Associations between the concurrent use of clinical decision support and computerized provider order entry and the rates of appropriate prescribing at discharge.

INTRODUCTION: Electronic health record systems used in conjunction with clinical decision support (CDS) or computerized provider order entry (CPOE) have shown potential in improving quality of care, yet less is known about the effects of combination use of CDS and CPOE on prescribing rates at discharge. OBJECTIVES: This study investigates the effectiveness of combination use of CDS and CPOE on appropriate drug prescribing rates at discharge for AMI or HF patients. METHODS: Combination use of CDS and CPOE is defined as hospitals self-reporting full implementation across all hospital units of CDS reminders, CDS guidelines, and CPOE. Appropriate prescribing rates of aspirin, ACEI/ARBs, or beta blockers are defined using quality measures from Hospital Compare. Multivariate linear regressions are used to test for differences in mean appropriate prescribing rates between hospitals reporting combination use of CDS and CPOE, compared to those reporting the singular use of one or the other, or the absence of both. Covariates include hospital size, region, and ownership status. RESULTS: Approximately 10% of the sample reported full implementation of both CDS and CPOE, while 7% and 17% reported full use of only CPOE or only CDS, respectively. Hospitals reporting full use of CDS only reported between 0.2% (95% CI 0.04 - 1.0) and 1.6% (95% CI 0.6 - 2.6) higher appropriate prescribing rates compared to hospitals reporting use of neither system. Rates of prescribing by hospitals reporting full use of both CPOE and CDS did not significantly differ from the control group. CONCLUSIONS: Although associations found between full implementation of CDS and appropriate prescribing rates suggest that clinical decision tools are sufficient compared to basic EHR systems in improving prescribing at discharge, the modest differences raise doubt about the clinical relevance of the findings. Future studies need to continue investigating the causal nature and clinical relevance of these associations.

Clozapine-associated extrapyramidal reaction.

OBJECTIVE: To report a case of extrapyramidal reaction associated with a dosage increase of clozapine. CASE SUMMARY: A 44-year-old white man with a 20-year history of chronic paranoid schizophrenia was admitted to an inpatient psychiatric facility. His prior medications restarted on admission were clozapine 650 mg at bedtime, haloperidol 10 mg at bedtime, clonazepam 2 mg/d, and aspirin 325 mg/d. Two days after admission (hospital day 3), clozapine and clonazepam were discontinued, and he was prescribed haloperidol 5 mg every morning and 10 mg every evening. Stabilization occurred over the following 24 days, with progressively lower dosages of haloperidol and increasing dosages of clozapine. Haloperidol was discontinued on day 24. On day 47, the patient was agitated and making bizarre statements; thus, the morning dose of clozapine was increased by 50 mg (total 450 mg/d). On day 48 at 2200, a dystonic reaction was diagnosed; he received intramuscular diphenhydramine 50 mg, which caused the reaction to subside. At the time of the adverse reaction, he was prescribed clozapine 450 mg/d, vitamin E 400 IU three times daily, aspirin 325 mg/d, and acetaminophen, milk of magnesia, and Maalox as needed. DISCUSSION: Although the risk of extrapyramidal symptoms (EPS) is significantly lower with clozapine than with conventional agents, elevated clozapine blood concentrations have been reported to cause EPS; other reports have cited severe dystonias and dyskinesias on abrupt clozapine withdrawal. Considering the medications prescribed at the time and the discontinuation of haloperidol 24 days before the event, clozapine was the most likely cause of the extrapyramidal reaction. CONCLUSIONS: Regardless of anticipated safety associated with novel antipsychotics such as clozapine, reports of dystonic reactions must be taken into account and patients monitored appropriately.

Atypical antipsychotic agents: a critical review.

