Articulos - Mirtazapina

Bueno despues de seguir leyendo encontre cosas bastante interesantes, bien enfocadas en el tema

Como bien es sabido la mirtazapina es un antidepresvio (varios de los antidepresivos apuntan a disminuir el cortisol entre otras cosas), pero a diferencia de otros, es el que en comparacion riesgos/beneficios/funciones es el que mas nos conviene a

nosotros

(gente que necesitan bajar el cortisol) para el PCT

Endocrinological effects of mirtazapine in healthy volunteers.
Schüle C, Baghai T, Bidlingmaier M, Strasburger C, Laakmann G.

Psychiatric Hospital, University of Munich, Munich, Germany.
[email protected]

OBJECTIVE: Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin (5-HT) but acts as an antagonist at presynaptic alpha2-receptors and at postsynaptic 5-HT2, 5-HT3 and histamine H1-receptors. In the present investigation, the influence of acute oral administration of 15-mg mirtazapine on the cortisol (COR), adrenocorticotropin (ACTH), growth hormone (GH) and prolactin (PRL) secretion was examined in 12 healthy male subjects, compared to placebo. METHODS: After insertion of an intravenous catheter, both the mean arterial blood pressure (MAP) and the heart rate were recorded and blood samples were drawn 1 h prior to the administration of mirtazapine or placebo (7:00 a.m.), at time of administration (8:00 a.m.) and during 5 h thereafter in periods of 30 min. Concentrations of COR, ACTH, GH and PRL were measured in each blood sample by double antibody radioimmunoassay and chemiluminescence immunoassay methods. The area under the curve (AUC; 0-300 min after mirtazapine or placebo administration) was used as parameter for the COR, ACTH, GH and PRL response. Furthermore, the urinary free cortisol excretion (UFC) was determined beginning at 8:00 a.m. (time of administration of placebo or mirtazapine) up to 8:00 a.m. the day after. RESULTS: Two-sided t-tests for paired samples revealed significantly lower COR AUC, ACTH AUC, UFC and PRL AUC values after 15-mg mirtazapine compared to placebo, whereas no significant differences were found with respect to GH AUC, MAP and heart rate. CONCLUSIONS: Since the acute inhibition of COR secretion in the healthy volunteers was paralleled by a simultaneous decrease of ACTH release, central mechanisms (e.g., inhibition of hypothalamic corticotropin releasing hormone (CRH) output) are suggested to be responsible for the inhibitory effects of mirtazapine on COR secretion. Our results are of particular interest in the light of the hypercortisolism observed in depressed patients and new pharmacological approaches such as CRH1 receptor antagonists.


http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12502011

PMID: 12502011
[PubMed - indexed for MEDLINE]

El estudio en lineas generales comenta que se hizo un estudio con 15mg/dia de mirtazapina para evaluar los niveles de cortisol, la adrenocorticotropin (la encargada de estimular la segregacion del cortisoll), la prolactina y la hormona del crecimiento. Todo esto en 12 hombres sanos, comparando con placebo

Los resultados muestran que al final es que se disminuyeron los niveles de cortizol paralelamente con los niveles de adrenocorticotropin

Time course of hypothalamic-pituitary-adrenocortical axis activity during treatment with reboxetine and mirtazapine in depressed patients.
Schüle C, Baghai TC, Eser D, Zwanzger P, Jordan M, Buechs R, Rupprecht R.

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University of Munich, Nussbaumstr 7, Munich, 80336, Germany.
[email protected]

RATIONALE: In healthy subjects, cortisol and ACTH secretion are acutely stimulated by reboxetine and inhibited by mirtazapine. However, it was not investigated so far whether reboxetine and mirtazapine may also differ in their impact on hypothalamic-pituitary-adrenocortical (HPA) axis activity in depressed patients and whether these effects are related to clinical outcome. OBJECTIVES: In the present study, we investigated the impact of 5-week treatment with reboxetine or mirtazapine on the combined dexamethasone suppression/corticotropin releasing hormone (DEX/CRH) test results in depressed patients. METHODS: Forty drug-free patients suffering from a major depressive episode (Diagnostic and Statistical Manual of Mental Disorders-IV criteria) were treated with either reboxetine (8 mg/day; n=20) or mirtazapine (45 mg/day; n=20) for 5 weeks. Before, after 1 and 5 weeks of therapy, the DEX/CRH test was performed and cortisol and ACTH concentrations were measured. RESULTS: During reboxetine treatment, a gradual and significant reduction in HPA axis activity as measured by the DEX/CRH test was seen, which was most pronounced after 5 weeks of treatment. In contrast, mirtazapine significantly reduced the cortisol and ACTH concentrations during the DEX/CRH test within 1 week. However, after 5 weeks of mirtazapine treatment, the cortisol and ACTH responses to the DEX/CRH test partially increased again both in responders and nonresponders. CONCLUSIONS: This is the first study demonstrating differential effects of various antidepressants on the time course of serial DEX/CRH test results in depressed patients.


http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16758243

PMID: 16758243
[PubMed - indexed for MEDLINE]

En sujetos sanos, la secrecion del cortisol y el adrenocorticotropin (ACTH) son estimuladas por la reboxetine, la cual es inhibida por la mirtazapina

El estudio se hizo en 40 sujetos con mirtazapina(45mg/dia) y reboxetine (8mg/dia) durante 5 semanas

El tratamiento con reboxetine causo una disminucion de la activdad del HPTA

En el caso de la mirtazapina, los niveles de cortisol y de la ACTH se vieron disminuidos en la 1º semana, pero sin embargo despues de la 5º semana el cortisol y la ACTH volvieron a aumentar parcialmente

Ahora pasemos a la parte triste! los efectos secundarios

Los efectos secundarios mas notorios son la sedacion, aumento en el apetito y el aumento de peso.

