To summarize and systematically review the efficacy and safety of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) for depression in stroke patients.
Prozac and Zoloft are both selective serotonin reuptake inhibitors (SSRIs). This class of medication is among the first options for treating major depressive disorder, which people usually call depression.
In this article, we discuss the differences between Prozac and Zoloft.
In addition, the FDA have approved Prozac for the treatment of:
Other SSRIs include:
Both Prozac and Zoloft are available in the forms of a liquid oral solution, a tablet, and a capsule.
The following table lists the different forms of each drug along with the available dosages in milligrams (mg) and milligrams per milliliter (mg/ml).
|Capsule||10 mg, 20 mg, 40 mg, 90 mg||25 mg, 50 mg, 100 mg|
|Tablet||60 mg||25 mg, 50 mg, 100 mg|
|Liquid||20 mg/5 ml||20 mg/ml|
When a person first starts taking antidepressants, they will typically begin on a smaller dosage and increase this over time. Doing this makes it possible to test how well the drug works and monitor its side effects, as the effectiveness and adverse effects can differ among individuals.
American Psychiatric Association guidelines report the following starting dosages and the usual effective dosages when treating MDD:
|Starting dosage||20 mg/day||50 mg/day|
|Usual effective dosages||20–60 mg/day||50–200 mg/day|
Some people may see improvements in their symptoms in the first 1–2 weeks of treatment, whereas it may take 2–4 weeks for others to notice changes.
Some studies have shown that all antidepressants require at least 4–6 weeks before they reach their maximal clinical effectiveness.
There are three phases of MDD therapy:
Doctors will usually recommend a maintenance phase for people with recurrent MDD or chronic depression.
If a person does not have a satisfactory response to medication, the doctor may try increasing the dosage. However, a higher dosage may cause more side effects, so doctors need to evaluate the risks and benefits of increasing it.
Another strategy to increase the effectiveness of the therapy is to add another medicine. A doctor may advise a person to combine Prozac or Zoloft with certain other antidepressants and other types of medication to improve their symptoms.
The doctor will determine which combinations are the most appropriate for each person while keeping in mind the possibility of drug interactions.
Doctors may also adjust medication dosages and regimens for people who are combining medication therapy and psychotherapy.
As Prozac and Zoloft are both SSRIs, people may experience similar side effects with these drugs.
Zoloft is more likely than Prozac to cause gastrointestinal tract side effects, such as nausea and diarrhea. Men taking Zoloft may also report more sexual dysfunction side effects, such as failure to ejaculate, than those using Prozac.
The following table lists the most common side effects of Prozac and Zoloft, which occur in at least 5% of people.
|decreased appetite||no data available||7%|
|anorexia||10%||no data available|
|anxiety||12%||no data available|
|agitation||no data available||8%|
|nervousness||13%||no data available|
|headache||21%||no data available|
|weakness/lack of energy||11%||no data available|
|flu-like symptoms||5%||no data available|
|decreased sex drive||no data available||6%|
|failure to ejaculate||no data available||8%|
When people are ready to come off their antidepressant medications, they should do so gradually. Stopping Prozac, Zoloft, or any other antidepressant abruptly can cause discontinuation symptoms.
Discontinuation symptoms may include:
Several short-term studies have shown that children, adolescents, and young adults under 24 years old have an increased risk of suicidal thoughts and behaviors when taking any antidepressants.
Doctors will monitor people taking Prozac, Zoloft, or any other antidepressant for worsening of depressive symptoms, suicidal thoughts, and unusual behaviors.
People with glaucoma and a history of seizures should use Prozac, Zoloft, and other SSRIs with caution because the drugs can make these conditions worse.
SSRIs, including Prozac and Zoloft, have similar drug interactions.
Serotonin syndrome is a potentially life-threatening interaction that occurs as a result of combining drugs that increase serotonin in the body.
Doctors should avoid prescribing Prozac, Zoloft, and other SSRIs alongside the following drugs:
Some of the signs and symptoms of serotonin syndrome include:
People cannot take MAOIs, another type of antidepressant, with Prozac, Zoloft, or any other SSRIs because the risk of developing serotonin syndrome is very high.
Anyone taking an MAOI must stop taking it at least 2 weeks before starting SSRI treatment.
Doctors have reported QT prolongation in people taking Prozac and Zoloft. QT prolongation is a potentially fatal heart rhythm dysfunction.
