Antidepressant Risks During Pregnancy and Breastfeeding
Expecting mothers struggling with significant depression often face difficult decisions on psychotropic medication use during pregnancy and breastfeeding. While this is a delicate topic of depression during pregnancy and how the mother is able care for herself and the baby during that time, recent research says that infants are at risk of developing withdrawal symptoms or Poor Neonatal Adaptation as a result of being exposed to psychotropic drugs within the womb. All psychotropic meds pass the placenta and are excreted in breast milk. Expecting and nursing mothers and their health care provider must seriously weigh the risks and costs for both mother and infant, and also should be informed about potential helpful safe solutions.
Poor Neonatal Adaption (PNA) is a response that occurs in newborns because of exposures to anti-depressants, anti-psychotics, and benzodiazepines during pregnancy. PNA is known by other names as well, but reflects newborns who are highly stressed from medication exposure during pregnancy. Like adults who withdraw quickly from these types of medications, infants also go through similar withdrawal symptoms. The onset of symptoms usually occurs immediately up to 2-6 days after birth and usually resolves quickly. Benzodiazepines withdrawal however may affect the infant for several months. Infants exposed to these medications experience symptoms of feeding difficulties, irritability, and tremors. Sometimes there are symptoms of drug toxicity. The symptoms are similar to drug withdrawal. There may be problems with jitteriness, trouble breathing, temperature instability, exaggerated reflexes, diarrhea, vomiting, sleeping problems, high pitched or frequent crying, lethargy, seizures, and either exaggerated or weak muscle tone. The acute symptoms appear to resolve without known consequences, but long-term information is simply not available.
In a recent study published in April 2015, scientists studied 247 infants who were exposed to an antidepressant medication during the last trimester of fetal life. A number of risk factors were analyzed for their possible association with the development of PNA. These included type of feeding, type and dosage of the antidepressant, prematurity, if the mother smoked and had anxiety and depression. Of the 247 infants accepted into the study, 157 infants or 64 percent developed poor neonatal adaptation. Those infants who were formula fed and had exposure to SSRIs developed PNA. In this study, the dosage of the SSRI meds did not matter, i.e. there was no statistical difference whether or not the mother’s SSRI dose was low, moderate, or high dose. Fewer problems were identified in this study when infants were breastfed or had both formula feeding and breast milk.
Research on antidepressant use during pregnancy is growing with risks and benefits hotly debated. A recent review study looked at several outcomes with animal and human studies. Many negative changes were noted in the animal studies. Rodents treated with SSRIs during pregnancy had increased problems with depression and anxiety behaviors and indeed most studies showed a decrease in social behavior. The review study showed that in four human studies there was no effect on infants having an anxiety problem, yet the outcome of one study suggested that children with autism were more likely to have a mother who was prescribed an SSRI during pregnancy. The authors’ conclusion was that “the findings in rodents exposed to SSRIs during development point to an increase in depression and anxiety-like behavior and alterations in social behavior, but the evidence is not robust enough to discourage the use of SSRIs during human pregnancy.”
A more recent study in Neuroscience, January 2015 studied exposure to paroxetine (Paxil) during development in a certain breed of rats. The researchers focused on rats genetically prone for anxious behavior and compared them to a breed that did not have that risk. The rodents genetically bred for naturally anxious behavior and had been exposed to Paxil during development had significant SSRI-induced gene changes within the brain’s hippocampus and amygdala. These are regions of the brain involved with emotional responses, like fear, anxiety, depression, etc. These rats had increased behavioral abnormalities with depression and anxiety. Not only did the genetic expression change and stress behaviors increase, there was a change in nerve development, energy metabolism, and structural changes to components with the nerve-synapse area, i.e. the relay station of nerves and neurotransmitters.
This animal study pointed out negative behavior and brain structure changes induced and worsened by SSRI exposure during development. While this is an animal study, it makes one wonder about the 10-20 percent of pregnant or nursing women who are on SSRIs and how it is affecting the children’s developing brain and later emotional health. In an age of rapid growth of knowledge and understanding, understanding gene profiles, epigenetics, biochemical uniqueness and increased susceptibility to depression and anxiety, this understanding cannot come soon enough for those facing these risks and decisions.