Aclaremos que las dosis y mayorias de los estudios en pacientes se hablan de dosis de 45mg/dia en general

La mayoria de los otros efectos adversos, vienen de la mano con elevadas dosis… síntomas similares a los de la gripe, fiebre, escalofríos, dolor de garganta, heridas en la boca u otros signos de infección, dolor en el pecho, frecuencia cardíaca más rápida que lo normal, crisis convulsivas, hasta dependiendo de la complejidad del estado del paciente, hablando de depresion, alucinaciones

Una buena pagina (en ingles) para ver los efectos secundarios y comentarios sobre estos


http://www.dr-bob.org/tips/split/Mirtazapine-side-effects.html

Comentarios finales del autor (j.c.) …

Hasta ahora, la dosis a tomar teniendo en cuenta riesgos/beneficios serian 15mg/dia en un periodo de 1 a 2 semanas

Faltan estudios que comenten si causa dependencia o efecto de abstinencia al dejarla de tomar, si es asi tal vez seria recomendable piramidar la dosis descendiendo al final de los dias de ingesta de mirtazapina

Si alguno considera que esta mal, o faltan detalles, sacarian algo o agregarian algo, seria interesante que lo hagan saber

jc>
Muy buen aporte. Gracias por compartirlo con la gente del foro.
Actualmente estoy investigando si las benzodiazepinas (al actuar sobre los receptores de la Dopamina) tienen algun efecto anticatabolico, debido a la inhibicion de la recaptacion del cotisol en los receptores del tejido muscular. Pero por ahora no pude confirmarlo, y por lo tanto es solamente una hipotesis. Ensima en los prospectos de todos los farmacos que traen benzodiazepinas no se trata el tema del cortisol o su recaptacion.
Si alguien tiene idea acerca de mi hipotesis le rogaria que me lo hiciera saber para poder sacarme la duda.
Desde ya un millon de Gracias.

Efectivamente compañero, las benzodiazepinas, reducen los niveles de ACTH y de cortisol … PERO!

Yo no usaria sinceramente esto sin prescripcion medica, te paso a comentar por que…

Causan confusion, puede resultar toxico para el higado algunos de estos medicamentos, tambien producir insuficiencia renal ,tomado junto con alcohol puede producir shock en el sistema nervioso central, vertigo, y lo PEOR DE TODO relacion de dependencia

MIS FUENTES para lo que te comente

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10418790&query_hl=23&itool=pubmed_docsum
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2300914&dopt=Abstract
http://www.benzo.org.uk/commit.htm
http://benzo.org.uk/manual/index.htm

Ademas, la vida media de estos en el cuerpo pasaria a tener hasta 10horas

Lo malo es el efecto rebote.

http://www.springerlink.com/index/UH173431637W2172.pdf


[B]
Journal of Neuroendocrinology,Volume 19 Issue 3 Page 213Issue 3 - 226 - March 2007 .

Neuroendocrinological Mechanisms of Actions of Antidepressant Drugs
[B]

C. Schüle.

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University of Munich, Munich, Germany

exacto compañero! pero si lees bien habla de que el tratamiento se efectuo durante 5 semanas, leyendo bastante en 1 semana creo que los efectos serian ampliamente beneficiosos

Pero si piensas… las semanas criticas del post ciclo son las 2 primeras o 3, hasta que llegamos al punto de consumir clomifeno, tamoxifeno, hcg, donde se regulariza el eje…
Un efecto rebote 5 semanas despues de empezar esto, nos llevaria a que se produzca en la ultima semana del post ciclo o una semana despues de haberlo finalizado
Para ese momento nuestro eje, ya estaria mejor, produciendo alguna que otra hormona, lo cual no importaria y frenaria los niveles de cortisol y de ACTH

Si, pienso que 2 o 3 semanas estaria bien,tal vez no sea tan alto el effecto rebote.
Aunque prefiria usar un antagonista de la angiotensina para controlar el cortisol (y hay otras opciones igualmente).
Tengo una caja de remeron de ya hace cierto tiempo pero no la he usado,primero he preferido hacerme analisis sanguineos antes del ciclo,en ciclo y post ciclo y asi ver el comportamiento del cortisol. ya he usado el antagonista de la angiotensina y me hice examenes y me fue bien,pero ahora lo quiero determinar de manera categorica y mas cientifica.

Respecto a la tu proposicion "produciendo alguna que otra hormona"

para ser especifico es la Testosterona:

**Neuropsychopharmacology. 2005 Oct;30(10):1906-12.

Testosterone suppression of CRH-stimulated cortisol in men.**

Rubinow DR, Roca CA, Schmidt PJ, Danaceau MA, Putnam K, Cizza G, Chrousos G, Nieman L.

Behavioral Endocrinology Branch, National Institute of Mental Health, Building 10-CRC, 10 Center Drive MSC 1276, Bethesda, MD 20892-1276, USA.

Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (p<0.05, 0.005, and 0.01, respectively) during testosterone replacement compared with the induced hypogonadal condition (leuprolide plus placebo); cortisol area under the curve was lower at a trend level (p<0.1). Paradoxically, CRH-stimulated corticotropin (ACTH) was increased significantly during testosterone replacement (p<0.05). The cortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (p<0.1). A mixed effects regression model showed that testosterone but not estradiol or CBG significantly contributed to the variance of cortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.

Que bien que aqui en venezuela ya exista alguien que tome en serio el papel de la ciencia junto con la practica para aplicarlo al fisicoculturismo, te felicito j.c !

Hola compañero pincho42, no vivo en venezuela, vivo en argentina

Es interesante lo que mencionas de la angiotensina, aunque al parecer (por lo poco que he leido sobre angiotensina) es mas efectiva la mirtazapina en el tema de reduccion del cortisol, ya que la angiotensina en algunos articulos que lei muestra una reduccion de la ACTH (ademas de otras cosas beneficiosas como la regulacion de la precion, pero estamos enfocandonos sobre el cortisol ahora). En cambio la mirtazapina afecta directamente los niveles de cortisol tanto como los de la ACTH

Mas adelante voy a investigar sobre este tema de la Angiotensina ya que me parecio interesante

Pero ahora, estoy enfocado al tema de la mirtazapina, busco y no encuentro articulos y/o informes que detallen que efecto traen en el SNC y que trastornos directos podria traer (pero de forma bien explicada).

**
Ejemplifiquemos mi teoria de cuando tomar la mirtazapina**

Supongamos que hacemos un ciclo de 8 semanas de sustanon250

http://img395.imageshack.us/img395/5004/image2gt8.jpg

Como podran apreciar en el caso del sustanon la ultima semana antes de empezar el post ciclo practicamente, es la mas critica, en esta semana, debido a la baja de testosterona, el cortisol consume mas ganancias :frowning:

Desafortunadamente, no tengo forma de medir los niveles a los que alcanzara el cortisol ni tampoco como son manejados por la mirtazapina.

En este caso, MI IDEA, es tomar la mirtazapina en el dia 60 hasta el dia 70 a razon de 15mg/dia, lo cual reduciria drasticamente y mantendria a raya al cortisol hasta que empezemos el postciclo. No pasaria las dosis de 15mg, ni la cantidad de 2 semanas tomando este medicamento debido a analisis de riesgos/beneficios basados en comparacion de otros estudios

La mirtazapina presenta una vida media plasmatica de 20 a 40 horas, dejando rastros en el organismo hasta 21 dias despues.

Todavia no busco informacion sobre si es conveniente superponer el consumo de la mirtazapina durante el postciclo, o durante el ciclo.

Tambien falta mas informacion sobre efectos de dependencia o trastornos graves por ser antidepresivo. Aun sigo buscando informacion

j.c.>
Como consigo ese soft que se llama testosim, no puedo encontarlo por ningun lado. Podrias pasarnos un Link.
Desde ya mil Gracias.

ES EPROGRAMA ES EL QUE ESTOY TRATANDO DE HACER EN EXCEL O ALGO PARECIDO SE VE BIEN PODRIAS DECIRNOS DONDE VERLO ME GUSTA EL DISEÑO ESE.

Perdon, no estoy muy seguro si puedo postear la direccion

en ese post, esta el creador, subiendo el link y explicando formulas y demas cosas que utilizo
http://www.planetaforos.com/showthread.php?t=3166&highlight=calculadora+testo

Saludos a todos :wink:

En 2 posts:

"pero estamos enfocandonos sobre el cortisol ahora").

Por supuesto estamos enfocados sobre el cortisol, 100% de acuerdo desde el principio.

** J Renin Angiotensin Aldosterone Syst. 2004 Jun;5(2):93-6.

Losartan may prevent the elevation of plasma glucose, corticosterone and catecholamine levels induced by chronic stress.**

Uresin Y, Erbas B, Ozek M, Ozkök E, Gürol AO.

Istanbul Faculty of Medicine, Department of Pharmacology and Clinical Pharmacology, Istanbul University, Capa, Turkey.

** Int J Neurosci. 2004 Mar;114(3):365-79.

The effects of losartan and immobilization stress on heart rate variability and plasma corticosterone levels in rats.**

Uresin AY, Tonyali H, Karamürsel S.

Istanbul University, Istanbul Faculty of Medicine, Department of Pharmacology and Clinical Pharmacology, Capa, Istanbul, Turkey.

**J Biol Chem. 1995 Sep 8;270(36):20942-51.

Losartan-sensitive AII receptors linked to depolarization-dependent cortisol secretion through a novel signaling pathway.**

Mlinar B, Biagi BA, Enyeart JJ.

Department of Pharmacology, Ohio State University, College of Medicine, Columbus 43210-1239, USA.

"es mas efectiva la mirtazapina en el tema de reduccion del cortisol"

Que bien, tienes estudios head to head comparando los Antagonistas de la Angiotensina contra la Mirtazapina que interesante, me gustaria verlos.

"Desafortunadamente, no tengo forma de medir los niveles a los que alcanzara el cortisol ni tampoco como son manejados por la mirtazapina."

Claro que si tienes te puedes hacer cortisol am y pm durante varios dias,yo me los he hecho.

