Tag Archives: SSRI antidepressants

Nasal Spray for Depression? Not So Fast.

By Kim Witczak
WoodyMatters

On February 12, a joint meeting of the FDA Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee endorsed Janssen Pharmaceuticals’ — a division of Johnson & Johnson — experimental nasal spray for depression despite a mixed bag of clinical trial results. The panel voted 14-2 to approve esketamine for major depression in patients who had not benefited despite trying two or more antidepressants. I serve as the consumer representative on the first committee and I was one of the two no votes.

This fast-acting nasal spray, esketamine, is a chemical mirror image of the anesthetic ketamine,  which is often used by veterinarians to sedate animals but is also a Schedule III drug known on the street as “Special K,” thanks to its dissociative and hallucinogenic effects.

Esketamine was developed in an effort to help the millions of people who suffer from persistent depression and do not respond to current antidepressant products. The nasal spray is seen as a potential substantial improvement over existing therapies for treatment-resistant depression (TRD), considered a serious or life-threatening condition.

In theory, a drug that provides rapid relief within 24 hours vs the standard four to six weeks for the current antidepressants on the market sounds good. However, the disease label of TRD is also the new buzzword allowing drug companies to obtain FDA Fast Track status or Breakthrough Therapy designation  without having to go through more rigorous testing protocols. Such designation gives a pharmaceutical company the ability to present smaller, fewer clinical trials in order to get their drug to market quicker.

While most approved antidepressants currently on the market had to show effectiveness data from at least two positive short-term trials, Janssen only presented one positive short-term trial and the second is an incomplete picture as it is from a trial testing esketamine’s effects after the drug is stopped. Janssen’s other trials failed to meet their primary endpoints for efficacy. Additionally, there were also clinical trial participant suicides that occurred during the studies. However, these were glossed over and presented as unrelated to the “study” drug. In my opinion, we need more information on the potential link to suicide before an assumption can be made that it’s safe.

Despite all of this, several members of the committees perceived this new drug as a potential “game changer” in the way depression is treated. I, however, am NOT one of them. I take my role as the consumer representative very seriously and want to make sure that any drug that the FDA approves shows greater benefit than potential harm. There are real-world implications once these drugs are approved and on the market, advertised with an FDA stamp of approval on them, and counted on without question by the doctors prescribing them and the potential millions of people who will take them.

Safety will always be my top priority and I didn’t feel this was similarly the case for the manufacturer as it rushed this esketamine nasal spray through the approval process. I cannot vote for something when the perceived benefits do not clearly and demonstrably outweigh the potential for known harms such as sedation, dissociation, and long-term cognitive or memory loss. These are all especially concerning considering the extremely limited positive clinical trial results.

Too many times I have seen that as soon as one of these controversial drugs gets approved, the drug company’s PR and advertising machine immediately kicks into hyperdrive. The media will be given talking points and tout it as a “breakthrough” treatment for depression that works within mere hours of inhaling the drug, and people will start lining up at their doctor’s offices. Fact in point, just a day after this meeting, news of this meeting and drug was all over the national media appealing to America’s “quick fix” culture.

At one time, SSRI antidepressants were seen as “game changers” beginning with the launch of Prozac (fluoxetine) in the late 1980s. Little did the medical establishment and general public know then what we clearly now know today about all the associated dangers, such as a risk for suicide and withdrawal issues, that come with taking these medicines. It is in the rush to market without sound clinical testing and trials that proves efficacy, without potential horrible side effects or outcomes, that we set society up for misuse of medical drugs and create the very real potential for heartache and disappointment for many.

Time will tell, but as I always say, we — the American public — are the real clinical trial. We pay the ultimate price for the lowering of FDA standards for drug approvals.

Kim Witczak is an advertising/marketing communications professional with over 20 years of experience for a variety of industries as well as non-profit/advocacy campaigns. She runs WoodyMatters, a non-profit patient safety advocacy organization focused on saving patients from adverse effects of unsafe medical products. 

