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ZAKA CLINIC GULBERG LAHORE

Saad Ullah Siddiqui

Uncover the truth about the placebo effect – is it a valid treatment or a scam? Explore insights with Meri Sehat for informed perspectives.

Placebo Effect – Treatment Or Scam?

Humza Khizer

Baby Blues (Postpartum Depression): Is There A New Treatment?

Overview

The entire process of pregnancy is very rewarding, but what happens after you have delivered the baby? Your body that has gone through so many constant changes over the 9 months, reverses them all to get you back to normal. This process often leads to postpartum <a href="https://www.merisehat.pk/disease/depression">depression</a>.

About 11% of women in the United States suffer from postpartum depression (PPD).<a href="#accordion">[4]</a>&nbsp;PPD affects not just the life of the mother but also the infant. If left untreated, it can get worse and affect your spouse or other people close to you. So far, the treatment used for PPD has been very generic; similar to that of major depressive episode (MDE) consisting of conventional antidepressants like SSRIs, benzodiazepines, and tricyclic antidepressants. FDA has recently approved the first-ever drug targeted toward treating postpartum depression. 
&nbsp;

Understanding The Latest Treatment For Postpartum Depression

Postpartum depression is best explained as a worsened form of postpartum blues or baby blues. Baby blues are experienced a few days after delivery. Some new moms, however, experience a much more severe case of baby blues that can be classified as postpartum depression and it can go on for over a year.<a href="#accordion">[8]</a>&nbsp;PPD is characterized by:

<ul>
	<li>Feeling depressed and low</li>
	<li>Sleeping too little or too much</li>
	<li>Feeling tired all the time</li>
	<li>Doubting yourself as a mother</li>
	<li>Thinking that you do not want the baby</li>
	<li>Excessive crying</li>
	<li>Loss of appetite</li>
	<li>Anxiety and panic attacks&nbsp;</li>
	<li>Thoughts of harming yourself or the baby</li>
	<li>Unable to think clearly or make the right decisions</li>
	<li>Increased anger and irritability</li>
	<li>Overall reduced interest in everything</li>
</ul>

If you or anyone that you know are facing any of these symptoms, immediately contact your physician and get yourself screened through the Edinburg Postnatal Depression Scale (EPDS). It is one of the most common and quickest screening tools with high accuracy and allows your physician to assess the situation better through the score.&nbsp; 
&nbsp;

A lot of factors contribute to postpartum depression.The biggest factor that is not only responsible for PPD but also for the baby blues is the drastic change in hormones. During pregnancy, your estrogen and progesterone levels are very high. As soon as the baby is delivered, these levels are dropped drastically.

Since estrogen is directly linked to increasing serotonin levels in our brain&nbsp;and progesterone is known for stimulating dopamine release, the decrease in the production of these hormones coupled with some underlying mental issues or previous history of depression or anxiety becomes the most common and the biggest cause of PPD.<a href="#accordion">[2][3][7]</a> 
&nbsp;

While screening of postpartum depression can be done by several tools that are used for Major Depressive Episodes (MDE), the most universally acceptable tool targeted especially for PPD is Edinburgh Postnatal Depression Scale or EDPS. EDPS is a 10-item questionnaire with a response score of 0 to 3. If the total score is over 12, then there is a need for further in-depth assessment of the situation and severity of the condition.&nbsp;

PPD is best diagnosed by your medical practitioner through regular visits. Your doctor asks a series of questions every few days to assess your mental health and well-being. Another way to differentiate PPD from baby blues is to ensure that the patient has at least 3-5 of the symptoms that make up PPD. The generalized diagnostic criteria used for PPD are similar to the one used for Major Depressive Episode (MDE). Immediate attention is recommended to avoid any worsening of the symptoms and from transitioning of PPD to postpartum psychosis. 
&nbsp;

So far, the treatment of postpartum depression is similar to that of conventional major depressive disorder. Special attention is paid to the excretion of the drug and the concentration of the drug removed from the body through breast milk.

