Depressione in gravidanza e nel puerperio Daniele La Barbera - - PowerPoint PPT Presentation

Depressione in gravidanza e nel puerperio

Daniele La Barbera

Dipartimento di Biomedicina sperimentale e Neuroscienze cliniche

Sezione di Psichiatrica Università di Palermo Caltanissetta, 28 Settembre 2010

Il tempo biologico e psichico della donna è un tempo ritmico. Tutta la vita psicobiologica e sessuale della donna è inserita in una dimensione temporale

Aree cliniche di confine tra ginecologia psicologia e psichiatria

• Sindrome premestruale
• Dismenorrea
• Pseudogravidanza psicogena
• Ipermenorrea, metrorragia
• Dolore pelvico
• Sterilità psicogena
• Aborto spontaneo
• Psicoprofilassi al parto
• Depressione in gravidanza
• Depressione puerperale
• Menopausa

Depressione Maggiore

• esordio: 3° decade di vita
• durata episodio: 20 settimane (mediana)
• frequenza episodi: 4 (mediana) nella vita

Depressione Maggiore

• 2 volte più frequente nelle donne:

15-54 anni  donne 21%, uomini 12%

(Burt e Stein, J Clin Psychiatry 2002; 63 (suppl 7): 9-15)

• prevalenza attuale o nel corso della vita

rapporto uomo: donna di 2:1

(Kuehner, Acta Psychiatr Scand 2003; 108: 163-174)

Perché la Depressione Maggiore è più frequente nelle donne ?

• fattori genetici: non vi sono dati univoci (?);
• eventi traumatici nell’infanzia: bambine più a rischio di abusi fisici e più

sensibili al loro effetto;

• fluttuazioni ormonali: le donne presentano episodi depressivi in risposta a

fluttuazioni degli ormoni sessuali e soffrono maggiormente di disfunzioni tiroidee;

• disturbi d’ansia: le donne ne soffrono maggiormente;
• stile cognitivo: donne più inclini alla ruminazione e all’autocommiserazione;
• ruolo sociale: nella donna sono più frequenti ruoli frustranti (casalinga),

conflittuali o eccessivamente onerosi (casa-lavoro, discriminazione..);

• eventi stressanti: le donne presentano più frequentemente un episodio

depressivo dopo un evento negativo rilevante. (Piccinelli e Wilkinson, Br J Psychiatry 2000; 177:486-492)

Depressione Maggiore

Modello eziopatogenetico

Ereditarietà Eventi di perdita precoci Sesso Personalità Eventi stressanti Alterazione del funzionamento cerebrale

Depressione

Disturbi d’Ansia Supporto sociale

?

Depressione Maggiore

eventi stressanti precoci  grave compromissione delle cure parentali: morte di un genitore, separazione-divorzio dei genitori,

violenza in famiglia, abusi fisici e sessuali.

(Piccinelli e Wilkinson, Br J Psychiatry 2000; 177:484-492)

Funzioni psicoendocrine

attività ipotalamo-ipofisi surrene

Personalità

bassa autostima, senso di impotenza

Supporto sociale

Sistema ipotalamo-ipofisi-surrene

L’elevazione dei livelli di glucocorticoidi è una caratteristica della risposta allo stress nei mammiferi. Stress cronico  persiste l’aumento dei glucocorticoidi, mentre si riducono i livelli di NA, 5HT, DA, GABA CRF  nell’animale induce comportamenti “depressivi”. Il riscontro di elevati livelli di glucocorticoidi si ritrova nel 20- 40% dei pazienti depressi ambulatoriali e nel 40-60% di quelli ricoverati (più frequenti nella depressione melancolica). In genere l’ipercortisolemia si risolve in seguito al trattamento; se persiste indica un rischio elevato di ricaduta.

Depressione Maggiore e sesso femminile

eventi stressanti precoci

Abusi sessuali Maggior sensibilità

7-19% bambine 69% depressione da adulti 3-7% bambini 27%

Estrogeni aumentano l’attività ipotalamo-ipofisi-surrene in risposta allo stress (Weiss et al, Am J Psychiatry 1999; 156:816-828; Kuehner, Acta Psychiatr Scand 2003; 108: 163-174)

Nelle donne:

• maggior frequenza di scarsa autostima, insicurezza, senso di

inadeguatezza, di impotenza e di disperazione;

• maggior tendenza alla ruminazione, all’autocommiserazione, al

pessimismo.

