DEPRESSION IN
Renato
COCCHI, neurologist and medical psychologist
Summary.
The clinical records of Ss, who had
specific antidepressant therapies added
to usual drug therapies, were
retrieved from a consecutive not selected
series of clinical records on 510
home reared Down's syndrome individuals.
The
records of 45 Ss (
The
M/F ratio of these 45 Ss was found inverted in comparison with the normal male prevalence among Down Ss, and an
anticipation of age of the onset of depression was observed in females.
The specific antidepressant drugs used,
were viloxazine, as the first choice drug in 38 Ss,
amitryptiline (6 Ss),
fluoxetine (2 Ss),
clomipramine (2 Ss), nortryptiline (2 Ss) and imipramine (1 S). Six cases, 5
treated by viloxazine and 1 by fluoxetine, had these
drugs substituted by another antidepressant.
Key
words: Down's syndrome; depression; epidemiology;
gender prevalence; symptoms; drug
therapy.
Drug modulation of stress reaction
Surely clinicians have paid attention to
coming out of depression and to its diagnosis in individuals with mental
retardation. If we consider the language and communication deficits in this
group, their lack of social skills and
socialisation, it becomes obvious that all the marks of loneliness are
present. So the mentally retarded, without any doubt has the risk of developing
mood troubles (Wells and Duncan 1980, Matson, 1982; Schloss 1982; Menolascino,
1990).
After study decades, we just have scarce
doubts that mentally retarded are can have and in facts suffer from affective
troubles. That so, even if we must ask
ourselves if they show all the range of mood troubles found in the general
population (Fleisher and Weiler, 1990).
According to Dosen, 1990, depression in
children with mental retardation has the same nurobiological and psychological
base of depression in normal children.
The illness can come out independently from sex, age and IQ, even if age
and IQ can influence its appearance, or these can modify it.
Since the end of the years 70 I was involved
in depression in mentally retarded people, either from a therapeutic point of
view (Cocchi and Occhialini, 1981 and 1982) and drug therapy in the Down syndrome of Down. So. On one hand I
became very sensitive to this problem, and on the other I could collect a large
own and usable casuistry for specific investigations.
Materials and methods.
I reexamined the clinical reports
belonging to 510 Down subjects raised in their families, coming from all
Italian regions and being a consecutive non selected series of patients visited from the January 1979 and March 31,
1994.
From these reports I excluded those belonging
to subjects with autism (DSM-III, R: 290.00).
Among the remaining ones I selected the
clinical reports of the subjects in whom I
prescribed a tricyclic or an atypical antidepressant drug. Even if they
own some antidepressant actions, I did not consider therapies made by glutamine, or S-adenosil-l-methionine, or
5-hydroxytriptophan, or carbamazepine or more than one of these drugs
contemporarily prescribed.
From the case reports so selected, then I
collected:
-
sex;
-
chromosomal diagnoses;
-
age at the first consultation (in months);
-
age (always in months) of the appearance of the symptoms that forced me to
prescribe of a specific antidepressant drug;
-
meaningful symptoms;
-
current therapy when the depression had its diagnosis;
-
antidepressants used with their daily doses.
Collected data had descriptive statistical
elaboration and analysed with the
Results.
Following the above defined criteria I found
out 45 records that are 8.82% of the whole series.
The
sex distribution was:
I
summarized these results in the tables no. 1-9.
Table 1: Distribution of chromosomal
diagnoses.
|
Chromosomal anomaly |
M |
% |
F |
% |
Total |
% |
|
Standard Trisomy 21 |
13 |
76.48 |
25 |
89.29 |
38 |
84.44 |
|
Translocations |
0 |
0.00 |
2 |
3.57 |
1 |
2.22 |
|
Mosaicisms |
2 |
11.76 |
1 |
3.57 |
3 |
6.67 |
|
Not known |
2 |
11.76 |
1 |
3.57 |
3 |
6.67 |
|
Totals |
17 |
100.00 |
28 |
100.00 |
45 |
100.00 |
Chi Square = 1.268 with 3 df; p = 1.00.
Table2: Average age, in months, as divided by gender.
|
Age |
M |
F |
|
Average |
138.24 |
87.50 |
|
SD |
108.58 |
55.52 |
|
minimum |
23 |
5 |
|
maximum |
474 |
231 |
The showy difference of the age at first
consultation is surely casual and due to a large extent from the presence of
range limits, mainly maximums, very different, by having a larger weight in the
average calculation.
Table 3: Average
gender age (in months) when
the
antidepressant drug was prescribed.
|
Age |
M |
F |
|
Average |
187.65 |
140.48 |
|
SD |
89.11 |
35.54 |
|
Minimum |
103 |
65 |
|
Maximum |
474 |
231 |
In spite of the bias made by a male subject nearly 40 years old, I dare
strongly suggest that Down females had reduced
ages when the depressive picture became evident.