Most research articles state that further evaluation and studies are needed with this topic of pregnancy, depression, and antidepressant use especially in the context of potential long-term effects. The Journal of Perinatology performed a follow up study on the long-term neurological development of children exposed to SSRI’s during pregnancy who experienced neonatal withdrawal problems. Thirty children who had withdrawal problems were evaluated from 2-6 years of age and compared to children who had not experienced SSRI exposure. Cognitive skills were similar between the two groups, but there was a noticeable trend with a smaller head circumference in the risk group compared to the non-treated children. In addition, children exposed to SSRIs had an increased risk of social-behavioral abnormalities. Longer-term outcomes are not available. The types of behavioral abnormalities were not listed with study abstract.
We certainly know that high stress during pregnancy, infancy, and toddler years programs the brain to be wired in a different manner that can affect neurological programming and stress tolerance for the life of the individual. This is a well-studied topic. But the added conundrum of psychotropic medication use during pregnancy and postnatal health will leave scientists evaluating this mix of variables for years to come. Many within the medical and research communities feel that the benefits of anti-depressant use for maternal depression outweigh any risks. The material presented here is not meant to dissuade one from appropriate medical care, but it is intended to help shed information on a delicate subject and complex decision making that may not always be openly discussed.
One way to help evaluate the risk for endangered infants is to identify women who are poor detoxifiers or have dysfunction with CYP450 2D6 gene. This is a gene involved with Cytochrome P 450 detoxification system within the liver that detoxifies toxins within the bloodstream. A roadblock that occurs here leads to trouble metabolizing meds and toxins. Indications of poor detoxification ability is often seen with sensitivity to medications, cleaning chemicals, perfumes or scented products, petroleum products, cigarette smoke, or alcohol intolerance, etc. Symptoms may include fatigue, skin rashes, brain fog, headaches, depression, anxiety, and poor focus, etc after exposure to minute amounts of chemicals. Presence of these detoxification intolerances within the expecting mother puts the infant at a much higher risk for SSRI toxicity and neonatal withdrawal symptoms.
On a different focus involving the liver and detoxification, there is information about how sertraline (SSRIs) can induce liver injury in some adults. The interesting connection and mechanism here has to do with the impairment of mitochondria within the liver induced by sertraline (Zoloft). A 2012 animal study demonstrated that sertraline caused mitochondrial impairment within the liver. The SSRI, Zoloft disrupted the core function of mitochondria or caused uncoupled oxidative phosphorylation. The end result was damaged mitochondria with depleted cellular levels of ATP, increased oxidative stress and free radicals leading to actual liver injury and damage. It is unknown if newborns experience this same phenomenon albeit transient with PNA and SSRI withdrawal, but clearly there is a metabolic and neurological stress response.
A cellular study evaluated other antidepressant types on the effects on mitochondria and how toxic the meds were to the mitochondria. The consequences depended on the type of medication used. The results showed that antidepressants inhibited various parts of major mitochondrial enzymatic pathways, i.e. mitochondrial complexes I, II, III, and IV. Most of the inhibitory damaging effect occurred with complex IV activity or COX enzyme. When the COX enzyme is deficient, this causes a traffic jam in energy production throughout the body. Without adequate amounts of COX enzyme, cells don’t receive enough energy to function properly. It ultimately affects multiple systems in the body. When the COX enzymes are blocked, it leads to high levels of oxidative stress, dysfunctional and broken mitochondria and even cell death. Studies on the effect of anti-depressants on mitochondrial health are mixed with incomplete consensus on whether or not there is benefit or harm.
The health of mitochondria is critical for every cell in the body, especially within the brain. Mitochondria play a key role in the how neurotransmitters cross the space between nerve cells within the brain. Mitochondria also supply the brain with energy, buffer calcium regulation, help with protein and fat synthesis, facilitate growth, and are heavily involved with keeping the brain resilient. High levels of inflammation, oxidative stress, high cortisol levels, insulin resistance, toxins, cholesterol damage, low antioxidant status, and many other things can damage the function of mitochondria. Unhealthy changes to the mitochondria play a defining role in the development of clinical depression.
