Julie A. Dopheide

Attention-deficit-hyperactivity disorder: an update.

Attention‐deficit‐hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that impairs social, academic, and occupational functioning in children, adolescents, and adults. In patients with ADHD, neurobiologic research has shown a lack of connectivity in key brain regions, inhibitory control deficits, delayed brain maturation, and noradrenergic and dopaminergic dysfunction in multiple brain regions. The prevalence of this disorder in the United States is 6–9% in youth (i.e., children and adolescents) and 3–5% in adults. Prevalence rates for youth are similar worldwide. Children with ADHD are at greater risk than children without ADHD for substance abuse and delinquency whether or not they receive drug therapy; however, early treatment with psychoeducation as well as drug therapy and/or behavioral intervention may decrease negative outcomes of ADHD, including the rate of conduct disorder and adult antisocial personality disorder. Drug therapy is effective for all age groups, even preschoolers, and for late‐onset ADHD in adults. Stimulants, such as methylphenidate and amphetamine, are the most effective therapy and have a good safety profile; although recent concerns of sudden unexplained death, psychiatric adverse effects, and growth effects have prompted the introduction of other therapies. Atomoxetine, a nonstimulant, has no abuse potential, causes less insomnia than stimulants, and poses minimal risk of growth effects. Other drug options include clonidine and guanfacine, but both can cause bradycardia and sedation. Polyunsaturated fatty acids (fish oil), acetyl‐l‐carnitine, and iron supplements (for youth with low ferritin levels) show promise in improving ADHD symptoms. As long‐term studies show that at least 50% of youth are nonadherent with their drug therapy as prescribed over a 1‐year period, longacting formulations (administered once/day) may improve adherence. Comorbid conditions are common in patients with ADHD, but this patient population can be treated effectively with individualized treatment regimens of stimulants, atomoxetine, or bupropion, along with close monitoring.

Mirtazapine: An Antidepressant with Noradrenergic and Specific Serotonergic Effects

Mirtazapine is a unique antidepressant that refines the specificity of effects on noradrenergic and serotonergic systems. It is an antagonist of presynaptic α2‐adrenergic autoreceptors and heteroreceptors on both norepinephrine and serotonin (5‐HT) presynaptic axons, plus is a potent antagonist of postsynaptic 5‐HT2 and 5‐HT3 receptors. The net outcome of these effects is increased noradrenergic activity together with specific increased serotonergic activity, especially at 5‐HT1A receptors. This mechanism of action maintains equivalent antidepressant efficacy but minimizes many of the adverse effects common to both tricyclic antidepressants and selective serotonin reuptake inhibitors. Mirtazapine has an onset of clinical effect in 2–4 weeks similar to other antidepressants, although sleep disturbances and anxiety symptoms may improve in the first week of treatment. It has minimal cardiovascular and anticholinergic effects, and essentially lacks serotonergic effects such as gastrointestinal symptoms, insomnia, and sexual dysfunction. Sedation, increased appetite, and weight gain are more common with mirtazapine than with placebo. An elimination half‐life of 20–40 hours enables once‐daily bedtime dosing. The recommended initial dosage is 15 mg once/day at bedtime, with an effective daily dosage range of 15–45 mg. Cases of overdose of up to 975 mg caused significant sedation but no cardiovascular or respiratory effects or seizures.