Table 4: Depressive symptoms not controlled by
the current therapy
|
Symptom |
M |
F |
||
|
|
Ss nr. |
% |
Ss nr. |
% |
|
Sadness |
10 |
58.82 |
18 |
66.67 |
|
Poor playing and social interest |
8 |
47.06 |
13 |
48.15 |
|
Irritability |
8 |
47.06 |
8 |
29.63 |
|
Low self-esteem |
7 |
41.18 |
8 |
29.63 |
|
Aggression |
6 |
35.29 |
3 |
11.11 |
|
Reduced use of the speech |
6 |
35.29 |
8 |
29.63 |
|
Crying without any reason |
0 |
0.00 |
6 |
22.22 |
|
Crying after frustration |
4 |
23.53 |
3 |
11.11 |
|
Spitefulness |
4 |
23.53 |
0 |
0.00 |
|
React. Depres. (by his father’s death) |
1 |
5.88 |
0 |
0.00 |
|
Bedwetting |
1 |
5.88 |
4 |
14.81 |
|
Brothers’ or sisters’ jealousy |
0 |
0.00 |
3 |
11.11 |
|
Eyelash and/or hair pulling |
0 |
0.00 |
2 |
7.41 |
Chi Square (only for the 8 common symptoms): 4.898,
with 7 df, p = 0.732 N.S.
There
is not any significant difference on the presence of 8 common symptoms. Of the
five uncommon ones, two pertain only to males (spitefulness and reactive
depression) and the three others only to females (weeping without any apparent
cause, jealousy, eyelash and/or hair pulling).
Table 5: Drugs
prescribed in males before adding the antidepressant drug.
|
Prescribed drug |
Mg/die (*) |
Ss nr. |
% |
|
S-adenosil-L-methionine |
100 |
11 |
64.71 |
|
Folates |
7.5 |
11 |
64.71 |
|
Carbamazepine |
100-200 |
9 |
52.94 |
|
Diazepam |
1-2.5 |
8 |
47.06 |
|
Pyridoxina |
150 |
8 |
47.06 |
|
Pyritinol |
50-100 |
6 |
35.29 |
|
Bromazepam |
0.5-1.5 |
5 |
29.41 |
|
Vit.s B1+B6+B12 |
125+125+mcg500 |
5 |
29.41 |
|
l-glutamine + pemoline |
45+5 – 90+10 |
5 |
29.41 |
|
l-glutammne |
125-250 |
3 |
17.65 |
|
Delorazepam |
0.5 |
2 |
11.76 |
|
A polyvitaminic drug (Berocca TM) |
|
2 |
11.76 |
|
Alpha-tocopherol |
50 |
2 |
11.76 |
|
Pyridoxine alphachetoglutarate |
300 |
2 |
11.76 |
|
5-hydrossitriptophan |
50-100 |
2 |
11.76 |
|
Clobazam |
10 |
1 |
5.88 |
|
Acetyl-carnitine |
250 |
1 |
5.88 |
|
Oxazepam |
15 |
1 |
5.88 |
|
Clonidine |
0.05 |
1 |
5.88 |
|
Naltrexon |
50 |
1 |
5.88 |
|
Thioridazine |
10 |
1 |
5.88 |
|
Biotin |
50 |
1 |
5.88 |
(*) Often I prescribed the drug every second day, for which the daily
dosing accounts
for the half.
Table 6:
Prescribed antidepressants in males .
|
Drug in mg/die |
1st choice |
2nd choice |
||
|
|
Sn no. |
% |
Ss no. |
% |
|
Viloxazinae 25-100 |
13 (*) |
76.48 |
|
|
|
Amitriptyline 10 + perphenazina 2 |
1 |
5.88 |
|
|
|
Amitriptyline 2-10 |
1 |
5.88 |
1 |
5.88 |
|
Fluoxetine 20 |
1 (*) |
5.88 |
|
|
|
Chlomipramine 10 |
1 |
5.88 |
|
|
|
Nortriptyline 10 |
|
|
2 |
11.76 |
|
Totals |
17 |
100.00 |
3 |
17.74 |
(*) 2 + 1 changes of the drug.
Table 7: Drugs prescribed in females
before adding the antidepressant drug.
|
Prescribed drug |
Mg/die (*) |
Ss nr. |
% |
|
Diazepam |
1-2.5 |
17 |
60.61 |
|
Carbamazepine |
50-200 |
17 |
60.61 |
|
S-adenosil-L-methionine |
100 |
15 |
53.57 |
|
Folates |
7.5 |
15 |
53.57 |
|
l-glutamine |
125-375 |
14 |
50.00 |
|
Vit.s B1+B6+B12 |
125+125+mcg500 |
13 |
46.43 |
|
Pyritinol |
50-100 |
11 |
39.29 |
|
Pyridoxine |
150 |
11 |
39.29 |
|
Arginine pidolate |
250 |
6 |
21.43 |
|
Delorazepam |
0.5 |
6 |
21.43 |
|
5-Hydroxitriptophan |
25-100 |
6 |
21.43 |
|
Biotin |
50 |
4 |
14.29 |
|
l-glutamine + pemoline |
45+5 – 90+10 |
4 |
14.29 |
|
Glycina (in: Biotassina TM) |
500 |
3 |
10.71 |
|
Oxazepam |
15 |
3 |
10.71 |
|
Bromazepam |
0.5-1.5 |
3 |
10.71 |
|
A polyvitaminic (Berocca TM) |
|
3 |
10.71 |
|
Acetyl-carnitine |
250 |
2 |
7.14 |
|
Taurine |
500 |
2 |
7.14 |
|
Pyridoxine alphachetoglutarate |
300 |
1 |
3.57 |
|
Pantotenate |
150 |
1 |
3.57 |
|
Alpha-tocopherol |
50 |
1 |
3.57 |
|
Baclofen |
5 |
1 |
3.57 |
|
l-carnitine |
500 |
1 |
3.57 |
(*) Often I prescribed the drug every second day, for which the daily
dosing accounts
for the half.
