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HYPNOTIC DRUG COMBINATION
612
PSYCHOTROPIC/HYPNOTIC DRUG COMBINATION SIR,-I should like to draw the attention of your readers
to a
number of side-effects found in 10 patients who were given ’ Mandrax’, a hypnotic agent containing methaqualone and diphenhydramine hydrochloride, in combination with thioridazine (’ Melleril ’); 6 of these patients were also having imipramine and amitriptyline. The side-effects reported within two days of the administration of these drugs included nasal bleeding, swelling, furring, fissuring, and discoloration of the tongue, excessive dryness of the mouth, and a feeling of " floating " in the mornings, akin to depersonalisation. All 10 patients had presented with depressive symptoms. This seems to be an example of drug potentiation between mandrax and the psychotropic drugs, leading to heightened anticholinergic activity, responsible for the side-effects. Blood-investigations were found to be normal except for a raised erythrocyte-sedimentation rate. On discontinuing the mandrax, but continuing the psychotropic agents, all sideeffects gradually disappeared within the next one to four days. Dandenong Psychiatric Centre, A. KESSELL Department of Mental Hygiene, A. G. WILLIAMS. Victoria.
SIDE-EFFECTS OF ORAL CONTRACEPTIVES
SIR,-Much of the reporting of oral-contraceptive sideseems to us to be of very little help, for it is so poorly controlled. Frequently the incidence of a side-effect during treatment is cited without mention of its incidence before taking the pills-the inference being that without treatment no such symptoms occur. Our own experience is necessarily limited, but when we
effects
to prescribe ’ Norinyl-1’ (norethisterone 1 mg., mestranol 0-05 mg.) in our practices almost a year ago we adopted the habit of asking every woman whether or not she had experienced certain symptoms in the month before starting the pill. Although the numbers are small, certain conclusions can be drawn which seem to us to be important. We found that the first-cycle incidences of breast discomfort, headache, and depression were 13%, 14%, and 6% respectively, but the significance of these figures is completely altered when they are compared with the pre-treatment
treatment
outside
incidences own
our
Those who wish to work out significances can do so from the ratios which show number of affected cycles out of the total observed, but it is quite obvious that norinyl-1 certainly did not increase breast discomfort, headache, or depression and may have brought about a genuine reduction. Other complaints which were greatly reduced by the oral contraceptive were dysmenorrhoea and premenstrual tension (P.M.T.) (but this has been generally accepted for most products) :
On the other hand, there is an undoubted increase in some complaints, and it seems to us that only by comparison with pre-treatment incidences can such true side-effects be
recognised. For the following table break-through bleeding (B.T.B.) was defined as bleeding requiring a pad or tampon occurring less than 25 days after the last such bleed (those women complaining of B.T.B. were not necessarily those complaining of spotting) :
not
claim for
a moment
that the various pre-
are
too
many
validity variables,
the attitudes and criteria of the doctors who ask the Nevertheless we have established in our own practices that this particular low-dose product certainly does not cause such complaints as breast discomfort, depression, and headaches, which are so often attributed to oral contraceptives; and the true side-effects-disturbed cycle control and nausea -are self-limiting. Further, no pregnancy has occurred. We do not have data to enable us to compare various products, and we cannot see that it is valid to compare results obtained in different groups of women by different doctors. Meanwhile we think that " before and after " comparisons from other doctors using other preparations could be most
questions.
helpful.
JOSEPH SLUGLETT. JUNE P. LAWSON.
Bristol 4.
Denham, Bucks.
NOT FORGETTING THE I.U.C.D.
SIR,-Intrauterine contraceptive devices are easy to forget, and the nylon threads which are attached to some may be difficult to feel. Tying a knot in the nylon makes it easier to feel and also serves, " knotwise ", as a reminder to feel for the thread again quite soon. Patients say that they often think that they can feel various " things " which just might be threads, but the knot is easier to be sure about. When we reflect that the Shirodkar suture is sometimes difficult to find again, the value of an extra landmarkl can be appreciated. Gull Lake, NOEL JACKSON. Saskatchewan, Canada.
