Then and now HIV consultation psychiatry update.

Over the last 2 decades, human immunodeficiency virus (HIV) illness has transformed to a chronic disease model. However, challenges, including the effects of co-morbid illnesses and the challenge of preventing future spread of the disease, continue to confront those infected with HIV. Addictions remain an important problem and a serious contributor to overall morbidity and mortality in this population. This book chapter seeks to illustrate the new developments in the treatment of these addictions as well as provide an overview of the medical updates regarding HIV and hepatitis C virus exposure prophylaxis and how they relate to the consultant psychiatrist.

A systematic review of the psychiatric side-effects of efavirenz.

Concerns regarding the use of efavirenz in patients with a history of mental illness may predispose clinicians to not offer this agent to psychiatrically ill populations in spite of the convenience of once daily dosing, which can result in improved adherence in these at-risk populations. This systematic review examines the current data regarding the neuropsychiatric effects of efavirenz, and also attempts to provide guidance to clinicians using efavirenz to treat patients with mental illness. The review identified high rates of neuropsychiatric side effects including vivid dreams, insomnia and mood changes in approximately 50% of patients who initiate efavirenz. The effects begin quickly, commonly peak in the first 2 weeks, and are generally mild and transient in nature. Isolated case reports and uncontrolled data suggest higher rates of severe side effects; however, there is no clear evidence of a broadly increased risk of suicide or dangerous behavior for patients taking efavirenz as part of their antiretroviral regimen.

Psychiatric treatment of persons with HIV/AIDS: an HIV-psychiatry consensus survey of current practices.

BACKGROUND: Only sparse evidence from controlled clinical trials is available to guide the psychiatric treatment of persons with HIV/AIDS. OBJECTIVE: The authors assessed and determined current treatment trends in AIDS psychiatry. METHOD: Members of the Organization of AIDS Psychiatry (OAP) participated in a web-based survey. RESULTS: Of 159 members, 62 (39%) responded to the survey. Consensus emerged regarding first-line treatment for depression (escitalopram/citalopram), for psychosis and secondary mania (quetiapine), and for anxiety (clonazepam). CONCLUSION: Consensus statements can serve as a preliminary step toward providing some standardization of care for persons with HIV/AIDS.

Impact of bereavement on progression of AIDS and HIV infection: a review.

BACKGROUND: Human immunodeficiency virus (HIV) disease is associated with bereavement and grief reactions brought about by the disease process itself and by the losses of loved ones. OBJECTIVE: The goal of this review is to assess the current literature regarding grief, HIV, and immunity. METHOD: The authors reviewed applicable articles retrieved from a MEDLINE literature search with the search terms "bereavement/HIV," "grief/HIV," and "immunity/grief/HIV." RESULTS: Data continue to emerge that suggest a profound role for bereavement in mediating HIV illness and the need to effectively deal with bereavement issues. CONCLUSIONS: Patients who experience maladaptive grief show more rapid losses of CD4 T-cells over time, even when controlling for age, health status, use of antiretrovirals, and illicit drug abuse. This immune dysfunction may be managed by a variety of psychotherapeutic techniques.

Effects of antipsychotic medications on sleep in schizophrenia.

Schizophrenia is often accompanied by sleep problems. Evidence exists that these sleep difficulties have significant effects on individuals with this disorder. The mainstay of treatment for this condition is the administration of medications that have effects on neurotransmitter systems, which play an important role in sleep-wake function, including histamine, acetylcholine, serotonin, norepinephrine and dopamine. Little systematic attention, however, has been paid to how the sleep effects of these agents might play a role in the course of treatment, function and quality of life of schizophrenia patients. Schizophrenia medications can improve sleep problems and reverse the sleep architectural derangements that are common among patients with schizophrenia and, therefore, have the potential to improve the quality of life and functional capacity of the patient. Conversely, some sleep-wake effects of these medications can impair patient function and quality of life. In this study, we review the effects of schizophrenia medications and discuss their relevance to optimizing the clinical treatment of people with schizophrenia with regard to sleep-wake function.

