Treatment resistance is reported in up to 40% of older patients with major depression. Before labeling an episode of depression as treatment resistant, it is important to ensure that the diagnosis is correct and that the patient has received and adhered to an adequate dose of treatment for an appropriate length of time. It is also important to assess the patient for comorbid physical and psychiatric conditions that can contribute to treatment resistance. In patients who do not experience remission of symptoms with an adequate trial of medication, the following options can be considered: augmenting the antidepressant with a drug that is not primarily an antidepressant, adding a second antidepressant to the first, switching to a different antidepressant medication, or switching to electroconvulsive therapy. This paper reviews the concept of treatment-resistant depression and discusses its assessment and management in the elderly. The author concludes that when a systematic stepped-care approach to treatment is followed, most older patients with major depression will experience remission of symptoms.

Background: While the adult form of adrenoleukodystrophy (ALD) has been associated with an elevated rate of affective disturbance, the myeloneuropathic form of the disease known as adrenomyeloneuropathy (AMN) has been associated with only occasional cases of major mental illness. Given that cerebral involvement occurs in up to half of AMN sufferers, we hypothesized that rates of mental illness may match those with adult ALD.

Objective: To describe the psychiatric, cognitive, and disability variables in a sample of Australian AMN sufferers.

Methods: Ten genetically confirmed AMN sufferers underwent diagnostic psychiatric interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders), rating scales of psychiatric disturbance (Brief Psychiatric Rating Scale, Hospital Anxiety and Depression Scale, Beck Depression and Anxiety Inventories, and Short-Form 36), and cognitive function (the Neuropsychiatry Unit Cognitive Assessment Tool and Mini-Mental State Examination).

Results: While the group as a whole was generally cognitively intact, it demonstrated a higher than expected prevalence of lifetime and current major affective illness. Current symptom levels were low at the time of study participation. Psychopathology did not relate to adrenal status, nor to level of physical or functional impairment.

Conclusion: This small sample suggests that the level of psychiatric morbidity in AMN patients is elevated, and the rate of affective disturbance approaches those of adult ALD sufferers. This may reflect that AMN is not a “pure” myeloneuropathy, and that mild cerebral involvement may be associated with affective illness.

The behavioral syndrome of trichotillomania (TTM) is well characterized, but challenges pertaining to TTM remain in several areas, including diagnostic classification, assessment of severity, and determination of relevance of comorbid psychiatric disorders. Acute pharmacological studies have focused on serotonin transport inhibitors, and preliminary evidence suggests that inhibition of both serotonin and norepinephrine transporters (ie, by clomipramine and venlafaxine) provides a clinical improvement. Dopamine antagonists are promising agents in need of systematic evaluation in TTM. Cognitive-behavioral therapy appears to achieve a decrease in acute symptoms in many patients. However, longitudinal maintenance of benefits has not been rigorously tested with either pharmacological or behavioral therapy. Clinical impressions and treatment data indicate that achieving durability of treatment benefits remains a major challenge in many patients with TTM, although there is evidence of improved outcome with comprehensive multimodal treatment.

Seasonal affective disorder (SAD) is a form of depression that starts in the fall and ends in the spring. This article reviews existing theories about the relationship between circadian rhythms and the disorder. Recent research indicates that as with pharmacologic antidepressants, at least 2–4 weeks are needed to demonstrate the effectiveness of bright-light therapy compared to placebo. The response to such treatment is strongest with precisely timed light exposure: treatment is optimal during the morning hours when the circadian systemt is susceptible to phase advance. Such clinical improvement is correlated with the magnitude of the phase shift induced. These observations suggest a model of circadian function in SAD and provide important guidelines for its treatment.

Restless legs syndrome (RLS) is a common neurological movement disorder, characterized by restless and unpleasant sensations in the deep inside of legs. The symptoms of RLS are less noticeable during daytime, but more prevalent at night. Therefore, the disorder can induce low quality of life, insomnia, and impairment of daytime activity. RLS in end-stage renal disease (ESRD) patients is especially problematic due to premature discontinuation of dialysis and increased mortality. The prevalence of RLS among dialysis patients is much higher compared to the prevalence of the same disorder in patients with normal renal functions. Even though there are recommended treatment guidelines for the general population established by Medical Advisory Board of the RLS foundation, which include the use of dopamine agonists, levodopa, gabapentin, benzodiazepines, and opioids, limited information is available on the effects of these therapies in ESRD patients. Since the existing clinical data were extrapolated from small sample sizes in short-term clinical trials, further clinical studies are still needed to better assess the efficacy, safety, and tolerability of these medications in patients with ESRD.

