Data from a variety of studies, including the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, have shown that fewer patients achieve remission from symptoms of major depressive disorder (MDD) and other depressive disorders after taking the first-prescribed antidepressant treatment than was expected. The goal of treatment is true remission: the complete absence of symptoms. Achieveing less than true remission is associated with MDD recurrence and continued impairment.

Prevention of mania and maintenance treatment in bipolar disorder is largely routed in the decision to use monotherapy or combination therapy in the treatment regimen. The ability to weigh efficacy against adverse effects is of particular importance in maintenance of this disorder, as most bipolar patients require lifelong use of medication. This discussion will focus on the above mentioned topics, using a case presentation as an example.

Bipolar disorder is an illness characterized by inherent mood instability that produces a predisposition to depressive, hypomanic, or manic episodes. This predisposition to affective episodes, rather than the episodes themselves (which can have many causes), is arguably the hallmark of bipolar disorder.

Most episodes of bipolar disorder, including the first episode, are depressive. This exposes an inherent flaw in our nosological system, which requires a manic or hypomanic episode for diagnosis of bipolar disorder. Treatment of a depressive episode in undiagnosed bipolar disorder can entail the use of medications that were developed to treat a different disorder (major depressive illness) and that may have mood-destabilizing or activating properties.

The recent shootings at Ft. Hood, allegedly by an army psychiatrist, have placed much needed focus on army mental health care. Questions are now being raised as to whether longstanding and severe shortages in the number of mental health professionals in the army may have led authorities to overlook danger signals in this psychiatrist, failing to remove him in order to retain a worker with rare and valuable psychiatric credentials for army service. Whether or not this is the case, examination of mental health care in the army shows a system that is indeed understaffed, under tremendous pressure, and near the breaking point.

In examining the challenges in treating comorbid attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD), there are a number of issues regarding misinformation and misconception that exist for clinicians. Like other ADHD comorbidities, there is a lack of screening, particularly among adult clinical populations who have the psychiatric comorbidity or, for patients with SUDs, there is the issue of prioritization, which condition to treat first, and determining the place of medication management—particularly stimulant medication—paramount in treatment planning.

The National Comorbidity Survey Replication by Kessler and colleagues found that of adult patients with major depressive disorder (MDD), 9.4% met Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised criteria for attention-deficit/hyperactivity disorder (ADHD). Among those with dysthymia, 22.6% also met criteria for ADHD. In addition, it is estimated that approximately a third of the United States population experiences MDD symptoms at any point in time. Kessler and colleagues also conducted a retrospective study on impairment of adults with ADHD and found that ADHD has a prevalence of ∼4.4% in the US adult population, which suggests that ∼9 million US adults may have ADHD.

This article summarizes results of all pharmacotherapy trials for obsessive-compulsive disorder (OCD) published from 2006 to 2008 as well as studies on markers for predicting response to treatment and neurobiological changes induced by pharmacotherapy. Results show that recent developments in the treatment of OCD have been modest and primarily involve evidence for the efficacy of escitalopram and other selective serotonin reuptake inhibitors (SSRIs); augmentation with antipsychotics in treatment-refractory patients and combination treatment with D-cycloserine and cognitive-behavioral therapy has also been effective. The efficacy of serotonin-norepinephrine reuptake inhibitors remains inconclusive. Studies on markers of clinical response have shown inconsistent results, however, duration and severity of OCD and the presence of comorbidities can often identify patients at risk for nonresponse. Lastly, successful treatment with an SSRI results in both serotonergic and dopaminergic changes, but more research is necessary in order to define the biological characteristics of responders and nonresponders.

Bipolar disorder is clinically characterized by fluctuating affect, and neuropsychologically by impairment in executive functions. Such phenomena are consistent with the centrality of emotional dysregulation and impulsivity to bipolar disorder. They are also consistent with a key role for prefrontal-subcortical (striatal-thalamic) and associated limbic circuitry in its mediation. Furthermore, there is growing data on the cellular mechanisms contributing to neuronal vulnerability in this mediating circuitry.

Most antidepressants and other psychotropics in clinical use are available as generic formulations (Table). The availability of lower-priced, generic drugs can benefit patients and third-party payers, but it should not be assumed that all generic drugs are equally beneficial. There are numerous reports in the literature of unexpected and untoward consequences that occur when a generic drug is substituted for the original brand-name drug. A previously stable clinical response may suddenly deteriorate, or the patient may experience new or more severe adverse events (AEs). The United States Food and Drug Administration requires that manufacturers of generic drugs demonstrate that their formulation has pharmacokinetic properties similar (or bioequivalent) to the brand-name drug. Bioequivalency studies are conducted in healthy volunteers, not in patients who would be treated with that drug. Moreover, bioequivalency studies are conducted on a current lot of the branded drug and do not account for variability between lots of the generic formulation. The manufacturer is only required to submit bioequivalency data that support the Abbreviated New Drug Application (ANDA); the FDA does not require disclosure of failed bioequivalence studies. Unlike brand-name drugs, lengthy and costly clinical studies are not required to show that the generic drug is effective and safe.