Knowing that mitochondria dysfunction is present with depression and mixing in high energy demand states of pregnancy or breastfeeding and then combining it with medications that show some potentially damaging effects to mitochondria, leaves many unanswered questions. How does this affect the infant? How does it affect the mother? What are the long-term risks for both? Do the withdrawal symptoms or social-behavioral challenges reflect undetected mitochondria challenges in the child? In this picture, we have absolutely no idea what the mitochondria health will be of those infants exposed to the psychotropic meds when they are senior citizens.
Pregnancy and birth is such a beautiful experience in life, yet it can be such a challenge and anguishing time for a mother suffering with depression. There are so many unanswered questions, but it does mean that we need to be careful, thoughtful, and have as much information as possible to make the best decisions at that moment time. The fact that newborns are in a high state of making new mitochondria with growth and development may lessen the risk, but we still need to be thoughtful for this fragile, delicate state.
All mitochondrial DNA is passed from generation to generation through only the mother. The father’s mitochondrial DNA is not passed to the offspring. This means that the health or lack of health of mom’s mitochondria is shared with all children born to her. If the mother herself is challenged with unhealthy mitochondria, increased risks occur for her children with mitochondrial health related concerns developing later in life.
Mitochondrial disorders affect about 1 in 4,000 individuals and the number is increasing as medicine learns more about scope of mitochondrial disorders. Mitochondrial disorders can happen at any age. Some of the most common symptoms are poor growth, poor muscle strength and coordination, pain, fatigue, poor endurance, neurological problems, autism and related disorders, vision or hearing loss, developmental delays, learning disabilities, heart, liver, kidney disease or failure, GI problems including constipation, diabetes, increased risk of infection or trouble recovering from minor illness, thyroid and adrenal dysfunction, autonomic dysfunction (POTS, blood pressure problems, temperature intolerance, etc), and cognitive changes with confusion, memory loss, and disorientation. The list of symptoms for PNA certainly has some cross-over into known mitochondrial disorders found later in life. Looking at this list makes one question the path of choices that we are facing.
Preparation, fortification, and protection of health before pregnancy, during, and after birth is fundamental for the woman and child. For those who are at risk for depression or have a history of depression, it is absolutely critical to thoroughly address this issue. Healthy management of leptin hormone, blood sugar, methylation defects (B12 and folate processing problems), autoimmune thyroid, reduced inflammation and stress management need to be present. The less stressed you are prior to conceiving and during pregnancy, the better you can stack the deck of genetic programming and mitochondrial health in your and your child’s favor.
By all means, protecting mitochondria is crucial in all aspects of health for mother and child. A diet rich in quality good fats, dark green leafy vegetables, and organic fruits and vegetables from all colors of the rainbow on a daily basis is important for mitochondrial health. Immensely important nutrients for mitochondria and neurotransmitter signaling include all B vitamins, especially the methylated forms of B12 and folate, the omega-3 fatty acids such as DHA, magnesium, iron, copper, and zinc. The antioxidants resveratrol, curcumin, PQQ, coenzyme Q10, lipoic acid, selenium, and manganese support and protect glutathione and help to recycle each other, which is fundamental to mitochondrial health and function. These same nutrients must be in ample supply for healthy fetal growth and development.
Earlier in this article, I noted that infants who were breastfed had less problems with PNA. While there were no particular reasons given, probably because there are several, it may be helpful to note that breast milk contains some of the highest amounts of the extreme antioxidant or redox agent, PQQ. PQQ is essential for mitochondrial formation and protection. It is also essential for healthy growth, development, and neurological protection.
Nutrients like PQQ, acetyl-l-carnitine, r-alpha lipoic acid, coenzyme Q10, glycerophosphocholine (GPC), and phosphatidylserine (PS) support mitochondria through birth of new mitochondria, providing building blocks for mitochondrial membranes, and helping the brain to regenerate after injury and stress. In addition to nutritional support, exercise and physical activity positively impact mitochondria and depression often better than antidepressants. Nutritional support is determined by how difficult and extensive the issues are.
Nourishing the brain and mitochondria with these nutrients provides healthy alternative choices when struggling with depression in the expecting mother, and also the baby. There are so many moving variables and factors with depression, pregnancy and newborn health development. Scientists will be engaged on this topic for years to come, but mothers need support today. Regardless of the choice to use or avoid antidepressants during pregnancy or postnatal, fortifying and protecting the brain with healthy nutrition is a win-win for mother and baby.
