36 - Interactions with other drugs4144

Interactions with other drugs41–44

Bipolar disorder CHAPTER 2 and a specificity approaching 100% in certain populations.32 Genetic testing in people from South-­East Asia is recommended before carbamazepine is prescribed. Carbamazepine is a known human teratogen (see Chapter 7). Carbamazepine commonly causes a chronic low white blood cell (WBC) count. One patient in 20,000 develops agranulocytosis and/or aplastic anaemia.33 Raised alkaline phosphate (ALP) and gamma-­glutamyl transferase (GGT) are common (a GGT of 2–­3 times normal is rarely a cause for concern34). A delayed multiorgan hypersensitivity reaction rarely occurs, mainly manifesting itself as various skin reactions, a low WBC count and abnormal LFTs. Fatalities have been reported.34,35 There is no clear timescale for these events. Some antiseizure drugs have been associated with an increased risk of suicidal behaviour. Carbamazepine has not been implicated, either in general36,37 or more specifically in those with bipolar illness.38 Pre-­treatment tests Baseline U&Es, FBC and LFTs are recommended by NICE. A baseline measure of weight is also desirable. On-­treatment monitoring In the UK, NICE recommends that U&Es, FBC and LFTs should be repeated after 6 months, and that weight (or BMI) should also be monitored. Discontinuation It is not known if abrupt discontinuation of carbamazepine worsens the natural course of bipolar illness in the same way that abrupt cessation of lithium does. In one small case series (n = 6), one patient developed depression within a month of discontinuation,39 while in another small case series (n = 4), three patients had a recurrence of their mood disorder within 3 months.40 Until further data are available, if carbamazepine is to be discontinued, it should be done slowly (over at least a month). Use in women of child-­bearing age Carbamazepine is an established human teratogen (see Chapter  7). Women who have mania are likely to be sexually disinhibited. The risk of unplanned pregnancy is likely to be above population norms (where 50% of pregnancies are unplanned). If carbamazepine cannot be avoided, adequate contraception should be ensured (note the interaction between carbamazepine and oral contraceptives outlined in the next section) and prophylactic folate prescribed. Interactions with other drugs41–­44 Carbamazepine is a potent inducer of hepatic cytochrome enzymes and is metabolised by CYP3A4. Plasma levels of most antidepressants, most antipsychotics, benzodiazepines, warfarin, zolpidem, some cholinesterase inhibitors, methadone, thyroxine, theophylline, oestrogens and other steroids may be reduced by carbamazepine, possibly