Sex Differences in Bipolar Affective Disorder: Neuroleptic Dosage Variance Dale A. D’Mello and John A. McNeil Bipolar affective disorder in men and women often differs in prevalence, age of onset, phenomenology, and longitudinal course. A study of 1 12 bipolar patients, comprising 72 women and 40 men who were discharged from an acute inpatient setting on antipsychotic drugs, is reported. Higher mean discharge neuroleptic doses were prescribed to men below the age of 40 and to women above the age of 40. The clinical implications of higher dosing patterns are discussed. 0 1990 by W. B. Saunders Company.
W
OMEN WITH BIPOLAR
DISORDER are more prone to depression.le4 They are more likely to develop the illness later in life,5 to cycle more rapidly,6 and to die from cardiovascular disease.7 Studies of sex differences in treatment response in bipolar disorder have not been previously reported. The purpose of this study was to survey antipsychotic use in an inpatient population to determine whether the demographic variables of age and sex influence neuroleptic dosage. METHOD A retrospective chart review was completed on all bipolar disorder patients who received care on a 30-bed inpatient psychiatric unit located at St. Lawrence Hospital in Lansing, MI, between the 198 1 and 1986. The focus of the study was neuroleptic dosage. Hence, only those bipolar patients who received neuroleptics at discharge were included in the study. For each patient, demographic data (name, age, sex, date of birth), admission legal status, final diagnosis, and details of discharge psychotropic regimen were noted. The final diagnosis (DSM-III) was made by a faculty psychiatrist following an extensive psychiatric history and physical examination and an average 3-week observation on the unit. The majority of patients (77%) required a combination of lithium and antipsychotics at discharge. In managing acute mania, it is customary to reduce and discontinue neuroleptics whenever possible, preceeding discharge to the community. Patients who are discharged on neuroleptics and lithium have usually failed to stabilize on lithium alone. Those patients who are discharged on neuroleptics without lithium have either refused to accept lithium, are intolerant of it, or have conclusively demonstrated a failure to respond to the drug. Discharge neuroleptic doses were converted to estimated equivalent amounts of chlorpromazine (CPZ Eq) on the basis of potency ratios suggested by previous reviews.8 To analyze age specific differences, the patient cohort was arranged into four subgroups: men and women; below and above 40 years. An arbitrary age cutoff of 40 years has been recommended in previous pharmaco-epidemiologic studies.9 The mean neuroleptic doses were computed for the four age-sex subgroups (Tables 1 and 2). A 5% rejection region was selected for statistical tests.
RESULTS One hundred and twelve bipolar, manic subjects were identified. These included 72 women and 40 men. The mean discharge neuroleptic dose for all bipolar subjects
From Michigan State University, East Lansing, MI. Presented at the World Psychiatric Association Regional Symposium 1988. Address reprint requests to Dale A. D’Mello, M.D.. St. Lawrence Lansing. MI 48915. Q 1990 by W.B. Saunders Company. OOIO-440X/90/3101-0020$03.00/0 80
Comprehensive
Psychiatry,
in Washington Hospital,
Vol. 3 1, No. 1 (January/February),
D.C., October
1210 W Saginaw,
1990: pp 80-83
81
SEX DIFFERENCES IN BIPOLAR DISORDER
Table 1. Mean Neuroleptic
Dose by Age and Sex Subjects Male Y Female
Age 40 Total
(n = 40) 659 2 379’ 350 ? 530$ 574 2 312
z
P
4.57 1.05 2.20
40), the dosage differences between men and women were not significantly different (z = 1.05, P = .2713). These results appear in Table 1. The mean dosage differences between the younger (~40) and older (>40) subgroups were compared. Among the population of male bipolar subjects. the younger population did not receive significantly higher doses than the older subgroup (z = I .77, P = .0891). Among female bipolar subjects, however, the older patients received significantly higher neuroleptics doses than the younger ones (2 = 4.00, P < .0001). These results are shown in Table 2. DISCUSSION
In this study younger men and older women received higher mean discharge neuroleptic doses. The fact that higher neuroleptic doses were prescribed for younger men may be explained by the fact that young men tend more than young women to be more violent, have greater body mass and, have higher testosterone levels. Young women, on the other hand, may benefit from the protective influence of estrogens, which have demonstrable antidopaminergic effects.” Most longitudinal studies of bipolar disorder show that cycle length tends to progressively diminish with each successive manic episode until it eventually stabilizes at lo-month intervals.’ Diminishing cycle length results in accelerating episode frequency. Rapid cycling affective disorder (three or more episodes per year) is known to be Table 2. Mean Neuroleptic
