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We comprehensively reviewed published literature to determine whether it supported the link between corrected QT (QTc) interval prolongation and torsade de pointes (TdP) for the 11 second-generation antipsychotics and seven second-generation antidepressants commonly implicated in these complications. Using PubMed and EMBASE, we identified four thorough QT studies (one each for iloperidone, ziprasidone, citalopram, and escitalopram), 40 studies specifically designed to assess QTc interval prolongation or TdP, 58 publications based on data from efficacy and safety trials, 18 toxicology studies, and 102 case reports. Thorough QT studies, QTc prolongation-specific studies, and studies based on efficacy and safety trials did not link drug-associated QTc interval prolongation with TdP. They only showed that the drugs reviewed caused varying degrees of QTc interval prolongation, and even that information was not clear and consistent enough to stratify individual drugs for this risk. The few toxicology studies provided valuable information but their findings are pertinent only to situations of drug overdose. Case reports were most informative about the drug-QTc interval prolongation-TdP link. At least one additional well established risk factor for QTc prolongation was present in 92.2 % of case reports. Of the 28 cases of TdP, six (21.4 %) experienced it with QTc interval <500 ms; 75 % of TdP cases occurred at therapeutic doses. There is little evidence that drug-associated QTc interval prolongation by itself is sufficient to predict TdP. Future research needs to improve its precision and broaden its scope to better understand the factors that facilitate or attenuate progression of drug-associated QTc interval prolongation to TdP. [ABSTRACT FROM AUTHOR]

Rationale: A recent publication asserted that even low-dose risperidone may induce corrected QT (QTc) interval prolongation up to 500 ms without drug-induced I blockade. We seek to better understand the complexity of any link between risperidone-induced/associated QTc interval prolongation and torsade de pointes (TdP). Objectives: The objective of this study is to systematically analyze all available case reports of risperidone, QTc interval prolongation, and/or TdP. Method: We identify case reports using PubMed, Medline, EMBASE, and Cochrane. Results: Of the 15 cases found, nine were adult women (ages 31, 33, 34, 37, 47, 'elderly', 77, 84, and 87 years) and one was a teenager. There were four men (ages 28, 29, 29, and 46 years) and one preadolescent boy. Besides risperidone administration or overdose, traditional risk factors for QTc interval prolongation and TdP included female sex ( n = 10), older age ( n = 4), heart disease ( n = 3), hypokalemia ( n = 2), bradycardia ( n = 1), liver disease ( n = 1), QTc interval prolonging drugs other than risperidone ( n = 8), and metabolic inhibitors ( n = 2). TdP occurred in four cases. Six patients died, and three deaths were probably related to TdP. Conclusion: Risperidone (when properly prescribed in patients free of other risk factors for QTc interval prolongation and TdP) is a relatively safe drug. Conventional statistics can neither predict the individual patient who will experience TdP nor determine the relationship of drug dose to QTc interval prolongation and TdP. Narrative medicine using a case report format appears to be an alternative and valuable additional approach to advance our understanding of this relationship and to reduce risks. [ABSTRACT FROM AUTHOR]

Patients with schizophrenia are at increased risk for developing the metabolic syndrome or its individual components due to their lifestyle, suspected genetic predisposition, and exposure to antipsychotic medications that can cause weight gain and other metabolic side effects. Despite the availability of clinical guidelines, screening for and monitoring of metabolic problems in this patient population continue to be suboptimal. We provide an overview specifically addressing 1) why patients with schizophrenia are at increased risk for metabolic problems; 2) how commonly used antipsychotic medications vary in terms of their metabolic liability; 3) how to effectively screen for and monitor metabolic problems in patients receiving antipsychotic medications; 4) what interventions can prevent, limit, or reverse the metabolic side effects of antipsychotic drug treatment; and 5) what are the barriers to the care of these patients. [ABSTRACT FROM AUTHOR]