The pharmacology, efficacy, and adverse effects of atypical antipsychotic agents when used to treat schizophrenia and other disorders are reviewed. Atypical antipsychotic agents were developed in response to problems with typical agents, including lack of efficacy in some patients, lack of improvement in negative symptoms, and troublesome adverse effects, especially extrapyramidal symptoms (EPSs) and tardive dyskinesia CTD). Atypical antipsychotics differ from typical psychotics in their "limbic-specific" dopamine type 2 (D2)-receptor binding and high ratio of serotonin type 2 (5-HT2)-receptor binding to D2 binding. In clinical trials in patients with non-treatment-resistant schizophrenia, risperidone and olanzapine were superior to placebo for positive and negative symptoms. Risperidone and olanzapine were superior to haloperidol on some measures. Quetiapine was better than placebo but was not better than typical antipsychotics. Head-to-head comparisons of atypical antipsychotics in non-treatment-resistant schizophrenia have been inconclusive. Clozapine remains the standard agent for treatment-resistant schizophrenia. Atypical agents are substantially more expensive than their typical antipsychotic counterparts. To fully determine the overall efficiency of these drugs, other potential benefits, such as improved quality of life, need to be factored in. Atypical antipsychotics are associated with a decreased capacity to cause EPSs, TD, neuroleptic malignant syndrome, and hyperprolactinemia. Clozapine carries a risk of agranulocytosis; the white blood cell count must be monitored. Atypical antipsychotics are increasingly being used for indications other than schizophrenia, such as the management of aggression, mania, and depression. Atypical antipsychotics are often considered first-line agents for treating schizophrenia and are promising treatment alternatives for other psychiatric and neurologic conditions.

Attenuation of antipsychotic-induced hyperprolactinemia with clozapine.

Hyperprolactinemia is a well-known consequence of conventional antipsychotic therapy. The atypical antipsychotic clozapine is reported to lack this effect. We describe a case of attenuated serum prolactin levels after conversion to clozapine therapy in an adolescent. A 13-year-old female patient developed hyperprolactinemia with galactorrhea and amenorrhea while receiving thioridazine 300 mg daily. These symptoms continued throughout 3 years of treatment with haloperidol 10 mg daily and then fluphenazine 10 mg daily. Subsequently, after an incomplete improvement in her psychiatric symptoms and hyperprolactinemia on thioridazine 150 mg and bromocriptine 15 mg daily, the patient was changed to clozapine at age 16. Clozapine 150 mg twice daily improved her psychiatric status and corrected her serum prolactin concentrations after 2 weeks; bromocriptine was able to be discontinued. We recommend systematic evaluation of atypical neuroleptics as alternative treatments for refractory hyperprolactinemia induced by conventional antipsychotics.

Antidepressant overdoses and resultant emergency department services: the impact of SSRIs.

Suicide is a major source of morbidity and mortality in patients with mental illness. The selective serotonin reuptake inhibitors (SSRIs) and other newer nontricyclic antidepressants appear to have less clinically significant toxicity in overdose, resulting in lower costs of treatment when compared with tricyclic antidepressant (TCA) overdoses. The resource utilization and cost of treatment for SSRI overdoses may not be less if (1) these agents are commonly ingested with other potentially toxic substances, or (2) health care practices have not changed in response to the apparent greater safety of SSRIs. This study evaluates demographic variables of antidepressant overdoses to determine whether differences exist in treatments and monitoring. Additionally, this study evaluates costs associated with care and the impact of co-ingestants on those same factors.

Preliminary comparison of predictive and empiric lithium dosing: impact on patient outcome.

OBJECTIVE: To evaluate whether initiating lithium with predictive dosing compared with empiric dosing improves outcome in patients with manic symptoms. DESIGN: The study was a randomized, single-blind design and used the Modified Slattery predictive method. SETTING AND PARTICIPANTS: Eighteen inpatients at an urban psychiatric hospital with a Mania Rating Scale (MRS) score greater than or equal to 24 were enrolled. OUTCOME MEASURES: The study endpoint was defined as an MRS rating less than or equal to 14 or discharge from the hospital. Assessments (MRS, Brief Psychiatric Rating Scale, Clinical Global Impression, Systematic Assessment for Treatment of Emergent Events Scale, quality of life measures) were completed at baseline, on days 3 or 4 and 7 or 8, and weekly thereafter. RESULTS: The predictive group achieved a therapeutic concentration significantly sooner than did the empiric group (p = 0.004); however, the mean serum lithium concentration at discharge did not differ between the groups. The predictive group was taking significantly higher dosages of antipsychotics in chlorpromazine equivalents on day 3 or 4 (p = 0.05). Significantly fewer gastrointestinal/genitourinary adverse effects on day 3 or 4 were reported by patients in the predictive group (p = 0.04). No difference was found between groups with any rating scale or other pharmacokinetic or medication item. Even though the difference did not meet statistical significance, the predictive group's length of stay in the acute unit was three days shorter than that of the empiric group, which may represent significant cost savings. CONCLUSIONS: The preliminary data do not suggest that patient outcome is improved by using Modified Slattery predictive dosing; however, the suggestion of a shorter length of stay in a restrictive unit merits further evaluation.