Depression affects 6.5 million of the 35 million Americans ≥65 years of age. While depression usually begins earlier in life and recurs periodically, it can present for the first time in people 80–90 years of age as well. Depression throughout the lifespan has a genetic/biological component but is also very much affected by social environmental factors. As people age, demographic factors, social support, and negative life events remain important to overall mental health, while physical illness and disability begin to take on a much more prominent role. Depression in the elderly is associated with impairment, dependency, disability, and significant distress for the individual and their family. This population is likely to present with concomitant cognitive dysfunction and medical illness, which can complicate the identification and treatment of psychiatric conditions. Bereavement is almost universal in late life and is sometimes a deterrent to appropriate diagnosis and treatment of depression. Physical frailty and diminishing social resources further complicate the treatment of depression in the elderly. Elderly individuals respond well to standard pharmacotherapy and psychotherapy treatments for depression. However, due to the high rate of relapse of depression in this population, continuous treatment is often warranted. This monograph will review depression in the elderly in the context of social disruptions, such as bereavement, caregiver strain, interpersonal conflict, role transitions, and social isolation; late-onset vascular depression and cognitive impairment; and physical illness including disability.

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.

In 1980, the diagnosis of posttraumatic stress disorder (PTSD) was established to recognize that exposure to events such as rape, physical assault, torture, or combat can leave long-lasting psychological scars in persons who undergo these experiences. The intention of the diagnosis was to acknowledge that exposure to a traumatic event was a sufficient explanation for the occurrence of longterm psychological problems. Prior to this formulation, stressful events were thought to precipitate symptoms that would resolve over time. The symptoms manifested by persons following adverse events were characterized as transient adjustment reactions. Longerterm symptoms were considered to be a reflection of underlying neurosis, rather than stress exposure per se.

The diagnosis of PTSD provided a paradigm for acknowledging that exposure to devastating trauma can produce symptoms that can be quite severe and chronic in nature. Although many of the symptoms of PTSD were similar to those that occur in other anxiety or mood disorders, the hallmark of PTSD appeared to be a preoccupation with the traumatic event and a resultant set of behavioral changes that occurred because of attempts to avoid reminders of the event.

In a variety of mammalian species, prenatal androgens organize brain structures and functions that are later activated by steroid hormones in postnatal life. In humans, studies of individuals with typical and atypical development suggest that sex differences in reproductive and nonreproductive behavior derive in part from similar prenatal and postnatal steroid effects on brain development. This paper provides a summary of research investigating hormonal influences on human behavior and describes how sex differences in the prevalences and natural histories of developmental psychopathologies may be consistent with these steroid effects. An association between patterns of sexual differentiation and specific forms of psychopathology suggests novel avenues for assessing the effects of sex steroids on brain structure and function, which may in turn improve our understanding of typical and atypical development in women and men.

Background: We investigated clinical factors to determine their relationship to treatment resistance among bipolar patients who had a consultation at a tertiary care facility.

Methods: Patients were separated into two categories: rapid-cycling disorders and nonrapid-cycling disorders. We hypothesized that there would be less usage of lithium carbonate among nonrapid-cycling treatment-resistant patients than among rapid cyclers and also that there would be higher rates of comorbidity seen among nonrapid-cycling than rapid-cycling patients in order to account for these particular patients being treatment resistant.

Findings: Continued recyling and persistent depression characterized rapid cyclers, whereas persistent depression characterized nonrapid cyclers. Less than 30% of patients had adequate lithium treatment and there was no significant difference comparing rapid cyclers with non-rapid cyclers. Rates of comorbidity were also not significantly different between these groups. We also assessed a number of other factors.

Conclusion: Some of these factors were significant, but when a Bonferonni correction was applied, these significant differences were not maintained. The study of treatment resistance among nonrapid-cycling bipolar patients merits further research.

During the past 10 years, there has been a welcome influx of novel agents for the treatment of epilepsy. Many show advantages compared to older agents, including better adverse effect profiles and lack of drug-drug interactions. The sheer number of agents now available makes distinction among them confusing at times. Agents differ in spectrum of action, pharmacokinetic profile (affecting dosing schedule and drug interactions), and titration time. This review highlights the differences between the various new agents and the more traditional antiseizure drugs. Evidence for the widespread use of these compounds outside their indication, particularly for diseases other than epilepsy, is reviewed as well.

In initial studies using animal models of depression, we primarily focused on the similarities of transcranial magnetic stimulation (TMS) to electroconvulsive therapy (ECT). However, our investigations show that TMS has its own, unique, potentially diagnostic and therapeutic effects, distinct from those of ECT. These effects need further exploration in animal and clinical studies.