Bipolar disorder, particularly bipolar type I disorder, is at least as highly comorbid with other psychiatric and behavioral disorders as any Axis I medical disorder (Slide 1). Two iterations of the National Comorbidity Survey study, which is epidemio-logic-based and not anecdotal evidence from clinical offices and hospital emergency rooms, have shown that these data are reflective of the overall population in the United States and potentially for all other countries across the world.

In particular, if the prevalence rates of all anxiety disorders are grouped together, they are almost as prevalent as bipolar disorder itself, and clinicians rarely see a patient with bipolar disorder who does not have an anxiety disorder. This finding raises the question that anxiety may not be a separate entity, but an additional fundamental component of bipolar symptomatology, at least for a substantial number of patients. Regardless, the role of anxiety in bipolar disorder is unique. Perugi and colleagues studied the time sequence of different anxiety disorders in relation to first presence and clinical recognition of bipolar disorder (Slide 2). In contrast to panic disorder/agoraphobia and obsessive-compulsive disorder (OCD), social anxiety or social phobia was shown to be prevalent in 94.7% of patients prior to onset of hypomania and the clinically recognizable problematic school and home situations before the diagnosis of the bipolar disorder. This finding suggests that there may be some fundamental aspect of social anxiety and other anxiety disorders that is a ties. These patients tend to be more unstable symptomatically and have multiple comorbidities.

A 27-year-old woman presented to the emergency room after having witnessed generalized tonic clonic seizure while asleep. Birth and development were normal. She had suffered a single febrile seizure at 13 months of age, but had no other seizure risk factors. She was otherwise well except for a history of depression for which she was taking sertraline. Depressive symptoms had been well controlled over the past 3 months, but she had been under increased stress working to finish a doctoral thesis. Neurological examination was normal. Magnetic resonance imaging (MRI) showed modest asymmetry of the hippocampi, slightly smaller on the right, but no abnormal signal and well-preserved laminar anatomy. An electroencephalogram was negative. She was discharged from the emergency room with no treatment. Three weeks later, the patient's boyfriend witnessed an episode of behavioral arrest with lip smacking and swallowing automatisms lasting 45 seconds, after which the patient was confused for 20–30 minutes. The next morning she and her boyfriend kept a previously scheduled appointment with a neurologist.

Pharmacologic knowledge can inform clinical decision-making, particularly the dosing and switching decisions made with antipsychotics. Of relevance are the pharmacokinetic (what does the body do to the drug) and the pharmacodynamic (what does the drug do to the body) properties of antipsychotics.

The goal of antipsychotic dosing is to achieve sufficient dopa-mine blockade in areas where dopamine excess can lead to psychosis, mania, or aggression. Using positron emission topography, one investigation showed that response rates were considerably higher in patients who achieved >65% striatal dopamine blockade. Conversely, striatal dopamine blockade >80% predicted the emergence of extrapyramidal symptoms (EPS) or akathisia.

There is, however, considerable intra-individual variability in achieving the desired 60% to 80% striatal dopamine blockade. Such variability is likely due to inter-individual differences in the absorption, distribution, metabolism and elimination of medications. At the same time, antipsychotics themselves differ in their general pharmacokinetic profiles. For example, ziprasidone absorption is ~50% less when ingested on an empty stomach than when taken with a meal; the degree of absorption depends on the caloric content, while the fat content is not relevant.

For most patients with major depressive disorder (MDD) the first-line treatment is one of the selective serotonin reuptake inhibitors (SSRIs). However, some practitioners prefer to utilize a serotonin norepinephrine reuptake inhibitor (SNRI) or the norepinephrine-dopamine reuptake inhibitor bupropion as their first-line antidepressant treatments (Slide 1). Differences of opinion regarding first, second, or third choice of antidepressant often stem from regional practices or individual training.

