Postpartum depression (PPD) is a pretty common problem, and yet there is insufficient awareness about the condition. Almost every sixth women who gives childbirth experiences PPD to some extent, with some studies suggesting that PPD may affect as many as 20% of women.(1)
As the name of the condition suggests, it occurs postpartum, that is, after giving birth. Most of these women are relatively healthy before giving birth, and they do not essentially show any signs of mental health issues. Of course, PPD’s risk is even higher in those prone to mental health issues, like women who were already experiencing depression.
PPD occurs a few weeks after giving birth to a child. Women with PPD do not feel excited about childbirth. Instead, the event makes them sad and insecure, and they start losing interest in various activities and become retarded and agitated. Those experiencing PPD feel a loss of energy and frequently complain about fatigue. They also have trouble concentrating, experience appetite changes, and many may even show suicidal tendencies – so, yes, the condition may be severe and life-threatening.
It is regretful that many women experiencing the condition do not seek medical attention for various reasons. Many simply do not want others to know about their mental health problem. Moreover, there is also some stigma associated with the condition.
One of the reasons why the condition is so challenging to manage is that science does not know what causes PPD and how it develops. It appears that the condition is multi-faceted that occurs for many reasons. This could be due to pre-existing anxiety or depression, stress caused by childbirth, certain pregnancy-related complications, social factors, nutritional deficiencies, pregnancy, and childbirth-related sleep changes, and more.
Researchers are still exploring why the conditions develop in some women and not in others. Indeed, they think that hormonal changes also play a significant role in the development of the disease. This is not just due to fluctuations in sex hormones like estradiol and progesterone, which definitely play a role in the disease condition. However, this could also be due to certain other hormones known to influence mood, like oxytocin and prolactin.
Further, in recent years, researchers have also paid greater attention to the changes in the hypothalamic-pituitary-adrenal axis (HPA). HPA plays an important role in stress responses. Studies show that HPA releases stress hormones before childbirth, and these hormones remain elevated for about 12 weeks in most women. This stress response is protective. However, in some women, this stress response is insufficient, which may also increase PPD risk.(1)
Postpartum Depression Treatment Approaches
Before we explore the role of IV ketamine therapy in managing postpartum depression (PPD), let us see various treatment approaches to the condition. Most likely, doctors would start treating the condition with cognitive behavior therapy (CBT), a kind of psychotherapy. It is a good choice for most women in the postpartum phase, as it is safe for breastfeeding women.
Since most women are breastfeeding during this phase, they do not generally want to use antidepressants. However, some of them may benefit from selective serotonin reuptake inhibitors (SSRIs), a type of antidepressant. Quite often, women need to use them for 6-12 months to experience their benefits.
In some very severe cases with psychotic symptoms, doctors may even consider ECT (Electroconvulsive therapy). So, yes, PPD can be quite severe, requiring even ECT.(1)
Since the condition is quite complex and hormones also play a role, the US FDA recently approved a progesterone metabolite called allopregnanolone for managing the condition. This hormone is given as a continuous 60-hour infusion and may help in many instances.(1)
So, as one can see, PPD is not to be neglected. In a small number of cases, it could be very severe, causing psychotic symptoms and may even increase suicide risk. Hence, doctors may even consider electric shock therapy (ECT) or prolonged hormonal infusions. This means that exploring the role of ketamine IV therapy is worthwhile in this condition. Considering this kind of therapy in moderate to severe instances may be a good idea.
Ketamine For Postpartum Depression
There are several reasons to consider IV ketamine therapy for PPD. Of course, any such treatment would be suitable for moderate to severe PPD.
Perhaps the most important reason for considering ketamine is that drugs like SSRIs are slow to act, and they must be taken for long. They only start acting after a few weeks but fail to help in many instances. More importantly, women taking these drugs cannot breastfeed.
Other options, like ECT, are reserved for more severe instances with psychotic signs and symptoms.
Hormone therapy may be worth exploring. However, considering it is given as 60 60-hour infusion, it isn’t easy to complete the treatment. Though hormone therapy is safe, it also fails in many instances. Which only means that there is a need for finding more effective treatments.
Hence, it would be right to say that there are some solid grounds for exploring ketamine therapy for PPD. Researchers have become interested in this therapy as it has already proven to be effective in major depression. Although PPD is different from major depression, it does share some of its traits. It is still a kind of depression.
Ketamine May Even Help Prevent PPD
Yet, another reason to consider ketamine is that it is even suitable for PPD prevention. This is unlike any of the existing treatment options. Of course, it cannot be used for PPD prevention in all patients but can be given in high-risk cases. Moreover, it is worth considering that many women undergo delivery via a caesarian section or surgery. In such cases, ketamine, which is already approved as an anesthetic and painkiller, may have additional benefits in preventing PPD.
