Ecstasy: dangers and controversies.

Ecstasy is a recreational drug that is increasing in popularity, particularly in young adolescents. Its appeal involves its euphoric effects and a feeling of empathy for others (hence the nickname "hug drug"). This appeal may be furthered by a misleading and anecdotal perception of safety. Cases of adverse effects, toxic reactions, and fatalities are increasingly being reported in the medical literature, as well as in the popular press. Adverse effects include hyperthermia, seizures, cardiac abnormalities, and hyponatremia. Long-term Ecstasy use may result in serotonin terminal degeneration and depletion, which may result in psychiatric and cognitive sequelae. Controversy surrounds the legalization of Ecstasy for medicinal purposes.

Prediction of valproate serum concentrations in adult psychiatric patients using Bayesian model estimations with NPEM2 population pharmacokinetic parameters.

Valproate serum concentrations between 45 and 125 microg/mL are associated with the drug's efficacy in acute mania. Adaptive control dosing of valproate has not been fully studied in psychiatry. The objective of this study was to derive population pharmacokinetic (PK) parameters for valproate in healthy volunteers and to test the ability of these PK parameters to estimate concentrations in adult psychiatric patients using a Bayesian program. Population PK parameters for oral valproate were estimated from 18 PK studies in six healthy volunteers (1) using NPEM2. A Bayesian PK program using these population parameters was used to predict valproate concentration-time points in a second cohort of 21 adult psychiatry patients using 0, 1, or 2 prior concentrations. Estimated population parameters (mean +/- SD) were: Ka, 1.15+/-1.75/h; V, 0.14+/-0.042 L/Kg; and CL, 0.902+/-0.133 L/h. Bayesian valproate estimations using these parameters were negatively biased (underestimations) using zero prior concentration and unbiased using 1 or 2 prior concentrations. Mean error values (95% CI) in microg/mL for predictions using 0, 1, or 2 prior concentration-time points were -12.0 (-22.5, -1.5), -9.5 (-19.1, 0.1), and -2.5 (-11.1, 6.1), respectively, and mean absolute error values in microg/mL (95% CI) were 19.8 (12.6, 27.1), 16.3 (9.4, 23.3), and 10.1 (4.9, 15.2), respectively. Population parameters derived from healthy adult volunteers provided biased predictions of valproate concentrations in adult psychiatric patients. However, estimates using 1 or 2 valproate concentration time points predicted future concentrations that were precise and unbiased, given the wide therapeutic target range.

Does the addition of pindolol accelerate or enhance the response to selective serotonin reuptake inhibitor antidepressants?

Although in the last few years new antidepressants have become available in the United States, responses in many patients differ, from none, to partial, to delayed therapeutic response to the agents. If the antidepressant properties of these drugs could be enhanced or accelerated, it might be possible to improve patient functioning and quality of life. Pindolol, a serotonin 1A autoreceptor antagonist, accelerates and augments the therapeutic effects of antidepressants, especially selective serotonin reuptake inhibitors.

Mirtazapine, an antidepressant.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of mirtazapine are reviewed. Mirtazapine is a new anti-depressant that blocks presynaptic alpha 2-adrenergic receptors and postsynaptic serotonin type 2 and type 3 receptors. Mirtazapine has FDA-approved labeling for treatment of depression. Limited data suggest it may also have beneficial anxiolytic and sedative effects. The drug is rapidly and completely absorbed after oral administration. It is biotransformed by hepatic demethylation and is suitable for once-daily doses. In several clinical trials, patients receiving mirtazapine showed significantly greater improvement as measured by scores on the Hamilton Rating Scale for Depression (HAM-D) compared with patients receiving placebo. Mirtazapine has been shown to be equally efficacious as amitriptyline, clomipramine, and doxepin as assessed by scores on the HAM-D or other depression rating scales. Mirtazapine is well tolerated. The most commonly reported adverse effects associated with mirtazapine are somnolence, increased appetite, weight gain, and dizziness. Few drug-drug interactions have been reported. The recommended starting dosage is 15 mg/day administered in a single dose at bedtime. Mirtazapine seems to be an effective, well-tolerated antidepressant and may be effective for treating comorbid anxiety disorders.