PSYCHIATRIC or

PSYCHOPHARMACOLOGICAL
EFFECTS OF HORMONES

ANDREA MARQUEZ LOPEZ MATO

INSTITUTE OF BIOLOGICAL PSYCHIATRY

BUENOS AIRES. ARGENTINA

www.ipbi.com.ar
 Ia- Unipolar Treatment Refractory
depressives receiving thyroid
hormone as add-on therapy

JUST REMEMBER
T4 is the predominant hormone released
with the majority of T3 being formed in the
periphery by enzymatic deiodination.

T3 &T4 have widespread effects increasing oxygen

consumption and carbohydrate absorption,
regulating growth and maturation (especially of the
CNS) and decreasing cholesterol levels.
The author declares to have
no conflicts of interest,
including any financial, personal
or other relationship
with other people or
organizations that
could have
inappropriately influenced her work
 PSYCHIATRIC EFFECTS OF
HORMONES

• The objetive of this presentation is to

show that hormones used as add-on drugs
may have psychopharmacological effects in
different psychiatric entities
• We present some clinical data from 15
years of work at the Institute of Biological
Psychiatry (ipbi), Buenos Aires, Argentina
 GROUP I

•Unipolar and bipolar TR depressive patients

receiving thyroid hormone as add-on therapy
GROUP II

•Females with menopausal depression receiving

estrogen, progestins, tibolone, soy bean
GROUP III

•Andropausic patients receiving DHEA

GROUP IV

•CFS patients receiving DHEA

 I- Unipolar and bipolar TR
depressives receiving thyroid
hormone as an add-on therapy
• I a Treatment refractory unipolar depressive
patient on add-on therapy with T3

• II b Treatment refractory “rapid cycling” bipolar

depressive patients on add-on therapy with T4
 Ia- Unipolar Treatment Refractory
depressives receiving thyroid hormone as
add-on therapy

RATIONALE
• Treatment-resistant depressed women, may have a
high frequency of serum thyroxine levels near the
lower limit of normal; who only respond after T3 was
added to their antidepressant regime
• Low dose (5-50 mg/d) T3 "augmentation therapy" is
the best documented treatment with thyroid hormones
in depression
 Ia- Unipolar Treatment Refractory
depressives receiving thyroid
hormone as add-on therapy

RATIONALE (cont)

• STAR D The lower side effect burden and ease

of use of T3 (50 µgs) augmentation suggest that
it has slight advantages over lithium (900mgs)
augmentation for depressive patients who have
had several failed medication
 Ia- Unipolar Treatment Refractory
depressives receiving thyroid
hormone as add-on therapy

• 120 patients mostly female

• TRD for at least 2 years
• 20% had blunted response to TRHST
(trait marker for UD)
• 50-150 µgs/d of triodothyronine was
administered with ATD therapy
 Ia- Unipolar Treatment Refractory
depressives receiving thyroid
hormone as add-on therapy

• 79% had a good response to new strategy

within first three months
• Measured by
• Clinical evaluation
• Subjective impression
• Beck or HAMD inventory
• Remission rates do not significately differenciate
from control groups not receiving T3
• T3 is a good add-on therapy for TRD
Unipolar Treatment Refractory
depressives receiving thyroid
hormone as add-on therapy

80
70
60
50
40
30
20
10
response remission
0
 Ib- Treatment refractory “rapid cycling”
bipolar depressive patients on add-on
therapy with T4

RATIONALE
• High-dose (250-500 micrograms/d) T4 is a well
documented therapy for "rapid cycling bipolar
disorder” refractory to lithium
Ib- Treatment refractory “rapid cycling”
bipolar depressive patients on add-on
therapy with T4

• 34 patients (80% females)

• Treatment refractory to various drugs (including
lithium)
• Medicated with lamotrigine, valproic acid and/or
oxcarbamacepine
• 33% had hiperresponsiveness to TRH stimulus (state
marker)
Ib- Treatment refractory “rapid cycling”
bipolar depressive patients on add-on
therapy with T4

90% responded
Measured by
• Clinical evaluation
• Subjective impression
• Beck inventory or HAMD
Improved remission rates
Cycle switch was less evident
Ib- Treatment refractory “rapid cycling”
bipolar depressive patients on add-on
therapy with T4

90
80
70
60
50
40
30
20
10
0 response less switching
in 5 years
 II- Females with menopausal
depression receiving estrogen,
progestin, tibolone, soy bean
• IIa - Females with menopausal depression receiving
soy bean natural supplements