Psychotropic Drug-Induced Reductions in Seizure Threshold

SummaryThere are no simple answers to questions such as ‘Which antidepressant is most likely to cause seizures?’ or ‘Which antipsychotic drug is the safest to use in a patient with a seizure disorder?’The risk of psychotropic drug-induced seizures is dependent on many factors beyond inherent differences in the propensity of individual drugs to lower seizure threshold. Individual patient variables that affect the likelihood of drug-induced seizures occurring include a history of epilepsy or seizures, a family history of epilepsy, and postnatal brain damage, head trauma and dementia. Once a drug is selected, seizure risk is directly dependent on dosage, rate and amount of dose titration, and concurrent use of other drugs.Setting aside these other risk factors, the likelihood of drug-induced seizures occurring does differ among psychotropic drugs. Among antipsychotic drugs, clozapine is associated with the highest risk of seizures, followed by chlorpromazine, with other phenothiazines and risperidone having a lower risk and haloperidol the least risk.Among antidepressants, maprotiline, amoxapine, amfebutamone (bupropion) and clomipramine pose the greatest risk along with other tricyclic antidepressants in high doses. Monoamine oxidase inhibitors (MAOIs), trazodone, nefazodone and the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) are associated with a lower risk of seizures.Benzodiazepines with long elimination half-lives are less likely to cause seizures during withdrawal than those agents with short to intermediate half-lives, although the rate and amount of dosage reduction are more important variables.Finally, most psychotropic drugs are metabolised by cytochrome P450 isoenzymes. Concurrent use of enzyme inhibitors or discontinuation of enzyme inducers may cause a significant increase in plasma concentrations of the psychotropic drug, increasing the likelihood of adverse effects and the potential for seizures.

Paliperidone: An improvement over risperidone?

The article by Dolder et al.[1][1] on paliperidone in this issue of AJHP provides a comprehensive review of the literature on paliperidone’s receptor-binding profile, pharmacokinetics, efficacy, adverse effects, and extended-release dosage form. Potential advantages and disadvantages of

A naturalistic comparison of adverse effects between slow titration and loading of divalproex sodium in psychiatric inpatients.

BACKGROUND This study compares the incidence, severity and onset of treatment-emergent adverse effects between slow titration and loading of divalproex sodium in psychiatric inpatients. METHOD Forty-seven patients were prescribed either loading or slow titration of divalproex sodium. Under single-blind conditions, adverse effects were assessed using a valproate adverse effects rating scale. Except for a statistically significant greater incidence of somnolence in the slow titration group, no statistically or clinically significant differences in incidence, severity or onset of treatment-emergent adverse effects were found between groups. RESULTS/CONCLUSION Overall, adverse effects were well tolerated by both groups.

Psychotropic medication use at a private eating disorders treatment facility: A retrospective chart review and descriptive data analysis

BACKGROUND The extent of psychotropic medication use in patients with eating disorders worldwide is unknown. OBJECTIVES THE PURPOSES OF THIS STUDY WERE TO: (1) describe the extent and pattern of psychotropic medication use at a private treatment facility for patients with eating disorders and (2) describe patient characteristics and treatment outcomes at the facility. METHODS This retrospective chart review included data from a private treatment facility (inpatient or outpatient) for patients with eating disorders in the greater Los Angeles area. Data from all patients of any age who attended the facility between January 1, 2004, and January 1, 2005, and who met the criteria for anorexia nervosa (AN), bulimia nervosa (BN), or eating disorder not otherwise specified (ED NOS) defined in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were included. Two investigators used a consistent chart-review method for recording clinical status, including treatment-related adverse effects and discharge status (improved, no change, or decompensated from admission). Improved was defined as meeting 1 or more of the following criteria: achieved ideal body weight, stabilized mood, decreased eating disorder symptoms (binge-purge, restrictive, or ritualistic behavior), eating disorder remission, or decreased suicidal ideation plus another improvement in this list. RESULTS Data from 60 patients were included (31 with AN, 28 with 13N, and I with ED NOS). Ages ranged from 12 to 47 years, and the mean duration of treatment was 35 days. Fifty-eight (96.7%) patients received a psychotropic agent; 35 (58.3%) patients were prescribed 2 or more agents concomitantly. Selective serotonin reuptake inhibitors (SSRls) were the most commonly prescribed class of psychotropic medication (86.7%), followed by antipsychotics (38.3%). Fluoxetine, escitalopram, and aripiprazole were the most commonly prescribed agents (41.7%, 28.3%, and 23.3%, respectively). A total of 63.3% of patients had a comorbid diagnosis of major depressive disorder, with 96.7% of these patients prescribed an antidepressant. At discharge, 51.6% of the inpatients and 37.9% of the outpatients had improved (AN, 52.6% and 33.3%, respectively; BN, 54.5% and 41.2%, respectively). Of the patients prescribed an SSRI, 40.4% had improved. In the inpatient setting, 35.5% of patients receiving an antipsychotic had improved, versus 6.9% in the outpatient setting. CONCLUSIONS The results of this retrospective chart review and descriptive analysis of data from patients at a private eating disorders treatment facility in the United States suggest that psychotropics, particularly antidepressants and antipsychotics, were highly utilized, largely to treat comorbid symptoms. Fluoxetine, escitalopram, and aripiprazole were the most commonly prescribed agents. We observed that psychotropic medication selection was based on patient comorbidities and symptom expression and severity.