This heart condition is more common in people who take other drugs that can prolong the QT interval on an electrocardiograph. These include certain antipsychotics, antibiotics, and anti-arrhythmic medications.
Some people can experience abnormal bleeding when combining Prozac, Zoloft, and other SSRIs with drugs that can increase bleeding, such as:
|Capsule (30 capsules)||10 mg: $3.00
20 mg: $3.00
40 mg: $3.00
|10 mg: $461.85
20 mg: $474.70
40 mg: $947.40
|no information available||no information available|
|Tablet (30 tablets)||10 mg: $4.00
20 mg: $26.76
60 mg: $96.35
|no information available||25 mg: $3.99
50 mg: $7.17
100 mg: $6.52
|25 mg: $313.61
50 mg: $313.61
100 mg: $313.61
|Liquid oral solution (1 bottle)||120 ml: $12.81||no information available||60 ml: $25.10||60 ml: $216.18|
People should not take Prozac and Zoloft together. These drugs are in the same drug class and have the same actions. Taking both drugs will not improve symptoms but can cause additional side effects.
When people are not feeling the intended effects of either Prozac or Zoloft, the doctor may increase the dosage or alter the treatment regimen by adding another antidepressant or antipsychotic drug that has different actions on the brain.
Prozac and Zoloft are part of the same family of antidepressants, and both raise the levels of serotonin in the brain. Both drugs have FDA approval for the treatment of MDD, and they also have other approved and nonapproved uses.
The safe warnings relating to taking Prozac or Zoloft are similar, as are many of the side effects, although these can vary from person to person. Zoloft may be harsher on the stomach, while Prozac is more likely to cause headaches.
Both drugs are generally effective and safe, but people taking Prozac or Zoloft should follow up with their doctor to discuss their symptoms and side effects to ensure that they are taking the most effective dosage.
If treatment is successful, the doctor will slowly reduce the dosage if possible to eventually stop the medication. People should not abruptly stop taking Prozac or Zoloft.
In this article, we discuss some of the possible hidden signs of depression. However, it is important to note that some of these signs can also indicate other medical issues.
We also cover what healthcare professionals believe to be common causes of depression, what a person should do if they think they or someone else has depression, and some sources of help for people with depression.
These changes in food intake can cause a person to start gaining or losing weight.
Dramatic weight changes can also exacerbate depression, as they can affect a person’s self-esteem.
There may also be physiological factors at play. For example, there is a link between carrying excess fat and increased inflammation in the body. This, in turn, may play a role in the development or increased severity of depressive symptoms.
There is a strong link between mood and sleep. A lack of sleep can contribute to depression, and depression can make it more difficult to sleep.
Sleeping too much can also be a sign that a person may have depression.
Some people with mood disorders may use alcohol or drugs to cope with their feelings of sadness, loneliness, or hopelessness.
The Anxiety and Depression Association of America (ADAA) report that in the United States, around 1 in 5 people with anxiety or a mood disorder such as depression also have an alcohol or substance use disorder.
Conversely, the same number of those with an alcohol or substance use disorder also have a mood disorder
Although everyone feels tired from time to time, people who have severe or persistent tiredness — especially if it accompanies other symptoms — may have hidden depression.
Sometimes, people refer to hidden depression as “smiling depression.” This is because people who hide their symptoms may put on a happy face when in the company of others.
However, it can be difficult to keep up this forced happiness, so the mask may slip and a person may show signs of sadness, hopelessness, or loneliness.
People with depression may also be more pessimistic. Studies suggest that those with major depressive disorder often have a more negative view of the future.
Being more realistic or pessimistic than others may be one sign of depression, especially if the person has other possible symptoms of depression.
When a person trails off during conversations or loses their train of thought, it can indicate issues with memory and concentration, which is a common symptom of depression.
A 2014 study suggests that these difficulties with concentration and focus can worsen the social impact of depression by making work life and personal relationships more challenging.
The National Institute of Mental Health list a “loss of interest or pleasure in hobbies and activities” as one of the telltale symptoms of depression.
Disinterest in activities that a person used to enjoy can be one of the first signs that other people notice when their loved one has depression.
Depression is a mental health condition, but it can also have physical consequences. In addition to weight changes and fatigue, other physical symptoms of hidden depression to look out for include:
Research also indicates that those with major depression are more likely than those without the condition to experience:
Many people do not associate anger and irritability with depression, but these mood changes are not unusual among those with the condition.
Instead of appearing sad, some people with hidden depression may display irritability and overt or suppressed anger.