Disturbi depressivi e caratteristiche di personalità

(Piccinelli e Wilkinson, Br J Psychiatry 2000; 177:484-492 Kuehner, Acta Psychiatr Scand 2003; 108: 163-174)

Disturbi depressivi e alterata attività tiroidea

Il 5-10% dei pazienti depressi presentava prima del disturbo una disfunzione tiroidea subclinica.

Ipotiroidismo subclinico

astenia, sonnolenza, rallentamento psico-motorio, deficit di concentrazione e di memoria, depressione

Ipotiroidismo

FT4 TSH basale TSH dopo TRH Grado 1

  

“ 2

=  

“ 3

= = 

(Esposito et al, 1997)

Depressione Maggiore

Caratteristiche cliniche

Nelle donne più frequente:

• la comparsa nel periodo novembre-febbraio
• un maggior numero di sintomi
• ipersonnia, iperfagia, reattività umore, ipersensibilità al rifiuto
• tentativi di suicidio (suicidio nell’uomo)

(Burt e Stein, J Clin Psychiatry 2002; 63 (suppl 7): 9-15)

• pubertà
• fase premestruale
• puerperio
• peri-menopausa
• gravidanza e aborto

(Burt e Stein, J Clin Psychiatry 2002; 63 (suppl 7): 9-15)

Nelle donne (predisposte) la depressione maggiore si manifesta più frequentemente nei periodi di intense fluttuazioni degli ormoni sessuali:

Disturbi Depressivi del Puerperio

• Maternity Blues (Postpartum Blues, Baby Blues)
• Depressione Maggiore ad esordio nel

postpartum

• Psicosi puerperale

Maternity Blues

• Prevalenza: 50-85% donne.
• Esordio: entro pochi giorni dal parto (48 ore).
• Sintomi: tristezza, tendenza al pianto, sentimenti di

insufficienza e di incapacità, irritabilità, ansia, difficoltà di concentrazione e di memoria, disturbi del sonno e dell’appetito, cefalea, astenia.

• Remissione: entro 2 settimane. Durata protratta:

comparsa di depressione postpartum.

(Burt e Stein, J Clin Psychiatry 2002; 63 (suppl 7): 9-15 Steiner et al. J Affect Disord 2003;74:67-83)

Depressione Post-partum

• Esordio: primi tre mesi dal parto (primo mese).
• Prevalenza: 10-22%
• Sintomatologia : sovrapponibile alla Depressione Maggiore
• Effetti sullo sviluppo psichico del bambino: attaccamento

insicuro e ambivalente, compromissione tono emozionale, sviluppo cognitivo e relazionale, manifestazioni psicopatologiche

• Prognosi: remissione entro 6-12 mesi

(Burt e Stein, J Clin Psychiatry 2002; 63 (suppl 7): 9-15 Steiner et al. J Affect Disord 2003;74:67-83)

Psicosi Post-partum

• Prevalenza: 0.1-0.3 % di puerpere.
• Esordio: prima settimana dopo il parto (48-72 ore).
• Sintomi: intense e rapide oscillazioni dello stato di

coscienza, allucinazioni visive o uditive a contenuto triste o terrifico, temi deliranti di tipo persecutorio o depressivo e incentrati sulla relazione madre-bambino, ansia, agitazione; rischio di suicidio e di infanticidio.

• Prognosi: favorevole con remissione in 6-12 mesi nell’ 80%

casi; tendenza alla ricorrenza nel postpartum (75-90%). 70% Disturbo Bipolare o Depressione Maggiore con aspetti psicotici

(Burt e Stein, J Clin Psychiatry 2002; 63 (suppl 7): 9-15 Steiner et al. J Affect Disord 2003;74:67-83)

• caduta ormoni placentari
• ipotiroidismo (in un sottogruppo)
• ambivalenza nei confronti del neonato
• stress connesso al ruolo materno
• esaurimento fisico; alterata attività asse ipotalamo-ipofisi-

surrene

• sonno insufficiente
• pregressi episodi di depressione o disturbo bipolare
• recenti eventi stressanti
• temperamento del neonato
• complicazioni perinatali
• scarso supporto familiare

