Antipsychotic polypharmacy and high doses have been associated with poorer outcome, longer hospital stays, and increased side effects. The present naturalistic study assessed the cognitive effects of antipsychotics in 56 patients with a diagnosis of schizophrenia or schizoaffective disorder, using the Brief Assessment of Cognition in Schizophrenia (BACS). Antipsychotic daily dose (ADD) was expressed as mg risperidone equivalents/day (RIS eq), using a model based on drug doses from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study for second generation antipsychotics (SGA) and chlorpromazine equivalents for first generation antipsychotics (FGA), with a 1/1 equivalence between haloperidol and risperidone. Increasing age was associated with polypharmacy, FGA prescription and decreasing BACS score. FGA prescription, in turn, predicted a poorer cognitive functioning, independently of age, PANSS subscores and ADD. ADD was associated with decreasing cognitive scores, an effect that remained significant after controlling for age, PANSS or polypharmacy. The detrimental cognitive effects of polypharmacy, in turn, appeared to be mediated by ADD. Different methods of data fitting suggested that ADD above 5-6 mg RIS eq/day were associated with lower BACS scores. Overall, these results show that increasing antipsychotic daily dose is associated with poorer cognitive functioning at doses lower than previously thought, independently of the number of antipsychotic drugs.
We have studied the modulation and pharmacological properties of two anion channels in T, ceils by recording single channel and transepithelial currents. One channel had an outwardly rectifying current-voltage Z/V curve, was rarely active in cell-attached patches, and was unaffected by CAMP. The other channel had lower conductance (8.7 pS at 37°C) and a more ohmic Z/V relationship. Exposure to CAMP increased the probability of observing low-conductance channel activity in cell-attached patches > 6-fold. Extracellular DIDS (4,4'-diisothiocyanatostilbene-2,2'disulfonic acid) or IAA-94 (an indanyloxyacetic acid) inhibited the outward rectifier but did not a&t the low-conductance channel or CAMP-stimulated transepithelial current. These results suggest the low-conductance Cl channel may contribute to apical membrane conductance during CAMP-stimulated secretion.
Lithium is an important medication in the treatment of mood disorders. However, clinicians are hesitant to use lithium in older adults for fear of its medical effects, particularly kidney disease. This review describes the current understanding of the epidemiology and mechanisms underlying chronic kidney disease (CKD) in older lithium users, with recommendations for using lithium safely in late life. Prevalence estimates of CKD in older lithium users range from 42-50%, which does not differ greatly from the 37.8% rates seen in community-dwelling non-lithium using, non-psychiatric populations. Clinical and pre-clinical data suggest a variety of synergistic mechanisms contributing to CKD in older lithium users, including aging, cardiovascular factors, oxidative stress, inflammation, nephrogenic diabetes insipidus, acute kidney injury, and medication interactions. With regards to CKD, lithium can be used safely in many older adults with mood disorders. Compared to patients with pre-existing CKD, those with an estimated glomerular filtration rate >60 mL/min/1.73 m(2) are probably not as susceptible to lithium-associated renal decline. Using lithium concentrations <0.8 mmol/L; monitoring lithium concentrations and renal function every 3-6 months; being vigilant about concurrent medication use (e.g., diuretics, anti-inflammatories); as well as preventing/treating acute kidney injury, nephrogenic diabetes insipidus, diabetes mellitus, hypertension, smoking, and coronary artery disease can all help prevent CKD and further renal decline in older lithium users.
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