Newborns and Antidepressants
Poor Neonatal Adaption (PNA) is a response that occurs in newborns because of exposures to anti-depressants, anti-psychotics, and benzodiazepines during pregnancy. PNA is known by other names as well, but reflects newborns who are highly stressed from medication exposure during pregnancy. Like adults who withdraw quickly from these types of medications, infants also go through similar withdrawal symptoms. The onset of symptoms usually occurs immediately up to 2-6 days after birth and usually resolves quickly. Benzodiazepines withdrawal however may affect the infant for several months. Infants exposed to these medications experience symptoms of feeding difficulties, irritability, and tremors. Sometimes there are symptoms of drug toxicity. The symptoms are similar to drug withdrawal. There may be problems with jitteriness, trouble breathing, temperature instability, exaggerated reflexes, diarrhea, vomiting, sleeping problems, high pitched or frequent crying, lethargy, seizures, and either exaggerated or weak muscle tone. The acute symptoms appear to resolve without known consequences, but long-term information is simply not available.
In a recent study published in April 2015, scientists studied 247 infants who were exposed to an antidepressant medication during the last trimester of fetal life. A number of risk factors were analyzed for their possible association with the development of PNA. These included type of feeding, type and dosage of the antidepressant, prematurity, if the mother smoked and had anxiety and depression. Of the 247 infants accepted into the study, 157 infants or 64 percent developed poor neonatal adaptation. Those infants who were formula fed and had exposure to SSRIs developed PNA. In this study, the dosage of the SSRI meds did not matter, i.e. there was no statistical difference whether or not the mother’s SSRI dose was low, moderate, or high dose. Fewer problems were identified in this study when infants were breastfed or had both formula feeding and breast milk.
Research on antidepressant use during pregnancy is growing with risks and benefits hotly debated. A recent review study looked at several outcomes with animal and human studies. Many negative changes were noted in the animal studies. Rodents treated with SSRIs during pregnancy had increased problems with depression and anxiety behaviors and indeed most studies showed a decrease in social behavior. The review study showed that in four human studies there was no effect on infants having an anxiety problem, yet the outcome of one study suggested that children with autism were more likely to have a mother who was prescribed an SSRI during pregnancy. The authors’ conclusion was that “the findings in rodents exposed to SSRIs during development point to an increase in depression and anxiety-like behavior and alterations in social behavior, but the evidence is not robust enough to discourage the use of SSRIs during human pregnancy.”
A more recent study in Neuroscience, January 2015 studied exposure to paroxetine (Paxil) during development in a certain breed of rats. The researchers focused on rats genetically prone for anxious behavior and compared them to a breed that did not have that risk. The rodents genetically bred for naturally anxious behavior and had been exposed to Paxil during development had significant SSRI-induced gene changes within the brain’s hippocampus and amygdala. These are regions of the brain involved with emotional responses, like fear, anxiety, depression, etc. These rats had increased behavioral abnormalities with depression and anxiety. Not only did the genetic expression change and stress behaviors increase, there was a change in nerve development, energy metabolism, and structural changes to components with the nerve-synapse area, i.e. the relay station of nerves and neurotransmitters.
This animal study pointed out negative behavior and brain structure changes induced and worsened by SSRI exposure during development. While this is an animal study, it makes one wonder about the 10-20 percent of pregnant or nursing women who are on SSRIs and how it is affecting the children’s developing brain and later emotional health. In an age of rapid growth of knowledge and understanding, understanding gene profiles, epigenetics, biochemical uniqueness and increased susceptibility to depression and anxiety, this understanding cannot come soon enough for those facing these risks and decisions.
Potential Long-term Concerns with PNA
Most research articles state that further evaluation and studies are needed with this topic of pregnancy, depression, and antidepressant use especially in the context of potential long-term effects. The Journal of Perinatology performed a follow up study on the long-term neurological development of children exposed to SSRI’s during pregnancy who experienced neonatal withdrawal problems. Thirty children who had withdrawal problems were evaluated from 2-6 years of age and compared to children who had not experienced SSRI exposure. Cognitive skills were similar between the two groups, but there was a noticeable trend with a smaller head circumference in the risk group compared to the non-treated children. In addition, children exposed to SSRIs had an increased risk of social-behavioral abnormalities. Longer-term outcomes are not available. The types of behavioral abnormalities were not listed with study abstract.
