Along with the development of selective sertonin reuptake inhibitors there has been a tremendous widening of the definition of depression and an impressive decrease in the placebodrug difference in controlled studies. In the early 1960s, about one third of depressed patients improved with placebo and two thirds with active compounds. Current controlled studies suggest that the situation has certainly not improved. The Sequenced Treatment Alternatives to Relieve Depression Study found that response rates to new compounds after the failure of the first antidepressant are low. The monoamine hypothesis of depression was formulated in the mid 1960s based on the antidepressant efficacy of the monoamine reuptake inhibitors, monoamine oxidase inhibitors, and the depressogenic effects of reserpine as a monoamine depleter. However, no monoamine-related finding has been found that is diagnostic for depression. A second major hypothesis regarding depression has been the stress cortisol hypothesis. However, blood cortisol levels are not diagnostic of depression. Psychiatric clinicians are convinced that there are patients for whom antidepressants have made the difference between life and death. However, physicians may generalize unjustifiably based on single dramatic cases to a much larger diagnostic group. Perhaps there are many causes of different types of human sadness, and perhaps only some of these involve mechanisms related to monoamines. Thus, perhaps only some kinds of depression are responsive to monoamine affecting antidepressants.

Introduction: The high percentage (between 40% and 60%) of resistance to first-line drugs, such as clomipramine or selective serotonin reuptake inhibitors, is a major problem in the pharmacologic management of obsessive-compulsive disorder (OCD). In these cases, different strategies have been employed with controversial outcomes. The meager information available on the association of two serotonergic drugs prompted us to explore the possible effectiveness and tolerability of citalopram+clomipramine in resistant OCD patients.

Methods: Twenty outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD, who had failed to respond to at least two trials with a selective serotonin reuptake inhibitor and were currently taking clomipramine at different doses, were administered citalopram at a maximum dose of 60 mg/day. The clinical assessment was carried out at baseline (t0) and at the 4th (t1), 12th (t2), 24th (t3), 36th (t4), and 48th (t5) week by means of the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Clinical Global Impression scale, and the Dosage Record and Treatment Emergent Symptom Scale. The response was defined as a 35% decrease of the Yale-Brown Obsessive Compulsive Scale total score.

Results: The results showed that ∼50% of the patients improved significantly after 1 month of this regimen and after 1 year of treatment.

Conclusion: This study, although carried out in a small sample and in an open fashion, represents one of the few experiences with the association of two serotonergic compounds in resistant OCD and confirms its potential usefulness and good tolerability profile. Controlled research on this association in OCD is recommended.

William Utermohlen was born in 1933. Upon completing his Bachelor's degree at the Pennsylvania Academy of Fine Arts, he joined the Army and then moved to England to study at the University of Oxford. This is where he met his wife, Patricia. Bill painted scenes from his childhood in Philadelphia, images of Vietnam War veterans, and pictures inspired by Dante's Inferno. Later, many of his paintings depicted family life, conversations with friends, and his home—they were happy pictures.

Complementary and alternative medicine (CAM) is very popular in the United States, Canada and other Western societies, and the number of patients seeking treatment by CAM practitioners is increasing. This trend also affects treatment-seeking patients with affective disorders. Many patients and mental health providers update their information and formulate opinions and decisions based on second-hand digested summaries and scientific reviews of the literature. This results in the proliferation of review articles and journals that are exclusively dedicated to reviews. Since most medical schools do not teach CAM and most continuing medical education programs still ignore these subjects, it is of interest to examine the reliability of reviews that claim to be “systematic” and not to take their procedures and conclusions for granted.

The management of fibromyalgia syndrome (FMS) has traditionally been multimodal and multidisciplinary, including education, physical modalities, and medication. In this article, an acronym is offered to help the clinician remember the important components of management. An improved understanding of the pathogenesis of FMS has allowed substantial refinements in its treatment. This is particularly true for medications that target specific symptom domains, allowing individualization of therapy. Since all FMS patients experience pain, there has been emphasis on that domain although medications are now available to address two or more domains with monotherapy. In addition, a logical basis is provided to help the clinician design strategic polypharmacy.

Although much attention has been paid to patients who lack insight into their obsessional beliefs, less importance has been given to individuals with obsessive-compulsive disorder (OCD) who display perceptual disturbances typically found in psychotic disorders, including schizophrenia, schizoaffective disorders, or mood disorders with psychotic features. We would like to call the attention to a phenomenon that has been neglected in the psychiatric literature: the occurrence of hallucinations and related phenomena in patients with OCD. In this case report, we describe five clinical vignettes of patients with OCD with hallucinations in several different sensory modalities, including the auditory, the visual, the tactile, the olfactory, and the cenesthetic ones. Further psychopathological research should clarify the clinical significance of hallucinations among patients with OCD.