A basic standard of practice in MDD treatment is to initiate monotherapy trials with several first-line choices of antidepressants before moving on to alternate strategies. This basic strategy was evaluated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Only approximately one third of the patients remitted after being treated with the study's first-line treatment, a 12-week trial of citalopram in doses up to 60 mg/day. As in other contemporary treatment studies, remission was defined as virtually complete relief of depressive symptoms. This is defined as a Hamilton Rating Scale for Depression score of ≤7 or a score of ≤5 on the self-report version of the Quick Inventory of Depressive Symptomatology.

For those who did not obtain an adequate response to the initial course of citalopram therapy, the STAR*D study compared several alternate treatments, including switching to another antidepressant, adjunctive therapy with another type of medication (ie, a medication that is not an antidepressant), or combination treatment (ie, adding another antidepressant). At the end of four sequential treatment trials, only approximately two thirds of the patients remitted. Of those, 40% to 70% relapsed within the next year despite continued therapy.

Thomas was a 40-year-old, white male, with a 16-year history of schizoaffective disorder (Slide 1). He first became ill at 24 years of age and had an unstable course for ∼10 years, characterized by frequent hospitalizations and partial adherence. Unfortunately, during episodes of psychosis, he was also extremely violent. During his first hospitalization, risperidone was initiated, which he used intermittently for ∼10 years. There are no records documenting his weight and metabolic parameters at 24 years of age prior to receiving psychiatric medications. During his last psychiatric hospitalization at 34 years of age, olanzapine was prescribed and he stabilized. He entered a period of stable outpatient treatment and had not had a psychiatric hospitalization for 6 years.

When Thomas began taking olanzapine, his weight was 200 lbs, which, given his height, corresponds to a body mass index (BMI) of 28, putting him in the overweight category. However, he had no metabolic monitoring for 3 years. After 3 years of treatment with olanzapine, he had gained substantial weight, increasing to 258 lbs, which corresponds to a BMI of 36 and class 2 obesity.

The renin angiotensin aldosterone system (RAAS) has been implicated in the pathogenesisof cerebrovascular diseases. During the past decades, AU: INCLUDE A NUMBER?RAAS has gained attention as an important therapeutic target in cardiovascular medicine.Modulation of the RAAS for primary and secondary stroke prevention seems an appealingstrategy. Several experimental studies have showed that pre-treatment with RAAS inhibitorsprior to the initiation of ischemia exerts favorable effects on infarct volume, brainedema, and cerebral blood flow in the marginal zone. Furthermore, the activation ofangiotensin receptor type 2 has been associated with neuroprotective effects. Accumulatingevidence based on recent clinical trials indicate that blockade of RAAS has a potentialrole in stroke prevention. This review summarizes the pathophysiological aspects of brainRAAS and its constituents, presents experimental data on the neuroprotective actions ofRAAS inhibitors and available evidence regarding their effects on stroke risk, and discussfuture directions for research.

One of the key messages of the Sequenced Treatment Alternatives to Relieve Depression study was that only one third of patients with a diagnosis of major depressive disorder (MDD) achieve remission after the first treatment with an antidepressant. Management of most patients after one or more failed trials moves beyond the currently available evidence base and therefore represents a significant clinical challenge. Over the course of the four treatment steps, the cumulative remission rate was 67% and remission was more likely to occur during the first two treatment levels (20% to 30%) rather than during levels 3 and 4 (10% to 20%). These finding suggest that after two consecutive unsuccessful antidepressant trials a change in pharmacologic mode of action has a low probability to affect the likelihood of remission from MDD. The switch to a third antidepressant treatment resulted in an even lower remission rate than the one achieved in the first two levels. Furthermore, the discontinuation rates due to treatment intolerance was shown to rise across sequenced levels. At this point, the search for effective and tolerable alternative options to pharmacotherapy is essential.

We report a case of conversion disorder (partial aphonia) that was successfully treated with speech therapy. During the one year duration of this illness, the patient regained transiently (minutes) her normal speech on a few occasions, independently of concomitant pharmacological interventions. One year after recovery she developed aphonia for the second time, which responded again to speech therapy, although the response rate was slower. Several mechanisms of conversion disorder are reviewed as specifically applied to this case. The possible role of pertinent shame mechanisms in the conversion pathology is discussed.