"Todavia no busco informacion sobre si es conveniente superponer el consumo de la mirtazapina durante el postciclo, o durante el ciclo."

Durante el ciclo,no lo necesitas ya que:

**Neuropsychopharmacology. 2005 Oct;30(10):1906-12.

Testosterone suppression of CRH-stimulated cortisol in men.**

Rubinow DR, Roca CA, Schmidt PJ, Danaceau MA, Putnam K, Cizza G, Chrousos G, Nieman L.

Behavioral Endocrinology Branch, National Institute of Mental Health, Building 10-CRC, 10 Center Drive MSC 1276, Bethesda, MD 20892-1276, USA.

**J Neuroendocrinol. 2001 May;13(5):442-52.

Androgens alter corticotropin releasing hormone and arginine vasopressin mRNA within forebrain sites known to regulate activity in the hypothalamic-pituitary-adrenal axis.**

Viau V, Soriano L, Dallman MF.

Department of Physiology, University of California, San Francisco 94143-0444, USA.

**Am J Physiol Renal Physiol. 2004 Sep;287(3):F452-9.

Androgens augment proximal tubule transport.**

Quan A, Chakravarty S, Chen JK, Chen JC, Loleh S, Saini N, Harris RC, Capdevila J, Quigley R.

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, USA.

…the increased proximal tubule volume reabsorption would increase extracellular volume and suppress systemic angiotensin II levels. A rise in extracellular volume in the DHT-treated animals would be consistent with three of our findings, including hypertension, increased weight gain, and lower serum angiotensin II levels. Weight gain over the 10-day period of DHT/vehicle injections was twofold higher in the androgen-treated animals (75 ± 13 vs. 37 ± 12 g, P < 0.05), and MAP in androgen-treated animals was 18% higher, as shown in Fig. 1 (104 ± 2 vs. 88 ± 4 mmHg, P < 0.005). Androgens may augment proximal tubule volume reabsorption via the proximal tubule renin-angiotensin system and raise extracellular volume and blood pressure.

lowers serum angiotensin II levels. The DHT-associated increase in proximal tubule transport results from upregulation of the effect of intraluminal angiotensin II and subsequent upregulation of NHE3. These results suggest that** androgens can augment proximal transport by stimulation of the proximal tubule renin-angiotensin system and may contribute to higher blood pressure. **

"Pero ahora, estoy enfocado al tema de la mirtazapina, busco y no encuentro articulos y/o informes que detallen que efecto traen en el SNC. "

**Pharmacol Rep. 2005 Nov-Dec;57(6):766-73.

Effects of some new antidepressant drugs on the glucocorticoid receptor-mediated gene transcription in fibroblast cells.**

Augustyn M, Otczyk M, Budziszewska B, Jagła G, Nowak W, Basta-Kaim A, Jaworska-Feil L, Kubera M, Tetich M, Leśkiewicz M, Lasoń W.

Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.

Antidepressant drugs are thought to counteract effects of hypercortisolemia, frequently associated with depression, by lowering cortisol level and by modifying the function of glucocorticoid receptors (GR). Indeed, classical antidepressants inhibit corticosteroid-induced gene transcription in cell cultures. The aim of the present study was to investigate effects of new generation antidepressant drugs on GR function in mouse fibroblast cells (L929), stably transfected with mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) plasmid (LMCAT cells). It has been found that reboxetine (at 10 and 30 microM), **venlafaxine, citalopram and mirtazapine **(at 30 microM), but not milnacipran, in statistically significant manner inhibited corticosterone-induced gene transcription. However, the effects of new generation antidepressant drugs were weaker than those evoked by imipramine, which was active already at 3 microM concentration. Further studies on the mechanism of antidepressant action on GR function revealed that protein kinase C, but not mitogen-activated protein kinases (MAPK), glycogen synthase kinase (GSK-3) and protein kinase B (PKB, Akt) play a role in this phenomenon.


En este articulo previo se puede ver que tanto Remeron como Effexor,Celexa y de manera mas efectiva por Tofranil
disminuyen la produccion de cortisol.


Los Mecanismos:

**Eur Neuropsychopharmacol. 2007 Jan;17(1):37-45.

Effects of neurosteroids on glucocorticoid receptor-mediated gene transcription in LMCAT cells–A possible interaction with psychotropic drugs.**

Basta-Kaim A, Budziszewska B, Jaworska-Feil L, Leśkiewicz M, Tetich M, Otczyk M, Kubera M, Lasoń W.

Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków,

Aberrant activity of hypothalamic-pituitary-adrenal (HPA) axis is often observed in psychiatric disorders and both antidepressant and antipsychotic drugs are known to ameliorate some deleterious effects of glucocorticoids on brain function. Some neurosteroids possess antidepressant and neuroleptic-like properties and attenuate the stress-activated HPA axis activity. However, intracellular mechanism of neurosteroid interaction with glucocorticoids has not been elucidated. We evaluated effects of some neurosteroids on functional activity of glucocorticoid receptor (GR) in vitro. A combined treatment with antipsychotic drugs and involvement of some protein kinases in allopregnanolone effect on GR function were also studied. The effects of allopregnanolone, its two isomers (5beta-pregnan-3alpha-ol-20-one and 5alpha-pregnan-3beta-ol-20-one) and dehydroepiandrosterone sulfate (DHEAS) on the corticosterone-induced chloramphenicol acetyl transferase (CAT) activity were evaluated in mouse fibroblast cells stably transfected with mouse mammary tumor virus (MMTV)-CAT plasmid. We found that allopregnanolone (1-100 microM) and, to a lesser extent, both its isomers inhibited the GR-mediated gene transcription in a concentration-dependent manner. In contrast, DHEAS at the concentration up to 100 microM was inactive. Further experiments revealed that allopregnanolone and antipsychotic drugs (chlorpromazine and clozapine) showed a moderate, additive inhibitory effect on the GR function. With respect to intracellular mechanism of allopregnanolone action, we showed that this neurosteroid inhibited protein kinase C (PKC) activity, decreased the level of PKCalpha isoenzyme in the membrane fraction and decreased the amount of active phosphorylated form of extracellular signal-regulated kinase-mitogen-activated protein kinase (ERK-MAPK) in LMCAT cells. Since PKC and ERK-MAPK inhibitors attenuate the corticosterone-mediated gene transcription, the above findings suggest that allopregnanolone effect on GR function involves interaction with these kinase pathways. On the other hand, allopregnanolone had no effect on protein kinase A (PKA) activity. These data indicate that pregnanolone derivatives, like antidepressants and antipsychotic drugs, may attenuate some glucocorticoid effects via inhibition of GR-mediated gene transcription. Furthermore, the inhibitory effect of allopregnanolone on the corticosterone-induced gene transcription in LMCAT cells depended on the inhibition of PKC and ERK-MAPK pathways.

**Neuropharmacology. 2005 Aug;49(2):156-64.

Inhibitory effect of imipramine on the human corticotropin-releasing-hormone gene promoter activity operates through a PI3-K/AKT mediated pathway.**

Basta-Kaim A, Budziszewska B, Jaworska-Feil L, Tetich M, Kubera M, Leśkiewicz M, Lasoń W.

Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.

Antidepressant drugs inhibit the corticotropin-releasing-hormone (CRH) gene promoter activity in the differentiated Neuro-2A cells, but a molecular mechanism of their action has been poorly recognized. The aim of the present study was to elucidate the involvement of some intracellular signal transduction pathways in imipramine-induced inhibition of CRH gene activity in the differentiated Neuro-2A cells, stably transfected with a human CRH promoter fragment linked to the chloramphenicol acetyltransferase (CAT) reporter gene. It was found that wortmannin (0.1muM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K) and forskolin (10, 25muM), an activator of adenylate cyclase enhanced the basal activity of CRH gene promoter, whereas inhibitors of protein kinase A, calcium/calmodulin kinase (CaMK) and mitogen-activated protein kinase (MAPK) had opposite effects. Moreover, wortmannin at a low concentration (0.01muM) significantly reversed the inhibitory effect of imipramine on CRH-CAT activity, whereas other protein kinase inhibitors were inactive or even enhanced the imipramine effects. The involvement of PI3-K/Akt pathway in the imipramine action was confirmed by Western blot study, which showed that this drug increased phospho-Ser-473 Akt level, but had no effect on total Akt and glycogen synthase kinase (GSK-3beta) levels. These results indicate that the inhibitory effect of imipramine on the CRH gene promoter activity in Neuro-2A cells is mainly connected with enhancement of PI-3K/Akt pathway.

**Br J Pharmacol. 2000 Jul;130(6):1385-93.

Antidepressant drugs inhibit glucocorticoid receptor-mediated gene transcription - a possible mechanism.**

Budziszewska B, Jaworska-Feil L, Kajta M, Lasoń W.

Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.

  1. Antidepressant drugs are known to inhibit some changes evoked by glucocorticoids, as well as a hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis, often observed in depression. 2. The aim of present study was to investigate effects of various antidepressant drugs on the glucocorticoid-mediated gene transcription in fibroblast cells, stably transfected with an MMTV promoter (LMCAT cells). 3. The present study have shown that antidepressants (imipramine, amitriptyline, desipramine, fluoxetine, tianeptine, mianserin and moclobemide), but not cocaine, inhibit the corticosterone-induced gene transcription in a concentration- and a time-dependent manner. 4. Drugs which are known to augment clinical effects of medication in depressed patients (lithium chloride, amantadine, memantine), do not affect the inhibitory effects of imipramine on the glucocorticoid receptor (GR)-mediated gene transcription. 5. Inhibitors of phospholipase C (PLC), protein kinase C (PKC), Ca(2+)/calmodulin-dependent protein kinase (CaMK) and antagonists of the L-type Ca(2+) channel also inhibit the corticosterone-induced gene transcription. 6. Inhibitors of protein kinase A (PKA) and protein kinase G (PKG) are without effect on the GR-induced gene transcription. 7. Phorbol ester (an activator of PKC) attenuates the inhibitory effect of imipramine on the GR-induced gene transcription. 8. Imipramine decreases binding of corticosterone-receptor complex to DNA. 9. It is concluded that antidepressant drugs inhibit the corticosterone-induced gene transcription, and that the inhibitory effect of imipramine depends partly on the PLC/PKC pathway.

**Acta Psychiatr Scand Suppl. 2007;(433):90-103.

Pathophysiology of hypercortisolism in depression.**

Carroll BJ, Cassidy F, Naftolowitz D, Tatham NE, Wilson WH, Iranmanesh A, Liu PY, Veldhuis JD.

