Oxytocin treatment for postpartum depression

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Oxytocin Treatment for Postpartum Depression Oxytocin (OT) has potential to be a treatment for Postpartum Depression (PPD) [1] . Oxytocin is released when a mother cares for her child, making the interaction pleasurable [2] . Mothers that report high levels of infant-mother bonding and demonstrate responsive and sensitive parenting generally show increased levels of OT and brain reward center activation during play sessions [1] . According to Slattery and Neumann, the oxytocin system of mothers experiencing PPD may have altered activity [3] . These mothers have trouble bonding with their infants when they are born [1] . An experiment found that mothers, who have low attachment ratings to adults and their infants, also have lower levels of OT when caring for their children [3] . It is thought that women experiencing PPD may benefit from intranasal OT because this treatment would help the mother feel happier and assist her in bonding with the child [1] . Another experiment shows that administering OT to a mother sheep increases the amount of care that she gives to offspring [2] . Further experimentation needs to be done in order to determine the effectiveness of OT as a treatment for Postpartum Depression [3] .

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Intranasal Administration

Intranasal (IN) administration, as opposed to more conventional routes, such as oral or intravenous infusion, offers an alternative method for drug delivery. This method is often the preferred method [4] . Oxytocin (OT) is a neuropeptide that can be administered in this manner. IN delivery methods are gaining popularity due to the non-invasive nature of the method. IN generally does not require complicated sterile preparations, is relatively painless, and often can be administered quickly by a medical doctor, or in some cases the patient. IN maximizes the convenience and comfort of the patient, making a treatment regimen more likely to be followed [4] . During Postpartum Depression (PPD), some women may be less likely to seek treatment if treatment is inconvenient. In addition, new mothers (especially if suffering with depression) may feel socially isolated or overwhelmed by responsibilities of caring for a new infant. IN not only provides a convenient delivery method, but is also a logical choice based on efficacy. Tissue in nasal cavities is highly vascular, providing a large surface area for absorption. Large surface areas allow for quick drug onset, meaning greater potential for the drug to reach the central nervous system without undergoing first-pass metabolism [4] . Avoiding first-pass metabolism allows more of the drug to be available for treatment. Gastrointestinal discomfort and digestive side-effects can also be avoided by IN dosage [4] . IN delivery allows OT to cross the blood brain barrier, expediting the drug to the central nervous system [5] and cerebrospinal fluid. The blood-brain-barrier normally protects the brain by blocking certain chemicals and toxins from reaching the brain. Increased levels of OT can be found in salivary samples after intranasal administration of the neuropeptide. Salivary OT levels can remain higher than baseline levels four hours after dosage, suggesting that OT is still producing an active response [5] . This may be an effective way of monitoring levels of OT levels during short-term treatment or help identify women at risk of or have a history of PPD. Though OT can be administered intravenously (and is sometimes the appropriate method depending on the medical situation), IN administration offers many advantages that make it an ideal choice for short-term treatment.

Side Effects

A review of 38 randomized and controlled trials suggests that short-term use of intranasal oxytocin appears to have few side-effects, with no difference when compared to a placebo group. Short-term use of intranasal oxytocin (OT) appears to be equally safe in vulnerable individuals as well as those deemed healthy. Three adverse incidents have been reported; two were thought to be caused by actual misuse of the nasal spray and one was linked with a more lengthy treatment regimen. The most frequently reported subjective sensation was calmness; however, there were no detectable differences between groups of OT use and placebo [6] . Given that Postpartum Depression (PPD) is not a chronic illness in nature, short-term intranasal OT treatment may be a logical application to alleviate some of the negative consequences associated with PPD. Effects of OT that may be beneficial are reduced levels of anxiety, increased trust levels and increased eye gaze [6] , all which could be beneficial side-effects for women suffering from PPD. Duration of treatment seems to be a key factor in safety. Allergic reactions, neurological disorders, and cardiovascular conditions should always be considered, but especially so if treatment is long-term. OT can modify heart rates and cause excessive fluid intake (antidiuretic effect). Intravenous infusion (IV) of oxytocin is often used to induce labor and enhance milk lactation during postpartum care. IV use can cause side-effects such as cardiovascular manifestations in the form of tachycardia and bradycardia. In addition, nausea, vomiting, and headaches can occur with IV application. Less frequently, water intoxication, skin rash, and anaphylactoid reactions have been reported [6] .