According to Dr. Jennifer Payne, director of the Women’s Mood Disorders Center at Johns Hopkins Medicine in Baltimore, MD, some health professionals consider changes in sex drive a key indicator for diagnosing episodes of major depression.
There are several reasons that a person’s libido might decrease when they have depression, including:
Scientists do not yet know the exact cause of depression. However, many experts think that several factors play a role in its onset, including:
Other steps to treat depression might include:
If a loved one appears to have signs of hidden depression, try to talk to them about their symptoms and offer nonjudgmental support and advice.
This can include:
People looking after someone with depression also need to practice good self-care in order to preserve their own mental well-being.
People with symptoms of depression should consider seeking help from a loved one or a healthcare professional, such as a doctor or psychotherapist.
Not everyone with depression will display the typical symptoms of sadness and despair.
Sometimes, the only signs a person may show are physical, such as fatigue, insomnia, or weight changes.
Other signs of hidden depression can include using alcohol or drugs, acting irritable or angry, and losing interest in pleasurable activities such as sex and hobbies.
People concerned that a loved one has hidden depression should try talking to them about their symptoms and offering nonjudgmental support and advice.
Individuals who suspect that they have depression should consider discussing it with a friend or mental health professional.
There are also a number of organizations that provide support to those dealing with depression.
Amitriptyline is a drug in the tricyclic antidepressant (TCA) family.
TCAs were introduced in the late 1950s as a treatment for depression. Since then, other less toxic drugs have become available. Among them are selective serotonin reuptake inhibitors, better known as SSRIs.
Doctors prescribe amitriptyline to people with depression who have not responded to other antidepressants. There are additional uses for amitriptyline that the Food and Drug Administration (FDA) have not approved.
Read on to learn more about the uses, side effects, warnings, and potential interactions of amitriptyline.
The structure of amitriptyline allows it to attach to receptors in the brain called alpha-adrenergic, histaminic, and muscarinic receptors. This means that amitriptyline can cause more side effects than some other TCAs.
Some examples of other drugs in the TCA class include:
There are six dosages of amitriptyline: 10 milligrams (mg), 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg.
Amitriptyline was once manufactured under the brand Elavil, but only generic forms of the drug are currently available.
Doctors prescribe amitriptyline to treat depression in adults.
Amitriptyline may also cause blurred vision, urinary retention, a rapid heartbeat, and acute-angle glaucoma when it binds to muscarinic receptors in the body.
When amitriptyline attaches to histaminic receptors, it may cause sedation, confusion, and delirium.
People who have seizures should use amitriptyline with caution because it can lower the seizure threshold.
Serious cardiac side effects can occur when amitriptyline binds to alpha-adrenergic receptors in the heart. Low blood pressure upon standing and heart rate fluctuations and irregularities are some of these effects.
When treating depression with amitriptyline, doctors usually prescribe a starting dosage of 25 mg per day — at bedtime because it can cause drowsiness. For off-label uses, doctors may prescribe dosages of 10–20 mg per day.
Depending on a person’s response to the medication, the doctor may increase the dosage by 25 mg every 3–7 days. The effective dosage of amitriptyline is one that controls symptoms without causing too many side effects.
The maximum daily dosage of amitriptyline is 150–300 mg per day.
When the dosage is correct, people should notice their symptoms improving within 2–4 weeks. The doctor will recommend maintaining an effective dosage for at least 3 months to prevent symptoms from returning.
If a person wants to stop taking amitriptyline, it is important to develop a tapering schedule with a doctor to prevent withdrawal symptoms. Stopping amitriptyline abruptly can cause side effects.
It is important to gradually reduce the dosage of amitriptyline to prevent withdrawal symptoms.
Withdrawal symptoms can include:
A doctor will recommend a tapering schedule. An individual approach is key because each person may have a different reaction to stopping the drug.
Keeping track of any symptoms and informing the doctor can help them judge whether to speed up or slow down the tapering.
Short-term studies have shown that antidepressants can increase the risk of suicidal thoughts and behaviors in children, adolescents, and young adults. Research has not shown that people older than 24 years experience these or similar effects.
Before prescribing amitriptyline to a child, adolescent, or young adult, the doctor should weigh the benefits and risks carefully. During treatment, doctors and caregivers need to monitor people taking amitriptyline for worsening symptoms of depression, suicidal thoughts, and unusual behaviors.
Anyone who has experienced an allergic reaction to amitriptyline should refrain from using this drug.