Quick Hits: Medical Treatment Adverse Event Death Drop and Antidepressant Tapering With Psychotherapy

Deaths related to the adverse events of medical treatments fell between 1990 and 2016. Researchers examined the causes of death listed on death certificates as well as data from the Global Burden of Diseases, Injuries and Risk Factor tool. Overall, the mortality rate due to adverse events declined by 21.4% from 1.46 per 100,000 people to 1.15 over the time period. However, researchers noted that age was a significant factor in mortality. The mortality rate for those aged 70 and over was nearly 20 times higher than for those between 15 and 49. Location also influenced the rate, with California having the lowest and Mississippi the highest. The most common reason for an adverse event from medical treatment was surgery and post-operative complications. Posted January 18, 2019. Via JAMA Network Open.

Tapering off antidepressants is more successful and a person has a lower risk for relapse if it is done along with psychotherapy. Researchers conducted a meta-analysis of 15 studies and found that after two years, the risk for relapse was between 15% and 25% for cognitive behavioral therapy and tapering compared to 35% to 80% with just regular clinical visits and tapering. The study’s authors note that in western countries, antidepressant prescriptions have doubled over the last decade. In addition, the average length of time on an antidepressant in the US is five years, and the medications are often prescribed by a primary care physician, not a psychiatrist. Posted January 22, 2019. Via Annals of Family Medicine.

Areas of the country where drugmakers spent more money marketing to doctors are linked to higher rates of opioid use, according to a new study. Researchers say that counties that had the most opioid marketing from pharmaceutical companies to healthcare providers subsequently had the highest rates of opioid prescribing and opioid overdose deaths. Between August 2013 and December 2015, drug companies spent about $40 million on opioid marketing to more than 67,000 physicians. The Northeast US had the highest marketing and the Midwest the lowest, the study found. Also, for every three additional payments made to doctors per 100,000 people in a county, opioid deaths increased 18%. Posted January 18, 2019. Via JAMA Network Open.

Why You Should Consider Acupuncture to Treat Depression

Bob, a 30-year-old real estate agent, had been suffering from insomnia for 6 months before he came to see me. His problem, he told me, was falling asleep. Once he finally got to sleep, he was down for the count, but before that, he would stare at the ceiling for hours, thinking about the day that had passed and worrying about the one to come.

In response to my questions, he also described other health problems, including poor digestion, fatigue and a short fuse. I asked him what other treatments he’d tried and he listed a few over-the-counter supplements and confided that he had started to see a psychotherapist. In fact, it was the therapy that had prompted Bob to find an acupuncturist. His new therapist had told him that he might be depressed, and suggested he try a medication for his condition. But Bob was keen to explore an alternative before taking that step.

He bristled at the idea that he had a “condition,” which felt like a reduction of his entire life to a simple diagnosis. It also sounded very permanent to him, as did a future of being medicated.

We talked and he was surprised to hear that I wasn’t completely opposed to the idea of antidepressants, but only when there is close monitoring and an endgame in mind. Together we explored the conditions that may — or may not — make medication a good idea.

Significant Side Effects Seen With Antidepressant Medications

In 2015, about 16 million American adults experienced at least one depressive episode in the prior year. The number taking medication for it grows each year. The reasons for this increase vary. They range from shifting attitudes about mental health and recognition of depression to expedient overprescribing in an increasingly burdened healthcare system.

Whatever the cause may be, this increase in the use of psychopharmaceutical medications is not a sustainable trend. While medications such as SSRIs (selective serotonin reuptake inhibitors) and TCAs (tricyclic antidepressants) may offer critical relief for some patients, their prevalence also speaks to a larger failure of mental health management. What’s more, there are significant side effects from these drugs that can paradoxically contribute to the very conditions for which patients are seeking help. These include:

  • Low libido and other sexual side effects
  • Increased appetite and weight gain
  • Nausea
  • Insomnia
  • Fatigue

Since depression is often accompanied by anxiety, patients often take a cocktail of medication that can compound these side effects.

At the YinOva Center, we encourage our patients to embrace the best that conventional medicine and traditional Chinese medicine (TCM) have to offer. In the case of depression, TCM has a valuable contribution to make. The therapeutic process of TCM allows us to create a customized treatment for each patient, using a combination of acupuncture, herbs and other adjunctive therapies.

When used in combination with talk therapy, behavioral counseling and other individualized therapies, acupuncture focuses on the patient more than the disease.

Psychotherapy, which offers individualized exploration and counsel, can also play an important role in treatment. Pharmacological intervention, on the other hand, is often less personalized and, from the patient’s point of view, sometimes feels more abstract. This is because medication is often seen as a one-size-fits-all treatment. And with antidepressants, patient response can vary greatly.