Experimentation

Intranasal oxytocin (OT) has been used to alleviate some of the symptoms associated with Postpartum Depression (PPD). Research by McErlean and Dadds suggests that intranasal OT, when combined with behavioral interventions, can remediate some of the mother-infant disturbances associated with PPD. This was the first study to evaluate both the individual effects of OT and the combined effects of OT in conjunction with maternal coaching. The study consisted of seventy-seven mothers (with sub-clinical levels of PPD) with infants ranging from eight to thirty weeks. In addition to the mother-baby interaction coaching, randomly selected mothers were treated with either 24IU OT or a placebo nasal spray over a period of two sessions; measurements were taken over a course of three time periods. Both questionnaire data and observational data, such as eye contact, positive vocalizations, and interaction quality, were used for evaluation purposes. There were significant interactions between the therapy and the OT in regard to maternal behavior. OT also seemed to benefit those mothers who were not involved with the therapy when compared to those that received the placebo nasal spray [1] . OT has also been linked with lowering the human stress response [3] . Lowering a stress response in women that are suffering from PPD may be beneficial to the infant-mother bond. Studies have shown that breast-feeding causes levels of plasma OT to increase in women. Experiments designed and performed in the 1980s helped researchers understand the correlation between breastfeeding prior to a stressful event and the decreased stress response observed during the peripartum period. As part of this experiment, lactating women were asked to either breastfeed their infant or hold their infant for a fifteen-minute period approximately thirty minutes before being subjected to a Trier Stress Test (TSST). During the TSST, women were asked to give an unprepared speech and calculate mental arithmetic in front of an audience. Results indicate that the women that breastfed their infant exhibited less stress during the TSST in comparison to the women that just held their infant [3] . Rising OT levels during breastfeeding may contribute to the lower stress situation.

Related Research Articles

<span class="mw-page-title-main">Childbirth</span> Expulsion of a fetus from the pregnant mothers uterus

Childbirth, also known as labour and delivery, is the completion of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or caesarean section. In 2019, there were about 140.11 million births globally. In the developed countries, most deliveries occur in hospitals, while in the developing countries most are home births.

<span class="mw-page-title-main">Postpartum depression</span> Endogenous major depressive episode experienced by women after giving birth

Postpartum depression (PPD), also called postnatal depression, is a type of mood disorder associated with childbirth, which can affect both sexes. Symptoms may include extreme sadness, low energy, anxiety, crying episodes, irritability, and changes in sleeping or eating patterns. Onset is typically between one week and one month following childbirth. PPD can also negatively affect the newborn child.

<span class="mw-page-title-main">Oxytocin</span> Peptide hormone and neuropeptide

Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin is released into the bloodstream as a hormone in response to sexual activity and during labour. It is also available in pharmaceutical form. In either form, oxytocin stimulates uterine contractions to speed up the process of childbirth. In its natural form, it also plays a role in bonding with the baby and milk production. Production and secretion of oxytocin is controlled by a positive feedback mechanism, where its initial release stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases. A similar process takes place during lactation and during sexual activity.

<span class="mw-page-title-main">Postpartum period</span> Time period beginning immediately after the birth of a child and extending for about six weeks

The postpartum period begins after childbirth and is typically considered to end within 6 weeks as the mother's body, including hormone levels and uterus size, returns to a non-pregnant state. The terms puerperium, puerperal period, or immediate postpartum period are commonly used to refer to the first six weeks following childbirth. The World Health Organization (WHO) describes the postnatal period as the most critical and yet the most neglected phase in the lives of mothers and babies; most maternal and newborn deaths occur during this period.

Biological half-life is the time taken for concentration of a biological substance to decrease from its maximum concentration (Cmax) to half of Cmax in the blood plasma, and is denoted by the abbreviation .