Disturbi del puerperio

Eziologia

(Burt e Stein, J Clin Psychiatry 2002; 63 (suppl 7): 9-15 Steiner et al. J Affect Disord 2003;74:67-83)

Depressione Maggiore in gravidanza

Rischi se la depressione non è trattata:

• scarsa igiene della gravidanza
• rischio suicida
• impulsività
• alterazioni neuro-endocrine (ipercortisolemia)
• stress materno prenatale -->minor peso e minore età gestazionale

Nell’animale lo stress materno --> aborto, basso peso, ipossia, ipotensione, ritardo di crescita, difficoltà di apprendimento

(Wisner et al, 2000)

Prevalenza:  9% primo episodio in gravidanza  14% ricaduta

What are the signs of depression during pregnancy?

Women with depression usually experience some of the following symptoms for 2 weeks or more:

• Persistent sadness
• Difficulty concentrating
• Sleeping too little or too much
• Loss of interest in activities that you usually enjoy
• Recurring thoughts of death, suicide, or hopelessness
• Anxiety
• Feelings of guilt or worthlessness
• Change in eating habits

What are possible triggers of depression during pregnancy?

• Relationship problems
• Family or personal history of depression
• Infertility treatments
• Previous pregnancy loss
• Stressful life events
• Complications in pregnancy

What can happen if depression is not treated?

Untreated depression can hurt the mother and her baby. Some women with depression have a hard time caring for themselves during pregnancy. They may: Eat poorly Not gain enough weight Have trouble sleeping Miss prenatal visits Not follow medical instructions Use harmful substances, like tobacco, alcohol, or illegal drugs

Depression during pregnancy can raise the risk of:

Problems during pregnancy or delivery Having a low-birth-weight baby Premature birth

Aborto

Entro 6 mesi dall’aborto :

• Depressione Maggiore - 11% primo episodio
• 54% se episodi pregressi
• rischio 5 volte maggiore in assenza

di figli

• Gravidanza entro 1 anno: aumenta il rischio di depressione

dopo 1 anno: non aumenta il rischio di depressione

(Burt e Stein, J Clin Psychiatry 2002; 63 (suppl 7): 9-15)

Le classi di psicofarmaci con i più intensi effetti teratogeni sono i Sali di litio e gli anticonvulsivanti

Gli SSRI sono i farmaci antidepressivi più comunemente prescritti, per la loro efficacia e per il miglior profilo di tollerabilità e sicurezza, rispetto ai più vecchi antidepressivi. Tuttavia studi hanno dimostrato che l’esposizione ai farmaci SSRI nella fase tardiva della gravidanza è associata a complicanze di breve periodo nei neonati, tra cui il distress respiratorio lieve, irritabilità, problemi di alimentazione, ittero e convulsioni.

• Vol. 279 No. 8, February 25, 1998

Nathalie A. Kulin,; Anne Pastuszak, & coll.

Context Although a large number of women of reproductive age use new selective serotonin reuptake inhibitors (SSRIs) and half of all pregnancies are unplanned, no data exist on the safety of these agents for the human fetus.

Objective To assess fetal safety and risk of fluvoxamine, paroxetine,

and sertraline. Design A prospective, multicenter, controlled cohort study. Setting Nine Teratology Information Service centers in the United States and Canada. Patients All women who were counseled during pregnancy following exposure to a new SSRI and followed up by the participating centers. Controls were randomly selected from women counseled after exposure to nonteratogenic agents.

• Vol. 279 No. 8, February 25, 1998

Nathalie A. Kulin,; Anne Pastuszak, & coll.