The following antidepressants are commonly used to treat postpartum depression due to their low levels of excretion in breast milk, making it safe for use if you are a breastfeeding mother:

<ul>
</ul>

<ul>
	<li>Fluoxetine</li>
	<li>Paroxetine</li>
	<li>Sertraline</li>
	<li>Bupropion</li>
	<li>Amitriptyline</li>
	<li>Doxepin</li>
	<li>Desipramine</li>
	<li>Tranylcypromine</li>
	<li>Trimipramine</li>
	<li>Desipramine</li>
	<li>Paroxetine</li>
	<li>Escitalopram</li>
</ul>

These antidepressants come with some common side effects that include nausea, vomiting, dizziness, sexual issues, diarrhea, blurry vision, weight gain, increased perspiration, etc.<a href="#accordion">[6]</a> 
&nbsp;

Brexanolone (under the brand name of Zulresso) got approved by the FDA as the first drug targeted toward PPD. Brexanolone is approved with a Risk Evaluation and Mitigation Strategy (REMS) which means that it is currently a controlled medicine available through a restricted distribution channel to carefully assess the conditions of the patients throughout the treatment. The program is currently known as Zulresso REMS Program.<a href="#accordion">[5]</a>&nbsp;Currently, to get Brexanolone administered to you for treating your PPD, you are required to enroll in the Zulresso REMS program.&nbsp; 
&nbsp;

<ul dir="ltr">
	<li>
	<h5>Mechanism Of Action</h5>
	</li>
</ul>

Brexanolone is a synthetic form of allopregnanolone. Allopregnanolone is a neurosteroid. Neuroactive steroids are a group of substances that change a receptor&rsquo;s response to a stimulus by binding to them.<a href="#accordion">[4]</a>&nbsp;Allopregnanolone is best understood as a metabolite of progesterone, which is a GABA-A receptor agonist. This means that progesterone is responsible for increasing GABA functions.

The exact mechanism of the drug and of allopregnanolone is still unknown. Their enhancement of the functions of GABA (Gamma-aminobutyric acid) means that it will inhibit neuronal excitability by blocking messages that are sent to our nervous system with the help of certain stimuli. This not only aids in dealing with depressive triggers but also helps with anxiety.<a href="#accordion">[1]</a> 
&nbsp;

<ul dir="ltr">
	<li>
	<h5>Dosage And Administration</h5>
	</li>
</ul>

Zulresso is administered intravenously. The dosage is determined by your doctor based on your weight and other factors. The drug is administered over a period of 2.5 days or 60 hours and requires constant monitoring due to the risk of unconsciousness.<a href="#accordion">[5]</a> 
&nbsp;

<ul dir="ltr">
	<li>
	<h5 dir="ltr">Adverse Effects</h5>
	</li>
</ul>

Since the drug is relatively new, there are a limited number of side effects reported so far. They include:

<ul>
	<li>Dry mouth</li>
	<li>Dizziness</li>
	<li>Flushed skin</li>
	<li>Losing consciousness</li>
</ul>

<h5 dir="ltr">Important!</h5>

FDA has advised to stop the treatment of Zulresso if more serious side effects occur that may include the worsening of PPD and suicidal thoughts especially in women under the age of 25. 
&nbsp;

Current research suggests that brexanolone may interact with other CNS depressants like opioids and benzodiazepines and increase the severity of the adverse effects with regard to sedation. Alcohol consumption is also not advised due to similar reasons.