ŒDEMA IN PREGNANCY
SIR,-I was interested in your leading article (July 22, p. 197) and in the resulting correspondence. I have collected data from 420 pregnant women who measured fluid intake and output at intervals throughout their pregnancies. 41 women
had
single infants of birth weight 9 lb. (4000 g.) or more:
24 had single infants of birthweight under 6 lb. (2700 g.). The mothers of infants of birthweight 9 lb. of more had a
negative mean fluid balance from thirty-two weeks to term (thirty-seventh week excepted): the 24 mothers of lowbirthweight infants retained fluid throughout pregnancy (thirty-eighth week excepted). Findings in mother and child for these 65 pregnancies are as follows: PreWeight of Hyper- Small Prema- Still- Deinfant (lb.) Œdema eclampsia tension for dates ture born formed Total -99 <6
16 3
4 11
1 3
0 12
0 7
0 4
0 4
41 24
Of the 355 mothers delivered of babies of intermediate
weight, 56 (15%) had oedema. Thus of the three groups of mothers, those with overweight babies had the highest incidence of oedema (39%); in those with underweight infants, oedema was the least common (12-5%). This accords with the findings of Thomson et al.l In both birthweight groups, all mothers with pre-eclampsia and most of those with oedema retained fluid throughout pregnancy, the amount being greater in those with pre-eclampsia than in those with oedema only. The greater the oedema, the larger the fluid retention. In a few cases, oedema came and went, and in these fluid balance was sometimes positive and sometimes negative. In those with hypertension only, a sudden rise in fluid retention was followed by a rising blood-pressure, and an increase in the output of urine, causing the fluid balance to change from positive to negative. The diuretic effect of a raised bloodpressure, would explain Professor MacGillivray’s (Aug. 19, p. 416) two kinds of pre-eclampsia with different amounts of total body-water. Mr. Sophian’s notion (Aug. 5, p. 309) that there must be the same underlying cause for oedema only, 1.
We would
have observed have any
including
began
incidences.
we
practices-there
Thomson, A. M., Hytton, F. E., Billewicz, W. J. J. Obstet Gynœc. Br. Commonw. 1966, 73, 553.
PSYCHOTROPIC/HYPNOTIC DRUG COMBINATION SIR,-I should like to draw the attention of your readers
to a
number of side-effects found in 10 patients who were given ’ Mandrax’, a hypnotic agent containing methaqualone and diphenhydramine hydrochloride, in combination with thioridazine (’ Melleril ’); 6 of these patients were also having imipramine and amitriptyline. The side-effects reported within two days of the administration of these drugs included nasal bleeding, swelling, furring, fissuring, and discoloration of the tongue, excessive dryness of the mouth, and a feeling of " floating " in the mornings, akin to depersonalisation. All 10 patients had presented with depressive symptoms. This seems to be an example of drug potentiation between mandrax and the psychotropic drugs, leading to heightened anticholinergic activity, responsible for the side-effects. Blood-investigations were found to be normal except for a raised erythrocyte-sedimentation rate. On discontinuing the mandrax, but continuing the psychotropic agents, all sideeffects gradually disappeared within the next one to four days. Dandenong Psychiatric Centre, A. KESSELL Department of Mental Hygiene, A. G. WILLIAMS. Victoria.