Researchers are already exploring using ketamine for PPD prevention in women who are expected to give childbirth by caesarian section. Such women would anyway be exposed to various anesthetics, so why not consider ketamine in such patients? Early studies comparing women who were given low-dose ketamine during the caesarian section found that it helped reduce PPD. The incidence of PPD in those given ketamine during surgical intervention was lower compared to those not given ketamine.(2)
It appears that certain changes that occur immediately postpartum, including certain hormonal changes, significantly increase PPD risk. It means that even a single ketamine IV infusion given before cesarean section can help either prevent PPD or significantly reduce its severity. Even more effective could be ketamine IV infusion given immediately postpartum to reduce pain. Since, anyway, analgesics are used during this period in women who give birth through a cesarian section, why not consider ketamine IV in such instances as it has additional benefits?(3)
Researchers think that this is mainly due to increased brain plasticity. Further, things like BMI and some other factors may also predict how good ketamine therapy can be. Researchers also propose using some other supplements like melatonin along with ketamine IV therapy, as they think that melatonin may boost ketamine’s activity.(3)
What is good about using ketamine therapy for preventing PPD is that it is being tested in many nations and not in the US alone. Although ketamine therapy has gained more attention in the US, researchers outside the US are also exploring this option. Thus, one of the highly extensive studies in China on 654 women found that ketamine can really help prevent PPD when used as a preventive measure.(4)
Ketamine Provides Rapid and Prolonged Relief
Ketamine is pretty good for preventing PPD. However, there are many studies showing that it is also good for depression management. In fact, intranasal ketamine is now a US FDA-approved remedy for managing resistant cases of depression. Thus, there is every reason to believe that it can be good for managing PPD. Moreover, PPD appears to be pretty severe in many cases.
Here, it is also vital to note that PPD develops within a few weeks postpartum. Antidepressants, like SSRIs, that are approved for PPD management are very slow to act. Most oral antidepressants take weeks to start acting, and by that, much precious time has been lost. Ketamine IV, thus, may be a better option for managing PPD. It works pretty quickly and within hours, with effect lasting for a week or more. Studies show that ketamine is not just good for depression but also for PPD, and its use often results in rapid improvement.(5)
Ketamine is also relatively safer, especially when compared with SSRIs. Oral antidepressants must be taken daily and cause much toxicity. Ketamine has a relatively short half-life of merely 2-4 hours.(6) This means that there is almost no ketamine left in the blood or patient’s body after 24 hours. Hence, those on ketamine therapy can breastfeed after a doctor’s recommendation. However, if one is using SSRIs, they barely and rarely help, and yet, women using these drugs are not allowed to breastfeed. Hence, this could be regarded as one of the significant benefits of IV ketamine in managing PPD.
One thing that many women might not like about ketamine weekly ketamine injections is that they require visiting clinics. Ketamine injections are generally given as slow IV infusion over 40 minutes. Further, due to its dissociative effect (mind-altering properties), patients need to stay in a clinic for a few hours after the infusion.
Hence, doctors have also been trying the so-called rapid ketamine injection. Regretfully, studies show that rapid ketamine injection is not good for preventing or managing PPD. Hence, that is not an option for preventing or managing the condition.(7)
Ketamine And CBT May Result in Prolonged Effect
Early studies have shown that CBT is quite good for PPD. It is among the treatments of choice. Hence, medications are reserved for those who do not respond to psychotherapy alone. Additionally, earlier studies in resistant depression show that ketamine therapy is quite good for combining with psychotherapy, and each of these therapies increases the efficacy of each other.
Thus, ketamine makes people more receptive to suggestions. It also helps carry out and maintain behavior changes due to certain brain changes, alterations in neurotransmitters, blocking of specific receptors, and improved brain plasticity. In short, ketamine increases the effectiveness of psychotherapy.
At the same time, psychotherapy may also enhance the effectiveness of ketamine IV therapy. Studies show that adding psychotherapy like CBT to ketamine therapy may increase its duration of action. This means that ketamine works even better and for longer when combined with psychotherapy. Not only that, combining these two therapies increases response rates to ketamine IV treatment and may reduce relapse rates in the long run.(8)
How Safe is Ketamine in Postpartum Females?
Since women experiencing PPD are young mothers and breastfeeding women, this question is highly relevant. Moreover, it is no secret that ketamine is a substance of abuse, a controlled substance, and also sold as an illicit drug.
However, here, it is worth remembering that any medication, if abused, can harm health. It is completely wrong to compare substance abuse and the therapeutic use of any medication. Just take the example of opioids. They are also very safe and excellent painkillers, but abusing them causes much harm.