Anyone over 50 and anyone with a history of heart trouble will undergo an electrocardiogram before beginning amitriptyline treatment. They will repeat this test during treatment so a doctor can check for new or worsening heart conditions.
Amitriptyline can worsen existing angle-closure glaucoma, urinary retention, and seizures. It is important to discuss any symptoms with a doctor, who can rule out these issues, before beginning treatment.
Doctors should prescribe lower doses of amitriptyline to people with liver or kidney failure.
When a person takes amitriptyline and certain other drugs, three critical interactions can occur: monoamine oxidase inhibitor (MAOI) interactions, QT prolongation interactions, and serotonin syndrome interactions.
MAOIs work by blocking the effect of the enzyme monoamine oxidase. This enzyme is responsible for breaking down monoamines in the body.
Monoamines include epinephrine, norepinephrine, dopamine, serotonin, and tyramine. When levels of these chemicals rise in the body, a person may experience:
MAOI drugs include :
The QT interval on an electrocardiogram is an important measure of the electrical conduction of the heart. When this interval lengthens, a person may experience an abnormal heart rhythm, which can lead to arrhythmia.
Amitriptyline can prolong the QT interval. Combining this drug with others that have the same effect puts a person at risk of developing arrhythmia.
Some examples of other drugs that can prolong the QT interval include:
Serotonin syndrome occurs when there is too much serotonin in the body. This can cause symptoms that can range in severity from mild-to-life-threatening.
Serotonin syndrome symptoms include:
Amitriptyline increases the amount of serotonin in the brain. When a person also takes other drugs that have this effect, it puts them at risk of developing serotonin syndrome.
Some other drugs that can increase the amount of serotonin in the brain include:
The manufacturer has discontinued the Elavil brand of amitriptyline, so only generic forms are available.
The following list shows the prices for 30 tablets of amitriptyline by dosage.
Doctors usually prescribe amitriptyline to treat depression. In addition, some off-label uses include treating anxiety, IBS, and chronic pain.
People taking amitriptyline may experience drowsiness, headaches, and dizziness, among other side effects, some of which are more severe.
Anyone taking any antidepressant should remain watchful for worsening of symptoms. Some people have experienced suicidal thoughts and behaviors while taking amitriptyline, and this requires immediate medical attention.
Also, some drugs can interact with amitriptyline. It is crucial that doctors and pharmacists carefully weigh the benefits and risks of adding amitriptyline to a person’s care plan.
One of the most unsettling things I see in the TBI community is when survivors feel isolated and lonely. There have been heart-wrenching posts and comments on our blog site about families that shun (or brush off) their own family members that have experienced a traumatic brain injury. Worse yet, I’ve heard people say that they are totally on their own because they just don’t have emotional support from family (or friends). There is no way that I can offer a solution that will work for everybody – for that matter, even for one survivor…but I’m gonna try to give some pointers that can alleviate some of the frustration and hurt that’s caused by loneliness and the things that can make it feel even worse.
The very first thing I’ve recognized as the rallying cry of survivors is “you don’t know it unless you’ve experienced it” – and that surely is true. Letting people know how your brain injury feels is like describing the color and texture of an abstract painting to a blind person. They have no point of reference to even work with. To many, the conditions, effects, and feelings experienced by a TBI survivor are inexplicable in words…although some are able to do it. I will be referencing a book offered by Lash & Associates Publishing to help find ways to combat the depression and anxiety that survivors experience, to find ways to cope, and to encourage caregivers as well.
In the book titled “Lost & Found” – a brain injury survivor herself, offers these succinct nuggets of wisdom: “Healing and rehabilitating from a brain injury takes a long time. It continues long after formal rehabilitation has ended. It is the hardest work I have ever done. It requires endless courage, determination, motivation, and
support. It usually involves rebuilding multiple areas of not just your life but also your being – all at once. How could there be an easy solution for all of that!
Brain injury doesn’t have to be a destination. It is a journey. Let it be only part of who you are to become. “Don’t accept timetables for recovery.”
— Jill Bolte Taylor, Ph.D., Neuroanatomist
Strategies are key in making “baby steps” toward better cognition, a better mood, a better outlook, and a better life. Much progress can be made with encouragement from friends or family…but what about those that don’t have that kind of social “safety net”? Be encouraged. Your will to improve is the key to doing the right things and working to get the right results. As always, there will be naysayers that will immediately point out that “you’ve been this way for a long time” or “you’re wasting your time.” Well, with that kind of encouragement, you’ll be better off doing your best – one step forward at a time. Don’t even consider the steps backward…life hands those to everyone anyway!