Psychoneuroendocrinology is the clinical study of hormone fluctuations and their relationship to human behavior. It may be viewed from the perspective of psychiatry, where in certain mood disorders, there are associated neuroendocrine or hormonal changes affecting the brain. It may also be viewed from the perspective of endocrinology, where certain endocrine disorders can be associated with negative health outcomes and psychiatric illness. Brain dysfunctions associated with the hypothalamus-pituitary-adrenal axis HPA axis can affect the endocrine system, which in turn can result in physiological and psychological symptoms. This complex blend of psychiatry, psychology, neurology, biochemistry, and endocrinology is needed to comprehensively understand and treat symptoms related to the brain, endocrine system (hormones), and psychological health..

<span class="mw-page-title-main">Postpartum bleeding</span> Loss of blood following childbirth

Postpartum bleeding or postpartum hemorrhage (PPH) is often defined as the loss of more than 500 ml or 1,000 ml of blood following childbirth. Some have added the requirement that there also be signs or symptoms of low blood volume for the condition to exist. Signs and symptoms may initially include: an increased heart rate, feeling faint upon standing, and an increased breathing rate. As more blood is lost, the patient may feel cold, blood pressure may drop, and they may become restless or unconscious. The condition can occur up to six weeks following delivery.

<span class="mw-page-title-main">Carbetocin</span> Pabal contains carbetocin used for preventing postpartum bleeding. Potent than oxytocin.

Carbetocin, sold under the brand names Pabal among others, is a medication used to prevent excessive bleeding after childbirth, particularly following Cesarean section. It appears to work as well as oxytocin. Due to it being less economical than other options, use is not recommended by NHS Scotland. It is given by injection into a vein or muscle.

<span class="mw-page-title-main">Allopregnanolone</span> Endogenous inhibitory neurosteroid

Allopregnanolone is a naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to treat postpartum depression. It is given by injection into a vein.

<span class="mw-page-title-main">Esketamine</span> Medication

Esketamine, also known as (S)-ketamine or S(+)-ketamine, is the S(+) enantiomer of ketamine, is a dissociative hallucinogen drug used as a general anesthetic and as an antidepressant for treatment of depression. It is sold under the brand names Spravato, Ketanest, among others. Esketamine is the active enantiomer of ketamine in terms of NMDA receptor antagonism and is more potent than racemic ketamine.

<span class="mw-page-title-main">Postpartum psychosis</span> Rare psychiatric emergency beginning suddenly in the first two weeks after childbirth

Postpartum psychosis(PPP), also known as puerperal psychosis or peripartum psychosis, involves the abrupt onset of psychotic symptoms shortly following childbirth, typically within two weeks of delivery but less than 4 weeks postpartum. PPP is a condition currently represented under "Brief Psychotic Disorder" in the Diagnostic and Statistical Manual of Mental Disorders, Volume V (DSM-V). Symptoms may include delusions, hallucinations, disorganized speech (e.g, incoherent speech), and/or abnormal motor behavior (e.g., catatonia). Other symptoms frequently associated with PPP include confusion, disorganized thought, severe difficulty sleeping, variations of mood disorders (including depression, agitation, mania, or a combination of the above), as well as cognitive features such as consciousness that comes and goes (waxing and waning) or disorientation.

<span class="mw-page-title-main">Demoxytocin</span> Chemical compound

Demoxytocin (INN), also known as desaminooxytocin or deaminooxytocin, as well as 1-(3-mercaptopropanoic acid)oxytocin ([Mpa1]OT), is an oxytocic peptide drug that is used to induce labor, promote lactation, and to prevent and treat puerperal (postpartum) mastitis. Demoxytocin is a synthetic analogue of oxytocin and has similar activities, but is more potent and has a longer half-life in comparison. Unlike oxytocin, which is given via intravenous injection, demoxytocin is administered as a buccal tablet formulation.