Comorbid HIV encephalopathy and cocaine use as a risk factor for new-onset seizure disorders.

Patients living with human immunodeficiency virus represent a growing population, and an increased number of central nervous system presentations can be expected over the next decade. Emerging data suggests that both HIV-seropositive patients and cocaine-abusing patients may be at special risk of seizure phenomena. This case report discusses the risks of new-onset seizure activity when these two risk factors converge, which is a common occurrence in this population. Data from the fields of neuroanatomy and neurovirology are presented to explain the heightened risk of this patient population and provide the practitioner with an improved understanding of the central nervous system complexities in HIV.

Oxycodone with an opioid receptor antagonist: A review.

The rationale for putting opioid antagonists with an agonist is to improve pain control, to reduce side effects, and/or to reduce abuse. The combination of prolonged release (PR) oxycodone and naloxone reduces constipation as demonstrated in multiple studies and has been designated a tamper-resistant opioid by the Food and Drug Administration. Bioequivalence of the combination product compared with PR oxycodone has not been established. Several of the pivotal studies provided suboptimal laxative support in the control arm of the randomized trials. Two noninferiority trials have demonstrated equivalent analgesia between PR oxycodone and the combination product at doses of less than 120 mg of oxycodone per day. There appears to be an analgesic ceiling above 80-120 mg of oxycodone per day. Safety monitoring during randomized trials was not been well described in published manuscripts. Benefits appear to be better for those with chronic noncancer pain compared with individuals with cancer when constipation was the primary outcome.

Early postexercise muscle glycogen recovery is enhanced with a carbohydrate-protein supplement.

In the present study, we tested the hypothesis that a carbohydrate-protein (CHO-Pro) supplement would be more effective in the replenishment of muscle glycogen after exercise compared with a carbohydrate supplement of equal carbohydrate content (LCHO) or caloric equivalency (HCHO). After 2.5 +/- 0.1 h of intense cycling to deplete the muscle glycogen stores, subjects (n = 7) received, using a rank-ordered design, a CHO-Pro (80 g CHO, 28 g Pro, 6 g fat), LCHO (80 g CHO, 6 g fat), or HCHO (108 g CHO, 6 g fat) supplement immediately after exercise (10 min) and 2 h postexercise. Before exercise and during 4 h of recovery, muscle glycogen of the vastus lateralis was determined periodically by nuclear magnetic resonance spectroscopy. Exercise significantly reduced the muscle glycogen stores (final concentrations: 40.9 +/- 5.9 mmol/l CHO-Pro, 41.9 +/- 5.7 mmol/l HCHO, 40.7 +/- 5.0 mmol/l LCHO). After 240 min of recovery, muscle glycogen was significantly greater for the CHO-Pro treatment (88.8 +/- 4.4 mmol/l) when compared with the LCHO (70.0 +/- 4.0 mmol/l; P = 0.004) and HCHO (75.5 +/- 2.8 mmol/l; P = 0.013) treatments. Glycogen storage did not differ significantly between the LCHO and HCHO treatments. There were no significant differences in the plasma insulin responses among treatments, although plasma glucose was significantly lower during the CHO-Pro treatment. These results suggest that a CHO-Pro supplement is more effective for the rapid replenishment of muscle glycogen after exercise than a CHO supplement of equal CHO or caloric content.

Treatment of fatigue and sleep disorders in cancer patients.

Sleep disorders are highly prevalent among cancer patients. These disorders can include disorders of sleep onset or maintenance or disorders of excessive sleepiness. A broad differential diagnosis is required to adequately treat these disorders. This review discusses current diagnoses and treatment associated with sleep difficulties that may be seen in cancer patients. With appropriate diagnosis and treatment, the prognosis is good for sleep improvement and improvements in quality of life.

Long-term and short-term effects of insomnia in cancer and effective interventions.