Further, when treating PPD, doctors use low-dose ketamine IV infusion given slowly over 40 minutes or even more. Such a dose does not cause any addiction or does not cause any severe toxicity. Of course, even a small dose also has mind-altering properties, so patients are expected to stay for a few hours in a clinic after the infusion. However, after a couple of hours, the person starts feeling quite well. There are almost no long-term side effects when ketamine is used under medical supervision.
Moreover, compared to some of the antidepressants and other drugs, ketamine is safer for breastfeeding women. This is because ketamine, unlike antidepressants, does not stay in the blood for long. After about 24 hours, ketamine is left in the body in traces. This means that most women can breastfeed after 24 hours without any risk.
And, yes, there is enough safety data to say that ketamine is almost not found in breast milk after 24 hours. The studies show that ketamine is found in considerable amounts in breast milk three hours after the infusion, and after that, its concentration starts falling quickly. After 12 hours, ketamine is only found in traces in breast milk. Hence, starting breastfeeding after 24 hours would be pretty safe.
The Bottom Line
PPD is quite a severe and common issue. It not only affects young mothers, but also the wellbeing of newborn children. It is vital to realize that depression in the condition may be quite severe in many cases, causing mothers to neglect their child, experience significant loss of interest in life, and even psychosis and suicidal thoughts.
Researchers have been experimenting with ketamine therapy for depression management for a long, with great success. Studies show that ketamine is good for both PPD prevention and management.
When it comes to using ketamine for PPD prevention, researchers are exploring its role in women who give childbirth through the cesarian section. In such cases, doctors need to use anesthetics and IV analgesics, so why not consider ketamine therapy, which has the additional benefit of lowering PPD risk?
However, in high-risk cases, it may be a good idea to use ketamine postpartum, like women known to be living with depression.
PPD treatment poses certain challenges. This kind of depression develops pretty quickly within a few weeks of a child’s birth. However, most modern antidepressants take weeks to start action. Thus, ketamine IV therapy has a special place in managing the condition as it starts working within hours. Moreover, with ketamine, there is no need for frequent dosing, as the effect of a single ketamine infusion lasts for a week.
Yet, another reason to consider ketamine in postpartum women is that ketamine may act for long, but it does not stay in the blood for long. Studies show that ketamine remains in the blood for about 12 hours after infusion. This means that one can start breastfeeding 24 hours after the infusion. It is something that is not possible when taking oral antidepressants.
What makes ketamine such a fantastic drug is that it keeps acting on the brain for long. This is because it alters brain plasticity. It changes the brain’s ability to form new connections. Hence, women who are given ketamine continue to experience its benefits for a week.
Surely, one would need to use multiple ketamine infusions for maximum effect. Generally, the treating doctor would decide on how many infusions are needed for optimal benefit. However, most women would need multiple infusions to consolidate its effect and ensure that benefits are persistent.
Finally, one should not forget that lifestyle changes and psychotherapy must not be neglected. Studies show that when ketamine is combined with lifestyle changes and psychotherapy, benefits are more profound. This is because ketamine makes people more receptive to psychotherapy. At the end of the day, one has to change the way of thinking to enjoy ketamine’s health benefits.
References
- Mughal S, Azhar Y, Siddiqui W. Postpartum Depression. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Mar 5]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK519070/
- Alipoor M, Loripoor M, Kazemi M, Farahbakhsh F, Sarkoohi A. The effect of ketamine on preventing postpartum depression. J Med Life. 2021;14(1):87–92.
- Li Q, Wang S, Mei X. A single intravenous administration of a sub-anesthetic ketamine dose during the perioperative period of cesarean section for preventing postpartum depression: A meta-analysis. Psychiatry Research. 2022 Apr 1;310:114396.
- Ma JH, Wang SY, Yu HY, Li DY, Luo SC, Zheng SS, et al. Prophylactic use of ketamine reduces postpartum depression in Chinese women undergoing cesarean section✰. Psychiatry Research. 2019 Sep 1;279:252–8.
- Guay É, Brouillette MJ, Drury J, Garel N, Greenway K. Rapid Improvement of Post-Partum Depression With Subanesthetic Racemic Ketamine. Journal of Clinical Psychopharmacology. 2024 Apr;44(2):196.
- Rosenbaum SB, Gupta V, Patel P, Palacios JL. Ketamine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Mar 5]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK470357/
- Xu Y, Li Y, Huang X, Chen D, She B, Ma D. Single bolus low-dose of ketamine does not prevent postpartum depression: a randomized, double-blind, placebo-controlled, prospective clinical trial. Arch Gynecol Obstet. 2017 May 1;295(5):1167–74.
- Wilkinson ST, Wright D, Fasula MK, Fenton L, Griepp M, Ostroff RB, et al. Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression. Psychotherapy and Psychosomatics. 2017 May 11;86(3):162–7.