<span class="mw-page-title-main">Nasal administration</span> Administration of drugs through the nose

Nasal administration, popularly known as snorting, is a route of administration in which drugs are insufflated through the nose. It can be a form of either topical administration or systemic administration, as the drugs thus locally delivered can go on to have either purely local or systemic effects. Nasal sprays are locally acting drugs such as decongestants for cold and allergy treatment, whose systemic effects are usually minimal. Examples of systemically active drugs available as nasal sprays are migraine drugs, rescue medications for overdose and seizure emergencies, nicotine replacement, and hormone treatments.

A uterotonic, also known as an oxytocic or ecbolic, is a type of medication used to induce contraction or greater tonicity of the uterus. Uterotonics are used both to induce labor and to reduce postpartum hemorrhage.

Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnancy, or after childbirth. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy. The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%. If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease. Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards. This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.

<span class="mw-page-title-main">Parental brain</span>

Parental experience, as well as changing hormone levels during pregnancy and postpartum, cause changes in the parental brain. Displaying maternal sensitivity towards infant cues, processing those cues and being motivated to engage socially with her infant and attend to the infant's needs in any context could be described as mothering behavior and is regulated by many systems in the maternal brain. Research has shown that hormones such as oxytocin, prolactin, estradiol and progesterone are essential for the onset and the maintenance of maternal behavior in rats, and other mammals as well. Mothering behavior has also been classified within the basic drives. Less is known about the paternal brain, but changes in the father's brain occur alongside the mother once the offspring is born.

Endocrinology of parenting has been the subject of considerable study with focus both on human females and males and on females and males of other mammalian species. Parenting as an adaptive problem in mammals involves specific endocrine signals that were naturally selected to respond to infant cues and environmental inputs. Infants across species produce a number of cues to inform caregivers of their needs. These include visual cues, like facial characteristics, or in some species smiling, auditory cues, such as vocalizations, olfactory cues, and tactile stimulation. A commonly mentioned hormone in parenting is oxytocin, however many other hormones relay key information that results in variations in behavior. These include estrogen, progesterone, prolactin, cortisol, and testosterone. While hormones are not necessary for the expression of maternal behavior, they may influence it.

<span class="mw-page-title-main">Oxytocin (medication)</span> Medication made from the peptide oxytocin

Synthetic oxytocin, sold under the brand name Pitocin among others, is a medication made from the peptide oxytocin. As a medication, it is used to cause contraction of the uterus to start labor, increase the speed of labor, and to stop bleeding following delivery. For this purpose, it is given by injection either into a muscle or into a vein.

Paternal depression is a psychological disorder derived from parental depression. Paternal depression affects the mood of men; fathers and caregivers in particular. 'Father' may refer to the biological father, foster parent, social parent, step-parent or simply the carer of the child. This mood disorder exhibits symptoms similar to postpartum depression (PPD) including anxiety, insomnia, irritability, consistent breakdown and crying episodes, and low energy. This may negatively impact family relationships and the upbringing of children. Parents diagnosed with parental depression often experience increased stress and anxiety levels during early pregnancy, labor and postpartum. Those with parental depression may have developed it early on but some are diagnosed later on from when the child is a toddler up until a young adult.

<span class="mw-page-title-main">Breastfeeding and mental health</span>

Breastfeeding and mental health is the relationship between postpartum breastfeeding and the mother's and child's mental health. Research indicates breastfeeding may have positive effects on the mother's and child's mental health, though there have been conflicting studies that question the correlation and causation of breastfeeding and maternal mental health. Possible benefits include improved mood and stress levels in the mother, lower risk of postpartum depression, enhanced social emotional development in the child, stronger mother-child bonding and more. Given the benefits of breastfeeding, the World Health Organization (WHO), the European Commission for Public Health (ECPH) and the American Academy of Pediatrics (AAP) suggest exclusive breastfeeding for the first six months of life. Despite these suggestions, estimates indicate 70% of mothers breastfeed their child after birth and 13.5% of infants in the United States are exclusively breastfed. Breastfeeding promotion and support for mothers who are experiencing difficulties or early cessation in breastfeeding is considered a health priority.

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