Chlorpromazine plasma levels, adverse effects, and tobacco smoking: case report.

Marked worsening of adverse effects and increased chlorpromazine plasma levels were observed in a 25-year-old schizophrenic outpatient who abruptly stopped smoking cigarettes. Presence and severity of adverse effects and chlorpromazine plasma levels correlated directly with tobacco smoking over a 16-month period.

Factors predicting the use of multiple psychotropic medications.

BACKGROUND: Recent studies have questioned the appropriateness of some types of psychotropic medication prescribing, especially by general practitioners. The purpose of this study is to investigate factors that predict prescribing of multiple psychotropic medications, a class that may represent more complicated cases. METHOD: This study analyzed data from the 1989 National Ambulatory Medical Care Survey (NAMCS). Multiple logistic regression methods were used to determine variables that predicted the provision or ordering of multiple psychotropic medications during a single office visit. RESULTS: Patients who visited psychiatrists were six times more likely to receive psychotropics in combination than patients visiting general practitioners. Patients diagnosed as manic were four times more likely to receive multiple psychotropics, and those diagnosed as schizophrenic were three times more likely Patients visiting physicians in the Northeast and South were significantly less likely to receive psychotropics in combination than patients in the Midwest. CONCLUSION: Although general practice physicians contribute to the use of multiple psychotropic medications, patients visiting psychiatric specialists are much more likely to be provided combination therapy.

Use patterns for antipsychotic medications in medicaid patients with schizophrenia.

OBJECTIVE: We investigated the use patterns for antipsychotic medications generated by Medicaid patients with schizophrenia. METHOD: Paid claims data from the California Medicaid program (Medi-Cal) were used to identify 2655 patients with schizophrenia. Data from 1987-1996 were used, during which time Medi-Cal maintained prior authorization restrictions on second generation antipsychotic drugs. Prescription records were used to identify 3 patterns of antipsychotic drug use: no drug therapy for over 1 year; delayed onset of antipsychotic drug therapy; and switches in antipsychotic drugs within 1 year. Multiple logistic regression models were used to identify factors affecting these antipsychotic drug use patterns. RESULTS: Conventional antipsychotic medications account for over 98% of all patient treatment episodes. Over 24% of patients with schizophrenia do not use any antipsychotic medication for periods lasting up to 1 year. Over 24% of treated patients delayed the use of antipsychotic medications at least 30 days. For those patients who did not delay their use of antipsychotic medications, over 47% switched or augmented their initial antipsychotic medication during the first treatment year. Only 11.6% of treated patients achieved 1 year of uninterrupted antipsychotic drug therapy. The mean duration of uninterrupted therapy was 142 days. DISCUSSION: Antipsychotic drug use patterns suggest that conventional antipsychotic medications do not meet the therapeutic needs of patients with schizophrenia.

Accuracy and safety of a priori lithium loading.

A 30 mg/kg loading dose of slow-release lithium carbonate (Lithobid) was given in three divided doses to 38 patients to evaluate the accuracy and safety of achieving a therapeutic level in 12 hours. No patient experienced any adverse effects during the loading procedure or in the 12 hours after loading was completed. Prediction error (actual minus predicted level) for males was -0.11 mEq/L +/- 0.03 (SEM) with a mean absolute error of 0.16 mEq/L +/- 0.09 (SEM). Prediction error for females was -0.04 mEq/L +/- 0.07 (SEM) with a mean absolute error of 0.28 mEq/L +/- 0.14 (SEM). Lithium loading is safe and slightly overestimates the level actually achieved, except in obese females.

The cost of antidepressant drug therapy failure: a study of antidepressant use patterns in a Medicaid population.

Paid claims data from the California Medicaid (Medi-Cal) program were used to examine the utilization of antidepressants and to estimate the costs of antidepressant treatment failure for patients with major depressive disorders (MDD). Data for 6713 new patient episodes of antidepressant therapy were available for the analysis; over 45% of these patients never achieved a minimum daily dose of antidepressants indicative of treatment for depression and were excluded from further analysis. That left a possible depression patient population of 3664 patients of which 2344 patients had a minimum of 1 full year of post-episode data for analysis. Only 81 patients (3.5%) displayed antidepressant use patterns consistent with the successful treatment of MDD; 296 patients (12.6%) displayed use patterns suggestive of antidepressant treatment failure. The remaining 1967 (84%) patients could not be clearly classified; they were either (1) patients being treated for problems other than MDD, (2) MDD patients who were being prescribed subtherapeutic doses by their physician due to side effects or other reasons, (3) MDD patients who were noncompliant for a variety of reasons, or (4) MDD patients who had prematurely terminated antidepressant therapy. Multivariate regression analysis was used to estimate the costs associated with MDD treatment failure. These analyses indicated that MDD treatment failure resulted in increased costs of approximately $1043 in the first post-episode year (p less than .10). These increased costs were primarily due to higher hospital costs ($921, p less than .05), while drug costs were reduced by $222 (p less than .001).