Acetylcysteine for treatment of autism spectrum disorder symptoms

PURPOSE Successful use of acetylcysteine to control irritability and aggressive behaviors in a hospitalized adolescent patient with autism spectrum disorder (ASD) is described. SUMMARY A 17-year-old Hispanic male with ASD and intellectual disability was hospitalized for inpatient psychiatric treatment due to impulsive and violent behavior. Despite receiving various medications in the initial weeks of hospitalization, including intramuscular lorazepam and diphenhydramine injections (four days a week on average), the patient continued to exhibit aggressive and unpredictable behaviors. Treatment with 20% acetylcysteine oral solution was initiated at a dosage of 600 mg twice daily as an adjunct to quetiapine therapy. Over the next six weeks, reductions in the patients aggressive behavior, tantrums, and irritability were noted. The use of as-needed medications to control aggression was decreased, and the dosage of quetiapine was lowered from 700 to 400 mg daily over the course of the hospitalization. Acetylcysteine was well tolerated, with no observed or reported adverse effects. Unlike clonidine or guanfacine (other medications used for ASD-related behavioral symptoms), acetylcysteine is not sedating; moreover, it lacks the metabolic, extrapyramidal, and endocrine adverse effects of atypical antipsychotics. Published data from small controlled trials and case reports suggest that acetylcysteine use is associated with improvements in irritability and aggression in prepubertal children with ASD; these therapeutic benefits may be associated with acetylcysteines glutamatergic, dopaminergic, antioxidant, and anti-inflammatory properties. CONCLUSION Treatment with acetylcysteine improved ASD symptoms, including irritability and aggression, in a teenage patient.

Vilazodone’s comparative merits yet to be demonstrated

The 2010 American Psychiatric Association (APA) guidelines for treating patients with major depression state that the effectiveness of antidepressant medications is generally comparable among and within classes of medications. No antidepressant is considered more effective or faster-acting than

Nonpsychiatric Medication Interventions Initiated by a Postgraduate Year 2 Psychiatric Pharmacy Resident in a Patient-Centered Medical Home

OBJECTIVE Studies have demonstrated the benefits of incorporating comprehensive medication management into primary care, but no study describes the types of nonpsychiatric medication-related interventions provided by a psychiatric pharmacist while providing comprehensive medication management. METHOD A chart review of Center for Community Health patients enrolled in the University of Southern California Psychiatric Pharmacy Clinic, Los Angeles, between July 1, 2013, and January 10, 2014, was conducted. Progress notes were reviewed to collect medication recommendations and interventions. The number and types of interventions were compared between groups based on substance abuse history, comorbid medical conditions, number of psychiatric diagnoses, and number of medications. An anonymous survey was distributed to primary care providers (PCPs) regarding perceptions and attitudes toward a postgraduate year 2 psychiatric pharmacy residents interventions pertaining to nonpsychiatric medications. RESULTS 177 nonpsychiatric medication interventions were documented. Fifty interventions required PCP approval, and 45% of those were accepted. Having a diagnosis of diabetes (P < .0001), hypertension (P < .0001), gastroesophageal reflux disease (P < .0001), ≥ 9 medications (P < .0001), or ≥ 5 medical diagnoses (P < .0001) were all associated with an increased mean number of interventions. Of the PCPs, 66% viewed the psychiatric pharmacist as a resource for addressing medical interventions by providing drug information. The PCPs were agreeable to having a psychiatric pharmacist provide drug information and monitor the patient but reported mixed opinions on whether a psychiatric pharmacist should comanage nonpsychiatric conditions. CONCLUSIONS Psychiatric pharmacists can successfully collaborate with PCPs in primary care clinics to provide comprehensive medication management that optimizes pharmacotherapy for patients with medical and psychiatric conditions. Continued efforts are needed to promote interdisciplinary approaches to provide comprehensive medication management services for patients with both psychiatric and medical disorders.