An atypical course of neuroleptic malignant syndrome.

Based on the discussion of NMS, certain conclusions may be reached in regard to this patient. In the psychiatric setting, agitation and confusion alone are not suggestive of NMS. However in this patient, the symptoms of agitation, the rapid development of EPS symptoms unresponsive to anticholinergic therapy, autonomic changes (tachycardia, diaphoresis, and incontinence), and elevated CPK, met most of the diagnostic criteria described in Table VI. However, this case may have described an atypical presentation of NMS because of the absence of temperature increases during the onset of symptoms and the 7-week hospitalization for NMS. The patient's later onset of temperature elevations was a result of an aspiration pneumonia. Pneumonia and renal failure significantly increased the morbidity and extended the course of the illness. As a result, the diagnosis and specific treatment of NMS were delayed because of atypical symptoms and complications. In this patient, treatment of NMS with bromocriptine did not start until 10 days into hospitalization. A delay in pharmacologic therapy in this patient may have contributed to persistence of symptoms. The patient showed signs of improvement on day 21 during combination bromocriptine, benztropine, and dantrolene therapy. Moreover, this case exemplifies the rigorous need for supportive therapy and adjunctive pharmacologic therapy for primary and secondary complications resulting from NMS. In conclusion, because of the wide range of risk factors and variations of NMS, a systematic approach to diagnosing and treating NMS is critical to a successful outcome. Discontinuation of antipsychotics, maintenance of supportive therapy aimed at preventing dehydration, hemodynamic, and electrolyte imbalances, and pharmacotherapy are essential in the treatment of NMS.

Management of psychotropic-induced hyperprolactinemia.

The effects of individual psychotropic medications on serum prolactin concentrations are described, and recommendations for dealing with adverse effects are provided. Hyperprolactinemia can result in galactorrhea, amenorrhea, irregular menses, and anovulation; in men, impotence and azoospermia, with or without lactation and gynecomastia, can occur. Antipsychotics may block dopamine receptors in the pituitary prolactin-secreting cells and prevent dopamine-induced reduction of prolactin release. The magnitude of the increase in prolactin concentration correlates with the amount of antipsychotic drug given. The treatment of choice is reduction of the antipsychotic dosage or discontinuation of therapy. If adjustments to the antipsychotic dosage fail to resolve symptoms, the dopamine agonists bromocriptine and amantadine may be tried. Antidepressants may produce elevated serum prolactin concentrations, especially with long-term administration. However, the frequency of antidepressant-induced hyperprolactinemia is much lower than that seen with antipsychotics, and serious adverse clinical effects are uncommon. Other psychotropic drugs such as lithium, valproic acid, buspirone, carbamazepine, and benzodiazepines either are only rarely associated with symptomatic hyperprolactinemia or do not produce clinically important changes in prolactin concentrations. Antipsychotic drugs are the psychotropic agents most likely to cause symptomatic hyperprolactinemia. Bromocriptine or amantadine may provide symptomatic relief if withdrawal or adjustment of the antipsychotic dosage does not eliminate the symptoms.

Profile of a sample of subjects admitted to an acute care psychiatric facility with manic symptoms.

A prospective survey was conducted on 155 consecutive subjects with manic symptoms admitted to an inpatient psychiatric facility to identify possible reasons for rehospitalization. Approximately one third were previously hospitalized at the same facility within the past month. Over half (57%) of the sample were admitted because of aggressive episodes. On admission, 80 percent were receiving carbamazepine or lithium for a mood disorder, and 52.3 percent were receiving multiple medications, of which antipsychotics accounted for over half. Forty-four percent of the sample had comorbid substance use on admission, with marijuana and stimulants accounting for the majority of illicit drug use. Medication noncompliance in 64 percent, and identifiable psychosocial stressors in 55 percent, were also likely contributors to rehospitalization. The data highlights specific treatment issues in the care of patients with a manic component to their illness, and suggests the need for individualized discharge planning with careful followup and continual patient education to assist in the transition from inpatient to society.

Pharmacologic treatment of cocaine abuse.

