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Second-generation antipsychotic medications (SGAs) have advanced the treatment of schizophrenia over the past 30 years. However, a number of potentially life-threatening cardiac side-effects associated with these treatments concern and can discourage prescribers from administering these evidence-based treatments. This review provides a practical, psychiatrist-oriented understanding of the relative frequencies, mechanisms, investigations and treatments associated with these cardiac toxicities. We aim to highlight that these are relatively rare complications of an effective class of drug and to promote the advantages of early involvement of cardiologists in the psychiatric multidisciplinary team to guide the investigation and management of these conditions.
After reading this article you will be able to:
•understand the relative incidence of cardiotoxic side-effects of the various SGAs
•perform preliminary investigations to diagnose the common cardiotoxic side-effects of SGAs
•understand the treatments for these cardiac side-effects and the role of cardiologists involved the care of these patients.
‘Rebound’ or ‘withdrawal’ symptoms are frequently observed after a sudden discontinuation of clozapine. We describe a patient with treatment-resistant schizoaffective disorder who developed agranulocytosis on clozapine but was successfully switched to treatment with olanzapine with no deterioration in her condition. We put forward three possible theories which may have accounted for the lack of rebound symptoms in this patient: the pharmacological profile of olanzapine, the anticholinergic effects of hyoscine hydrobromide, and the possibility that this patient may not be treatment-resistant and so have a reduced risk of rebound psychosis due to displaying a different pathophysiology.
Clozapine has a range of serious adverse effects that may give rise to an increased risk of death.
To compare reasons for discontinuation of clozapine with reasons for discontinuation of risperidone long-acting injection in age-matched individuals treated in the same clinical environment.
Comparison of patients receiving clozapine and an age-matched control group receiving risperidone injection.
We established outcome for 529 consecutive patients receiving clozapine and 250 receiving risperidone (161 discontinuers from each group were compared). Adverse effects (odds ratio OR=2.19, 95% CI 1.31–3.67) and death (OR=7.0, 95% CI 2.09–23.5) were more commonly observed as reasons for discontinuation of clozapine than of risperidone. Clozapine was less likely to be withdrawn because of ineffectiveness than was risperidone (OR=0.034, 95% CI 0.01–0.14). Standardised mortality ratio (SMR) was significantly raised for patients receiving clozapine (SMR=4.17, 95% CI 2.78–6.26). Pneumonia was the most common single cause of death.
Clozapine use in patients with severe mental illness was associated with a significantly increased risk of death compared with that for the general population. Causation could not be established. Adverse effects and death are common causes of clozapine discontinuation.
To evaluate the prescribing of valproate in clozapine-treated individuals who may be at risk of seizure. We collected point-prevalent clinical characteristics and demographics of all in-patients prescribed clozapine in an acute mental health trust. Data were collected from case notes, electronic records and drug charts, and analysed against a set audit standard.
Data were collected for 81 in-patients. Of all deemed to be at risk of seizure (n=37) only 24% were prescribed valproate at a therapeutic plasma level.
The majority of patients prescribed clozapine at risk of seizures were not adequately protected from this risk. Clear guidelines are required.
To review the evidence for this use of pramipexole in the treatment of unipolar and bipolar depression, a literature search on Embase and Medline was conducted in December 2003. The search was updated in July 2004. The reference sections of retrieved papers were searched for further relevant references.
There are limited data on the clinical use of pramipexole in affective disorders. Only two double-blind trials in bipolar depression and one in unipolar depression were retrieved. Most information is in the form of case reports and open studies. No dose-response relationships have been established and a wide range of doses has been employed in the reports.
In view of the fact that the evidence for the use of pramipexole is still limited at the time of writing, its routine clinical use cannot be recommended. The data appear promising, but further research is required to determine its role in affective disorders.
The study aimed to identify the predictors of drop-out from clozapine treatment by examining the demographic and clinical characteristics of patients registered on clozapine within a 6-month period in one NHS Trust.
During the study period, 54 patients were registered and began clozapine treatment and 31% had discontinued within 6 months. Two people died and the remainder discontinued because of non-compliance or side-effects, including neutropenia. Two factors were predictive: the age of the patient (older patients were more likely to discontinue) and the hospital where the initial registration was made.
Neither ethnicity, previous registration nor the individual prescriber are a bar to successful persistence with clozapine. However, one set of hospitals with a history of evidence-based practice and high clozapine prescribing was more successful in retaining patients on maintenance treatment. Although specific data are needed to identify more subtle contributing factors to continuation, it is clear that there is scope for improving the rate of persistence with clozapine treatment.
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