Psychiatric Pharmacist Management of Depression in Patients With Diabetes

To The Editor: Previous studies have concluded that depression is a risk factor, as well as a consequence, of diabetes.1–3 The presence of untreated depression in patients with diabetes has been associated with a multitude of negative consequences and cost implications, including poor self-care and poor treatment adherence, worsening glycemic control, an increase in severity or number of diabetic complications, an increased likelihood of adverse cardiovascular events, higher rates of functional disability, higher all-cause mortality, and an increase in health care use and expenditures.4,5 Despite the well-established relationship between depression and diabetes, depression is underdiagnosed and undertreated in patients with diabetes.6 A growing body of evidence suggests that collaborative care may be an effective intervention to improve outcomes in patients with depression and diabetes.7–9 This report describes the outcome of depression management in patients with diabetes treated by a psychiatric pharmacist within a collaborative practice model in a safety net clinic in downtown Los Angeles, California. Method. A chart review was conducted to identify adults with diabetes who were diagnosed with depression and subsequently referred to the psychiatric pharmacist for management. The psychiatric pharmacist clinic occurred 1 day per week. Referrals were made by the primary care providers or the clinic psychologist. Upon referral, a diagnosis of major depressive disorder (MDD) was confirmed by the psychiatric pharmacist using DSM-IV-TR criteria.10 Demographic information, hemoglobin A1c (HbA1c) levels, Patient Health Questionnaire-9 (PHQ-9)11 scores, and types of depression treatment (ie, medication, psychotherapy) were recorded. Patients were excluded from analysis if they had fewer than 2 appointments or if they had comorbid schizophrenia, bipolar disorder, or active substance abuse. Depressive symptoms were treated in accordance with the American Psychiatric Association’s practice guideline for treating patients with MDD.12 Diabetes care was delivered by the primary care provider. According to the collaborative practice agreement, the psychiatric pharmacist could initiate, change, or discontinue medications and obtain laboratory measures. Other services such as reviewing laboratory results, obtaining medication histories, and offering medication education were also provided. Response was defined as a reduction in PHQ-9 score from baseline greater than or equal to 50%, and remission was defined as a PHQ-9 score less than 5.13,14 Results. During the 6-month study period (from October 2011 through March 2012), the psychiatric pharmacist treated a total of 15 patients with diabetes and depression. The majority of patients were male (n = 9, 60%) and obese (mean BMI [kg/m2] = 31.8), with a mean age of 55.6 years. Patient ethnicities were predominantly African American and Hispanic (> 80%). Patients had a mean of 3 medical conditions, including diabetes. The mean PHQ-9 score at baseline was 18.6, which reflects moderately severe depression. The mean HbA1c level of 8.5% indicates that patients were above the American Diabetes Association treatment goal.15 Patients were followed for an mean of 3.75 months. Of the 15 initial patients, 6 (40%) were lost to follow-up. The mean change in PHQ-9 scores from baseline for the 9 remaining patients was −9.5 (range, 0 to −15). Response to therapy was achieved in 89% of patients (n = 8), and one third of patients (n = 3) attained remission of depressive symptoms. Selective serotonin reuptake inhibitors and mirtazapine were the only prescribed antidepressants (Figure 1). Figure 1. Treatment Modalities for Depression Management Findings from this study demonstrate that medication management by a psychiatric pharmacist can effectively improve depressive symptoms in patients with diabetes. Psychiatric pharmacists complete 2 years of postgraduate training16 with an emphasis on providing comprehensive medication therapy management to patients with medical and psychiatric disorders.17 The psychiatric pharmacist was able to dedicate 30–60 minutes at each visit obtaining medication/medical histories, providing medication education to dispel myths, and building rapport with patients so they were more comfortable taking psychotropic medications. Forty percent of patients were lost to follow-up; however, this high attrition rate is common among the homeless population.18 Future work will focus on a larger-scale analysis of the effectiveness of psychiatric pharmacists’ abilities to improve outcomes for the low-income and homeless subset of patients with coexisting diabetes and MDD.