Isoniazid-induced psychosis.

Dept. of Psychiatry, State Univ. of New York, Upstate Syracuse, NY
Psychosomatics (Impact Factor: 1.67). 11/2009; 50(6):640-1. DOI: 10.1176/appi.psy.50.6.640-a
Source: PubMed
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    ABSTRACT: AIMS: Tuberculosis and mental illness share common risk factors including homelessness, HIV positive serology, alcohol/substance abuse and migrant status leading to frequent comorbidity. We sought to generate a comprehensive literature review that examines the complex relationship between tuberculosis and mental illness. METHODS: A literature search was conducted in MedLine, Ovid and Psychinfo, with further examination of the references of these articles. In total 316 articles were identified. It was not possible to conduct a formal meta-analysis due to the absence of randomised controlled data. RESULTS: Rates of mental illness of up to 70% have been identified in tuberculosis patients. Medications used in the treatment of common mental illnesses, such as depression, may have significant interactions with anti-tuberculosis agents, especially isoniazid and increasingly linezolid. Many medications used in the treatment of tuberculosis can have significant adverse psychiatric effects and some medications such as rifampicin may reduce the effective doses of anti-psychotics y their enzyme induction actions. Treatment with agents such as cycloserine has been associated with depression, and there have been reported cases of psychosis with most anti-tuberculous agents. Mental illness and substance abuse may also affect compliance with treatment, with attendant public health concerns. CONCLUSIONS: As a result of the common co-morbidity of mental illness and tuberculosis, it is probable that physicians will encounter previously undiagnosed mental illness among patients with tuberculosis. Similarly, psychiatrists are likely to meet tuberculosis among their patients. It is important that both psychiatrists and physicians are aware of the potential for interactions between the drugs used to treat tuberculosis and psychiatric conditions.
    General hospital psychiatry 05/2013; 35(4). DOI:10.1016/j.genhosppsych.2013.03.018 · 2.90 Impact Factor
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    ABSTRACT: A high proportion of people with severe mental health problems are unemployed but would like to work. Individual Placement and Support (IPS) offers a promising approach to establishing people in paid employment. In a randomized controlled trial across six European countries, we investigated the economic case for IPS for people with severe mental health problems compared to standard vocational rehabilitation. Individuals (n=312) were randomized to receive either IPS or standard vocational services and followed for 18 months. Service use and outcome data were collected. Cost-effectiveness analysis was conducted with two primary outcomes: additional days worked in competitive settings and additional percentage of individuals who worked at least 1 day. Analyses distinguished country effects. A partial cost-benefit analysis was also conducted. IPS produced better outcomes than alternative vocational services at lower cost overall to the health and social care systems. This pattern also held in disaggregated analyses for five of the six European sites. The inclusion of imputed values for missing cost data supported these findings. IPS would be viewed as more cost-effective than standard vocational services. Further analysis demonstrated cost-benefit arguments for IPS. Compared to standard vocational rehabilitation services, IPS is, therefore, probably cost-saving and almost certainly more cost-effective as a way to help people with severe mental health problems into competitive employment.
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    ABSTRACT: Isoniazid represents a first-line anti-tuberculosis medication in prevention and treatment. This prodrug is activated by a mycobacterial catalase-peroxidase enzyme called KatG in Mycobacterium tuberculosis), thereby inhibiting the synthesis of mycolic acid, required for the mycobacterial cell wall. Moreover, isoniazid activation by KatG produces some radical species (e.g., nitrogen monoxide), that display anti-mycobacterial activity. Remarkably, the ability of mycobacteria to persist in vivo in the presence of reactive nitrogen and oxygen species implies the presence in these bacteria of (pseudo-)enzymatic detoxification systems, including truncated hemoglobins (trHbs). Here, we report that isoniazid binds reversibly to ferric and ferrous M. tuberculosis trHb type N (or group I; Mt-trHbN(III) and Mt-trHbN(II), respectively) with a simple bimolecular process, which perturbs the heme-based spectroscopic properties. Values of thermodynamic and kinetic parameters for isoniazid binding to Mt-trHbN(III) and Mt-trHbN(II) are K = (1.1±0.1)×10(-4) M, k on = (5.3±0.6)×10(3) M(-1) s(-1) and k off = (4.6±0.5)×10(-1) s(-1); and D = (1.2±0.2)×10(-3) M, d on = (1.3±0.4)×10(3) M(-1) s(-1), and d off = 1.5±0.4 s(-1), respectively, at pH 7.0 and 20.0°C. Accordingly, isoniazid inhibits competitively azide binding to Mt-trHbN(III) and Mt-trHbN(III)-catalyzed peroxynitrite isomerization. Moreover, isoniazid inhibits Mt-trHbN(II) oxygenation and carbonylation. Although the structure of the Mt-trHbN-isoniazid complex is not available, here we show by docking simulation that isoniazid binding to the heme-Fe atom indeed may take place. These data suggest a direct role of isoniazid to impair fundamental functions of mycobacteria, e.g. scavenging of reactive nitrogen and oxygen species, and metabolism.
    PLoS ONE 08/2013; 8(8):e69762. DOI:10.1371/journal.pone.0069762 · 3.53 Impact Factor