Lithium teratogenicity

Both lithium and valproate are teratogenic. In this case, women thinking of having children may be advised to switch to alternate treatments before the pregnancy. 

Doses of verapamil reported to have antimanic effects have ranged from 80 mg b.i.d. to 160 mg t.i.d. Typically, the initial dose is 80 mg two or three times daily, with rapid escalation up to, but not exceeding, 480 mg/day. (Personal communication with Dubovsky and Giannini indicates some patients may require and safely tolerate doses up to 640 mg/day.) The drug is usually well tolerated, and no specific laboratory monitoring is required. Further, its lack of teratogenic potential makes this (and perhaps other CCAs) attractive alternatives to agents such as lithium, VPA, and CBZ. 

The issue of lithium-induced dysmorphogenesis is not settled. An earlier report suggested an increase in cardiac anomalies—especially Ebstein s anomaly —in lithium babies, and it is listed as such in Table 59-1 in this book. However, more recent data suggest that lithium carries a relatively low risk of teratogenic effects. Further research is needed in this important area. 

The teratogenic effects of lithium have been reviewed in several articles (466,467,488) two reviews of drug-related congenital malformation briefly mentioned lithium and cardiovascular teratogenesis (480,489). The authors concluded that while the risk of cardiovascular malformation is lower than once believed, it is nevertheless increased. 

The cardiovascular teratogenicity of lithium has been summarized in a review of managing bipolar disorder during pregnancy and postpartum (473). While the risk of Ebstein s anomaly is increased, likely 10-20 times more than in the general population, the absolute risk (0.05-0.10%) is small. Fetal ultrasonography was advised at 18-20 weeks of gestation in cases of first trimester lithium exposure (488). 

Warner JP. Evidence-based psychopharmacology 3. Assessing evidence of harm what are the teratogenic effects of lithium carbonate J Psychopharmacol 2000 14(l) 77-80. 

SAFETY PROFILE An experimental teratogen. Other experimental reproduedve effects. Readily forms an explosive peroxide. A very dangerous fire hazard when exposed to heat, flame, or oxidizers. Mixture with lithium tetrahydroaluminate may ignite or... 

Drugs known to be teratogenic include cytotoxics, warfarin, alcohol, lithium, methotrexate, phenytoin, valproate, ACE inhibitors and isotretinoin. Selective interference can produce characteristic anatomical abnormalities, and the phocomelia (flipper-Uke) limb defect was one factor that caused thalidomide to be so readily recognised. (For an account of thalidomide see p. 81.)... 

Carbamazepine is possible lithium alternative. However, recent findings indicate that it is less safe than previously thought probable teratogen. 

Some mood stabilizers have an increased teratogenic risk during the first trimester (e.g., carbamazepine, lithium, oxcarbazepine, and valproate) this risk is greater if the patient is on multiple agents... 

Leonard A. Hantson P and Gerber GB (1995) Mutagenicity, carcinogenicity and teratogenicity of lithium compounds. Mutat Res 339 131-137. 

Carbamazepine is an anticonvulsant beneficial in the treatment of bipolar I disorder, and, as in the case of valproate, it may be more advantageous than lithium in non-classical bipolar conditions such as mixed mood states and rapid cycling conditions. It appears to have a teratogenic effect and, like valproate, has been associated with an increased risk of neural tube defects. ... 

A young female patient who suffers from bipolar affective disorder (BAD) has been managed with lithium. If she becomes pregnant, which one of the following drugs is likely to be effective in bipolar affective disorder with minimal risk of teratogenicity ... 

LD50 (oral, rat) 1870 mg/kg, (IP, mouse) 143 mg/kg poison by skin contact, inh., IP routes highly toxic corrosive tumorigen mutagen experimental teratogen TSCA listed Precaution Violent reactions with lithium under nitrogen atmosphere... 

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