I posted an article earlier about how morphine had totally cleared a case of
OCD up that didn't respond to anything even cingulectomies. There's another
article in the literature about a case where a drug that prevents the body
from producing cortisol among other things helped together with Prozac. One
possible explanation could be that cortisol prevents the boey from releasing
the opiates that it makes, and so if you lower cortisol, you raise endogenous
opiates. However this is but speculation on my part.
There are several problems with {*filter*} that prevent the production of cortisol.
metyrapone and aminogluthethimide also inibit the production of
mineralcorticoids like DHEA, (which can make you tired) and of estrogen.
Ketoconazole on the other hand inihibits the production of cortisol and
testosterone, although at the sort of doses we're looking at here the effect
would probably be pretty mild. But any fiddling with sex hormones can wreak
serious havoc in a pregant woman, or in a woman soon to become pregnant.
Ketoconazole, which the authors tried first, can cause liver problems, so
regular {*filter*}work is necessary. Nonetheless ketoconazole is frequently
prescribed by doctors to help with various ailments including AIDS (Cortisol
suppresses the immune system) prostate cancer (testosterone causes it to
grow, but large doses of ketoconazole prevent this) and Cushing's (which is
caused by too much cortisol.)
Prog. Neuro-Psychopharmacology & Biol. Psych 1996. Vol.20. pp.1067-1079
Copyright Elsevier Science Inc. This article is reproduced for educational
purposes under the "fair use" doctrine. Any other use is forbidden.
POTENTIATION OF FLUOXETINE BY AMINOGLUTETHIMIDE,
AN ADRENAL STEROID SUPPRESSANT, IN OBSESSIVE-COMPULSIVE
DISORDER RESISTANT TO SSRIs: A CASE REPORT *
GUY CHOUINARD 1,2,3 MARIE-CLAIRE BELANGER 1,2, LINDA BEAUCLAIR1.2
SARAH SULTAN 1,2, and BEVERLEY E. P. MURPHY2
1Clinical psychopharmacology Unit, Allan Memorial Institute, Montreal;
2Department of Psychiatry. McGill University; Montreal, Canada; 3Department
of Psychiatry. University of Montreal, Hopital Louis-H. Lafontaine, Montreal,
Canada (Final Form, June 1996)
Abstract
1 The role of serotonin in the aetiology of obsessive-compulsive disorder
(OCD) has been established through considerable indirect evidence (Landry and
Choumard, 1990). The strongest evidence comes from the fact that {*filter*} known
to be serotonin-selective reuptake inhibitors (SSRIS) have been found to be
useful in the pharmacotherapy of OCD (Landry and Chouinard, 1990).
2. The authors investigated a new treatment approach by adding an adrenal
steroid suppressant to a SSRI. fluoxetine, in the case of a severe
obsessive-compulsive patient who was drug-resistant to clomipramine and SSR
Is.
3. We found that the combination of aminoglutethimide 250 mg qid and
fluoxetine 40 mg die significantly improved the patient's condition.
Moreover, during a four and a half year period. each time we tried to
decrease either fluoxetine or the steroid suppressant, the patient started to
relapse, suggesting that the adrenal steroid suppressant had a potentiating
effect on the SSRI.
Keywords: aminoglutethimide. clomipramine. fluoxetine. obsessive-compulsive
disorder, adrenal suppression. serotonin-selective reuptake inhibitor,
cortisol
Abbreviations: obsessive-compuIsive disorder (OCD). serotonin-selective
reuptake inhibitor (SSRI), serotonin reuptake inhibitor (SRI), dexamethasone
suppression test (DST). Yale Brown Obsessive-Compulsive Scale (Y-Bocs).
Dehydroepiandrosterone (DHEA), Dehydroepiandrosterone-sulfate (DHEA-S).
adrenocorticotropic hormone (ACTH). complete {*filter*} count (CBC). thyroid
stimulating hormone (TSH).
Part of the work was presented at the ACNP Meeting, San Juan. Puerto Rico,
December 10-16,1994.
Introduction
The involvement of serotonin in obsessive-compulsive disorder (OCD) has been
hypothesized based on the observation that the serotonin reuptake inhibitor
(SRI) clomipramine, and other serotonin-selective reuptake inhibitors
(SSRIs) such as fluoxetine, setraline, fluvoxamine and zimelidine were
efficacious in the treatment of OCD (Fontaine and Chouinard, 1985, 1989).
Furthermore, clomipramine has been found to have greater anti-obsessive
effects compared with other types of antidepressants which preferentially
block the uptake noradrenalin over serotonin (Ananth et al. 1981;
Clomipramine Collaborative Study Group, 1991)
Since there is evidence that steroids are involved in the maintenance of
major depression and that adrenal steroid suppression agents
(aminoglutethimide, ketoconazole and/or metyrapone) may lead to an
improvement of depression (Murphy et al., 1991), the authors investigated
this approach by adding an adrenal steroid suppressant to the treatment of
a severe obsessive-compulsive patient who was drug-resistant to SSRIs and SRIs
including clomipramine.