Pacific Behavioral Research Foundation, Carmel, CA, USA.


Por supuesto existen opciones naturistas mas optimas como
los flavonoides (de venta libre en farmacias)

hypericin (0.2 mg/kg), hyperoside (0.6 mg/kg), isoquercitrin (0.6 mg/kg) and miquelianin (0.6 mg/kg) given daily by gavage for two weeks significantly down-regulated circulating plasma levels of ACTH and corticosterone by 40 - 70 %.

La Glutamina ayuda bastante:

**Metabolism. 2006 Sep;55(9):1239-47.

The effect of glutamine on prevention of glucocorticoid-induced skeletal muscle atrophy is associated with myostatin suppression.**

Salehian B, Mahabadi V, Bilas J, Taylor WE, Ma K.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R Drew University of Medicine and Science, Los Angeles, CA 90059.

Excess glucocorticoids (GCs) cause muscle atrophy. Glucocorticoid-induced muscle atrophy is associated with increased intramuscular myostatin expression. Myostatin is a negative regulator of skeletal muscle mass. Glutamine prevents GC-induced muscle atrophy. We hypothesized that glutamine effect on reversal of GC-induced muscle atrophy is mediated in part by suppression of myostatin. We administered daily to male Sprague-Dawley rats dexamethasone, dexamethasone plus glutamine, saline or saline plus glutamine, all pair-fed. Animals were killed on day 5. Body weight and weights of gastrocnemius muscles were measured. Myostatin expression was measured by Northern and Western blots, and was compared with glyceraldehyde-3-phosphate dehydrogenase. Myoblast C2C12 cells were exposed to dexamethasone, or dexamethasone and glutamine, and their myostatin messenger RNA and protein expression compared with glyceraldehyde-3-phosphate dehydrogenase. Myostatin promoter activity was measured by luciferase activity of transfected C2C12 cells, grown in medium including dexamethasone, or dexamethasone plus glutamine. Rats that received dexamethasone showed significant body and muscle weight loss accompanied by an increase in intramuscular myostatin expression, compared with their saline-treated controls. Pair-fed rats given dexamethasone plus glutamine had significantly less reduction in body and muscle weights and lower myostatin expression when compared with those treated with dexamethasone alone. In C2C12 myoblast cells, addition of glutamine to dexamethasone prevented the hyperexpression of myostatin induced by dexamethasone. Myostatin promoter activity increased in cells exposed to dexamethasone, but this increase was partially blocked by addition of the glutamine. Administration of glutamine partially prevents GC-induced myostatin expression and muscle atrophy, providing a potential mechanism for the prevention of muscle atrophy induced by glucocorticoids.


Respecto a:

**“que trastornos directos podria traer” **

** Am J Kidney Dis. 2006 Oct;48(4):e61-2.

Recurrent hyponatremia associated with citalopram and mirtazapine.**

Bavbek N, Kargili A, Akcay A, Kaya A.

Department of Nephrology, Fatih University Medical School, Ankara, Turkey.

**Pharmacopsychiatry; 04, 2001.

Subclinical Pancreatitis Related to Mirtazapine **

Sommer, M.; Dieterich, A.; Krause, C.; Rüther, E.; Wiltfang, J.

**Pharmacopsychiatry; 06, 2002

Body Weight, the Tumor Necrosis Factor System, and Leptin Production during Treatment with Mirtazapine or Venlafaxine. **

Kraus, T.; Haack, M.; Schuld, A.; Hinze-Selch, D.; Koethe, D.; Pollmächer, T.

y alucinaciones visuales.


y como el cortisol produce el catabolismo al nivel muscular:

**Endocrinology. 2007 Jan;148(1):452-60.

Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy.**

Gilson H, Schakman O, Combaret L, Lause P, Grobet L, Attaix D, Ketelslegers JM, Thissen JP.

Unite de Diabetologie et Nutrition, Universite Catholique de Louvain, B-1200 Brussels, Belgium.

Glucocorticoids mediate muscle atrophy in many catabolic states. Myostatin expression, a negative regulator of muscle growth, is increased by glucocorticoids and myostatin overexpression is associated with lower muscle mass. This suggests that myostatin is required for the catabolic effects of glucocorticoids. We therefore investigated whether myostatin gene disruption could prevent muscle atrophy caused by glucocorticoids. Male myostatin knockout (KO) and wild-type mice were subjected to dexamethasone treatment (1 mg/kg.d for 10 d or 5 mg/kg.d for 4 d). In wild-type mice, daily administration of low-dose dexamethasone for 10 d resulted in muscle atrophy (tibialis anterior: -15%; gastrocnemius: -13%; P < 0.01) due to 15% decrease in the muscle fiber cross-sectional area (1621 +/- 31 vs. 1918 +/- 64 microm(2), P < 0.01). In KO mice, there was no reduction of muscle mass nor fiber cross-sectional area after dexamethasone treatment. Muscle atrophy after 4 d of high-dose dexamethasone was associated with increased mRNA of enzymes involved in proteolytic pathways (atrogin-1, muscle ring finger 1, and cathepsin L) and increased chymotrypsin-like proteasomal activity. In contrast, the mRNA of these enzymes and the proteasomal activity were not significantly affected by dexamethasone in KO mice. Muscle IGF-I mRNA was paradoxically decreased in KO mice (-35%, P < 0.05); this was associated with a potentially compensatory increase of IGF-II expression in both saline and dexamethasone-treated KO mice (2-fold, P < 0.01). In conclusion, our results show that myostatin deletion prevents muscle atrophy in glucocorticoid-treated mice, by blunting the glucocorticoid-induced enhanced proteolysis, and suggest an important role of myostatin in muscle atrophy caused by glucocorticoids.