For over 20 years, researchers have used the tracer [18F]fluorodeoxyglucose (FDG) in positron emission tomography (PET) imaging. FDG PET imaging has been utilized to study the characteristic metabolic changes in Alzheimer’s disease (AD), and as more molecular imaging tracers become available for human research, PET will likely assume many new roles for investigating more specific abnormalities, such as amyloid deposition, in the future.

FDG is a glucose analog that images glucose metabolism and also illustrates neural firing. Different synapse activity, particularly excitatory activity from glutamate release, appears to change FDG uptake. AD will affect both brain infrastructure by decreasing the amount of cell bodies and synapses as well as decreasing synaptic activity, which are both changes that decrease the amount of FDG. AD is not a perfectly uniform process, and this is reflected by distinct progressive patterns of decreased FDG and decreased metabolism across different regions of the brain.

FDG enters the brain via blood flow, and then into brain tissue by both diffusion and facilitated transport. Once it enters the glia and neurons, FDG can be phosphorylated, a step that is essentially irreversible, but then cannot be processed further by the cells, effectively trapping the FDG in situ. The amount of trapping that occurs in the brain over the first 10–20 minutes is very high and constitutes over 80% of the uptake. Thus, after the first 10–20 minutes uptake phase, a pattern of FDG emerges that mirrors the distribution of glucose metabolism in all subcortical and cortical structures.

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy treatments for obsessive-compulsive disorder (OCD). Clomipramine is effective in OCD but associated with more adverse events. Typically, higher doses of antidepressants are required for OCD. Up to 50% of patients do not respond to initial treatment of OCD. Treatment options for nonresponders include augmentation of antidepressants with atypical antipsychotics, among other strategies. First-line treatments for anxiety disorders include SSRIs, serotonin norepinephrine reuptake inhibitors, and pregabalin. Tricyclic antidepressants are equally effective as SSRIs, but are less well tolerated. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of dependency and tolerance. Other treatment options include irreversible and reversible monoamine oxidase inhibitors, the atypical antipsychotic quetiapine, and other medications. Cognitive-behavioral therapy has been sufficiently investigated in controlled studies of OCD and anxiety disorders and is recommended alone or in combination with the above medications.

All three serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit the reuptake of both serotonin and norepinephrine but they do so with differing affinity ratios. Venlafaxine has a 30-fold higher affinity for serotonin than for norepinephrine while duloxetine has a 10-fold selectivity for serotonin. Milnacipran has a balanced (1:1) ratio of potency for inhibition of reuptake of the two neurotransmitters. The most frequent adverse event with SNRIs is nausea. Not unexpectedly, adverse effects related to a noradrenergic stimulation, such as dry mouth, sweating, and constipation, are found more frequently with SNRIs than with selective serotonin reuptake inhibitors. At true SNRI doses, venlafaxine is associated with dose-dependent cardiovascular phenomena (principally increased blood pressure), an effect which is less frequent with duloxetine and rare with milnacipran. Serious and potentially fatal hepatotoxity has been reported with duloxetine. This problem appears to be unique to duloxetine and not a characteristic of the SNRI class. There are differences in overdose toxicity between venlafaxine and the other SNRIs, possibly related to its increased cardiotoxicity.

Central nervous system (CNS) vasculitis is a rare entity, especially when it occurs in isolation; it is seen more commonly as part of a multisystem vasculitis. Common presenting symptoms include persistent headache, encephalopathy, and multifocal signs. We discuss the case of a 68-year-old female who presented twice in 1 month with confusion and choreaform movements. Extensive workup was negative for a connective tissue disease or other conditions in the differential, including neurosarcoidosis, Creutzfeldt-Jakob disease, and neurosyphilis. The only significant findings were elevated erythrocyte sedimentation rate, inflammatory signs in the CNS, and diffuse slowing of the electroencephalogram. A presumptive diagnosis of isolated angiitis of the central nervous system (IACNS) was made and the patient was successfully treated with steroids. She recovered fully with no residual symptoms. The diagnosis of IACNS is often difficult given there are no definitive laboratory investigations or pathognomonic presentation. However, a series of signs, symptoms, and laboratory findings have been proposed that are helpful in making the diagnosis. To our knowledge, IACNS presenting primarily with delirium has not been previously reported in the literature. The diagnosis of IACNS is purely speculative for this case, as the gold standard for diagnosis, a leptomeningeal cortical biopsy, was not performed.

Cardiovascular disease (CVD) remains the number one cause of death in the United States and most developed countries and is expected to remain so for much of this century. Rates of obesity have increased 2–4-fold over the last 2 decades in the US and this condition is linked with early development of hypertension, hyperlipidemia, diabetes, and atherosclerosis. The prevalence of diabetes is also increasing, and the rise of diabetes in young people 18–29 years of age was 40% in the period between 1990 and 2001. The World Heart Federation (WHF) has estimated that CVD will become the number one cause of death in the world by 2020, surpassing infectious disease in developing countries. Metabolic disorders are on the rise in general. However, as highlighted in the discussions presented in this supplement, patients with serious mental illness appear to represent a special population who are particularly vulnerable, with rates that surpass the general population.