Although the FDA has taken the position that bioequivalence and therapeutic equivalence are equal, many questions related to the use of generic drugs remain unanswered. The following question-and-answer session is an excerpt of an interview with Pierre Blier, MD, PhD, conducted by Diane Sloan, PharmD, which addresses the issue of generic substitution of psychotropic drugs.

Treatment with the newer generation antidepressants is considered generally effective for most patients with major depressive disorder when taken in accordance with treatment guidelines. However, multiple clinical studies have demonstrated that rates of patient adherence to antidepressants are inadequate, specifically with regard to long-term maintenance treatment. Tolerability issues associated with antidepressants can increase the risk for patient nonadherence and result in subsequent relapse of depressive symptoms. Comorbid symptoms of anxiety also influence psychiatrists' choice of antidepressants for patients with depression. Physicians can improve long-term patient outcomes for patients with major depressive disorder by considering the possibility of drug-drug interactions before prescribing a specific antidepressant.

Medical presentations can be designed as a data dump or as a story. One effective communication strategy is to organize a lecture as a three act play, starting with previews as the first act and ending with reviews as the third act. Previews facilitate learner achievement and may help learners view a medical instructor more positively. Reviews also help consolidate audience learning and ensure that messages have been clearly delivered and received. The main act is in the middle and is the content itself. Delivering this content in small multiples gives learners manageable packets of information and can help them to see the differences and similarities between conditions, deepening their understanding of what was presented.

Applying principles of adult learning can enhance the effectiveness of a medical presentation. A previous “Trends in Psychopharmacology” presented an overview of these principles and discussed targeting the learner rather than the content or the lecturer as the focus for a medical presentation. Here we cover the concept of presenting content to a learner as a story and show how to organize or “storyboard” it as a three act play.

Lectures can be arranged as a dull recitation of facts or as a story that makes the facts come alive. Generally speaking, a participant is less interested in hearing the facts that a lecturer has to present than in listening to a story the lecturer has to tell. Organizing content into a “three act play” can make a lecture memorable and its lessons practical. Classically, teachers have explained the three parts as: “Say what you are gonna say; say it; then say what you said.” More specifically, the previews are the first part, the presentation itself is the second part, and the reviews are the third part of this structure.

When patients do not respond to an initial course of antidepressant treatment, clinicians may opt for a number of alternatives. First, re-evaluating the diagnosis to make sure that no comorbidities were missed, and that the diagnosis of major depressive disorder (MDD) is accurate, particularly with respect to recognition of clinical features that might suggest previously unrecognized bipolarity or psychotic features. Secondly, clinicians should ensure that the patient has adhered to the recommended medication. When finally reaching the point of certainty or near certainty that the patient has not benefited from a truly adequate course of treatment lasting ≥8 weeks, the next major considerations usually are to either switch antidepressants or to augment the original choice of treatments. Lastly, selection of the most appropriate “next choice” strategy should take into account the tolerability of and degree of improvement observed with the initial antidepressant medications. Many clinicians prefer to switch patients who have poorer tolerability and minimal symptom improvement and try to augment therapy when the initial antidepressant has been well tolerated and resulted in some degree of symptom improvement.

The presentation of fibromyalgia syndrome (FM) is heterogeneous. Hence, the goal of treatment is to develop an individualized approach that takes into account the severity of the patient's pain, the presence and severity of other symptoms and comorbidities or stressors, and the degree of functional impairment. This includes the identification and treatment of all pain sources that might be present in addition to FM, such as peripheral pain generators (eg, comorbid osteoarthritis or neuropathic pain) or visceral pain disorders (eg, comorbid irritable bowel syndrome). It is also important to address other symptoms or disorders that commonly occur in patients with FM, such as fatigue, sleep disturbances, and comorbid sleep disorders (eg, sleep apnea). Cognitive impairment, stiffness, mood disorders, and anxiety disorders are also commonly reported in patients with FM. Finally, the treatment should strive to improve the patient's function and global health status. In most cases, the management involves both pharmacologic and nonpharmacologic treatments (Slide 1).

Multifunctional drugs are those with more than one therapeutic mechanism. Trazodone is a multifunctional drug with dose-dependent pharmacologic actions. That is, it has hypnotic actions at low doses due to blockade of 5-HT2A receptors, as well as H1 histamine receptors and α1 adrenergic receptors. Higher doses recruit the blockade of the serotonin transporter (SERT) and turn trazodone into an antidepressant. Although trazodone has traditionally been used as a low dose hypnotic, a new controlled release formulation that has the potential to improve the tolerability of high doses may provide an opportunity to revisit this multifunctional drug as an antidepressant as well.