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PSYCHIATRIC or PSYCHOPHARMACOLOGICAL EFFECTS OF HORMONES ANDREA MARQUEZ LOPEZ MATO INSTITUTE 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 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 0 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 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 IIa- 50 patients receiving ATD therapy with or without soybean preparations Percentage of improved patients 90 80 70 60 50 40 30 ATD plus Soy bean derivates 20 10 0 Response (HAMD 6 weeks) No remission evaluated ATD alone IIb- Female MDD receiving ATD therapy with (140) or without tibolone (77) 95% 95 90 Improvement 85 80% 80 75 ATD plus tibolone 70 Response (HAMD 6 weeks) No remission evaluated ATD alone Improvement in depression IIc- 120 patients receiving combined HRT with different forms of progesterone 70 60 50 RTH with 56%PG Natural 40 30 20 RHT with MedroxiPG RTH32% with any progestins 10 0 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 longterm (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 48% 60 Clinical Improvement 50 40 DHEA 30 20 10 0 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 CFS patients receiving DHEA as add-on therapy Clinical Improvement Ferran Scale 80 Duloxetine: 60 /120 mgs Pregabalin:150/450 mgs DHEA 100/200 mgs Duloxetine 78 76 74 72 Duloxetine plus pregabalin 70 68 66 64 Duloxetine Plus pregabalin 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 placebocontrolled 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