Dose by Age and Sex Subjects’ Age 40yr
Sex
~40 yr
>40 yr
z
P
Male Female
659 ? 379 314 k 156
350 + 530 523 i 278
1.77 4.00
,089 1
W
OMEN WITH BIPOLAR
DISORDER are more prone to depression.le4 They are more likely to develop the illness later in life,5 to cycle more rapidly,6 and to die from cardiovascular disease.7 Studies of sex differences in treatment response in bipolar disorder have not been previously reported. The purpose of this study was to survey antipsychotic use in an inpatient population to determine whether the demographic variables of age and sex influence neuroleptic dosage. METHOD A retrospective chart review was completed on all bipolar disorder patients who received care on a 30-bed inpatient psychiatric unit located at St. Lawrence Hospital in Lansing, MI, between the 198 1 and 1986. The focus of the study was neuroleptic dosage. Hence, only those bipolar patients who received neuroleptics at discharge were included in the study. For each patient, demographic data (name, age, sex, date of birth), admission legal status, final diagnosis, and details of discharge psychotropic regimen were noted. The final diagnosis (DSM-III) was made by a faculty psychiatrist following an extensive psychiatric history and physical examination and an average 3-week observation on the unit. The majority of patients (77%) required a combination of lithium and antipsychotics at discharge. In managing acute mania, it is customary to reduce and discontinue neuroleptics whenever possible, preceeding discharge to the community. Patients who are discharged on neuroleptics and lithium have usually failed to stabilize on lithium alone. Those patients who are discharged on neuroleptics without lithium have either refused to accept lithium, are intolerant of it, or have conclusively demonstrated a failure to respond to the drug. Discharge neuroleptic doses were converted to estimated equivalent amounts of chlorpromazine (CPZ Eq) on the basis of potency ratios suggested by previous reviews.8 To analyze age specific differences, the patient cohort was arranged into four subgroups: men and women; below and above 40 years. An arbitrary age cutoff of 40 years has been recommended in previous pharmaco-epidemiologic studies.9 The mean neuroleptic doses were computed for the four age-sex subgroups (Tables 1 and 2). A 5% rejection region was selected for statistical tests.
RESULTS One hundred and twelve bipolar, manic subjects were identified. These included 72 women and 40 men. The mean discharge neuroleptic dose for all bipolar subjects
From Michigan State University, East Lansing, MI. Presented at the World Psychiatric Association Regional Symposium 1988. Address reprint requests to Dale A. D’Mello, M.D.. St. Lawrence Lansing. MI 48915. Q 1990 by W.B. Saunders Company. OOIO-440X/90/3101-0020$03.00/0 80
Comprehensive
Psychiatry,
in Washington Hospital,
Vol. 3 1, No. 1 (January/February),
D.C., October
1210 W Saginaw,
1990: pp 80-83
81
SEX DIFFERENCES IN BIPOLAR DISORDER
Table 1. Mean Neuroleptic
Dose by Age and Sex Subjects Male Y Female
Age 40 Total
(n = 40) 659 2 379’ 350 ? 530$ 574 2 312
z
P
4.57 1.05 2.20
40), the dosage differences between men and women were not significantly different (z = 1.05, P = .2713). These results appear in Table 1. The mean dosage differences between the younger (~40) and older (>40) subgroups were compared. Among the population of male bipolar subjects. the younger population did not receive significantly higher doses than the older subgroup (z = I .77, P = .0891). Among female bipolar subjects, however, the older patients received significantly higher neuroleptics doses than the younger ones (2 = 4.00, P < .0001). These results are shown in Table 2. DISCUSSION
In this study younger men and older women received higher mean discharge neuroleptic doses. The fact that higher neuroleptic doses were prescribed for younger men may be explained by the fact that young men tend more than young women to be more violent, have greater body mass and, have higher testosterone levels. Young women, on the other hand, may benefit from the protective influence of estrogens, which have demonstrable antidopaminergic effects.” Most longitudinal studies of bipolar disorder show that cycle length tends to progressively diminish with each successive manic episode until it eventually stabilizes at lo-month intervals.’ Diminishing cycle length results in accelerating episode frequency. Rapid cycling affective disorder (three or more episodes per year) is known to be Table 2. Mean Neuroleptic
Dose by Age and Sex Subjects’ Age 40yr
Sex
~40 yr
>40 yr
z
P
Male Female
659 ? 379 314 k 156
350 + 530 523 i 278
1.77 4.00
,089 1