During the clinical trials, patients who were taking antidepressants also showed a more severe case of sedation as compared to the ones who did not or were a part of the placebo studies. 
&nbsp;

Conclusion

Considering the rapid onset of action with brexanolone especially when compared to the long-term treatments offered by conventional antidepressants, it is believed that brexanolone can take over the go-to therapy for PPD. However, a much more convenient way of administration would be through oral pills instead of I/V. There are still many concerns left that can only be answered through long-term data in a lesser restricted environment as opposed to a clinical trial setting.&nbsp; 
&nbsp;

Key Points

<ul>
</ul>

<ul>
	<li>Current antidepressant therapies employed for PPD are based on&nbsp;long-term treatment.</li>
	<li>Brexanolone&rsquo;s onset of action is fast and has shown significant improvement in women of all ages suffering from PPD.</li>
	<li>Some women under the age of 25 were observed to experience severe side effects that even led to the worsening of their PPD.</li>
	<li>The drug is still under strict observation with the help of the REMS program.</li>
	<li>Administration coupled with the duration over which it has to be administered can make it difficult to commercialize as compared to drugs that are available in the form of oral pills.&nbsp;</li>
</ul>

[1] Allen B, Vespa PM. Antiseizure medications in critical care: An update. Curr Opin Crit Care. 2019;25(2):117-125

[2] ATP Science, 2021. HOW DOES PROGESTERONE CREATE A DOPAMINERGIC RESPONSE?. [Online] .

[3] Debra Fulghum Bruce, P., 2020. Postpartum Depression. [Online].

[4] Fala, L., 2019. Approved by the FDA Specifically for Postpartum Depression in Adults. [Online]

[5] Federal Drug Administration, 2019. FDA approves first treatment for post-partum depression. [Online]

[6] Fields, L., 2021. Which Antidepressants Treat Postpartum Depression?. [Online]

[7] Matthew Hoffman, M., 2021. Estrogen and Women's Emotions. [Online]

[8] Mayo Clinic, 2022. Postpartum depression. [Online]

Umna Salah

Introduction

Would you believe me if I say I could treat your headache with an M&amp;M? Well chances are that if that M&amp;M was disguised as a mainstream painkiller, you might believe it and stop complaining about your<a href="https://merisehat.pk/disease/tension-headaches"> headache</a>. That&rsquo;s basically how the magic pill everyone calls a &ldquo;placebo&rdquo; works. 
&nbsp;

Understanding the role of the placebo effect in medical treatment

Although it is possible to heal oneself mentally, the placebo effect is more complex than just happy thinking. The placebo effect is a phenomenon&nbsp;where individuals claim to have improved after receiving a fake or nonexistent&nbsp;therapy, i.e., a &quot;placebo.&quot;

Any positive results they claim, are simply their anticipation that their ailment is being treated. This is because the placebo cannot truly cure any condition. In medicine, a&nbsp;placebo is any chemical, medication, or another form&nbsp;of treatment that has the appearance of being a medical intervention but isn&#39;t. 
&nbsp;

Early clinical trials compared the placebo&rsquo;s effectiveness to a group of patients who did not take any medicine. Currently, it&rsquo;s necessary to have a third group of participants after learning that the basic act of ingesting an empty tablet creates a placebo effect.

Placebos play a crucial role in clinical trials since they are frequently administered to individuals in the control group. The researchers then compare outcomes from the placebo and the actual medication. In other words, a person&#39;s confidence in the value of the treatment causes them to believe that they are feeling better; researchers rely on this belief to assess the new drug&#39;s efficacy. 
&nbsp;

For instance, a new medicine to decrease cholesterol might be administered to some research participants, while others&nbsp;would receive a placebo. No participant in the trial will be aware of whether they received the real treatment or a placebo. The results of the study&#39;s participants after the medication and placebo treatments are compared to assess the new drug&#39;s efficacy and look for any negative effects<a href="#accordion">[2]</a>.&nbsp;Once the medication outperforms a placebo effect,&nbsp;it is approved.