Main Outcome Measures Rates of major congenital malformations. Results A total of 267 women exposed to an SSRI and 267 controls were studied. Exposure to SSRIs was not associated with either increased risk for major malformations (9/222 live births [4.1%] vs 9/235 live births [3.8%] in the controls, relative risk, 1.06, 95% confidence interval, 0.43-2.62) or higher rates of miscarriage, stillbirth, or prematurity. Mean (SD) birth weights among SSRI users (3439 [505] g) were similar to the controls (3445 [610] g) as were the gestational ages (39.4 [1.7] weeks vs 39.4 [1.9] weeks). Conclusion The new SSRIs, fluvoxamine, paroxetine, and sertraline, do not appear to increase the teratogenic risk when used in their recommended doses

Volume 193, Issue 6, December 2005 Anna Sivojelezova Citalopram use in pregnancy: Prospective comparative evaluation of pregnancy and fetal outcome Objective

Citalopram is a selective serotonin reuptake inhibitor indicated for depression. The safety of this medication in pregnancy has not been fully established. The purpose

• f this study was to investigate whether citalopram is associated with an increased

incidence of adverse pregnancy outcomes.

Study design

Pregnant women who contacted the Motherisk Program, a Teratogen Information Center in Toronto, Ontario, with regard to the safety of citalopram in pregnancy were enrolled in the study. The exposed women were matched to a disease-matched group

• f women and a nonteratogenic group.

All women were matched for age (± 2 years) and gestational age at time of first call to the Motherisk (± 2 weeks). A structured telephone follow-up interview was conducted following the expected date of confinement.

Volume 193, Issue 6, December 2005 Results

The total number of pregnant women enrolled in this study was 396 (132 women in each group). A total of 125 women took citalopram at least in the first trimester. Seventy-one (54%) women continued to take the drug throughout pregnancy. One hundred fourteen women (86%) had live births, 14 (11%) had spontaneous abortions, 2 (1.5%) had elective terminations, and 2 (1.5%) experienced stillbirths. Fetal survival rates, mean birth weights, and duration of pregnancy were not statistically different among the 3 groups. Of 108 live-born infants whose mothers were exposed to citalopram in the first trimester, there was 1 (0.9%) male infant born with a major malformation. There was a relative risk of 4.2 (95% confidence interval 1.71-10.26) in neonates exposed to citalopram close to term to be admitted to special-care nurseries as compared with the unexposed infants.

Conclusion

Citalopram use during the period of embryogenesis in pregnancy is not associated with an apparent major teratogenic risk. Late pregnancy use of citalopram is associated with increased risk of poor neonatal adaptation syndrome, recently described with

• ther selective serotonin reuptake inhibitors.

Neonatal Adaptation Syndrome

In recent years there has been increasing recognition of a set of neurobehavioral signs in infants born to mothers taking antidepressants. This ‘syndrome’ has been given a number of names including Neonatal Adaptation Syndrome, Neonatal Abstinence Syndrome, Neonatal Withdrawal Syndrome and Neonatal Serotonergic Syndrome. . Newborn babies exposed to antidepressants in utero may manifest: Insomnia or somnolence Agitation , tremors, jitteriness, shivering and/ or altered tone Restlessness, irritability &constant crying Poor feeding, vomiting or diarrhoea Poor temperature control, hypoglycaemia Tachypnoea, respiratory distress, nasal congestion or cyanosis Seizures

Reports of incidence suggest 30% of SSRI exposed full term babies show poor neonatal adaptation – this compares with approximately 10% of non exposed babies . It is usually short lived with a median duration of 3 days, and 75 % complete resolution by 5 days. However there have been reports of adaptation signs lasting up to 4 weeks. Premature babies are more vulnerable to NAS, and are more likely to develop signs, which may be more severe. One study reported 100% of exposed babies born before 37 weeks developed signs of NAS. Premature babies have been found to require 4 times as long in NICU compared to an age controlled non exposed group. Symptoms can vary greatly in severity from mild transitory symptoms to more severe symptoms including seizures and dehydration.

Jul 2010

. Use of antidepressants during pregnancy and the risk of spontaneous abortion

Hamid Reza Nakhai-Pour, MD PhD, Perrine Broy, BSc and Anick Bérard, PhD

Background: The risk of relapse of depression or the diagnosis of some other psychiatric disorders during pregnancy necessitates the use of antidepressants despite possible adverse effects. Whether such use increases the risk of spontaneous abortion is still being debated. We evaluated the risk of spontaneous abortion in relation to the use of antidepressants during pregnancy.