Sleep disorders and insomnia are more prevalent in patients with cancer than in the normal population. Sleep disorders consist of delayed sleep latency, waking episodes after sleep onset, unrefreshing sleep, reduced quality of sleep, and reduced sleep efficiency. Sleep disorders cluster with pain, fatigue, depression, anxiety, and vasomotor symptoms, depending on stage of disease, treatment, and comorbidities. Premorbid sleep problems and shift work have been associated with a higher prevalence of cancer; in fact, shift work has been labeled a carcinogen. Treatment for insomnia includes cognitive behavioral therapy with sleep hygiene, bright-light therapy, exercise, yoga, melatonin, and hypnotic medications. Unfortunately, there are few randomized trials in cancer-related sleep disorders such that most recommendations particularly for hypnotics are based on treatment for primary insomnia. In this article, insomnia is reviewed as a predisposing factor to cancer, prior to and during treatment, in cancer survivorship and in advanced cancer. Recommendations for treatment are based on low-quality evidence but are also reviewed.

A randomized, double-blind, placebo-controlled trial of eszopiclone for the treatment of insomnia in patients with chronic low back pain.

STUDY OBJECTIVES: Insomnia, which is very common in patients with chronic low back pain (LBP), has long been viewed as a pain symptom that did not merit specific treatment. Recent data suggest that adding insomnia therapy to pain-targeted treatment should improve outcome; however, this has not been empirically tested in LBP or in any pain condition treated with a standardized pain medication regimen. We sought to test the hypothesis that adding insomnia therapy to pain-targeted treatment might improve sleep and pain in LBP. DESIGN: Double-blind, placebo-controlled, parallel-group, 1-mo trial. SETTING: Duke University Medical Center Outpatient Sleep Clinic. PATIENTS: Fifty-two adult volunteers with LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age: 42.5 y; 63% females). INTERVENTIONS: Subjects were randomized to eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg twice a day. MEASUREMENTS AND RESULTS: ESZ SIGNIFICANTLY IMPROVED TOTAL SLEEP TIME (MEAN INCREASE: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with placebo. Changes in pain ratings were significantly correlated with changes in sleep. CONCLUSIONS: The addition of insomnia-specific therapy to a standardized naproxen pain regimen significantly improves sleep, pain, and depression in patients with chronic low back pain (LBP). The findings indicate the importance of administering both sleep and pain-directed therapies to patients with LBP in clinical practice and provide strong evidence that improving sleep disturbance may improve pain. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00365976.

Oxycodone combined with opioid receptor antagonists: efficacy and safety.

INTRODUCTION: A mu receptor antagonist combined with oxycodone (OXY) may improve pain control, reduce physical tolerance and withdrawal, minimizing opioid-related bowel dysfunction and act as an abuse deterrent. AREAS COVERED: The authors cover the use of OXY plus ultra-low-dose naltrexone for analgesia and the use of sustained-release OXY plus sustained-release naloxone to reduce the opioid bowel syndrome. The authors briefly describe the use of sustained-release OXY and naltrexone pellets as a drug abuse deterrent formulation. Combinations of ultra-low-dose naltrexone plus OXY have been in separate trials involved in patients with chronic pain from osteoarthritis and idiopathic low back pain. High attrition and marginal differences between ultra-low-dose naltrexone plus OXY and OXY led to discontinuation of development. Prolonged-release (PR) naloxone combined with PR OXY demonstrates a consistent reduction in opioid-related bowel dysfunction in multiple randomized controlled trials. However, gastrointestinal side effects, including diarrhea, were increased in several trials with the combination compared with PR OXY alone. Analgesia appeared to be maintained although non-inferiority to PR OXY is not formally established. There were flaws to trial design and safety monitoring. Naltrexone has been combined with OXY in individual pellets encased in a capsule. This combination has been reported in a Phase II trial and is presently undergoing Phase III studies. EXPERT OPINION: Due to the lack of efficacy the combination of altered low-dose naltrexone with oxycodone should cease in development. The combination of sustained release oxycodone plus naloxone reduces constipation with a consistent benefit. Safety has been suboptimally evaluated which is a concern. Although the drug is commercially available in several countries, ongoing safety monitoring particularly high doses would be important.