1 in 3 persons reportedly experiences the placebo effect<a href="#accordion">[1]</a>.&nbsp;A placebo can be in the form of a sugar pill, an injection of salt water, or even a bogus surgical procedure. It would not have any therapeutic effects. 
&nbsp;

Numerous factors contribute to the phenomenon, including:

<ul>
	<li>Expectations or beliefs that their health will improve. The placebo effect is more likely to influence those who are motivated and anticipate their treatment to be effective.</li>
	<li>The idea of receiving care as a result of research participation could lower stress levels and release the body&#39;s natural painkillers.</li>
	<li>Classical conditioning or the long-term association people form between a specific action, like taking pills, and beneficial&nbsp;outcomes.</li>
	<li>A strong bond of trust between medical professionals and their patients, or between researchers and study subjects. Reaction to a treatment may be influenced by hearing a knowledgeable specialist they trust speak enthusiastically about it.</li>
</ul>

According to a study on irritable bowel syndrome, patients receiving a placebo benefit 40-50% of the time when they have a good relationship with their healthcare provider<a href="#accordion">[3]</a>. 
&nbsp;

Other possible explanations for a placebo effect can be:

<ul>
	<li>A patient, who had severe symptoms when they signed up for the treatment or clinical trial, felt a visible change during that period. They think it&rsquo;s the meds when, in reality, the symptoms improved on their own during the natural course of the illness.</li>
	<li>A patient, who had high hopes that the new treatment will work, will pay more attention to improvement signs instead of signs that they may be getting worse. 
	&nbsp;</li>
</ul>
<quillbot-extension-portal></quillbot-extension-portal>

Taking a placebo has no known adverse effects. However, there are rare circumstances when a placebo can result in what is known as a &quot;nocebo effect,&quot; or a bad outcome. The same principles apply here: it&#39;s more probable that the person will have a negative consequence when they expect one.

A study found that 76% of the side effects, such as headaches and fatigue, that 45,380 people who received the COVID-19 vaccination or a placebo experienced,&nbsp;weren&#39;t brought on by the vaccine at all. Rather, it was just a nocebo response!<a href="#accordion">[3]</a>.

In another trial, participants were given placebo opioids. Respiratory depression is a common opioid adverse effect. Despite having no active components, the researchers discovered that the placebo medication, nevertheless, caused respiratory depression<a href="#accordion">[4]</a>.

Increases in dopamine and opioid receptor activation have also been linked to significant placebo reactions. These two substances play a part in the brain&#39;s motivation and reward systems. Contrarily, nocebo decreases the activation of opioid and dopamine receptors. Some of these neurological alterations take place in parts of the brain that antidepressant medications frequently target. The 50&ndash;75% placebo response rate in antidepressant trials may be explained by this<a href="#accordion">[4]</a>. 
&nbsp;

<ul>
	<li>Pain</li>
</ul>

The power of a placebo to lessen pain is known as placebo analgesia. It is thought to function in one of two ways: either natural painkillers called endorphins are released, or the person&rsquo;s perception of pain is altered.&nbsp;

Additionally, it has been discovered that genuine analgesics work better when they are administered to a patient who is aware that they are receiving the medication rather than when it is done covertly. The placebo effect can be seen as supporting a real intervention in this situation. 
&nbsp;

<ul>
	<li>Depression</li>
</ul>

Antidepressants are thought to work mostly through the placebo effect. An analysis of eight studies indicated that placebo antidepressants were beneficial over 12 weeks, highlighting the potential long-term effects of placebos. 
&nbsp;

<ul>
	<li>Anxiety</li>
</ul>

Trials for anti-anxiety medications are particularly prone to the placebo effect, which greatly delays the development and testing of new medications. 
&nbsp;

<ul>
	<li>Cough</li>
</ul>

According to a review of clinical trials including cough medicines, &quot;only 15% of the cough reduction is attributed to the active ingredient, and 85% of the cough reduction is related to treatment with placebo.&quot; 
&nbsp;

<ul>
	<li>Erectile Dysfunction</li>
</ul>

Participants in one study were divided into three groups. The first group was informed that they would receive genuine erectile dysfunction therapy, while the second group was informed that they would either receive a placebo or a genuine treatment, and the third group was informed that they would only receive a placebo&nbsp;for erectile dysfunction.

