Table 2.
Butyrophenone, Diphenylbutylpiperidine, and Thioxathene Derivates and Pregnancy
| Study, Drug, and Sample size | Drug, Daily Dose, and Timing of Exposure During Pregnancy | Major Malformations | Pregnancy and Neonatal Outcomes |
| Dieulangard et al100 (N = 1) | HAL, dose and timing of exposure: N/A | Limb malformations; concomitant drug use | N/A |
| Kopelman et al101 (N = 1) | HAL, 15 mg (wk 1–7) | Limb malformations; concomitant drug use and infectious mononucleosis | Infant’s death due to subdural hemorrhage |
| Council on drugs102 (N = 1) | HAL, dose and timing of exposure: N/A | Limb malformations; concomitant drug use | N/A |
| Godet and Marie-Cardine103 (N = 29) | HAL, dose and timing of exposure: N/A | N = 3, further clinical details: N/A; concomitant drug use: N/A | Increased rates of prematurity (12.3%); concomitant drug use: N/A |
| Reis and Källén44 (N = 77) | HAL, doses: N/A (first trimester) | Microphtalmia plus gastroschisis (N = 1), renal dysplasia plus pes equinovarus (N = 1); concomitant drug use: N/A | Gestational diabetes (N = 1); concomitant drug use: N/A; neonatal complications: N/A |
| Diav-Citrin et al106 (N = 188) | HAL, 10 mg (wk 34 to delivery) and 12.5 mg/mo, long-acting injectable formulation (wk 1–35), dose: N/A (2 wk during the second trimester) and 150 mg/mo, long-acting injectable formulation (throughout pregnancy), 10 mg (wk 1–30) | Severe bullous emphysema (N = 1); finger's anomalies (N = 1); cystic hygromas (N = 1); carbamazepine syndrome, developmental delay, and congenital heart defect (N = 1); ventricular septum defect and genu varum (N = 1); in some instances, concomitant drug use | Perinatal complications: (N = 9) (including feeding and respiratory problems, arrhythmia, irritability, and hypotonia); in some instances, concomitant drug use |
| Van Waes and Van de Velde105 (N = 96) | HAL, 1.2 ng—median—(first trimester) | No | Spontaneous abortions (N = 4), stillbirths (N = 4); concomitant drug use: N/A |
| Sexson and Barak107 (N = 1) | HAL, 2–6 mg (wk 1–34) | No | Continue tongue thrust (withdrawal emergent syndrome); probable concomitant drug use (primidone, phenytoin) |
| Mohan et al108 (N = 1) | HAL, dose and timing of exposure: N/A | No | Severe hypothermia; concomitant benztropine use |
| O'Collins and Comer109 (N = 1) | HAL, 200 mg every 2 wk, long-acting injectable formulation (throughout pregnancy) | No | Continue tongue thrust, torticollis, and tonic-clonic movements; no concomitant drug use |
| Walloch et al110 (N = 1) | HAL, 5 mg (wk 27 to prior delivery) | No | Healthy |
| Hansen et al111 (N = 1) | HAL, 300 mg (single overdose during the last month) | No | Fetal akinesia and neuromuscular depression; no concomitant drug ingestion |
| Newport et al67 (N = 13) | HAL, 2.25–10 mg—range—(last 3 mo) | No | Cardiovascular complications (N = 2), respiratory complications (N = 1), hypotonia (N = 1); in some instances, concomitant drug use |
| Diav-Citrin et al106 (N = 27) | PEN, 2.9 mg—median—(wk 1–13) | Limb deformities (N = 1); no concomitant drug use | N/A |
| Reis and Källén44 (N = 5) | PMZ, dose: N/A (first trimester) | No | No |
| Bjarnason et al112 (N = 1) | PMZ, 1 mg (throughout pregnancy) | No | Premature birth; concomitant drug use |
| Reis and Källén44 (N = 98) | FPX, dose: N/A (first trimester) | Situs inversus plus patent ductus arteriosus (N = 1), cerebral cyst plus malformation of large veins (N = 1), cleft palate plus accessory thumb (N = 1); concomitant drug use: N/A | Gestational diabetes (N = 1); concomitant drug use: N/A; neonatal complications: N/A |
| Reis and Källén44 (N = 5) | CPX, dose: N/A (first trimester) | No | No cases of gestational diabetes; neonatal complications: N/A |
| Reis and Källén44 (N = 75) | ZPX, dose: N/A (first trimester) | Hypospadias plus urinary tract malformations (N = 3), ventricular septum defects in one case complicated by pylorostenosis and in another case by atrial septum defect (N = 4), congenital cataract plus undescended testis (N = 1), congenital heart block plus tracheomalacia (N = 1); concomitant drug use: N/A | Gestational diabetes (N = 5); concomitant drug use: N/A; neonatal complications: N/A |
Note: HAL: haloperidol; N/A: data not available; PMZ: pimozide; FPX: flupenthixol; CPX: chlorprothixene; ZPX: zuclopenthixol; PEN: penfluridol.