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Older adults represent the fastest growing demographic in both developing and developed countries. Understanding pharmacokinetic and pharmacodynamic principles relevant to psychopharmacology in geriatric patients is increasingly important to optimize psychiatric treatment. This review discusses the four pharmacokinetic processes (absorption, distribution, metabolism, and excretion) with regard to age-related changes. These include a generally slower rate of absorption, increases in the ratio of adipose to lean body mass and volume of distribution of medications, reductions in phase I metabolism, and decreases in renal function. In addition, this review discusses pharmacodynamic factors relevant to pharmacotherapy in older age, such as changes in receptor density and homeostatic and regulatory mechanisms. Geriatric psychopharmacology will benefit from an expanding evidence base as research on pharmacokinetics and pharmacodynamics increasingly includes older individuals. Older adults represent the fastest growing demographic in both developing and developed countries. Understanding pharmacokinetic and pharmacodynamic principles relevant to psychopharmacology in geriatric patients is increasingly important to optimize psychiatric treatment. This review discusses the four pharmacokinetic processes (absorption, distribution, metabolism, and excretion) with regard to age-related changes. These include a generally slower rate of absorption, increases in the ratio of adipose to lean body mass and volume of distribution of medications, reductions in phase I metabolism, and decreases in renal function. In addition, this review discusses pharmacodynamic factors relevant to pharmacotherapy in older age, such as changes in receptor density and homeostatic and regulatory mechanisms. Geriatric psychopharmacology will benefit from an expanding evidence base as research on pharmacokinetics and pharmacodynamics increasingly includes older individuals. [[ Psychiatr Ann. 2015;45(7):336–341.]

Purpose of Review We review 2016–2019 peer-reviewed literature which summarizes the factors contributing to high expense of treating depression among adults in the USA, and interventions that have been conducted to decrease depression treatment expenditures. Recent Findings Treatment expenditures associated with depression are high and growing, driven in part by increased health care utilization and a shift toward increased insurance coverage of medications and therapies. The majority of identified articles describe the elevated financial burden associated with treating individuals with chronic medical conditions who also have a depression diagnosis. The few available studies documenting health care system-level interventions identify that multi-target treatment for comorbid illness, collaborative care management, and integration of psychiatric treatment into primary care show promise for reducing depression treatment expenditures. Summary Additional research is needed to identify innovative, cost-effective state, and federal payer-initiated depression treatment models, and evaluation of collaborative care and integrated care models implemented to scale across multiple health care systems.

Background. Anxious depression, defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, may represent a relatively common depressive subtype, with distinctive features. Objective. The objective of this study was to determine the prevalence of anxious depression and to define its clinical correlates and symptom patterns. Method. Baseline clinical and sociodemographic data were collected on 1450 subjects participating in the STAR*D study. A baseline Hamilton Rating Scale for Depression (HAM-D) Anxiety/Somatization factor score of [ges ]7 was considered indicative of anxious depression. The types and degree of concurrent psychiatric symptoms were measured using the Psychiatric Diagnostic Screening Questionnaire (PDSQ), by recording the number of items endorsed by study participants for each diagnostic category. MDD symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology (IDS-C30). Results. The prevalence of anxious depression in this population was 46%. Patients with anxious MDD were significantly more likely to be older, unemployed, less educated, more severely depressed, and to have suicidal ideation before and after adjustment for severity of depression. As far as concurrent psychiatric symptoms are concerned, patients with anxious depression were significantly more likely to endorse symptoms related to generalized anxiety, obsessive compulsive, panic, post-traumatic stress, agoraphobia, hypochondriasis, and somatoform disorders before and after adjustment for severity of depression. Anxious-depression individuals were also significantly less likely to endorse IDS-C30 items concerning atypical features, and were significantly more likely to endorse items concerning melancholic/endogenous depression features. Conclusion. This study supports specific clinical and sociodemographic correlates of MDD associated with high levels of anxiety (anxious depression).

The article critically reviews selected, clinically significant, adverse endocrine and metabolic effects associated with psychotropic drug treatments, including hyperprolactinaemia, hyponatraemia, diabetes insipidus, hypothyroidism, hyperparathyroidism, sexual dysfunction and virilization, weight loss, weight gain and metabolic syndrome (type 2 diabetes mellitus, dyslipidaemia and hypertension). Such effects are prevalent and complex, but can be managed clinically when recognized. They encourage continued critical assessment of benefits versus risks of psychotropic drugs and underscore the importance of close coordination of psychiatric and general medical care to improve long-term health of psychiatric patients. Options for management of hyperprolactinaemia include lowering doses, switching to agents such as aripiprazole, clozapine or quetiapine, managing associated osteoporosis, carefully considering the use of dopamine receptor agonists and ruling out stress, oral contraceptive use and hypothyroidism as contributing factors. Disorders of water homeostasis may include syndrome of inappropriate antidiuretic hormone (SIADH), managed by water restriction or slow replacement by hypertonic saline along with drug discontinuation. Safe management of diabetes insipidus, commonly associated with lithium, involves switching mood stabilizer and consideration of potassium-sparing diuretics. Clinical hypothyroidism may be a more useful marker than absolute cut-offs of hormone values, and may be associated with quetiapine, antidepressant and lithium use, and managed by thyroxine replacement. Hyper-parathyroidism requires comprehensive medical evaluation for occult tumours. Hypocalcaemia, along with multiple other psychiatric and medical causes, may result in decreased bone density and require evaluation and management. Strategies for reducing sexual dysfunction with psychotropics remain largely unsatisfactory. Finally, management strategies for obesity and metabolic syndrome are reviewed in light of the recent expert guidelines, including risk assessment and treatments, such as monoamine transport inhibitors, anticonvulsants and cannabinoid receptor antagonists, as well as lifestyle changes.

