Medicine Digest Psychology
Behaviour problems and demen- tia: mortality risks with different antipsychotics
The use of antipsychotics for elderly
people with dementia and behavioural disturbances is generally discouraged because of the risk of increased mor- tality. For some patients however, their use might be considered because the patient’s behaviour poses a risk to them- selves or to others. US data have shown the relative risks with different antipsy- chotics. The study included data for 75445 people aged 65 or older living in nursing homes in 45 states and newly prescribed an antipsychotic in 2001–2005. Within the first 180 days of treatment there were 6598 non-cancer deaths (37.1 deaths per 100 person–years.) Compared with risperidone, there was a significant dou- bling of mortality risk with haloperidol and a significant 20% reduction in risk with quetiapine. Aripiprazole, olanzap- ine, and ziprasidone were associated with risks similar to that of risperidone. The effects of haloperidol and quetiapine were most marked soon after the initia- tion of treatment.
Quetiapine seemed to be the safest of
the antipsychotics. Huybrechts KF et al. Differential risk of death in older residents in nursing homes prescribed specific anti- psychotic drugs: population-based cohort study. BMJ 2012; 344 (March 17); 16 (e977); McCleery J, Fox R. Antipsychotic prescribing in nursing homes. Ibid: 7 (e1093) (editorial).
Lithium toxicity
Lithium is effective in the treatment of bipolar disorder, providing protection against both depression and mania, but there are concerns about potential tox- icity, in particular its effects on the kid- neys and risk of teratogenicity. Present guidelines suggest avoiding lithium in pregnancy but the degree of risk is un- known, as is the extent of renal toxicity. A systematic review and meta-analysis has clarified some issues. The analysis included 385 studies,
including 22 randomised, controlled tri- als, 197 case-control, uncontrolled co- hort, or cross-sectional studies, and 166 case reports. Overall, lithium reduced glomerular filtration rate by 6.22mL/ min and urinary concentrating ability by 15% of normal maximum. The risk of chronic renal failure was low, with 0.5% of patients needing renal replacement
60 Africa Health
therapy. The risk of hypothyroidism was increased almost six-fold. There was also an increased risk of hyperparathyroid- ism with an average increase in blood calcium levels of 0.09mmol/L and in parathyroid hormone levels of 7.32pg/ mL. Weight gain was greater with lithium than with placebo but not greater than with olanzapine. In this study there were no significant increases in risk of con- genital malformations, alopecia, or other skin disorders. Lithium treatment increases the risks
of hypothyroidism and hyperparathyroid- ism. The risk of end-stage renal failure is low but urinary concentrating abil- ity may be impaired, leading to clinical nephrogenic diabetes insipidus. The risk of teratogenicity is uncertain but there was no significant increase in congenital malformations in this study. Serum cal- cium levels should be checked before and during treatment. Lancet editorialists conclude that these data confirm that, on balance, lithium is the treatment of
choice for bipolar disorder. McKnight RF et al. Lithium toxicity profile: a system- atic review and meta-analysis. Lancet 2012; 379: 721–8; Malhi GS, Berk M. Is the safety of lithium no longer in balance? Ibid: 690–2 (comment).
by shorter routes. It also resulted in a re- setting of the phase of the theta rhythm on hippocampal electroencephalogram. Direct stimulation of the hippocampus had no effect. No adverse events oc- curred.
Entorhinal stimulation enhanced spa-
tial memory. Much more research will be needed to determine the clinical impli- cations of this research.
Sulthana N et al. Memory enhancement and deep- brain stimulation of the entorhinal area. NEJM 2012; 366: 502–10; Black SE. Brain stimulation, learning, and memory. Ibid: 563–5 (editorial).
Dutasteride for localised prostate cancer
Localised prostate cancer is relatively benign and many men may receive un- necessary treatment. Treatment with a 5α-reductase inhibitor might reduce the need for more aggressive therapy. Researchers in North America have sug- gested that dutasteride treatment might benefit men with low-risk prostate can- cer.
The trial, at 65 centres in the USA and Neurology
Deep brain stimulation and memory
Deep brain stimulation has been used
to treat Parkinson’s disease, dystonia, depression, and obsessive-compulsive disorder. Animal experiments have sug- gested that stimulation of entorhinal- hippocampal pathways may improve memory. Studies in humans have shown negative effects on memory but it is possible that stimulation at certain sites during information processing could en- hance memory. Now studies on patients with implanted electrodes for seizure diagnosis prior to epilepsy surgery have shown some enhancement of memory when applied during learning. Seven subjects each completed a spa- tial learning task (learning destinations within a virtual environment). Four had entorhinal electrodes and five had at least one hippocampal electrode (four had both). Focal electrical stimulation below the after discharge threshold was given in half of the learning trials. Ento- rhinal stimulation during learning im- proved memory for location and enabled subjects to reach landmarks quicker and
Canada, included 289 men aged 48–82 with low-volume, Gleason score 5–6 prostate cancer and at least one repeat biopsy during follow-up. They had all chosen active surveillance rather than more aggressive treatment. Randomisa- tion was to dutasteride 0.5mg daily or placebo, and follow-up was for 3 years with repeat biopsies at 18 months and 3 years. At 3 years, the rate of prostate cancer progression was 38% (dutaste- ride) vs 48% (placebo), a significant dif- ference. The rates of adverse events were similar in the two groups. Sexual adverse events or breast enlargement occurred in 24% vs 15%. There were no deaths from prostate cancer and no subject devel- oped metastatic disease. Cardiovascular adverse events occurred in 5% of each group.
Dutasteride might benefit men with
low-risk prostate cancer who choose ac- tive surveillance. A Lancet commentator, however, points to previous evidence that dutasteride might have no effect on prostate cancer mortality (or might even increase the risk) and concludes that dutasteride, or any other treatment, can- not be recommended for these men. He believes that neither treatment nor diag- nosis should be attempted for low-risk
disease. Fleshner NE et al. Dutasteride in localised prostate cancer management: the REDEEM randomised, dou- ble-blind, placebo-controlled trial. Lancet 2012; 379: 1103–11; Parker C. What (if anything) to do about low-risk prostate cancer. Ibid: 1078–80 (comment).
July 2012
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