Individuals receiving certain atypical antipsychotic medications are at risk of gaining weight and developing metabolic problems. There are no established drug treatments to prevent or counter these problems. However, the antihyperglycaemic agent metformin appears promising in some recent studies and we review the literature that evaluates metformin for limiting or reversing atypical antipsychotic drug-induced weight gain and glucose metabolism dysregulation. These studies suggest that metformin is beneficial if started early in antipsychotic drug treatment. Metformin has also been shown to prevent or delay the onset of type 2 diabetes mellitus in high-risk individuals from the general population. Based on these findings, we identify antipsychotic drug-treated patients who might benefit from metformin therapy and offer clinical guidelines for its use. Further long-term studies are needed to extend our observations and improve this strategy. [ABSTRACT FROM AUTHOR]

The quinidine-like effects of some antidepressant drugs (particularly tricyclic antidepressants) and many antipsychotic drugs (particularly the phenothiazines) confound treatment of psychosis and depression in patients with major mental illness. This is especially true among elderly patients with existing risk factors for corrected QT (QTc) interval prolongation. We used PubMed, previously reported review articles and the extensive personal files of the authors to identify cases of subjects aged ≥60 years who developed QTc interval prolongation, polymorphic ventricular tachycardia (PVT)/lorsade de pointes (TdP) and/or sudden cardiac death while taking antipsychotic or antidepressant drugs or a combination of these medications. We identified 37 patients who had taken, in total, 46 antipsychotic or antidepressant drugs. Our most striking finding was that almost four-fifths of our cases involved women. When the 14 critically ill subjects receiving haloperidol intravenously were excluded, 91.3% of our subjects were women. Almost three-quarters of our study subjects had cardiovascular disease. Intravenous administration of haloperidol in the critically ill and profoundly agitated elderly warrants particular comment. Of the 14 subjects in this category identified, six were men and eight were women. In 13 cases, the drug dose far exceeded the 2 mg necessary to produce an antipsychotic effect. These clinicians were using an agent to achieve sedation that usually requires very high doses in the critically ill and profoundly agitated elderly to achieve this effect. Inclusion criteria for our literature review required antipsychotic and/or antidepressant drug-induced QTc interval prolongation. Even so, our finding that 31 of our 37 subjects developed PVT is sobering. However, the reader should not conclude that drug-induced QTc interval prolongation is highly predictive of PVT or its TdF subtype. All of our study subjects had at least two risk factors for TdP, with age and sex being the most common. We included the rare case of a patient with congenital long QT syndrome who developed further lengthening of the QTc interval and TdP when prescribed an antidepressant drug well known to produce QTc interval prolongation. We conclude with recommendations for clinicians not expert in the specialty of cardiology to deal with the many questions raised in this review. Specifically, such clinicians treating elderly patients with antipsychotic and antidepressant drugs that may prolong the QTc interval should aggressively obtain a baseline ECG for elderly female patients with additional risk factors such as personal or family history of pre-syncope or syncope, electrolyte disturbances or cardiovascular disease.… [ABSTRACT FROM AUTHOR]

Clinical and demographic data were collected on 203 state mental hospital patients whose length of stay was greater than one year. They comprised 45% of the average adult census and 37% were less than 35 years old. Males were younger and females more educated and likely to have been married at one time. The majority have diagnoses of schizophrenia or organic mental disorders; a few have personality disorders. Patients were treated with drugs but risk/benefit parameters remain to be defined. Thirty-two percent of patients have had a violent episode during the past six months. The prevalence of neurological abnormalities supports the need for specialized neurological and neuropsychological consultation and medical consultation. Most patients require the level of care provided by a hospital, while 15% are ready for discharge but have no housing available. Intermediate care facilities could provide alternatives for some patients otherwise unable to leave the hospital. The implications raised by these findings are discussed. [ABSTRACT FROM AUTHOR]