Acute neurologic effects of alcohol and drugs.

Neurologic effects of acute drug intoxication are varied. This article discusses the acute neurologic effects of certain drugs as well as associated treatments and guidelines to management.

Comparison of polysomnographic data in age-, sex- and Axis I psychiatric diagnosis matched HIV-seropositive and HIV-seronegative insomnia patients.

OBJECTIVE: There is a high prevalence of insomnia in HIV-seropositive patients. Insomnia is associated with poorer disease outcomes, cognitive impairment and HIV-associated dementia. However there is limited data characterizing the type of sleep disturbances, and the cause. Previous studies report conflicting results, and observed changes in the distribution of REM and SWS were hypothesized to result from co-morbid mood disorders, although this is not established. We carried out this study to determine if there are differences in polysomnographic (PSG) sleep data in age-, sex- and Axis I diagnoses- matched HIV-seropositive and HIV-seronegative patients. METHODS: Eighteen HIV-seropositive insomniacs were matched to HIV-seronegative insomniacs based on age, sex and Axis I diagnoses. Participants spent 2 consecutive nights in a sleep lab recording of PSG data. RESULTS: Multivariate analysis revealed an overall significant match-by-variable interaction (p=0.0126). Follow-up analysis show that compared to HIV-seronegative insomnia controls, HIV-seropositive insomniacs have significantly longer SOL, 8% decreased sleep efficiency, and 8-10% decreased time spent in REM sleep (p's<0.05). CONCLUSION: This study provides preliminary evidence that even after accounting for differences in age, sex and psychiatric diagnoses, HIV-seropositive patients with insomnia have significantly worse sleep than HIV-seronegative patients with insomnia. SIGNIFICANCE: Unlike what previous authors have proposed, our results do not support the view that comorbid psychiatric disorders like depression are responsible for the observed differences in PSG findings and the greater incidence of insomnia, in HIV-seropositive patients when compared with other groups of insomnia patients. This suggests the presence of other etiologies including neuronal damage, psychosocial stressors, or comorbid medical conditions. Further studies are needed to determine the extent to which these play a role in insomnia in the HIV-seropositive population.

The association of fatigue with depression and insomnia in HIV-seropositive patients: a pilot study.

OBJECTIVE: Fatigue is a pervasive symptom associated with HIV, resulting in significant functioning impairment; but little is known about its etiology or treatment. In patients with primary insomnia, data have shown improvement in fatigue following successful treatment of insomnia. However, little is known about the role of insomnia in patients with fatigue in HIV. This manuscript seeks to test the hypothesis that insomnia severity is correlated with increased fatigue in HIV-seropositive patients. METHODS: Fifty-seven ambulatory HIV-seropositive patients, aged 18-60 years, with a DSM-IV-TR diagnosis of insomnia, were administered the Insomnia Severity Index (ISI), Piper Fatigue Scale (PFS), Hospital Anxiety and Depression scale, and Hamilton Depression Rating Scale (HAM-D). Their most recent CD4 count and time since diagnosis of HIV were recorded. Regression analysis was carried out with PFS as the dependent variable. RESULTS: A higher ISI score correlated with higher PFS score, (R2 = 0.1713, P = 0.0042). Overall depression severity was not significantly correlated with PFS score, except in the most severely depressed subgroup, in which the HADS depression score was the strongest predictor of PFS (R2 = 0.182, P = 0.0009). In participants without depression, ISI accounted for most of the variance in fatigue (R2 = 0.6035, P = 0.0011). CONCLUSIONS: Greater insomnia severity is associated with greater fatigue severity in HIV seropositive patients. Depression may contribute to both fatigue and insomnia. In the absence of depression, the treatment of insomnia may emerge as a treatment strategy to help alleviate fatigue. Further studies are needed to confirm these data. CLINICAL TRIAL INFORMATION: Clinical Trials.Gov: The Treatment of Insomnia in Patients with HIV Disease. Registry Number: NCT00465972. URL: http://www.clinicaltrials.gov/ct2/show/NCT00465972?term = HIV+insomnia&rank = 1.

