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