Jonathan R. Stevens

Neuropsychiatric Effects of Prescription Drug Abuse

Prescription drugs have become a major category of abused substances, and there is evidence that the prevalence of prescription drug abuse may soon overtake that of illicit drugs. Study of prescription drugs has been hampered by vague terminology, since prescription drugs are only separated from other drugs of abuse by social and legal constructs. Reviewed herein is published literature on the abuse of four major categories of abused prescription drugs: sedative-hypnotics, stimulants, anabolic steroids, and anticholinergics. The review emphasizes evidence regarding the effects of these drugs on neural systems. Other abused prescription drugs that fall outside of the major categories are also briefly addressed.

Insulin Overdose Among Patients With Diabetes: A Readily Available Means of Suicide

Have you ever worried that one of your depressed patients might use the insulin that you prescribed to commit suicide? The following case vignette and discussion explore the complex relationship between diabetes and depression, outline important risk factors for suicide, and describe the frequency and lethality of suicide attempts by insulin overdose. In addition, we offer a 5-step approach for the management of depressed patients who are prescribed insulin.

Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

BACKGROUND Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. OBJECTIVE We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. METHODS Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. RESULTS Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. CONCLUSIONS High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

Strategies for the Prescription of Psychotropic Drugs with Black Box Warnings

BACKGROUND The Black Box Warning (BBW) is the Food and Drug Administrations highest level of drug warning. It signifies that a medication has serious (or potentially life-threatening) side effects and is prominently displayed on a medications package insert. It literally consists of the medication warning and is surrounded by a bold black border. OBJECTIVE This article aims to review data related to BBWs on psychotropic medications currently used in clinical practice, with special attention to clinical situations and questions relevant to consultation-liaison psychiatrists. RESULTS We review 3 clinical advisories or BBWs for psychotropic medications (i.e., antidepressant medication and suicidality in the pediatric population, stimulant medication and sudden death in the pediatric population, and antipsychotic medication and increased mortality in the elderly) and discuss the effect they have had on prescribing practices. We provide a table of current BBWs relevant to psychotropic medications. CONCLUSIONS BBWs can have unintended and far-reaching consequences, albeit with a limited ability to target specific populations and practice patterns. Although it is critical for clinicians to be aware of these serious potential side effects and to inform patients about these warnings, medications with boxed warnings remain Food and Drug Administration-approved and may have critically important therapeutic roles.

The Use of Transdermal Therapeutic Systems in Psychiatric Care: A Primer on Patches

BACKGROUND Numerous currently available medications that act in the central nervous system can be delivered transdermally. Such medications include cholinesterase inhibitors for dementia, methylphenidate (MPH) for attention-deficit hyperactivity disorder, monoamine oxidase inhibitors (MAOIs) for depression, dopamine agonists for Parkinson disease and restless leg syndrome, and clonidine for attention-deficit hyperactivity disorder and impulse-control disorders. OBJECTIVE This article aims to review the literature related to transdermal delivery systems from the perspective of clinical practice and research related to their use in the treatment of psychiatric conditions. RESULTS Most of the currently available transdermal systems have psychotropic properties or utility in the behavioral health arena and, therefore, are of clinical relevance to consultation-liaison psychiatrists or practitioners of psychosomatic medicine. We discuss their efficacy and safety profiles. We provide a table of these agents and their uses. CONCLUSIONS Transdermal delivery (i.e., patches) for medicines with psychotropic properties allows mental health providers to customize therapy for patients by altering the duration of therapy, minimizing first-pass metabolism and the potential for drug-drug interactions, and decreasing the risk for gastrointestinal irritation.

Elevated Clozapine Serum Level After Treatment With Amiodarone

Cardiovascular conditions, including arrhythmias, occur in many patients with psychotic disorders, just as they do in patients without psychiatric disturbances. Therefore, awareness of potential drug–drug interactions between psychotropics (e.g., atypical antipsychotics) and cardiac medications (e.g., antiarrhythmics) is crucial for practitioners of medicine and psychiatry. Although elevated serum clozapine levels and clozapine toxicity have been reported as unintended consequences of the coadministration of clozapine with a variety of drugs (e.g., fluvoxamine, cimetidine, and modafinil), 1,2 it has not yet been associated with coadministration of amiodarone (Cordarone). Amiodarone, a Class III antiarrhythmic agent, widely used in intensive care units for the treatment of life-threatening ventricular arrhythmias (its FDA-approved use), 3 is also increasingly used to treat common tachyarrhythmias (e.g., atrial fibrillation, atrial flutter, and supraventricular tachycardias [its off-label uses]). 4 Given that amiodarone and its metabolites are potent inhibitors of the hepatic metabolism of many drugs, potentially harmful drug–drug interactions may result from their coadministration with other agents. 5 We describe the development of an elevated serum clozapine concentration in an elderly man who received amiodarone to manage ventricular tachycardia (VT) and discuss potential mechanisms of this interaction.