Incremental strategies are the ticket to incremental change. Biting off more than you can chew is not a good plan! Start off small, find strategies that work for YOU, and repetition is a good thing. If you’re repeating a step, and you know that you are…that’s a great thing! If you recall how your brain used to process information, but you realize that it has changed…good for you! That is a baseline for working on your cognition. Remember, working in tandem with your doctors, therapists, caregivers, etc. is also very important. You’re not going to make measurable progress without someone that can see your “mile markers” and take note of them. Caregivers can also help with that.
Here’s an excerpt from Lost & Found that is a prime example of working toward healing: “Know that in time, as you heal, it won’t always be this hard. You won’t have to plan and strategize each and every little step you take. So remember you are healing, imagine yourself with a cast on your head and be kind to yourself. Treat yourself like you would any loved one with a serious health issue.
Remember to reward yourself for every successful task and effort, no matter how small. Pat yourself on the back and take a break doing something that will make you smile. We have to be our own cheerleaders now, like the supportive people in our lives were when we were growing up.”
Wow…that’s powerful, but also takes grit and determination. Believing in yourself is always easier when you have cheerleaders – but for those who don’t, that excerpt makes a lot of sense.
Emotional healing can come through a combination of things – here are a few (a more detailed version is available in the book, Lost & Found), but here’s a brief overview… Keep a grateful journal or victory log; Discover your “inner poet” by writing phrases that are meaningful to you; Journaling about your day can help you build confidence and see progress; Keep your perspective by noting improvements on a calendar; Challenge and learn from negative thoughts; Take time to smile; Forgive yourself – can’t do what you used to do? You’re only human! Remember that you’re still the same unique and valuable person that you always were; Try to have positive people around you…that supports your life moving in a positive direction; Work with art. Creative outlets are rewarding and fun. These are things that encourage and grow you as a person – with or without others’ approval.
Many times, people in your life are grieving the loss of the “old you” and trying to establish how to interact with the “new you” – just like you are. That can also make an awkward transition for family and friends. Seeking spiritual counsel can be a huge boost as well – if you attend a church, synagogue, etc., or want to…that could be a great way to grow your positivity in life and make some new acquaintances too.
Here’s another excerpt from Lost & Found: “Keep in mind that your family members and friends may be grieving too. They have lost the person you used to be and the roles you used to play in their lives. They don’t know how much of your former self will return, or when.”
And a quote from the same book: “Honoring your feelings is what helps you move beyond the pain.”
— Janelle Breese-Biagioni
This last excerpt from the book really sums up what so many TBI survivors need to hear…
“Remember you are healing, even if you can’t see a wound! Think of your brain in a cast, as it would be if you broke any other part of your body. If you broke your leg, you wouldn’t expect yourself to run a marathon right away, even if you were previously a marathon runner. First, you would be in a cast and you would rest a lot. Then you would start walking with crutches on even surfaces. The next step might be walking with a cane. You get the idea; it would take a lot of healing before you could run again, never mind run a marathon! Most of us try to run marathons with our brains all the time!
You won’t be able to do everything you used to, at least not right away. Everything will be harder and take a lot longer to do than it used to. You can compensate by cutting back, simplifying and being kind and patient with yourself. Avoid the tendency to push yourself too hard. Rehabilitation is a delicate balance between challenging yourself enough to promote healing and not so much that you have discouraging setbacks.
So picture yourself with a cast on your head and remember to rest, celebrate the smallest gains and balance out all the hard work with something that makes you smile, every day. You are engaged in one of the toughest challenges of your life, if not the hardest but it will get easier in time.”
In closing, the hardest takeaway from all this is that “going it alone” is hard but doing it without positive people surrounding you may be even harder. Cheerleaders are great, but they have to be rooting for the home team…and you’re the captain of the home team! Make the best choices that you possibly can and be encouraged – knowing that if all else doesn’t go as planned, you can rely on yourself to try and make things better. And you can also claim all of the credit. As always, be sure to let your doctor(s) know your intentions, and hopefully, they’ll be excited for your long-term efforts to improve. TBI is tiring, overloading, depressing at times, and can cause irrational behavior. With all that said, there’s always room to plan for incremental change.
Here’s a great and inspirational quote from Beverly Bryant:
“Being a brain injury survivor = Being a stranger in a familiar place.”