We certainly know that high stress during pregnancy, infancy, and toddler years programs the brain to be wired in a different manner that can affect neurological programming and stress tolerance for the life of the individual. This is a well-studied topic. But the added conundrum of psychotropic medication use during pregnancy and postnatal health will leave scientists evaluating this mix of variables for years to come. Many within the medical and research communities feel that the benefits of anti-depressant use for maternal depression outweigh any risks. The material presented here is not meant to dissuade one from appropriate medical care, but it is intended to help shed information on a delicate subject and complex decision making that may not always be openly discussed.
Increased PNA Risk and Chemical Sensitivity
One way to help evaluate the risk for endangered infants is to identify women who are poor detoxifiers or have dysfunction with CYP450 2D6 gene. This is a gene involved with Cytochrome P 450 detoxification system within the liver that detoxifies toxins within the bloodstream. A roadblock that occurs here leads to trouble metabolizing meds and toxins. Indications of poor detoxification ability is often seen with sensitivity to medications, cleaning chemicals, perfumes or scented products, petroleum products, cigarette smoke, or alcohol intolerance, etc. Symptoms may include fatigue, skin rashes, brain fog, headaches, depression, anxiety, and poor focus, etc after exposure to minute amounts of chemicals. Presence of these detoxification intolerances within the expecting mother puts the infant at a much higher risk for SSRI toxicity and neonatal withdrawal symptoms.
Zoloft, Liver and Mitochondrial Injuries
On a different focus involving the liver and detoxification, there is information about how sertraline (SSRIs) can induce liver injury in some adults. The interesting connection and mechanism here has to do with the impairment of mitochondria within the liver induced by sertraline (Zoloft). A 2012 animal study demonstrated that sertraline caused mitochondrial impairment within the liver. The SSRI, Zoloft disrupted the core function of mitochondria or caused uncoupled oxidative phosphorylation. The end result was damaged mitochondria with depleted cellular levels of ATP, increased oxidative stress and free radicals leading to actual liver injury and damage. It is unknown if newborns experience this same phenomenon albeit transient with PNA and SSRI withdrawal, but clearly there is a metabolic and neurological stress response.
A cellular study evaluated other antidepressant types on the effects on mitochondria and how toxic the meds were to the mitochondria. The consequences depended on the type of medication used. The results showed that antidepressants inhibited various parts of major mitochondrial enzymatic pathways, i.e. mitochondrial complexes I, II, III, and IV. Most of the inhibitory damaging effect occurred with complex IV activity or COX enzyme. When the COX enzyme is deficient, this causes a traffic jam in energy production throughout the body. Without adequate amounts of COX enzyme, cells don’t receive enough energy to function properly. It ultimately affects multiple systems in the body. When the COX enzymes are blocked, it leads to high levels of oxidative stress, dysfunctional and broken mitochondria and even cell death. Studies on the effect of anti-depressants on mitochondrial health are mixed with incomplete consensus on whether or not there is benefit or harm.
Healthy Mitochondria
The health of mitochondria is critical for every cell in the body, especially within the brain. Mitochondria play a key role in the how neurotransmitters cross the space between nerve cells within the brain. Mitochondria also supply the brain with energy, buffer calcium regulation, help with protein and fat synthesis, facilitate growth, and are heavily involved with keeping the brain resilient. High levels of inflammation, oxidative stress, high cortisol levels, insulin resistance, toxins, cholesterol damage, low antioxidant status, and many other things can damage the function of mitochondria. Unhealthy changes to the mitochondria play a defining role in the development of clinical depression.
Knowing that mitochondria dysfunction is present with depression and mixing in high energy demand states of pregnancy or breastfeeding and then combining it with medications that show some potentially damaging effects to mitochondria, leaves many unanswered questions. How does this affect the infant? How does it affect the mother? What are the long-term risks for both? Do the withdrawal symptoms or social-behavioral challenges reflect undetected mitochondria challenges in the child? In this picture, we have absolutely no idea what the mitochondria health will be of those infants exposed to the psychotropic meds when they are senior citizens.