The recent surge in the use of cocaine has imposed increased financial burdens on society in terms of cocaine-related crimes, and funding for hospitalization/medical treatment and long-term rehabilitation programs. Unfortunately, healthcare costs secondary to chronic cocaine use are likely to increase in the future as drug research into cocaine abuse and effective treatment programs are severely lacking. This article reviews existing literature on treatment of cocaine abuse and is intended to serve as a practical guide to the general clinician involved in drug management of cocaine abuse. Antidepressant agents and the dopamine agonists are emphasized because most of the studies showing benefit have used these agents. Advantages and disadvantages of various interventions are objectively assessed. Additionally, specific implications for both acute and chronic management of cocaine abuse are given along with discussion and recommendations regarding comorbidity.

A placebo-controlled trial of nadolol in the treatment of neuroleptic-induced akathisia.

BACKGROUND: Although propranolol has been documented to be useful in treatment of neuroleptic-induced akathisia, preliminary anecdotal reports on the efficacy of nadolol in treatment of this condition are contradictory. METHOD: To evaluate the efficacy of nadolol in treatment of this condition, a double-blind, placebo-controlled trial was conducted in 20 psychiatric inpatients. Patients with akathisia of at least moderate severity were randomly assigned to receive nadolol 40 to 80 mg/day or placebo. Patients were rated daily for 4 days, then every other day for 15 days by means of the Extrapyramidal Symptom Rating Scale. RESULTS: No significant differences were found between or within groups in subjective restlessness scores. In objective akathisia scores, there were no significant differences between groups; however, beginning at Day 9, both groups showed significant improvement compared with Day 1. There was no difference between groups in number of responders. CONCLUSIONS: The authors' data do not support the efficacy of nadolol in the treatment of neuroleptic-induced akathisia and do not provide support for a peripheral site of action for beta-blockers in treatment of this condition.

Psychiatric applications of bromocriptine therapy.

Bromocriptine, an ergot alkaloid derivative that possesses both dopamine agonist and antagonist activity, has been studied in a broad spectrum of psychiatric illnesses. The literature consists primarily of case reports and small trials limited by methodological shortcomings. The authors critically review these reports, focusing on efficacy, mechanistic issues, dosing, side effects, predictors of response, monitoring parameters, and practical guidelines. Preliminary data suggest bromocriptine may have promise in the treatment of neuroleptic malignant syndrome, cocaine withdrawal, and depression. At present, the agent appears less efficacious in the treatment of tardive dyskinesia, mania, and schizophrenia; however, doses in these trials may have been excessive, producing primarily postsynaptic agonist effects. More extensive clinical trials are required to clearly define the role of bromocriptine in psychiatry.

Characterizing anticholinergic abuse in community mental health.

To identify factors associated with anticholinergic abuse in patients taking antipsychotics and anticholinergics and to document the extent of extrapyramidal side effects in anticholinergic abusers, 21 anticholinergic abusers were matched with 21 controls without a history of anticholinergic abuse for diagnosis and antipsychotic dose. Data were collected prospectively, and extrapyramidal side effects and abnormal involuntary movements were evaluated using the Modified Simpson Angus Scale and the Abnormal Involuntary Movement Scale. The abuse group reported significantly more subjective effects from anticholinergic agents than did those in the control group (mean +/- SD = 10.5 +/- 5.4 vs. 6.5 +/- 3.7, p less than 0.05). The abuse group was significantly more likely to report feeling a buzz (p less than 0.05) and difficulty learning (p less than 0.05) when taking anticholinergic medications. Abusers reported abusing significantly more drugs in the past (2.7 +/- 2.1 vs. 0.8 +/- 0.9, p less than 0.01) and had taken antipsychotics (12.7 +/- 6.3 vs. 8.7 +/- 5.4 years, p less than 0.05) and anticholinergics (10.9 +/- 3.1 vs. 6.1 +/- 4.6 years, p less than 0.01) significantly longer than controls had. Patients in the control group spent significantly more years working full-time than did abusers (6.2 +/- 7.3 vs. 0.7 +/- 1.4, p less than 0.01). There was a nonsignificant trend for abusers with a longer duration of antipsychotic use to have higher Abnormal Involuntary Movement Scale scores (r = 0.40, p less than 0.10). Although these drugs are potentially abusable, the term "anticholinergic abuse" should be reevaluated in light of accumulating evidence that many patients taking these drugs report improved functioning, with improvement in negative symptoms and minimal or no adverse anticholinergic effects.