Even though all three groups received placebo starch tablets, they all showed the same amount of significant improvement.&nbsp; 
&nbsp;

<ul>
	<li>IBS</li>
</ul>

According to a meta-analysis, the placebo response rate in IBS patients ranged from 16.0-71.4%. In another trial, the patients showed improvement despite being informed that their treatment would consist of a placebo. 
&nbsp;

<ul>
	<li>Parkinson&rsquo;s Disease</li>
</ul>

According to an analysis of 11 clinical trials, 16% of Parkinson&#39;s patients who were placed in the placebo groups had significant improvements, which often&nbsp;lasted for six months. Dopamine release in the striatum appears to play a role in the effect. 
&nbsp;

<ul>
	<li>Epilepsy</li>
</ul>

In anti-epileptic medication trials, the placebo response ranges from 0-19%. A 50% reduction in their typical seizure frequency was considered a &quot;placebo response&quot; for this trial. 
&nbsp;

Due to its effects on a variety of ailments, doctors utilize placebos for clinical purposes all around the world. According to 2008 Danish research, 48% of doctors had prescribed placebos at least 10 times in the previous year. These placebos were typically vitamins for weariness and antibiotics for viral diseases. In related research of Israeli doctors, it was shown that 60% gave patients placebos to discourage them from asking for unnecessary medication or if they &quot;needed calming.&quot;

There are moral issues with this approach. First, the patient is misled by the doctor. Second, the placebo is still regarded as an effective treatment if it has the desired outcome. Third, by giving a patient a placebo to make them feel better, the accurate diagnosis of a serious illness is being put off; doctors and pharmacists can be accused of fraud. 
&nbsp;

Although there are more morally right uses of placebos in medical practice, there will likely always be arguments for and against their usage, just like in any other ethical debate.

For instance, some burn sufferers may benefit from using placebos. Opioid pain treatment is not always possible due to the respiratory depression it causes. In this case, an injection of saline disguised as a potent painkiller can lessen the patient&#39;s suffering. 
&nbsp;

According to Robert Buckman, a renowned clinical oncologist, &ldquo;Placebos are remarkable medications. They appear to have some impact on almost all symptoms known to man, and they are effective in at least one-third of patients and occasionally as many as 60%. They cannot be taken in an overdose and have no major negative effects. They are, in a nutshell, the world&#39;s pharmacopeia&#39;s most flexible, adaptive, powerful, safe, and affordable medications4.&rdquo;

However, it should be kept in mind that there is still much we don&#39;t know about placebos; studies are continuous, and each year we learn more. 
&nbsp;
<quillbot-extension-portal></quillbot-extension-portal>

Key Takeaways

<ul>
	<li>The placebo effect is a phenomenon&nbsp;where individuals claim to have improved after receiving a fake or nonexistent&nbsp;therapy, or &quot;placebo.&quot;</li>
	<li>Any positive results claimed are attributable to a person&#39;s anticipation that their ailment is being treated because the placebo cannot truly cure any condition. In medicine, a&nbsp;placebo is any chemical, medication, or another form&nbsp;of treatment that has the appearance of being a medical intervention but isn&#39;t.</li>
	<li>Placebos play a crucial role in clinical trials since they are frequently administered to individuals in the control group. The outcomes from the placebo and the actual medication can be contrasted by researchers.</li>
	<li>A placebo may be in the form of a sugar pill, an injection of salt water, or even a bogus surgical procedure. To put it another way, a placebo has no therapeutic effects. One in three persons reportedly experiences the placebo effect.</li>
	<li>Taking a placebo has no known adverse effects. However, there are rare circumstances where taking a placebo could result in what is known as a &quot;nocebo effect,&quot; or a bad outcome. The same principles apply here: It&#39;s more probable that an individual has a negative consequence if they expect one.</li>
</ul>
<quillbot-extension-portal></quillbot-extension-portal>