Hydromorphone-OROS formulation.

IMPORTANCE TO THE FIELD: Hydromorphone is a semi-synthetic opioid approved in the USA for the treatment and relief of moderate to severe pain and postoperative pain. However, the compound is short-acting, and there is no extended-release formulation clinically available. A previous hydromorphone extended-release formulation that successfully came to market was subsequently withdrawn on account of safety concerns. Clinical need supports the presence of an extended-release formulation of hydromorphone. AREAS COVERED IN THIS REVIEW: Medline articles showing from a search of 'hydromorphone and OROS' were included in the review. In addition, searches were done relating to published data regarding regulatory affairs dealing with this specific topic. Physicians prescribing information for hydromorphone was also reviewed. WHAT THE READER WILL GAIN: The reader will gain an increased understanding of the use of an extended-release formulation of hydromorphone using the OROS technology and will appreciate that this technology has safety advantages compared with previous extended-release formulations of hydromorphone. TAKE HOME MESSAGE: Hydromorphone-OROS is an effective agent for the long-acting control of pain and a welcome addition to other available opioid formulations.

Neurologic aspects of drug abuse.

Neurologic aspects of drug abuse vary. This article explains the general nature of drug abuse, identifies the physiologic effects of certain drugs, and briefly describes the neurobiology of addiction. This article also reviews available treatment options for those addicted to substances of abuse, and clarifies common misconceptions, including the differences between tolerance, abuse, and addiction.

Low-dose doxepin for the treatment of insomnia: emerging data.

BACKGROUND: Doxepin is a tricyclic compound that has been used extensively for the treatment of depressive and anxiety disorders for approximately thirty years. It was noted early to have sedative effects and assist with the improvement of disrupted sleep patterns, but in higher antidepressant doses it was also noted to have significant anticholinergic and antinoradrenergic properties. These properties led to significant dose-limiting side effects, which at times precluded its effective use. Recently, doxepin has seen renewed interest in low doses as an H1 specific antagonist in sleep disorders. OBJECTIVE: The review seeks systematically to examine currently published data on the use of doxepin for the treatment of insomnia, and its pharmacological basis. METHODS: Medline articles showing from a search of 'doxepin and insomnia' were included in the review. RESULTS/CONCLUSION: Currently available data support the use of low-dose doxepin as preferential H1 antagonist for the treatment of primary insomnia. There are likely preferential effects upon sleep maintenance insomnia compared with sleep initiation given the role of histamine in the sleep-wake cycle.

The pharmacologic management of insomnia in patients with HIV.

Insomnia is common in human immunodeficiency virus (HIV) seropositive populations. Some studies have estimated as many as 70% of HIV patients experience insomnia at some point during their illness. Insomnia has been linked to reduced quality of life as well as treatment non-adherence in these patients. However, there has been very limited research on the treatment of insomnia in this setting. Lacking treatment trials, we carried out a review of the available literature relevant to the pharmacologic treatment of insomnia in HIV seropositive individuals in order to provide guidance for the clinical management of this complex population. A systematic MEDLINE search was performed using as search terms each of the FDA approved or commonly prescribed insomnia medications and "insomnia and HIV." In addition, we reviewed the published literature on HIV therapies and common comorbid conditions and their interactions with insomnia therapies. We found 4 primary factors affecting the pharmacotherapy of insomnia in individuals with HIV: (1) medications used to treat HIV; (2) antibiotics used to treat opportunistic infections; (3) the HIV infection itself; and (4) conditions frequently associated with HIV infection. The means by which these factors affect the expected risk-benefit profile of insomnia therapies is discussed, and recommendations are made for choosing medications in patients encountered in clinical practice.