• IIb - Females with menopausal depression receiving

tibolone (STEARS)

• IIc - Females with menopausal depression receiving

combined HRT with different form of progestins
 II- Females with menopausal depression
receiving estrogen, progestin, tibolone, soy
bean
RATIONALE
• Ovarian steroids have widespread effects
throughout the brain on serotonin pathways,
catecholaminergic neurons, and the basal
forebrain cholinergic system

• Ovarian steroids have measurable effects on

affective state as well as cognition
 II- Females with menopausal depression
receiving estrogen, progestin, tibolone,
soy bean
ARGENTINA TREATMENTS

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IIa- 50 patients receiving ATD therapy with
or without soybean preparations

90
Percentage of improved

80
70
60
patients

50 ATD plus
40
Soy bean
30 derivates
20
10 ATD alone
0

Response (HAMD 6 weeks)

No remission evaluated
 IIb- Female MDD receiving ATD therapy with
(140) or without tibolone (77)
95%
95

90

Improvement 85
80%

80
ATD
75 plus
tibolone ATD alone
70

Response (HAMD 6 weeks)

No remission evaluated
 IIc- 120 patients receiving combined HRT
with different forms of progesterone

70
Improvement in depression

60
RTH with
56%PG
Natural
50

40

30 RTH32%
with
RHT with
any
20 Medroxi-
progestins
PG
10

Response defined by HAMD and clinical evaluation

 III- PADAM patients receiving DHEA
supplements

RATIONALE
• DHEA is a precursor hormone which counteracts
the aging and immuno-suppressive effects
caused by corticosteroids

• Supplementing DHEA has been shown to have

anti-obesity effects, antiaging properties and
stabilization of neurotrasmision
 III- PADAM patients receiving DHEA
supplements

RATIONALE (cont)
• Several studies adress the benefits of a long-
term (1 year), medium dose of 50- 100 mgs/d
replacement therapy in different groups of aging
men who presented clinical characteristics of
partial androgen deficiency (PADAM)
 III- PADAM patients receiving DHEA
supplements

• 44 patients
• HAM D ≥ 15
• Receiving several ATD therapies
• 21 received ATD alone
• 23 received DHEA suplementation
 III PADAM patients receiving DHEA
supplements

76%
80

70

Clinical 60 48%
Improvement
50
DHEA
40

30

20

10 No DHEA
0
 IV - CFS patients receiving DHEA

RATIONALE
• Chronic Fatigue Syndrome (CFS) is
characterized by a persistent debilitating
fatigue, muscle & joint related symptoms and
neuropsychiatric symptoms
• Pathogenesis is associated with abnormalities
of the endocrine system with impairment of the
adrenal axis response
 IV- CFS patients receiving DHEA

RATIONALE
• Majority of patients with CFS have a serum
cortisol and dehydroepiandrosterone sulfate
(DHEA-S) deficiency which might be related to
the neuropsychiatric symptoms
 IV- CFS patients receiving DHEA as
add-on therapy

200 patients receiving:

• Pregabalin alone
• Pregabalin plus duloxetine
• Pregabalin plus duloxetine plus DHEA
 CFS patients receiving DHEA as add-on therapy
Duloxetine: 60 /120 mgs
Clinical Pregabalin:150/450 mgs
Improvement DHEA 100/200 mgs
Ferran Scale

80 Duloxetine
78
76
74 Duloxetine
plus
72
pregabalin
70
68 Duloxetine
Plus
66 pregabalin
64 plus DHEA
 PSYCHOPHARMACOLOGICAL
EFFECTS OF HORMONES

DISCUSSION BEFORE CONCLUSIONS

• All patients received treatment on a clinical open basis
• Patients were evaluated by different physicians over time
• Hormonal replacement or add-on treatments may be off the
label indications in some cases
• Results must be reproduced in placebo-controlled studies
PSYCHOPHARMACOLOGICAL
EFFECTS OF HORMONES

CONCLUSIONS

Hormones or endocrine enhancers

can boost or augment
psychopharmalogical
action of drugs by direct action on the
receptors or as an add-on effect.
THANK YOU

ANDREA MARQUEZ LOPEZ MATO

INSTITUTE OF BIOLOGICAL PSYCHIATRY

BUENOS AIRES. ARGENTINA

www.ipbi.com.ar
www.aapb.org.ar