There are two questions that I am commonly asked about acupuncture: How long does it take for the treatments to work and how long does it last? These are of particular concern for patients who are struggling with depression, because it has such broad effects on their lives. To approach these questions we consider a few factors, including how long the depression has been an issue, what precipitated it, circumstances that trigger or worsen it, and tools that the patient may already have, including everything from novel coping strategies to medications.

We then come up with realistic goals and clearly defined strategies for reaching them. Commonly, I recommend weekly treatments for 5 weeks as a starting point, with tangible benchmarks. With that we should see some shift and we can make decisions about how to progress.

If, on the other hand, we are not seeing the changes we want, we reevaluate our strategy and also consider other treatments and therapies that may be of help. This can also happen at the same time that a patient is beginning pharmaceutical treatments, which can take weeks or months to show improvements. They are not mutually exclusive, and acupuncture can also help to reduce the dosage of medications needed.

Studies Back Acupuncture for Depression

Medical studies have confirmed the benefit of acupuncture as a treatment option for depression. For example, a 2013 study published in PLOS that enrolled more than 750 people with severe depression found that those who received acupuncture saw their level of depression decline slightly more than those who received just counseling, and much more than patients who received usual care, such as medication. And the benefits of acupuncture lasted as long as 12 months after treatment ended for some patients.

(Incidentally, there is also evidence that acupuncture is effective for other types of mental illnesses, especially addiction.)

The most common thread I see among patients struggling with depression is a sense of disconnection in their lives, which is not helped by their medication. Antidepressants are a tool that can help a patient’s ability to embrace all aspects of their life, but antidepressants also miss the nuance of personal experience. In Chinese medicine, the integration of mental health with physical health and consciousness is fundamental. Not only is this connection essential to making meaningful change, missing it prevents us from fully understanding the individual parts.

The use of TCM that includes acupuncture provides a safe and effective complement in the integrative treatment of depression. When used in combination with talk therapy, behavioral counseling and other individualized therapies, it focuses on the patient more than the disease. In the care of depression, this can make all the difference.

SSRI Antidepressants Linked to Low Birth Weight, Prematurity

SSRIs (selective serotonin reuptake inhibitors), the most popular kind of antidepressants prescribed, when taken by pregnant women, increase the chance that their child will be born prematurely or with low birth weight, according to a new study.

Infants exposed to SSRIs during 2 or more trimesters weighed an average of 205 grams (7.2 ounces) less than infants whose mothers did not receive the antidepressants, say researchers from Norway and Canada. In addition, the infants would also be born, on average, 4.9 days earlier, they reported in the International Journal of Epidemiology.

“Severe depression or depression not responding to non-pharmacological therapy may negatively affect the course of pregnancy and the pre- and post-partum period,” co-author Katerina Nezvalova-Henriksen, PhD, a researcher at the University of Oslo School of Pharmacy, said in a statement. “The risks and benefits of SSRI therapy should therefore be carefully evaluated in each individual case.”

As many as 10% of pregnant women take SSRIs — which have many side effects to begin with — for depression.

The researchers used data from the Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway to measure the effect of SSRIs and maternal depression on birth weight and gestational length. A total of 27,756 siblings were included: 94 were prenatally exposed to SSRIs and 27,500 were unexposed to any antidepressant medication. The remainder received another kind of antidepressant.

Maternal SSRI use in 1 trimester, lifetime history of major depression or depressive symptoms during pregnancy were not associated with low birth weight or premature birth. This indicates that maternal depression, shared genetics or family environment cannot completely explain the association between exposure to SSRIs and the negative pregnancy outcomes, according to the researchers.

A host of studies in recent years has come out with conflicting conclusions as to whether SSRIs taken in pregnancy impact the baby or lead to birth defects. Some studies have claimed, for example, a link between SSRI use and autism, as well as a higher risk of diabetes and obesity in offspring.

Is Ketamine Safe and Effective for Depression?

The anesthetic ketamine, used in both humans and animals, is perhaps best known as an illegal party drug due to its hallucinogenic effects. However, a growing body of research indicates that the drug may have a powerful new medical use: as a fast-acting antidepressant without the side effects seen in most prescription antidepressants.