Table 8:
Prescribed antidepressants in females .
|
Drug in mg/die |
1st choice |
2nd choice |
||
|
|
Ss no. |
% |
Ss no. |
% |
|
Viloxazine 25-100 |
25 (*) |
89.29 |
|
|
|
Amitriptyline10 + perphenazine 2 |
|
|
1 |
3.57 |
|
Amitriptyline 2-10 |
2 |
7.14 |
|
|
|
Fluoxetine 20 |
|
|
1 |
3.57 |
|
Chlomipramine 10 |
|
|
1 |
3.57 |
|
Imipramine |
1 |
3.57 |
|
|
|
Totals |
28 |
100.00 |
3 |
10.71 |
(*) changes of the drug.
Table 9: Comparison between 28 drugs (as a
whole) prescribed during
the consultation preceding that where I
prescribed the antidepressant.
|
|
M |
F |
|
Totals of the drugs used |
23 |
24 |
|
Totals of prescribed drugs |
87 |
160 |
|
Average drugs for each S. |
3.78 |
5.71 |
|
Common drugs to males and females |
19 |
19 |
|
Drugs used only in males or females |
4 |
5 |
Discussion.
This investigation has many limits. It was
made in Down subjects already in therapy with drugs, according to the guideline
previously described (Cocchi, 1993). Some of these drugs have some
antidepressant activity (glutamine, carbamazepine, s-adenosil-l-methionine,
5-hydroxitripttophan).
The
so made selection results narrower than what it had been suitable, if symptoms
as sleep and/or feeding disorders, bowel function (Eg. constipation), and
others also, the current therapies did not control or greatly mitigated.
If
we exclude some cases where I used the antidepressant drug to improve the nighttime sphincteral action,
for primary or secondary bedwetting, the symptoms I found have primarily
psychic expressions. Somehow they already relate this form of depression with
those of the adult.
In
spite of that, the 8.82% of clear depressions, out of the whole series of 510
Down subjects is already a notable percentage.
Differently to what asserted in general
for the mental retarded (Dosen, 1992), in this group of depressed Down there is
clear female prevalence. This is a fact even more notable when the whole series
shows instead the usual male prevalence as about 150/100. This datum relates
therefore these depressive forms with those found in normal subjects.
Although an exact judgment is not easy, it
seems however probable that this type of depressive symptoms has the trend to
anticipate the time of their appearance in the females. This too, if confirmed,
would be an aspect usually found in the epidemiology of the normal subjects.
There did not result any gender difference as
for the distribution of the chromosomal anomalies and I can say the same as for
most symptoms I collected.
On
the origin of this depression, it is probable that a reactive component
creditable to the perception of the social impact of the same disability makes
up an important causal factor. Nevertheless I cannot exclude the illness as the
same, because of its metabolic homoeostatic impairment (Cocchi, 1993), acting
as a preexisting cause of notable strength.
For
what concerns the symptoms I considered, the sadness, the irritability, the low
self-esteem, the aggressiveness or the self-aggression, all were already
mentioned by Dosen, 1992 as characteristic of the children with a major
affective disorder (DSM-III, R: 296.22;
296.23). The other symptoms too, have been asserted as depressive ones by
different authors ( Matson, 1983; McGee and Menolascino, 1990).
Although in the literature there is
reference to the depression in
As
for the drugs' choice, the preference given to the viloxazine is due to two
features of this compound, its primarily noradrenergic action and its ability of
not lowering the epileptic threshold (Cocchi and Occhialini, 1981 and 1982).
The datum of only 6 cases out 45 needed to have a more powerful antidepressant,
usually a tricyclic one, may be a justification of being the first choice
right. As habitually I do, the daily
doses are always low, but more effective
made by the synergy derived from the
prescription of several drugs.
Conclusions.
The
investigation on the clinical reports of 510 Down persons, all seen by the same
professional, coming from all the parts of
The
type of depression pointed out has usually psychic expressions, and resembles
much to that of same age normal individuals, with a larger prevalence in the
females, where an early onset seems appearing.
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di scelta nella depressione degli epilettici e dei cerebropatici: 13
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epilessia. Rapporto su 8
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First published in Internet on December 2002. Copyright
by Renato Cocchi, 2002.
Author’s address:
dr Renato COCCHI, via Rabbeno, 3
42100 Reggio Emilia (Italy)
renatococchi@libero.it
Drug modulation of stress reaction