Traditional guidelines call for treatment of major depression with a sequence of single antidepressants. Augmentation with a second agent generally only occurs when the first agent is well tolerated and when it also provides at least some symptomatic improvement on its own. Since this standard approach leads to low rates of attaining and sustaining remission by the first agent, with diminishing returns for each subsequent agent, there is growing dissatisfaction with this approach to the treatment of major depression. One new trend is to attempt to enhance the rates of sustained remission from a major depressive episode by combining two therapeutic agents from the very initiation of treatment of a major depressive episode.

Traditional treatment of major depression begins with a single “first line” antidepressant, and if it does not work or is not tolerated, trying another and then another. Unfortunately, this strategy results in disappointing remission rates for the first antidepressant (Figure 1), and disappointing rates of maintaining any improvement that is attained by this first agent because of high relapse rates over the next year despite continuing treatment with the first antidepressant (Figure 2A). And that is the good news. The bad news is that with each subsequent antidepressant treatment administered remission rates are progressively reduced (Figure 1). For those patients who do improve, they are progressively less likely to sustain their therapeutic gains despite continuing to take the drug that led to their initial improvement (Figure 2).

Individuals suffering from drug addiction may also manifest features of bipolar spectrum disorders. Hyperthymic and cyclothymic temperaments may render individuals vulnerable to later development of substance abuse. Bipolar disorders themselves may be altered or precipitated by substance use, most notably by stimulants (amphetamines), alcohol, and cannabinoids.The clinical usefulness of mood stabilizers, particularly antiepileptics, has been established as safe and effective in substance abusers with and without comorbid mood disorders. Most studies on this issue have been of short duration and focused on the resolution of a currently manifest period of illness. Few studies have been conducted on the usefulness of these drugs on the long-term longitudinal course of these diseases, such as frequently encountered recurrent relapses into states of agitation, impulsivity, and/or dissatisfaction. As opposed to the clinical experience with traditional antidepressants and neuroleptics, antiepileptics do not induce counter-polar states (depressed patients abruptly turning manic or hypomanic; nor patients currently hypomanic or manic turning abruptly depressed). Many clinicians consider antiepileptic mood stabilizers to be the preferred category of medications for the treatment of such patients. Valproate appears to be a potentially fruitful medication to study in these dual diagnosis patients due to preliminary evidence demonstrating its anticraving efficacy.

The issues surrounding generic drug substitution in patients with epilepsy are complex.The substitution of one formulation of an antiepileptic drug (AED) for another is controversial. Well-reasoned and defensible cases can be made both for and against such substitution. Although regulatory agencies require that generic and proprietary drugs have similar pharmacokinetic bioequivalence data, their therapeutic efficacy may not necessarily be identical. The paroxysmal nature of epilepsy, the narrow therapeutic index of some AEDs, the need to. individualize therapy to achieve seizure control, and the negative consequences of uncontrolled epilepsy distinguishes epilepsy from other clinical conditions. Epilepsy management with AEDs requires careful dose titration and consistent drug exposure at the optimal level for each patient, which can be altered if a different formulation of the AED is substituted. Unexpected variability in plasma concentrations could occur when a patient who has been receiving one formulation of an AED (generic or brand) receives an alternate formulation.Thus, no substitutions should be made for people with epilepsy without the knowledge and approval of the prescribing physician. Patients should be consulted about the substitution, with all risks and benefits carefully explained.

Background: Continuous performance tasks (CPTs) embedded in a virtual reality (VR) classroom environment have been shown to be a sensitive and user-friendly assessment tool to detect cognitive deficits related to attention-deficit/hyperactivity disorder (ADHD). The aim of the current study was to compare the performance of children with ADHD on a VR-CPT while on and off treatment with methylphenidate (MPH) and to compare the VR-CPT to a cgrrently used CPT, Test of Variables of Attention (TOVA).

Methods:Twenty-seven children with ADHD underwent the VR-CPT, the same CPT without VR (no VR-CPT), and theTOVA, 1 hour after the. ingestion of either placebo or 0.3 mg/kg MPH, in a double-blind, placebo-controlled, crossover design. Immediately following CPT, subjects described their subjective experiences on the Short Feedback Questionnaire.

Results: MPH reduced omission errors to a greater extent on the VR-CPT compared to the no VR-CPT and the TOVA, and decreased other CPT measures on all types of CPT to a similar degree. Children rated the VR-CPT as more enjoyable compared to the other types of CPT.

Conclusions: It is concluded that the VR-CPT is a sensitive and user-friendly assessment tool in measuring the response to MPH in children with ADHD.