Case Report
Mr. A. is a 49-year-old male with OCD and sensory tics. He had a gradual
deterioration of his OCD (DSM-IlI-R,1980) that began in childhood and became
clinically significant 18 years ago. Past history of major depression or
other psychiatric disorders was negative. The patient had four admissions to
psychiatry for his OCD. He was previously married, had a daughter, and was
able to function reasonably well as an accountant. At the time of
presentation, his main obsession concerned animal faeces. He spent most of
his time anticipating an encounter with, or avoiding contact with, or the
sight of bird droppings, dogs, cats, horses or any possible source of animal
contamination. From 1990 to 1991, he became so incapacitated by his illness
that he was housebound, unable to work and had to move into a supervised
group setting in order to be assisted with the activities of daily living.
The patient's condition had proved refractory to trials of clomipramine,
sertraline, phenelzine, trimipramine and pimozide (Table 1). He had a
partial response to fluoxetine 80 to 100 mg per day. In view of our previous
success with adrenal steroid suppression in major depression (Murphy et al.,
1991), the authors decided to offer this treatment to the patient and to
hospitalize him. At baseline, his Hamilton Depression Scale score was 9 and
he had a normal response on the dexamethasone suppression test (DST) (Meltzer
and Fang, 1983; Shapiro and Lehman, 1983). His Yale-Brown
Obsessive-Compulsive Scale (Y-Bocs) score was 38/40 (Fig 1), and he had a
score of "Severe" on the Clinical Global Impression of Obsessive-Compulsive
Disorder Rating Scale (Fig 2) with obsessions and rituals of 8 hours duration
each (Fig 3). All laboratory parameters (electrolytes, liver enzymes, urea,
creatinine, CBC, Gamma-GT, cortisol, DHEA, DHEA-S, ACTH, thyroid,
testosterone, free testosterone and prolactin) were within the normal range.
[Segment about all the tests they ran and when they ran them.]
Table 1
Summary of Previous Treatments
Year Treatment Improvement
1975 Behaviour Therapy No change
1984/1987 Behaviour Therapy Minimal
1993/1995 Behaviour Therapy Minimal
1970 Phenelzine Sulfate and No change
Trimipramine
1971 Clomipramine 300 mg Very minimal, if any
1980 Fluoxetine 80/100 mg Minimal
Sertraline 200 mg No change
1990 Pimozide, unknown dosage No change
Hospitalized 4 times Minimal
Table 2
[All that the {*filter*} work that was done.]
[Lots of tables with lots of test scores.]
After a brief treatment with ketoconazole (which was discontinued because of
side effects [liver enzymes elevation and tiredness]), Mr. A was started on a
combination of aminoglutethimide 250 mg qid (Fig 4) and hydrocortisone 20 mg
qd for a period of one month with some improvement (Table 3). This regimen
is essentially similar to that employed by Santen et a (1977) to achieve
medical adrenalectomy in postmenopausal women with advanced {*filter*} carcinoma.
Hydrocortisone is used to prevent a sudden drop in cortisol levels and to
prevent a rise in ACTH levels in response to negative feedback which may
overcome the adrenal blocking action of aminoglutethimide.
Fluoxetine 20-40 mg per day was added with further improvement. After nine
months of this combination, the hydrocortisone 20 mg per day was decreased to
10 mg per day for one week and then discontinued, resulting in a progressive
improvement over a one-month period achieving a 40 to 50 % decrease on the
Y-Bocs score (Fig 1). The hydrocortisone was discontinued after nine months
in order to avoid excessive adrenal suppression and AGTH levels have remained
in the high normal range.
Over the last four and a half years, Mr. A has been treated with a
combination of aminoglutethimide and fluoxetine. His condition worsened on
four different occasions; each time coincided with an attempt to decrease
either medication. The first two times occurred during the first six months:
in August 1991, after decreasing aminoglutethimide from 1000 mg to 625 mg,
and in February 1992, after decreasing fluoxetine from 40 mg to 20 mg per
day. His condition worsened for a third time in March 1993, during a
first attempt to gradually discontinue aminoglutethimide. The fourth time
(January 1995) occurred two weeks after the second unsuccessful attempt to
discontinue the adrenal suppressant medication (Fig 5).
Table 3:
Aminoglutethimide and Hydrocortisone Drug Schedule
Days Arninoglutethimide Hydrocortisone
1 - 3 250 mg Q.D. 20 mg/day hs
4 - 6 250 mg B.l.D. (500 mg/d) 20 mg/day hs
7 - 9 250 mg T.l.D.
...
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Another unconventional approach to treatment refractory OCD