Pregnancy and birth is such a beautiful experience in life, yet it can be such a challenge and anguishing time for a mother suffering with depression. There are so many unanswered questions, but it does mean that we need to be careful, thoughtful, and have as much information as possible to make the best decisions at that moment time. The fact that newborns are in a high state of making new mitochondria with growth and development may lessen the risk, but we still need to be thoughtful for this fragile, delicate state.
Mitochondrial Disorders
All mitochondrial DNA is passed from generation to generation through only the mother. The father’s mitochondrial DNA is not passed to the offspring. This means that the health or lack of health of mom’s mitochondria is shared with all children born to her. If the mother herself is challenged with unhealthy mitochondria, increased risks occur for her children with mitochondrial health related concerns developing later in life.
Mitochondrial disorders affect about 1 in 4,000 individuals and the number is increasing as medicine learns more about scope of mitochondrial disorders. Mitochondrial disorders can happen at any age. Some of the most common symptoms are poor growth, poor muscle strength and coordination, pain, fatigue, poor endurance, neurological problems, autism and related disorders, vision or hearing loss, developmental delays, learning disabilities, heart, liver, kidney disease or failure, GI problems including constipation, diabetes, increased risk of infection or trouble recovering from minor illness, thyroid and adrenal dysfunction, autonomic dysfunction (POTS, blood pressure problems, temperature intolerance, etc), and cognitive changes with confusion, memory loss, and disorientation. The list of symptoms for PNA certainly has some cross-over into known mitochondrial disorders found later in life. Looking at this list makes one question the path of choices that we are facing.
Combating Depression During Pregnancy and Postpartum
Preparation, fortification, and protection of health before pregnancy, during, and after birth is fundamental for the woman and child. For those who are at risk for depression or have a history of depression, it is absolutely critical to thoroughly address this issue. Healthy management of leptin hormone, blood sugar, methylation defects (B12 and folate processing problems), autoimmune thyroid, reduced inflammation and stress management need to be present. The less stressed you are prior to conceiving and during pregnancy, the better you can stack the deck of genetic programming and mitochondrial health in your and your child’s favor.
By all means, protecting mitochondria is crucial in all aspects of health for mother and child. A diet rich in quality good fats, dark green leafy vegetables, and organic fruits and vegetables from all colors of the rainbow on a daily basis is important for mitochondrial health. Immensely important nutrients for mitochondria and neurotransmitter signaling include all B vitamins, especially the methylated forms of B12 and folate, the omega-3 fatty acids such as DHA, magnesium, iron, copper, and zinc. The antioxidants resveratrol, curcumin, PQQ, coenzyme Q10, lipoic acid, selenium, and manganese support and protect glutathione and help to recycle each other, which is fundamental to mitochondrial health and function. These same nutrients must be in ample supply for healthy fetal growth and development.
Earlier in this article, I noted that infants who were breastfed had less problems with PNA. While there were no particular reasons given, probably because there are several, it may be helpful to note that breast milk contains some of the highest amounts of the extreme antioxidant or redox agent, PQQ. PQQ is essential for mitochondrial formation and protection. It is also essential for healthy growth, development, and neurological protection.
Nutrients like PQQ, acetyl-l-carnitine, r-alpha lipoic acid, coenzyme Q10, glycerophosphocholine (GPC), and phosphatidylserine (PS) support mitochondria through birth of new mitochondria, providing building blocks for mitochondrial membranes, and helping the brain to regenerate after injury and stress. In addition to nutritional support, exercise and physical activity positively impact mitochondria and depression often better than antidepressants. Nutritional support is determined by how difficult and extensive the issues are.
Nourishing the brain and mitochondria with these nutrients provides healthy alternative choices when struggling with depression in the expecting mother, and also the baby. There are so many moving variables and factors with depression, pregnancy and newborn health development. Scientists will be engaged on this topic for years to come, but mothers need support today. Regardless of the choice to use or avoid antidepressants during pregnancy or postnatal, fortifying and protecting the brain with healthy nutrition is a win-win for mother and baby.
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