**Am J Physiol Endocrinol Metab. 2003 Aug;285(2):E363-71.

Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression.**

Ma K, Mallidis C, Bhasin S, Mahabadi V, Artaza J, Gonzalez-Cadavid N, Arias J, Salehian B.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA.

The mechanisms by which excessive glucocorticoids cause muscular atrophy remain unclear. We previously demonstrated that dexamethasone increases the expression of myostatin, a negative regulator of skeletal muscle mass, in vitro. In the present study, we tested the hypothesis that dexamethasone-induced muscle loss is associated with increased myostatin expression in vivo. Daily administration (60, 600, 1,200 micro g/kg body wt) of dexamethasone for 5 days resulted in rapid, dose-dependent loss of body weight (-4.0, -13.4, -17.2%, respectively, P < 0.05 for each comparison), and muscle atrophy (6.3, 15.0, 16.6% below controls, respectively). These changes were associated with dose-dependent, marked induction of intramuscular myostatin mRNA (66.3, 450, 527.6% increase above controls, P < 0.05 for each comparison) and protein expression (0.0, 260.5, 318.4% increase above controls, P < 0.05). We found that the effect of dexamethasone on body weight and muscle loss and upregulation of intramuscular myostatin expression was time dependent. When dexamethasone treatment (600 micro g. kg-1. day-1) was extended from 5 to 10 days, the rate of body weight loss was markedly reduced to approximately 2% within this extended period. The concentrations of intramuscular myosin heavy chain type II in dexamethasone-treated rats were significantly lower (-43% after 5-day treatment, -14% after 10-day treatment) than their respective corresponding controls. The intramuscular myostatin concentration in rats treated with dexamethasone for 10 days returned to basal level. Concurrent treatment with RU-486 blocked dexamethasone-induced myostatin expression and significantly attenuated body loss and muscle atrophy. We propose that dexamethasone-induced muscle loss is mediated, at least in part, by the upregulation of myostatin expression through a glucocorticoid receptor-mediated pathway.


Para completar,simplemete lo que concluye el estudio es que se crea tolerancia.

**Pharmacopsychiatry 2005; 38

Influence of reboxetine and mirtazapine on hypothalamic-pituitary-adrenocortical activity in depressed patients **

C Schüle, TC Baghai, D Eser1, R Rupprecht.

Results: Both drugs were comparable in their antidepressant efficacy (65% responders after 5 weeks, respectively). During reboxetine treatment, a gradual but non-significant reduction in HPA axis function was seen being the lowest after 5 weeks. In contrast, mirtazapine significantly downtuned HPA axis activity already within one week both in responders and non-responders; however, after 5 weeks of mirtazapine treatment the cortisol and ACTH secretions increased again.

Si quieres ahondar mas sobre algun detalle especifico,puedes preguntarme con toda libertad.

Sobre los otros estudios, esta bien

Faltaria sobre los efectos psicologicos, tambien sobre los efectos sedantes que tiene (falta saber que rango de duracion tienen, varios comentan que solamente en la noche, pero otros comentan que andubieron dopados todo el dia, como zombies, tambien vale aclarar que tenian dosis elevadas a comparacion de lo que yo supongo que se deberia tomar)…

Estube buscando en jornales medicas, y no encontre sobre estos efectos psicologicos, el lugar donde encontre de medicos orientados a probleas psicologicos es el link que puse en el primer post. Pero seria de utilidad tener mayor informacion sobre estos efectos. Tambien fijarte si genera trastornos psicologicos.

Mi idea seria evitar toda posible dependencia, y efectos sedantes a lo largo del dia, con dosis bajas, tomandose en la noche.

PD: Intenta poner un breve resumen sobre el articulo, ya que yo no tengo problemas con leer ingles, pero hay varios en el foro que no tienen idea. Asi ademas evitamos problemas de que sea movido a la parte de TUPINCHO en ingles :smiley:

Nos seguimos hablando

Saludos

[size=5]
OK COMO DICEN LOS GRINGOS SI NO SE HA ROTO PARA QUE ARREGLARLO LOS ROIDS Y EL HGH SON MUY EFECTIVOS PARA VENIR A METER EN LA ECUACION ANTIDEPRESIVOS QUE SI BIEN HAY UNA TEORIA QUE DICE MUCHAS COSAS HAY MUY POCA GENTE QUE LO HA USADO POR LA GRAN CANTIDAD DE EFECTOS SECUNDARIOS NADA AGRADABLES . ESTE CASO ES ALGO SIMILAR AL CYTADREN DECIAN QUE TENIA EFECTOS SOBRE EL CORTISOL PERO LOS EFECTOS SECUNDADIOS SON MUY FUERTES .