Benzodiazepines in schizophrenia.

Benzodiazepines have a checkered history in the United States; public and professional attitudes about them have ranged from their being wonder drugs in the 1970s to being virtually purged from many formularies as addictive and dangerous in the 1980s. The attitude today is that they are useful for specific indications. In the last 20 years they have been investigated as adjunctive agents to conventional antipsychotic drugs in the treatment of schizophrenia. Benzodiazepines may be effective in schizophrenia because stress is one mediator of relapse in these patients. In addition, inhibition of dopamine neurotransmission through gamma-aminobutyric acid-enhancing activity may provide a direct antipsychotic effect. As monotherapy or adjuncts to antipsychotic agents, benzodiazepines produced antipsychotic effects in schizophrenia in approximately 50% of controlled trials. Although there is no particular benzodiazepine of choice, low-potency compounds with long elimination half-lives are recommended. Adverse effects of concern include sedation and cognitive impairment, behavioral disinhibition, exacerbation of psychotic symptoms, and the potential for dependence, withdrawal, and abuse. The recent arrival of atypical antipsychotic drugs has significantly slowed research and interest in benzodiazepines in schizophrenia beyond their initial beneficial sedative effects for acute psychotic episodes.

How to counsel patients about depression and its treatment.

To provide effective counseling for patients receiving drug therapy for depression, one must understand the natural course of mood disorders, the appropriate dose and duration of antidepressant therapy, and how to individualize the discussion of potential adverse effects and use of alcohol. Patients must understand that effective antidepressant treatment requires several weeks before onset of clinical effect, and 6-12 months of therapy is necessary to prevent relapse. Discussion of adverse effects must address what the patient should do if an adverse effect occurs, with the focus on common, expectable effects of the particular drug. Rather than merely telling patients not to drink alcohol, appropriate counseling should focus on the possible consequences of drinking while taking antidepressant drugs.

Management of and counseling for psychotropic drug-induced sexual dysfunction.

Clinicians are increasingly faced with the need to identify, treat, and counsel patients regarding psychotropic drug-induced sexual dysfunction. Antipsychotic and antidepressant drugs have both rational mechanisms to explain their effects on sexual function and established literature documenting these effects. The agents have potential for causing decreased libido, delayed ejaculation, and anorgasmia. Management and counseling can be highly effective for patients taking these agents.

Reemergence of positive symptoms after initial response to risperidone.

Risperidone was effective in successfully treating a patient's negative symptoms of schizophrenia as well as reducing adverse effects from typical antipsychotic drugs. Auditory hallucinations reemerged after 8 months, however, and again after 24 months of risperidone therapy. Reemergence of psychotic symptoms after initial response might be explained by inadequate dosage, by the natural course of the patient's schizophrenia independent of drug therapy, or by the possibility that, for this patient, risperidone was less effective than chlorpromazine for the positive symptom of auditory hallucinations.

Antidepressants and the risk of seizures.

As new antidepressants have been marketed, the issue of drug-induced seizures has assumed new relevance. The risk of such seizures depends on at least three critical factors. Of most importance are an individual's predisposing factors that may increase the risk, followed by the amount and rate of dosage titration, and the relative epileptogenic potential of the particular drug.

Antidepressants in chronic pain: a review of efficacy.

Antidepressant drugs have gained widespread clinical usage alone or as adjuncts in the treatment of chronic pain disorders. Of 17 controlled studies of antidepressants in chronic pain, 13 demonstrated significant pain relief with antidepressants compared to placebo. These studies were too different from one another to allow any general conclusions concerning efficacy, however. Five studies of either migraine or chronic tension headache all demonstrated superior efficacy of antidepressants versus placebo, while those of back and arthritic pain yielded mixed results. Of 3 studies of pain of several etiologies, 2 failed to demonstrate efficacy of antidepressants over placebo. These studies do not provide answers to many clinical questions on the use of antidepressants for chronic pain, such as drug of choice or appropriate dosage. Rather, they suggest that these agents may be beneficial in some patients with chronic pain.

