment of violence and aggression of various etiologies, including psychotic aggression and impulsive aggression due to schizophrenia, mood disorders, ADHD, or trauma, and predatory aggression due to psychopathy and other personality disorders. These guidelines have been developed from a collection of prescribing recommendations, clinical trial results, and years of clinical experience in treating patients who are persistently violent or aggressive in the California Department of State Hospital System. Many of the recommendations provided in these guidelines employ off-label prescribing practices; thus, sound clinical judgment based on individual patient needs and according to institution formularies must be considered when applying these guidelines in clinical practice.

California State Hospital Violence Assessment and Treatment (Cal-VAT) guidelines.

Here we provide comprehensive guidelines for the assessment and treatment of violence and aggression of various etiologies, including psychotic aggression and impulsive aggression due to schizophrenia, mood disorders, ADHD, or trauma, and predatory aggression due to psychopathy and other personality disorders. These guidelines have been developed from a collection of prescribing recommendations, clinical trial results, and years of clinical experience in treating patients who are persistently violent or aggressive in the California Department of State Hospital System. Many of the recommendations provided in these guidelines employ off-label prescribing practices; thus, sound clinical judgment based on individual patient needs and according to institution formularies must be considered when applying these guidelines in clinical practice.

Glucosidase inhibition assay as prescreen for natural products

A glucosidase inhibition assay has been used to evaluate extracts from higher plants. An enzyme inhibition of fifty percent or more correlated with the observed cytotoxicity of the extracts

Reverse transcriptase inhibition as prescreen for potential antiviral bioactives

Extracts from higher plants were evaluated for inhibitory activity against avian myeloblastosis virus reverse transcriptase. The assay may serve as a useful prescreen for potential anti-HIV bioactives