psychiatric or psychopharmacological effects of hormones andrea marquez lopez mato institute of...
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PSYCHIATRIC or PSYCHOPHARMACOLOGICAL
EFFECTS OF HORMONES
ANDREA MARQUEZ LOPEZ MATOINSTITUTE OF BIOLOGICAL PSYCHIATRY
BUENOS AIRES. ARGENTINA www.ipbi.com.ar
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
•Unipolar and bipolar TR depressive patients receiving thyroid hormone as add-on therapy
•Females with menopausal depression receiving estrogen, progestins, tibolone, soy bean
•Andropausic patients receiving DHEA
•CFS patients receiving DHEA
GROUP I
GROUP II
GROUP III
GROUP IV
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
0
10
20
30
40
50
60
70
80
response remission
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
0
10
20
30
40
50
60
70
80
90
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
Estro
gens
Proges
tins
Estro
gens/
Pro
gestin
s
SERMs
STEARS
Estro
gens/
Andro
gens
ARGENTINA TREATMENTS
II- Females with menopausal depression receiving estrogen, progestin, tibolone,
soy bean
IIa- 50 patients receiving ATD therapy with or without soybean preparations
0
10
20
30
40
50
60
70
80
90P
erce
nta
ge
of
imp
rove
d
pat
ien
ts
ATD plus
Soy bean derivates
ATD alone
Response (HAMD 6 weeks)No remission evaluated
IIb- Female MDD receiving ATD therapy with (140) or without tibolone (77)
Improvement
70
75
80
85
90
95
95%
ATDplus
tibolone ATD alone
80%
Response (HAMD 6 weeks)No remission evaluated
IIc- 120 patients receiving combined HRT with different forms of progesterone
56%
32%
0
10
20
30
40
50
60
70
Imp
rov
eme
nt
in d
ep
ress
ion
Response defined by HAMD and clinical evaluation
RTH with Natural PG
RHT with Medroxi-PG
RTH with anyprogestins
0
10
20
30
40
50
60
70
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
• 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)
RATIONALE (cont)
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
Clinical Improvement
0
10
20
30
40
50
60
70
80
76%
48%
DHEA
No DHEA
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
Duloxetine: 60 /120 mgs Pregabalin:150/450 mgsDHEA 100/200 mgs
64
66
68
70
72
74
76
78
80 Duloxetine
Duloxetine plus pregabalin
Duloxetine Pluspregabalin plus DHEA
Clinical Improvement Ferran Scale
CFS patients receiving DHEA as add-on therapy
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 MATOINSTITUTE OF BIOLOGICAL PSYCHIATRY
BUENOS AIRES. ARGENTINA www.ipbi.com.ar
www.aapb.org.ar