Methods: Using a nested case–control study design, we obtained data from the Quebec Pregnancy Registry for 5124 women who had a clinically detected spontaneous abortion. For each case, we randomly selected 10 controls from the remaining women in the registry who were matched by the case’s index date (date of spontaneous abortion) and gestational age at the time of spontaneous abortion. Use of antidepressants was defined by filled prescriptions and was compared with

• nonuse. We also studied the classes, types and doses of antidepressants.

Results: A total of 284 (5.5%) of the women who had a spontaneous abortion had at least one prescription for an antidepressant filled during the pregnancy, as compared with 1401 (2.7%) of the matched controls (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.83–2.38).. When we looked at antidepressant use by type versus no use, paroxetine use alone (OR 1.75, 95% CI 1.31–2.34) and venlafaxine use alone (OR 2.11, 95% CI 1.34–3.30) were associated with an increased risk of spontaneous abortion.

Interpretation: The use of antidepressants, especially paroxetine, venlafaxine or the combined use of different classes of antidepressants, during pregnancy was associated with an increased risk of spontaneous abortion

• Fluoxetine promotes gliogenesis during neural differentiation

in mouse embryonic stem cells Kusakawa S, Nakamura K, Miyamoto Y, Sanbe A, Torii T, Yamauchi J, Tanoue A

• Sept. 2010

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for treatment of mood disorders and depression, even during pregnancy and lactation. SSRIs are thought to be much safer than tricyclic antidepressants, with a low risk of embryonic toxicity. Several recent studies, however, have reported that fetal exposure to SSRIs increases the risk of adverse effects during fetal and neonatal

• development. This is consistent with our previous finding that fluoxetine, a prototypical SSRI,

profoundly affected the viability of cultured embryonic stem (ES) cells as well as their ability to differentiate into cardiomyocytes. Furthermore, we found that fluoxetine induced fluctuations in ectodermal marker gene expression during ES cell differentiation, which suggests that fluoxetine may affect neural development. In the present study, we investigated the effects of fluoxetine on the process

• f differentiation from ES cells into neural cells using the stromal cell-derived inducing activity (SDIA)
• method. Fluoxetine treatment was found to enhance the expression of glial marker genes following

neural differentiation, as observed by immunocytochemical analysis or quantitative RT-PCR. The promoter activity of glial marker genes was also significantly enhanced when cells were treated with fluoxetine, as observed by luciferase reporter assay. The expression of neuronal markers during ES cell differentiation into neural cells, on the other hand, was inhibited by fluoxetine treatment. In addition, FACS analysis revealed an increased population of glial cells in the differentiating ES cells treated with fluoxetine. These results suggest that fluoxetine could facilitate the differentiation of mouse ES cells into glial cell lineage, which may affect fetal neural development

Citalopram Risks: Has been associated with a rare

but serious newborn lung problem (persistent pulmonary hypertension of the newborn, or PPHN) when taken during the last half of pregnancy; has been associated with septal heart defects; has been associated with a birth defect that affects the brain and skull (anencephaly), a birth defect that affect sutures on the head (craniosynostosis) and a birth defect that affects the abdominal organs (omphalocele) Recommendation: Consider as an option during pregnancy

Fluoxetine Risks: Has been associated with PPHN when taken during the last half of pregnancy Recommendation: Consider as an option during pregnancy

Paroxetine Risks: Has been associated with fetal heart defects when takenduring the first three months

• f pregnancy; has been associated with PPHN when

taken during the last half of pregnancy; has been associated with anencephaly, craniosynostosis and

• mphalocele

Recommendation: Avoid during pregnancy

Sertraline Risks: Has been associated with PPHN when taken during the last half of pregnancy; has been associated with septal heart defects; has been associated with omphalocele Recommendation: Consider as an option during pregnancy

Amitriptyline Risks: Suggested risk of limb malformation in early studies, but not confirmed by newer studies Recommendation: Consider as an option during pregnancy

Nortriptilina Risks: Suggested risk of limb malformation in early studies, but not confirmed by newer studies Recommendation: Consider as an option during pregnancy

• Some studies associate the use of antidepressants

during pregnancy with preterm birth, but other studies don't support this link.

• Use of more than one type of SSRI during the first

trimester of pregnancy has been associated with an increased prevalence of septal heart defects.

Grazie per l’attenzione