As Nature reports, in many clinical trials to date people who have not responded to standard antidepressant treatment — such as SSRIs including Prozac — seem to respond to ketamine. And while it can take weeks to feel better after starting a prescription antidepressant, the therapeutic effects of ketamine are seen in a matter of hours.

Despite the seemingly “miracle drug” nature of ketamine, there are serious concerns about its use in depression. First, it is unclear how the drug works to alleviate depression. Second, there are no long-term studies on its long-term use. Studies that have already been done indicate the antidepressant effects of ketamine can last from between a few days to a few weeks.

And due to the addictive nature of ketamine itself, there are worries that sustained use of it may lead to dependence.

On May 4, Nature published the results of the latest trial involving ketamine, bolstering its potential as an antidepressant treatment. Researchers, examining the drug in mice, found that that the mood boosting effects may not be caused by ketamine itself, but instead by one of the metabolites ((2R,6R)-hydroxynorketamine) formed when the drug is broken down into smaller pieces.

Even more promising, the ketamine given to the rats did not increase side effects, even though the dose was much stronger than what would be given to humans for depression. The researchers say they want to take the metabolite into testing in humans, though that is likely years away.

The largest trial ever of ketamine in depression was done in 2013 with 73 participants. The drug lead to a decline in depression symptoms 24 hours after treatment in 64% of patients, all of whom had tried at least 3 other drugs without any results.

Despite the lack of clear-cut evidence of its benefits and unknowns about its long-term risk, many doctors are already offering ketamine as a depression treatments to patients, though this is an off-label use.

Side effects of ketamine can include confusion, lucid daydreaming, fuzzy vision, and a “high” feeling, though they tend to go away quickly, according to these doctors. Patients, who are usually given ketamine via infusion, are carefully monitored and must have pre-arranged transport home. They can’t drive or use heavy machinery for 24 hours.

Drug companies are even trying to cash in on the ketamine craze. Janssen Pharmaceutical is testing a form of ketamine it developed, called esketamine, in 5 clinical trials. It would be given via a nasal spray. Another is rapastinel, under development by Allergan. Both drugs had “breakthrough therapy designation” from the FDA, meaning they will go through the regulatory process at a much quicker rate.

Antidepressant Birth Defect Risk Limited to Paxil and Prozac

Researchers from the Centers for Disease Control found that women taking paroxetine (Paxil) during their first trimester of pregnancy more than doubled their risk of five out of seven serious birth defects, while those taking fluoxetine (Prozac) had a higher risk of two serious birth defects. Via Medpage Today. Posted July 9, 2015.

–Alanna McCatty

Drugs in Pregnancy Part 6: Antidepressants

In Part 6 of our 7-part Drugs in Pregnancy series, we tackle the difficult issue of antidepressants during pregnancy. As we noted in the intro to this series, about 90% of pregnant women take at least 1 medication during pregnancy, with 70% taking at least 1 prescription drug, according to the National Birth Defects Prevention Study. That said, it’s safe to say most pregnant women don’t want to do anything to harm their unborn child, but they’re often in a bind when they have to take certain meds — and few drugs fit that description better than the antidepressants that allow them to function, says Lori Wolfe, a certified genetic counselor who advises women about the risks of medication use in pregnancy and while breastfeeding. (Wolfe is also the president of of MotherToBaby, a free, national informational service of the non-profit Organization of Teratology Information Specialists).

For more on pregnancy and drugs, see the other chapters in our series, and check out our Drug  Classification of Prescriptions Medicines During Pregnancy. And always ask your doctor or other healthcare provider what course of treatment is best for you and your baby.

Suffering from Depression When Pregnant

Kelly Kautz, who has suffered from depression and anxiety since she was 13 years old, tried to go off her antidepressant before becoming pregnant. “I had been on them for about 10 years and thought maybe I don’t need them anymore,” says Kautz. “But when I was off them, the symptoms were so horrible that it was really the only way I could get through the pregnancy safely.”

Kautz had been on Cymbalta before the pregnancy and asked her psychiatrist for advice. “He looked it up, saw that it was a Class C drug, and he actually became really uncomfortable seeing me because of the medical risk, and he dropped me as a patient,” says Kautz.

She discussed antidepressant use with her ob/gyn, who had her switch to Prozac. Because of a small concern with Prozac and fetal heart defects, Kautz’s ob/gyn ordered additional ultrasounds to make sure the baby was developing correctly. Kautz also took the lowest dose possible to further minimize any risk. Because she breastfed her son, now 2, her doctor switched her again, to Zoloft, because it doesn’t accumulate in breastmilk at the levels of Prozac.