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 alpha 2-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.

Antipsychotic drug use patterns and the cost of treating schizophrenia.

This study investigated the relationships between antipsychotic drug use patterns and direct costs for 3,321 Medi-Cal patients with schizophrenia. Ordinary least-squares regression models were used to estimate the impact on costs of receiving antipsychotic drug treatment, delays in treatment, changes in therapy, and continuous therapy. Average costs were $25,940 per year per patient. Having used an antipsychotic drug was correlated with lower psychiatric hospital costs ($2,846 less) but higher nursing home costs. Completing one year of uninterrupted drug therapy was correlated with higher nursing home costs. Delayed drug treatment and changes in therapy increased the cost by $9,418 and $9,719, respectively.

Pharmacists as drug prescribers: validation of certification exams and evaluation instruments.

The purpose of this article is to discuss the validity and reliability of certification tests and evaluation instruments for pharmacists as drug prescribers. Under California Law AB 717, the University of Southern California is operating one of two pilot programs to train and evaluate prescribing pharmacists. Various instruments have been created and administered, and validity results are presented. The presentation is organized into two areas dealing with the development of the examination instrument and then the assessment of the prescriptions written by pharmacists. The reliability of the three sections of the certification examination as measured by internal consistency was as follows: clinical therapeutics (KR 20=.84), physical assessment (KR 20=.88), and law (KR 20=.84). The exam was given to a group of physicians (N=14) to establish a cutting score. Thirty pharmacists who took the exam did slightly better than the physicians on clinical therapeutics, but the physicians performed better than pharmacists on physical assessment (p less than .01). A prescription evaluation form was constructed to evaluate the performance of the pharmacists as prescribers. The reliability of the form as measured by coefficient alpha was .84. Concurrent validity was explored by assessing the relationship between performance on the certification exam and judges' appropriateness scored on prescriptions for ambulatory hypertensive patients. These results indicate that the pharmacists, who passed the exam, can prescribe as appropriately as physicians.

Clinical pharmacy services in mental health facilities.

The needs for clinical pharmacy services in mental health facilities have been identified, and a general, applicable role model description, which already is in practice across the country, has been given. Examples of implementation methods for institutions and for ambulatory care facilities have been described. Many pharmacists, particularly more recent graduates, already possess the skills necessary to provide clinical services in mental health facilities. These developments signal an end to the developmental phase of clinical mental health pharmacy practice and a beginning to the implementation phase of clinical mental health pharmacy practice.

Tardive dyskinesia with low-dose, short-term neuroleptic therapy.

The development, treatment, and outcome of a case of tardive dyskinesia following short-term, low-dose neuroleptic therapy is described. Thirty weeks of treatment with haloperidol, in doses never exceeding 10 mg daily, produced tardive dyskinesia symptomatology. Upon discontinuing haloperidol, the symptoms decreased significantly in severity within the first four weeks and disappeared completely within 12.5 weeks. This case is compared with the classical description of tardive dyskinesia symptomatology, etiology, response to treatment and degree of reversibility. Atypical features are explained and clinical implications of the case are offered.

Political and legal aspects of pharmacist prescribing.

The appropriateness of pharmacist prescribing is examined, and limits that should be incorporated into legislation are discussed. Arguments that support pharmacist prescribing are that (1) in current practice, pharmacist consultation has evolved into prescribing; (2) there is a need for pharmacists to prescribe; (3) nurse practitioners and physicians' assistants, whose training in clinical pharmacology is conducted by pharmacists, have authority to prescribe in many states; (4) as the need for dispensing functions decreases, new functions must be assumed; and (5) pharmacist prescribing in pilot studies has been safe, effective, and either equal or superior to physician prescribing. Negative aspects of pharmacist prescribing include (1) not all pharmacists are competent to prescribe, (2) pharmacists are not trained in diagnosis, (3) physicians oppose it, (4) it could increase patient-care costs, and (5) pharmacists' access to patient information is not adequate for competent prescribing. Based on these arguments, legislation regulating pharmacist prescribing should contain certain limits: (1) certification to prescribe should be based on demonstrated competence, (2) pharmacists who prescribe must have access to medical records, (3) pharmacists must prescribe within established working relationships with physicians, and (4) pharmacist prescribing should be limited to long-term therapy for chronic disease and therapy for acute self-limiting illnesses that are not diagnostically complex. These limitations have been incorporated into California law. A bill is pending that allows pharmacists, within specified guidelines, to initiate drug treatment.