A 48-year-old man is prescribed sodium valproate for prophylaxis against bipolar mania. He develops a confusional state despite liver function tests being within the normal range.
Which of the following conditions related to valproate use is most likely to be associated with the above presentation?
A. Valproate is associated with elevated plasma ammonia. In some people, hyperammonaemia may be clinically significant, resulting in hyperammonaemic encephalopathy characterized by varied clinical presentation, including irritability, agitation, drowsiness, asterixis, coma, and paradoxical seizures. Other symptoms may include loss of appetite, nausea, and vomiting. Valproic acid-induced hyperammonaemic encephalopathy may occur in people with normal liver function, despite normal doses and serum levels.It is more common in children with urea cycle enzyme deficiencies. Other risk factors include concomitant antiepileptic prescriptions (especially topiramate), underlying liver disease or hypoalbuminaemia, initiation of high-dose and long-term therapy. Propionate, a metabolite of valproate reduces the hepatic N-acetylglutamate concentration, which is an obligatory activator of carbamoyl phosphate synthetase 1 (CPS-1), the first enzyme of the urea cycle. Another potential mechanism may be via valproate-induced reduction in hepatic carnitine levels.
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All of the following patients are under carbamazepine therapy for bipolar disorder.
In which of the following patients will you discontinue the carbamazepine treatment immediately?
C. Nausea, ataxia, and dizziness are common side-effects of carbamazepine; usually, none of these in isolation warrants a cessation of therapy. A maculopapular rash is noted in nearly 1 in 10 patients receiving carbamazepine. This usually occurs within 2 weeks of therapy and often requires cessation of treatment if associated with an abnormal blood count. Although leucopenia is seen in 1–2% of patients, serious agranulocytosis occurs rarely (about eight per million prescriptions). This bone marrow toxicity warrants a cessation of therapy and is indicated by a total white blood cell (WBC) count of less than 3000 per mm3 or a neutrophil count less than 1500 per mm3 . Hyponatraemia is a common side-effect but levels up to 125 mEq/L can be managed conservatively without requiring sudden cessation of treatment. Elevation of thyroid-stimulating hormone does not necessitate stopping carbamazepine.
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Which of the following predicts a good prophylactic effect of lithium in bipolar disorder?
D. Various clinical, biological, and genetic factors that predict lithium responsiveness in prophylaxis of bipolar disorder have been studied. The presence of typical features of bipolar disorder, good inter-episode clinical recovery, a family history of bipolar disorder, experiencing mania as the first bipolar episode, and a good response to lithium in the acute manic phase predict lithium responsiveness. The presence of neurological signs, comorbid substance use, and the presence of rapid cycling predict a poor response to lithium. The lithium response in a sample composed of relatives of lithium responder probands was 67% compared with 30% in the control group; this indicates that lithium responsiveness may have a certain degree of heritability.
Which of the following situations associated with parental loss carries the highest risk of developing depression as an adult?
C. Parental divorce between birth and age 7, regardless of subsequent remarriage, was predictive of a twofold higher depression risk. The relative risk of depression was highest for children whose single parent remarried into a conflictual relationship following divorce. It was shown that the quality of parental relationship, especially in relation to continuing conflict among those taking parental responsibilities, has a major effect on the subsequent risk of depression. Although childhood socioeconomic status was found to be a significant predictor of later depression, the risk for depression associated with parental divorce was found to be of a similar magnitude across categories of childhood socioeconomic status. There is little evidence that childhood bereavement itself predisposes to adult depression.
Adverse life events are consistently associated with depression.
Which of the following statements with respect to the above relationship is NOT true?
E. Only 30% of those with depression give no history of significant life events. Depression itself may generate negative life events (reverse causality). Similarly, there may be a genetic contribution to the experience of adverse life events, making the gene–environment interaction more complex. The Life Events and Difficulties Scale is considered to be the standard life events assessment instrument. This scale is based on contextual measurement of the threat posed by life events (i.e. an event can be considered as significant only in accordance with social and cultural backgrounds and the life situation in which it occurs). It is shown that suicide attempters have a higher rate of life events than those with depression. Loss, humiliation, or separation events highly correlate with depression.
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