Currently, 13% of pregnant women take an antidepressant during pregnancy, most commonly prescribed for depression and anxiety. According to American College of Obstetricians and Gynecologists (ACOG) guidelines, all psychotropic medications cross the placenta, are present in amniotic fluid, and can enter human breast milk. When possible, before becoming pregnant ask your doctor about getting off your antidepressant or switching to one with the fewest fetal risks, says Wolfe, as most psychotropic drugs take several weeks before they reach their full efficacy in the body.

Since 50% of pregnancies are unplanned, chances are, if you are being treated for depression, you may be on such a drug before realizing you are pregnant. Don’t stop any medication without a doctor’s oversight — stopping could result in a relapse of your underlying psychiatric condition.

A recent review (PDF) of the current literature of antidepressant use during pregnancy found a potentially significant increased risk for miscarriage, preterm birth, and low birthweight (less than 2,500 gm, or 5.5 lbs.). Exposure to psychotropic drugs in utero can put infants at risk of developing symptoms of Poor Neonatal Adaptation (PAN), including mild neurologic, autonomic, respiratory and gastrointestinal abnormalities. However, the review authors could not definitely conclude whether the mother’s underlying mental illness, antidepressants or a combination of both are what led to the increased risks.

Striking a Balance

In some cases, the risks to the mother and baby of not taking the psychotropic drug outweigh the risks to the fetus from taking the drug or switching to a safer medication. Consider these statistics: 15% of pregnant women with untreated depression attempt suicide. Those who stop taking antidepressants during pregnancy are 5 times more likely to have a relapse in depression than women who continue taking these drugs during pregnancy. The ACOG guidelines say untreated or inadequately treated maternal psychiatric illness can lead to poor prenatal care, inadequate nutrition, increased use of alcohol and tobacco, reliance on other medications or herbal supplements, and poor mother-infant bonding. “With antidepressants, we recommend you get on an antidepressant that works for you,” says Wolfe.

No antidepressant has received an A classification for use during pregnancy by the FDA. Most older antidepressants fall in the B or C categories of no known or limited risk in humans, or a slight associated risk in animal studies. (See a list of the classifications.)

A large, long-term study found antidepressant use during pregnancy associated with increased rates of preterm birth, a growing problem in pregnancies in the United States. In general, all antidepressants pose a small withdrawal risk for babies at birth, which may include, but are not limited to, jitteriness, irritability, tremors, difficulty eating or sleeping, and some problems with breathing. If possible, avoid taking antidepressants near the time of delivery to limit neonatal withdrawal symptoms.

Selective serotonin reuptake inhibitors (SSRIs) are the antidepressant class most often prescribed for pregnant women, with sertraline (Zoloft) and fluoxetine (Prozac) 2 of the most common SSRIs prescribed during pregnancy (they’re also the drugs most studied). Though both are listed as Class C drugs, neither has been found to have an increased risk of birth defects above baseline for the general population. In the SSRI class, pregnant women should never take paroxetine (Paxil), listed as a Class D drug by the FDA, because it has been shown to have a 1.5% to 2% increased risk above baseline in fetal cardiac malformations in human studies.

Other antidepressants to avoid if possible — and absolutely during the first trimester because of their risk of birth defects — include those containing lithium, valproate/valporic acid, carbamazepine or certain benzodiazepines.

Supplements aren’t necessarily a safer option. Not enough is known to determine the safety of SAMe, a popular supplement for depression. 5 Hydroxy-Tryptophan, a.k.a., 5-HTP, may be unsafe if taken during pregnancy or breastfeeding. St. John’s Wort has been found to cause birth defects in unborn rats, and has been shown to cause colic, drowsiness and listlessness in breastfed infants whose mothers take it.

Further Reading

Antidepressant Use During Pregnancy May Lead to Childhood Obesity and Diabetes

According to new research, women who take antidepressants during pregnancy may be unknowingly predisposing their infants to type 2 diabetes and obesity later in life. Research demonstrated for the first time in an animal model that maternal use of a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs) resulted in increased fat accumulation and inflammation in the liver of the adult offspring. Via Toronto Sun. Posted June 19, 2014.

–Alanna McCatty