SIDE-EFFECTS OF ORAL CONTRACEPTIVES
SIR,-Much of the reporting of oral-contraceptive sideseems to us to be of very little help, for it is so poorly controlled. Frequently the incidence of a side-effect during treatment is cited without mention of its incidence before taking the pills-the inference being that without treatment no such symptoms occur. Our own experience is necessarily limited, but when we
effects
to prescribe ’ Norinyl-1’ (norethisterone 1 mg., mestranol 0-05 mg.) in our practices almost a year ago we adopted the habit of asking every woman whether or not she had experienced certain symptoms in the month before starting the pill. Although the numbers are small, certain conclusions can be drawn which seem to us to be important. We found that the first-cycle incidences of breast discomfort, headache, and depression were 13%, 14%, and 6% respectively, but the significance of these figures is completely altered when they are compared with the pre-treatment
treatment
outside
incidences own
our
Those who wish to work out significances can do so from the ratios which show number of affected cycles out of the total observed, but it is quite obvious that norinyl-1 certainly did not increase breast discomfort, headache, or depression and may have brought about a genuine reduction. Other complaints which were greatly reduced by the oral contraceptive were dysmenorrhoea and premenstrual tension (P.M.T.) (but this has been generally accepted for most products) :
On the other hand, there is an undoubted increase in some complaints, and it seems to us that only by comparison with pre-treatment incidences can such true side-effects be
recognised. For the following table break-through bleeding (B.T.B.) was defined as bleeding requiring a pad or tampon occurring less than 25 days after the last such bleed (those women complaining of B.T.B. were not necessarily those complaining of spotting) :
not
claim for
a moment
that the various pre-
are
too
many
validity variables,
the attitudes and criteria of the doctors who ask the Nevertheless we have established in our own practices that this particular low-dose product certainly does not cause such complaints as breast discomfort, depression, and headaches, which are so often attributed to oral contraceptives; and the true side-effects-disturbed cycle control and nausea -are self-limiting. Further, no pregnancy has occurred. We do not have data to enable us to compare various products, and we cannot see that it is valid to compare results obtained in different groups of women by different doctors. Meanwhile we think that " before and after " comparisons from other doctors using other preparations could be most
questions.
helpful.
JOSEPH SLUGLETT. JUNE P. LAWSON.
Bristol 4.
Denham, Bucks.
NOT FORGETTING THE I.U.C.D.
SIR,-Intrauterine contraceptive devices are easy to forget, and the nylon threads which are attached to some may be difficult to feel. Tying a knot in the nylon makes it easier to feel and also serves, " knotwise ", as a reminder to feel for the thread again quite soon. Patients say that they often think that they can feel various " things " which just might be threads, but the knot is easier to be sure about. When we reflect that the Shirodkar suture is sometimes difficult to find again, the value of an extra landmarkl can be appreciated. Gull Lake, NOEL JACKSON. Saskatchewan, Canada.
ŒDEMA IN PREGNANCY
SIR,-I was interested in your leading article (July 22, p. 197) and in the resulting correspondence. I have collected data from 420 pregnant women who measured fluid intake and output at intervals throughout their pregnancies. 41 women
had
single infants of birth weight 9 lb. (4000 g.) or more:
24 had single infants of birthweight under 6 lb. (2700 g.). The mothers of infants of birthweight 9 lb. of more had a
negative mean fluid balance from thirty-two weeks to term (thirty-seventh week excepted): the 24 mothers of lowbirthweight infants retained fluid throughout pregnancy (thirty-eighth week excepted). Findings in mother and child for these 65 pregnancies are as follows: PreWeight of Hyper- Small Prema- Still- Deinfant (lb.) Œdema eclampsia tension for dates ture born formed Total -99 <6
16 3
4 11
1 3
0 12
0 7
0 4
0 4
41 24
Of the 355 mothers delivered of babies of intermediate
weight, 56 (15%) had oedema. Thus of the three groups of mothers, those with overweight babies had the highest incidence of oedema (39%); in those with underweight infants, oedema was the least common (12-5%). This accords with the findings of Thomson et al.l In both birthweight groups, all mothers with pre-eclampsia and most of those with oedema retained fluid throughout pregnancy, the amount being greater in those with pre-eclampsia than in those with oedema only. The greater the oedema, the larger the fluid retention. In a few cases, oedema came and went, and in these fluid balance was sometimes positive and sometimes negative. In those with hypertension only, a sudden rise in fluid retention was followed by a rising blood-pressure, and an increase in the output of urine, causing the fluid balance to change from positive to negative. The diuretic effect of a raised bloodpressure, would explain Professor MacGillivray’s (Aug. 19, p. 416) two kinds of pre-eclampsia with different amounts of total body-water. Mr. Sophian’s notion (Aug. 5, p. 309) that there must be the same underlying cause for oedema only, 1.
We would
have observed have any
including
began
incidences.
we
practices-there
Thomson, A. M., Hytton, F. E., Billewicz, W. J. J. Obstet Gynœc. Br. Commonw. 1966, 73, 553.