COMO DIJO DAN DUCHAINE ALGUNA VEZ "

JUGAR CON EL CORTISOL ES MUCHO MAS PELIGROSO QUE HACERLO SOLO CON ROIDS POR LO QUE YO NO LO RECOMIENDO

"…

AQUI LO QUE DEBE PREVALECER ES ES SENTIDO COMUN :twisted:
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La verdad que este post se ha vuelto realmente muy interesante. Estan surgiendo nuevas tecnicas para combatir el cortisol, y es bueno que estemos al tanto de ellas, siempre y cuando tengamos en cuenta sus efectos secundarios.
Muchas Gracias a todos por sumar.

Compañero policia, es solo una teoria de como y cuando tomar mirtazapina, que le falta preparacion, y la puse para que entre todos intentemos llegar a una idea, y en caso de que lleguemos a la conclusion de que los efectos son demasiado malos, se descartara como toda teoria

Si fuera por esa mentalidad, de que uno opina que algo tiene demasiados efectos secundarios, nunca se hubiera puesto en practica uso de sustancias en personas. Ni nuevos medicamentos saldrian al mercado. Todo tiene su efecto y cotra efecto. No discuto que sea peligroso, pero que cosa no lo es? en este ambiente tomamos muchas cosas que pueden dejarnos afectados durante mucho tiempo, alguno ha leido los efectos secundarios de un medicamento comun en varios como el VALIUM? o efectos secundarios como el de la TESTOSTERONA? es impresionante, pero se encontraron dosis y formas de administracion

YO NO ESTOY RECOMENDANDO QUE SE USE TODAVIA, falta informacion, SI es que lo pruebo, lo probare en un futuro, cuando tenga mas bases teoricas y seguridad de como actuar ante cada caso.

Espero que esto no se tome como una ofensa, no es mi intencion, igual aprecio mucho tu opinion policia

Aca dejo un cuadro bastante interesante de estudios medicos comparando efectos en placebo

Vala aclarar que las dosis fueron de 5mg inicialmente, aumentando hasta 60mg/dia.
N = cantidad de sujetos

Mirtazapine(n=453) Placebo(n=361)

Body as a Whole
Asthenia 8% 5%
Flu Syndrome 5% 3%
Back Pain 2% 1%
Digestive System
Dry Mouth 25% 15%
Increased Appetite 17% 2%
Constipation 13% 7%
Metabolic and Nutritional Disorders
Weight Gain 12% 2%
Peripheral Edema 2% 1%
Edema 1% 0%
Musculoskeletal System
Myalgia 2% 1%
Nervous System
Somnolence 54% 18%
Dizziness 7% 3%
Abnormal Dreams 4% 1%
Thinking Abnormal 3% 1%
Tremor 2% 1%
Confusion 2% 0%
Respiratory System
Dyspnea 1% 0%
Urogenital System
Urinary Frequency 2% 1%

Los efectos mas comunes, fueron somnolencia y sequedad en la boca, seguido por el aumento de peso (pero en general se habla de periodos superiores a 4 semanas de tratamiento

Physical and Psychological Dependence

Mirtazapine has not been systematically studied in animals or humans for its potential for abuse, tolerance or physical dependence. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted and/or abused once marketed. Consequently, patients should be evaluated carefully for history of drug abuse, and such patients should be observed closely for signs of mirtazapine misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

En lineas generales, se comenta que la mirtazapina no ha sido estudiada sistematicamente (ni en animales ni humanos) la tolerancia o dependencia. Pero que en general no se ven esta tendencia

Initial Treatment

The recommended starting dose for mirtazapine tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for mirtazapine has not been adequately explored, patients not responding to the initial 15 mg dose may benefit from dose increases up to a maximum of 45 mg/day. Mirtazapine has an elimination half-life of approximately 20 to 40 hours; therefore, dose changes should not be made at intervals of less than one to two weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose.

Este fragmento, comenta la forma e que se recomienda empezar a tomar a pacientes con problemas que requieran el uso de la mirtazapina.

Se recomienda con las dosis de 15mg/dia, en una sola dosis, preferiblemente antes de ir a dormir. Se controla y se establece la eficacia de la mirtazapina. Alli empiezan a subir hasta 45mg/dia (pero esto ya sobrepasa las dosis seguras, y lleva a mayor cantidad de efectos secundarios)

Sigo manteniendo en base a esto que la dosis a tomar serian 15mg/dia durante un periodo inferior a las 2 semanas (y basandome en el fragmeto que menciona que varios estudios no revelan tendencia a dependecia, serian dosis lineales y no piramidales)

Amigos si no he leído mal se recomienda su uso para estabilizar el eje afectado por prolactina. Hay sustancias mas efectivas para el cortisol en eso coincido con el policia. La dosis es de 2.5 mg por dos semanas.

Dado a que en este post se estan tratando temas con amplisima profundidad y abal cientifico, me gustaria saber si alguno contiene alguna publicacion sobre la inhibicion de la recaptacion del cortisol por parte los OREXIGENOS, por ejemplo la ciproheptadina.
Es decir, dejando de lado que nos estimule el apetito, y que por lo tanto no perderiamos tantos kilos despues de un ciclo en el cual tenemos una retencion hidrica y grasa corporal importante; ¿este tipo de drogas tienen incidencia sobre el cortisol?.
Desde ya un Millon de Gracias.

Si no me equivoco, por las dosis, creo que estas hablando de la bromocriptina, la mirtazapina no modifica los niveles de prolactina