Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions.

Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.

Precision and personalized assessment, diagnosis and treatment in psychiatry.

"Precision medicine" and "personalized medicine" constitute goals of research since antiquity and this was intensified with the arrival of the "evidence-based medicine." precision and personalized psychiatry (3P) when achieved will constitute a radical shift in our paradigm and it will be even more transformative than in other fields of medicine. The biggest problems so far are the problematic definition of mental disorder, available treatments seem to concern broad categories rather than specific disorders and finally clinical predictors of treatment response or side effects and biological markers do not exist. Precision and personalized psychiatry like all precision medicine will be a laborious and costly task; thus the partnership of scientists with industry and the commercialization of new methods and technologies will be an important element for success. The development of an appropriate legal framework which will both support development and progress but also will protect the rights and the privacy of patients and their families is essential.

Economics of decriminalizing mental illness: when doing the right thing costs less.

The United States' criminal justice system has seen exponential growth in costs related to the incarceration of persons with mental illness. Jails, prisons, and state hospitals' resources are insufficient to adequately treat the sheer number of individuals cycling through their system. Reversing the cycle of criminalization of mental illness is a complicated process, but mental health diversion programs across the nation are uniquely positioned to do just that. Not only are these programs providing humane treatment to individuals within the community and breaking the cycle of recidivism, the potential fiscal savings are over 1 billion dollars.

Expert Consensus on Screening and Assessment of Cognition in Psychiatry.

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

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.

Incidence and costs of polypharmacy: data from a randomized, double-blind, placebo-controlled study of risperidone and quetiapine in patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: The use of adjunctive psychotropics and the costs of polypharmacy in patients randomized to receive risperidone or quetiapine were compared in a placebo-controlled double-blind study conducted in India, Romania, and the United States. METHODS: The efficacy and safety of risperidone, quetiapine, and placebo were compared in a 14-day monotherapy phase in patients experiencing an acute exacerbation of symptoms of schizophrenia or schizoaffective disorder. This was followed by a 28-day, additive-therapy phase during which addition of antipsychotics or other psychotropic medications was permitted. Risperidone was received by 153 patients in the monotherapy phase and 133 in the additive therapy phase, quetiapine by 156 and 122, respectively, and placebo by 73 and 53. Rates of polypharmacy were examined using the Cochran-Mantel-Haenszel, Kaplan-Meier, and Cox regression methods. Costs of polypharmacy were analyzed by non-parametric Wilcoxon 2-sample tests. RESULTS: Primary study results have been reported elsewhere (Potkin et al., Schizophr Res 2006;85:254-65). Mean (+/-SD) doses at the additive-therapy baseline were 4.7 +/- 0.9 mg/day of risperidone and 579.0 +/- 128.9 mg/day of quetiapine. Additional psychotropics were received by 36% of the risperidone group, 58% of the quetiapine group (p < 0.01), and by 58% of the placebo group. Antipsychotics accounted for > 95% of the added psychotropics, the most common being olanzapine and haloperidol. The relative risk (quetiapine vs. risperidone) for antipsychotic polypharmacy was 1.90 (p = 0.001; 95% CI 1.29, 2.80). The mean projected cost of additional antipsychotics per randomized patient during the additive-therapy phase was $57.03 in the risperidone group and $101.64 in the quetiapine group (p < 0.01). CONCLUSIONS: The results confirm earlier reports of higher rates of polypharmacy with quetiapine than with risperidone. The findings also reveal substantial between-treatment differences in costs associated with polypharmacy. Limitations of the study include that the study was of short duration and that a high proportion of patients were recruited from countries other than the United States.

High-cost use of second-generation antipsychotics under California's Medicaid program.

OBJECTIVE: The high costs associated with second-generation antipsychotic medications raise concerns that prior-authorization restrictions may be implemented to restrict use. This study assessed patterns of antipsychotic use to identify uses that are associated with high economic cost but for which there is no documented efficacy. METHODS: California Medicaid fee-for-service pharmacy claims were analyzed from May 1999 through August 2000 for patients who received risperidone, olanzapine, or quetiapine. RESULTS: Of the 116,114 patients who received at least one of these agents, 4.1 percent received a combination regimen. Polypharmacy was the most expensive form of second-generation antipsychotic use, costing up to three times more per patient than monotherapy. CONCLUSION: Restricting polypharmacy may reduce costs and prevent the need for prior-authorization restrictions.

Preemptive analgesia: is pain less costly when you pre-pay for it?

ISSUE: Early treatment of pain could thwart the development of chronic persistent painful conditions.