Current measures for major depressive disorder focus primarily on the assessment of depressive symptoms, while often omitting other common features. However, the presence of comorbid features in the anxiety spectrum influences outcome and may effect treatment. More comprehensive measures of depression are needed that include the assessment of symptoms in the anxiety–depression spectrum. This study examines the reliability and validity of the Symptoms of Depression Questionnaire (SDQ), which assesses irritability, anger attacks, and anxiety symptoms together with the commonly considered symptoms of depression. Analysis of the factor structure of the SDQ identified 5 subscales, including one in the anxiety–depression spectrum, with adequate internal consistency and concurrent validity. The SDQ may be a valuable new tool to better characterize depression and identify and administer more targeted interventions.

Objective: We previously found that 46% of the first 1450 outpatients with depression participating in the multicentre Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project qualified for the designation of anxious depression. This study was designed to replicate and extend our initial findings in a subsequent, larger cohort of outpatient STAR*D participants with nonpsychotic major depressive disorder (MDD). Methods: Baseline clinical and sociodemographic data were collected on 2337 consecutive STAR*D participants. A baseline 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor score of 7 or higher was designated as anxious depression. We identified concurrent Axis I disorders with the Psychiatric Diagnostic Screening Questionnaire (PDSQ), using a 90% specificity threshold. Depressive symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30). Results: The prevalence of anxious depression in this population was 45.1%. Patients with anxious MDD were significantly more likely to be in primary care settings and to be women, nonsingle, unemployed, Hispanic, less educated, and suffering from severe depression, both before and after adjustment for overall depression severity. Patients with anxious depression were significantly more likely to meet PDSQ thresholds for generalized anxiety disorder, panic disorder, obsessive–compulsive disorder, posttraumatic stress disorder, agoraphobia, hypochondriasis, and somatoform disorder, both before and after adjusting for baseline depression severity. Individuals with anxious depression were also significantly less likely to endorse IDS-C30 items concerning atypical features and were significantly more likely to endorse items concerning melancholic-endogenous depression features, both before and after adjusting for baseline depression severity. Conclusions: This study clearly replicates our previous STAR*D findings and supports the notion that anxious depression may be a valid diagnostic subtype of MDD, with distinct psychiatric comorbidities and clinical and sociodemographic features.

Although often overlooked, the interaction of psychotropic medications with food or dietary health supplements can be clinically relevant, and in some cases it may be catastrophic. In this review, we highlight clinically significant drug-food interactions in psychiatry, including those related to hypertensive crises with monoamine oxidase inhibitors, absorption of medications (such as levothyroxine, ziprasidone, and lurasidone), coadministration with food, the excretion of lithium and other medications in the setting of dietary changes, and the impact of grapefruit juice, St. John's wort, cruciferous vegetables, charbroiled meats, dietary supplements, and alcohol on drug metabolism. Routine inquiry about dietary habits and use of dietary supplements as well as enhanced anticipation and monitoring for potential drug-food interactions is an integral component of optimal psychopharmacologic practice. [ Psychiatr Ann . 2016;46(8):448–455.]

Drug interactions may reflect pharmacokinetic processes, pharmacodynamic processes, or both. Some interactions are classified as idiosyncratic, as their mechanisms are not yet understood. Drug interactions involving psychotropic medications are ubiquitous; they typically result in changes in drug levels and/or drug effects. Fortunately, most drug interactions in psychiatry do not result in serious harm. Some drug interactions, however, are potentially catastrophic. The focus of this review is on the principal mechanisms of drug interactions and on potentially serious and life-threatening adverse consequences (eg, serotonin syndrome, hypertensive crises, arrhythmias, anticholinergic toxicity, seizures, dermatologic emergencies, bleeding, respiratory depression) of drug interactions in psychiatry. Patients with refractory psychiatric disorders, as well as medical comorbidity, often require treatment with complex drug regimens. The risk of catastrophic drug interactions involving psychotropic medications may be minimized by knowledge of the mechanisms of drug interactions and by familiarity with the rare, yet potentially life-threatening drug interactions that involve psychotropic medications. [ Psychiatr Ann . 2016;46(8):439–447.]

Objective: Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy controls. A previous study by our group reported that depressed patients with elevated cholesterol levels (≧200 mg/dl) were significantly more likely to be nonresponders to fluoxetine treatment than depressed patients with nonelevated cholesterol levels. However, very little is known regarding cholesterol in patients with treatment-resistant depression (TRD). The purpose of this study was to compare cholesterol levels at baseline between depressed patients with and without TRD and to test whether cholesterol levels at baseline can predict clinical response in patients with TRD treated with open-label nortriptyline (NT). Methods: Ninety-two patients with TRD entered a 6-week open trial of NT. Baseline cholesterol levels were randomly collected for 59 of these patients. Controlling for age and gender, we compared baseline cholesterol and triglyceride levels for 35 patients with TRD who did not respond to NT with 205 non-TRD patients who responded to an 8-week open trial of fluoxetine. Furthermore, with the use of logistic regression, we tested whether baseline cholesterol levels predicted clinical response to NT in the patients with TRD. Results: Patients with TRD had higher triglyceride levels at baseline compared with depressed patients without TRD. Cholesterol defined as a dichotomous variable being elevated if equal to or greater than 200 mg/dl, predicted poor response to a 6-week open trial of NT in patients with TRD. Conclusions: The results of this study confirm the relationship between hypercholesterolemia and poor outcome in the treatment of MDD for patients with TRD.