The 15 patients with the highest numbers of assaultive incidents over a one year period in a state mental hospital were identified and information collected regarding a variety of clinical and demographic characteristics. The results showed a group of patients who are relatively young, manifest severe symptomatology that is generally unresponsive to treatment, and have now been hospitalized continuously for greater than four years. The patients experienced the onset of symptoms as teenagers in most cases, showed poor psychosocial adjustment beyond childhood, and had positive family histories for mental illness or alcohol abuse. Patients with psychotic disorders predominated and tended to have positive symptoms rated as severe to very severe on the Global Rating Scale for Psychosis. Patients with nonpsychotic or personality disorders always showed a high frequency of self-injurious behavior in addition to their aggressive behavior toward others. A number of patients had a history of head trauma with EEG abnormalities. This information provides a starting point for subsequent studies examining potential distinctions between this subpopulation of patients and others, the motivation and circumstances of such incidents, and the interaction between the behaviors and their effects on those around them. [ABSTRACT FROM AUTHOR]

Among 20 chronically psychotic patients, half of whom received lithium and half of whom received the combination of lithium and carbamazepine, thyroxine levels were slightly higher and thyroid stimulating hormone levels were slightly lower among the patients receiving lithium compared with the patients receiving the combination of lithium and carbamazepine. The clinical implications of our findings are discussed. [ABSTRACT FROM AUTHOR]

Eight patients (7 men and 1 woman, mean age 43.1 ± 8.9 years) with psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome) underwent treatment with demeclocycline in an effort to normalize serum sodium levels and thereby protect the PIP patients against complications including hyponatremic seizures and coma. There tended to be an improvement (p=.080) in early morning serum sodium following treatment with demeclocycline (baseline 132.6±SD 3.3 and treatment serum sodium 134.8±SD 3.3 mEq/1). At the same time, there was an increase (p=.043) in urinary specific gravity following treatment with demeclocycline (baseline 1.0047±SD .0029 and treatment urinary specific gravity 1.0063±SD .0026). Clinical indications for and potential mechanisms of action of demeclocycline treatment in the PIP syndrome are discussed. [ABSTRACT FROM AUTHOR]

Three male chronically psychotic patients (mean age 33.0±S.D. 7.2 years), two with schizoaffective disorder and one with organic affective disorder, received carbamazepine (CBZ) because of affective symptoms (and, in one case, partial complex seizures) refractory to management with antipsychotic drugs. Coincident with CBZ administration (and clinical improvement), hyponatremia developed thought to be due to the antidiuretic effect of this drug. Lithium was added to counteract the antidiuretic effect of CBZ. Further clinical improvement ensured, serum sodium levels became normal, and there was an increase in the white blood cell count in each patient. The clinical implications of our findings are discussed. [ABSTRACT FROM AUTHOR]

Thirty-six chronically psychotic patients (nine men and 27 women, mean age 56.7+/−S.D. 13.4 years) were found to have elevated thyroid stimulating hormone (TSH) levels during review of thyroid function screening tests of 1150 patients over a 15 month period in a 700 bed state mental hospital. This study population of 36 patients was more likely to be female and older than the general hospital population. The spectrum and frequency of psychiatric diagnoses included dementia (3); schizoaffective disorder (12); bipolar disorder (6); schizophrenic disorder (4); organic affective disorder (7); major depression (3); and mental retardation (1). Only nine of these 36 patients failed to receive the goitrogens lithium (LI), carbamazepine (CBZ) and/or phenytoin (PTN) and five of those nine patients had a history of thyroid disease. Sex did not predict age, thyroxine (T) level, triiodothyronine (T) uptake, or TSH. The distribution of psychiatric diagnoses were the same for both sexes. Expectedly, there was an inverse relationship between TSH and T and T uptake. Using T to separate grades 1 and 2 hypothyroidism revealed that six (17%) patients had grade 1 disease. Men were more likely to have a seizure disorder and receive LI, CBZ, and PTN. Women were more likely to have a history of thyroid disease. The goitrogenic effects of LI+CBZ seemed additive compared with patients receiving LI alone. While T, T uptake, and LI levels were the same for the two groups, patients receiving LI+CBZ had higher TSH values (p=0.028) than did patients receiving LI alone. A history of thyroid disease did not alter T or T uptake but was associated with a higher TSH (p=0.039). The clinical implications of our findings are discussed. [ABSTRACT FROM AUTHOR]