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C H A P T E R 2 2 Psychotherapeutic agents

TABLE 22.2

DRUGS IN FOCUS Antimanic drugs

Drug name

Dosage/route

Usual indications

aripiprazole (Abilify)

30 mg/day PO

Treatment of acute manic and mixed episodes of bipolar disorders Long-term maintenance of people with bipolar disorders; decreases occurrence of acute mood episodes Treatment of manic episodes of manic- depressive or bipolar illness; maintenance therapy to prevent or diminish the frequency and intensity of future manic episodes; currently being studied for improvement of neutrophil counts in people with cancer chemotherapy- induced neutropenia and as prophylaxis of cluster headaches and migraine headaches; not recommended for children <12 years Management of acute manic episodes associated with bipolar disorder, in combination with lithium or valproate, or as monotherapy Adjunct or monotherapy for the treatment of manic episodes associated with bipolar disorder Treatment of acute manic and mixed episodes of bipolar disorders

lamotrigine (Lamictal)

25 mg/day PO up to 200 mg/day

500–1000 mg/day based on serum lithium levels

lithium salts (Lithicarb, Quilonum SR)

olanzapine (Zyprexa, Zyprexa Zydis)

10 mg/day PO; range 5–20 mg/day

quetiapine (Seroquel)

50 mg PO b.d., titrate to a maximum 800 mg/day

ziprasidone (Zeldox)

40 mg PO b.d. with food; maximum 80 mg b.d.

severe hyponatraemia may occur. (Hyponatraemia leads to lithium retention and toxicity.) Pregnancy and breastfeeding are also contraindications because of the potential for adverse effects on the fetus or neonate; breastfeeding should be discontinued while using lithium and women of childbearing age should be advised to use birth control while taking this drug. Caution should be used in any condition that could alter sodium levels , such as protracted diarrhoea or excessive sweating; with suicidal or impulsive individuals; and in people who have infection with fever, which could be exacerbated by the toxic effects of the drug. Adverse effects The adverse effects associated with lithium are directly related to serum levels of the drug. • Serum levels of less than 1.5 mEq/L : CNS problems, including lethargy, slurred speech, muscle weakness and fine tremor; polyuria, which relates to renal toxicity; and beginning of gastric toxicity, with nausea, vomiting and diarrhoea. • Serum levels of 1.5 to 2 mEq/L : Intensification of all of the foregoing reactions, with ECG changes. • Serum levels of 2 to 2.5 mEq/L : Possible progression of CNS effects to ataxia, clonic movements, hyperreflexia and seizures; possible CV effects such as severe ECG changes and hypotension; large output

of dilute urine secondary to renal toxicity; fatalities secondary to pulmonary toxicity. • Serum levels greater than 2.5 mEq/L : Complex multiorgan toxicity, with a significant risk of death. Clinically important drug–drug interactions Some drug–drug combinations should be avoided. A lithium–haloperidol combination may result in an enceph- alopathic syndrome, consisting of weakness, lethargy, confusion, tremors, extrapyramidal symptoms, leucocy- tosis and irreversible brain damage (see Box 22.6). If lithium is given with carbamazepine, increased CNS toxicity may occur and a lithium–iodide salt com- bination results in an increased risk of hypothyroidism. People who receive either of these combinations should be monitored carefully. In addition, a thiazide diuretic– lithium combination increases the risk of lithium toxicity because of the loss of sodium and increased retention of lithium. If this combination is used, the dose of lithium should be decreased and the person should be monitored closely. In the following instances, the serum lithium level should be monitored closely and appropriate dose adjustments made. With the combination of lithium and some urine-alkalinising drugs, including antacids, there is a possibility of decreased effectiveness of lithium. If lithium is combined with indomethacin or with some nonsteroidal anti-inflammatory drugs, higher plasma