Birth seasonality in bipolar disorder, schizophrenia, schizoaffective disorder and stillbirths.

BACKGROUND: More than 40 studies have been done on seasonal birth patterns for schizophrenia, but only two small studies have been done for DSM-III-R bipolar disorder and none for schizoaffective disorder. Two studies have also reported a significant relationship between schizophrenia births and stillbirths. METHODS: In the largest study to date, birth data from four states was obtained on 126,987 state psychiatric hospitals inpatients divided into 'process' schizophrenia (disorganized, catatonic, undifferentiated), paranoid schizophrenia, schizoaffective disorder, bipolar disorder and major depression. Time series analysis compared these births to all general births and to stillbirths. RESULTS: 'Process' schizophrenia, paranoid schizophrenia, schizoaffective disorder and bipolar disorder all had statistically significant seasonal excess births from December through March (p = 0.0000). The largest excess was 5.8% for bipolar disorder. Major depression had significant excess births from March through May. Time series analysis showed statistically significant coherences between major depression and bipolar disorder (0.995) and between schizoaffective disorder and both 'process' schizophrenia (0.977) and bipolar disorder (0.977). Unexpectedly, a significant coherence was also found between paranoid schizophrenia and bipolar disorder (0.972). Excess stillbirths were found for each month from January through June and a significant coherence was found between stillbirths and paranoid schizophrenia (0.998). CONCLUSIONS: This study demonstrates that DSM-III-R bipolar disorder and schizoaffective disorder both have an excess of winter births, similar to that found in schizophrenia. Time series analysis, however, suggests that the causes may not be identical. Major depression, by contrast, has an excess of spring births.

An inpatient trial of the safety and efficacy of losartan compared with placebo and enalapril in patients with essential hypertension.

The antihypertensive activity and safety of losartan, a specific and selective antagonist of angiotensin II (subtype 1) receptors, was evaluated in 100 inpatients with mild to moderate essential hypertension. After a 2-week, single-blind, out patient placebo lead-in period, the last 2 days of which included inpatient monitoring of baseline blood pressure, the patients were assigned randomly to receive once-daily doses of either placebo; 50, 100, or 150 mg losartan; or 10 mg enalapril. Patients were treated double blind for 5 days, followed by a day for the study of drug withdrawal. Beginning with the first dose, the three doses of losartan and enalapril significantly decreased peak and trough systolic and diastolic blood pressures compared with placebo (p < or = 0.05). The area under the blood pressure curve was analyzed as an assessment of total blood pressure change throughout the day. On day 1, total blood pressure reduction with losartan (50-150 mg) was slightly less than with enalapril. By day 5 of double-blind treatment, the reduction in blood pressure in these groups was similar, suggesting that losartan has a slower onset of action than enalapril. No rebound hypertension was observed after study-drug discontinuation. Losartan was well tolerated in this trial, with an adverse event profile similar to placebo and enalapril.

Clinical profile of angioedema associated with angiotensin converting-enzyme inhibition.

Based on data from three studies with complete recording of adverse events in about 12,000 patients each, we determined that angioedema in association with the angiotensin converting-enzyme inhibitor enalapril maleate occurred during the first week of therapy at the rate of one case per 3000 patients per week. Thereafter, the incidence was 14-fold lower, without evidence of a temporal trend in incidence beyond the first week of therapy. The cumulative incidence was one case per 1000 patients treated (0.1%). An additional 138 case reports consistent with the diagnosis of angioedema were obtained from our overall controlled and marketed experience using enalapril in more than 1.2 million patients. These reports were examined to further characterize the reaction. The cases generally were mild, and they resolved on discontinuation of drug therapy. Seven patients experienced angioedema or urticaria in association with both enalapril and captopril, a structurally different angiotensin converting-enzyme inhibitor. This further suggested that the side effect is mechanism based. If angioedema is suspected, therapy with any angiotensin converting-enzyme inhibitor should be interrupted promptly, respiratory distress should be treated appropriately, and subsequent therapy should be initiated with an agent from an alternative class of medication.

The safety and tolerability of lisinopril in clinical trials.

The safety and tolerability of lisinopril were assessed in 1,476 patients [1,165 hypertensives and 311 patients with congestive heart failure (CHF)] and 211 normal volunteers. The duration of lisinopril therapy ranged from 1 day to 16 months, with a mean duration of 105 days. In the hypertensive population, the most frequent clinical adverse experiences on lisinopril alone were headache, dizziness, cough, and diarrhea. Not all of these adverse experiences were thought to be drug related. Five percent of patients were discontinued because of adverse clinical experiences; cough and dizziness were the most common reasons for discontinuation. Two of 1,165 (0.17%) hypertensive patients treated with lisinopril died, compared to 0.41% of hypertensive patients on other therapies. Neither case was considered to be drug related. In patients with CHF, the most frequent clinical adverse experiences were dizziness, diarrhea, hypotension, fatigue, headache, and rash. Not all of these adverse experiences were thought to be drug related. The percent of CHF patients discontinuing because of an adverse clinical experience was 7.4%; the most frequent causes for discontinuation were hypotension, dizziness, or renal impairment. Twelve deaths occurred in 311 CHF patients treated with lisinopril (3.9%) compared to 4/104 (3.8%) of CHF patients treated with placebo and 2/65 (3.1%) treated with captopril. Hypotension, orthostatic effects, or dizziness following the initial lisinopril dose occurred infrequently in patients treated with lisinopril. In hypertensive patients with normal renal function, including those treated previously or concomitantly with diuretic therapy, a first-dose hypotensive episode was reported in six of 955, or 0.6%. The incidence was higher (6.7%) in hypertensive patients with impaired renal function.(ABSTRACT TRUNCATED AT 250 WORDS)