Psychopharmacology in HIV-infected patients.

Neuropsychiatric disorders and syndromes may be underdiagnosed and inadequately treated in individuals infected with HIV. Depression in particular is among the most prevalent diagnoses, and data from controlled clinical studies have shown that antidepressant medications are efficacious and safe for treating depression in HIV-infected persons. A significant shortcoming of this literature is that most of the available data are from studies conducted before the advent of highly active antiretroviral therapy. In addition, apart from antidepressant medications, controlled studies systematically assessing efficacy and safety issues for other classes of psychotropic drugs (e.g., antipsychotic and anxiolytic medications) in HIV-infected persons are lacking. This review summarizes essential findings pertaining to the use of psychotropic medications to treat depression and other neuropsychiatric disorders in the context of HIV. It includes a discussion of clinically relevant treatment considerations (e.g., side effects, drug-drug interactions) derived from the existing literature as well as judgments that clinicians face in the absence of research data. Despite some shortcomings of the existing literature, overall there is compelling evidence that the appropriate use of psychotropic medications (coupled with behavioral therapy) can improve the quality of life of mentally ill HIV-infected individuals.

Prevalence, diagnosis, and pharmacological treatment of mood disorders in HIV disease.

Human immunodeficiency virus seropositive (HIV+) individuals are at a heightened risk of developing mood disorders and related syndromes. Over the past several decades, increased rates of mood disorders, including depression and mania, have been reported among HIV+ individuals. Because alterations in mood may impact on quality of life and perhaps reduce adherence to antiretroviral treatment regimens that are critical for preventing disease progression, recognition and effective treatment of mood disorders is essential. There are accumulating data showing that antidepressants and mood stabilizers, as well as other novel agents, might benefit HIV+ individuals suffering from a concomitant mood disturbance. This review highlights the relevant studies that have examined prevalence rates of mood disorders in HIV+ individuals, characteristics of HIV disease that influence the diagnosis and psychopharmacologic treatment of mood disorders, including complex interactions with antiretroviral medications, as well as the available evidence regarding the efficacy of agents used to treat depression and mania in the context of HIV disease.

Neurobiological mechanisms in addictive and psychiatric disorders.

The studies reviewed indicate that brain stress system play an important role in the acquisition and maintenance of drugs of abuse that target the brain's reward centers. In doing so, they may destabilize these areas, making the perception of pleasure more elusive and difficult to attain. Withdrawal from drugs of abuse leads to the activation of brain CRF systems that may produce the anxiogenic response associated with drug withdrawal. More research, however, is needed to investigate the role of brain stress systems and neuropeptides in other drug withdrawal symptoms such as anhedonia. A better understanding of the brain systems underlying drug withdrawal may help in the development of improved pharmacotherapies that can alleviate drug withdrawal symptoms. The second part of the article indicated that there is a very high comorbidity between depression and drug dependence. The reviewed studies suggest that depressed patients initiate drug-taking behavior to self-medicate the symptoms associated with their psychiatric disorder. Chronic use of drugs of abuse, however, may exacerbate the symptoms of pre-existing mental disorders and subsequently increase drug-taking behavior. Conversely, professional treatment of pre-existing psychiatric disorders may decrease the use of illicit substances.

Neuropsychopharmacologic treatment of depression and other neuropsychiatric disorders in HIV-infected individuals.

How can neuropsychiatric disorders and syndromes be underdiagnosed and inadequately treated in individuals infected with human immunodeficiency virus? Depression in particular is among the most prevalent diagnoses and there is a solid foundation of data from controlled clinical studies that has begun to examine the efficacy of various antidepressants in HIV-infected persons. This article summarizes essential findings pertaining to the use of psychotropic medications to treat depression and other neuropsychiatric disorders in the context of immunodeficiency. This includes discussion of clinically significant treatment considerations (eg, efficacy, side effects, drug-drug interactions) derived from the existing literature. Taken together, there is compelling evidence that psychopharmacologic intervention can improve the quality of life of mentally ill HIV-infected individuals.

Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice.

γ-Aminobutyric acid (GABA) inhibits insulin secretion through GABA(B) receptors in pancreatic ß-cells. We investigated whether GABA(B) receptors participated in the regulation of glucose homeostasis in vivo. BALB/c mice acutely pre-injected with the GABA(B) receptor agonist baclofen (7.5mg/kg, i.p.) presented glucose intolerance and diminished insulin secretion during a glucose tolerance test (GTT, 2g/kg body weight, i.p.). The GABA(B) receptor antagonist 2-hydroxysaclofen (15 mg/kg, i.p.) improved the GTT and reversed the baclofen effect. Also a slight increase in insulin secretion was observed with 2-hydroxysaclofen. In incubated islets 1.10(-5)M baclofen inhibited 20mM glucose-induced insulin secretion and this effect was reversed by coincubation with 1.10(-5)M 2-hydroxysaclofen. In chronically-treated animals (18 days) both the receptor agonist (5mg/kg/day i.p.) and the receptor antagonist (10mg/kg/day i.p.) induced impaired GTTs; the receptor antagonist, but not the agonist, also induced a decrease in insulin secretion. No alterations in insulin tolerance tests, body weight and food intake were observed with the treatments. In addition glucagon, insulin-like growth factor I, prolactin, corticosterone and growth hormone, other hormones involved in glucose metabolism regulation, were not affected by chronic baclofen or 2-hydroxysaclofen. In islets obtained from chronically injected animals with baclofen, 2-hydroxysaclofen or saline (as above), GABA(B2) mRNA expression was not altered. Results demonstrate that GABA(B) receptors are involved in the regulation of glucose homeostasis in vivo. Treatment with receptor agonists or antagonists, given acutely or chronically, altered glucose homeostasis and insulin secretion alerting to the need to evaluate glucose metabolism during the clinical use of these drugs.