Amen to that!
If you’d like to know more about the Lash & Associates book titled “Lost & Found”…just click this link!
Date: March 11, 2019
Source: University of North Carolina Health Care
Summary: With a weak alternating electrical current sent through electrodes attached to the scalp, researchers successfully targeted a naturally occurring electrical pattern in a specific part of the brain and markedly improved depression symptoms in about 70 percent of participants in a clinical study.
The research, published in Translational Psychiatry, lays the groundwork for larger research studies to use a specific kind of electrical brain stimulation called transcranial alternating current stimulation (tACS) to treat people diagnosed with major depression.
“We conducted a small study of 32 people because this sort of approach had never been done before,” said senior author Flavio Frohlich, PhD, associate professor of psychiatry and director of the Carolina Center for Neurostimulation. “Now that we’ve documented how this kind of tACS can reduce depression symptoms, we can fine tune our approach to help many people in a relatively inexpensive, noninvasive way.”
Frohlich, who joined the UNC School of Medicine in 2011, is a leading pioneer in this field who also published the first clinical trials of tACS in schizophrenia and chronic pain.
His tACS approach is unlike the more common brain stimulation technique called transcranial direct stimulation (tDCS), which sends a steady stream of weak electricity through electrodes attached to various parts of the brain. That approach has had mixed results in treating various conditions, including depression. Frohlich’s tACS paradigm is newer and has not been investigated as thoroughly as tDCS. Frohlich’s approach focuses on each individual’s specific alpha oscillations, which appear as waves between 8 and 12 Hertz on an electroencephalogram (EEG). The waves in this range rise in predominance when we close our eyes and daydream, meditate, or conjure ideas — essentially when our brains shut out sensory stimuli, such as what we see, feel, and hear.
Previous research showed that people with depression featured imbalanced alpha oscillations; the waves were overactive in the left frontal cortex. Frohlich thought his team could target these oscillations to bring them back in synch with the alpha oscillations in the right frontal cortex. And if Frohlich’s team could achieve that, then maybe depression symptoms would be decreased.
His lab recruited 32 people diagnosed with depression and surveyed each participant before the study, according to the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard measure of depression.
The participants were then separated into three groups. One group received the sham placebo stimulation — a brief electrical stimulus to mimic the sensation at the beginning of a tACS session. A control group received a 40-Hertz tACS intervention, well outside the range that the researchers thought would affect alpha oscillations. A third group received the treatment intervention — a 10-Hertz tACS electrical current that targeted each individual’s naturally occurring alpha waves. Each person underwent their invention for 40 minutes on five consecutive days. None of the participants knew which group they were in, and neither did the researchers, making this a randomized double-blinded clinical study — the gold standard in biomedical research. Each participant took the MADRS immediately following the five-day regimen, at two weeks, and again at four weeks.
Prior to the study, Frohlich set the primary outcome at four weeks, meaning that the main goal of the study was to assess whether tACS could bring each individual’s alpha waves back into balance and decrease symptoms of depression four weeks after the five-day intervention. He set this primary outcome because scientific literature on the study of tDCS also used the four-week mark.
Frohlich’s team found that participants in the 10-Hertz tACS group featured a decrease in alpha oscillations in the left frontal cortex; they were brought back in synch with the right side of the frontal cortex. But the researchers did not find a statistically significant decrease in depression symptoms in the 10-Hertz tACS group, as opposed to the sham or control groups at four weeks.
But when Frohlich’s team looked at data from two weeks after treatment, they found that 70 percent of people in the treatment group reported at least a 50 percent reduction of depression symptoms, according to their MADRS scores. This response rate was significantly higher than the one for the two other control groups. A few of the participants had such dramatic decreases that Frohlich’s team is currently writing case-studies on them. Participants in the placebo and control groups experienced no such reduction in symptoms.
“It’s important to note that this is a first-of-its kind study,” Frohlich said. “When we started this research with computer simulations and preclinical studies, it was unclear if we would see an effect in people days after tACS treatment — let alone if tACS could become a treatment for psychiatric illnesses. It was unclear what would happen if we treated people several days in a row or what effect we might see weeks later. So, the fact that we’ve seen such positive results from this study gives me confidence our approach could help many people with depression.”
Frohlich’s lab is currently recruiting for two similar follow-up studies.
Other authors of the Translational Psychiatry paper are co-first authors Morgan Alexander, study coordinator and graduate student, and Sankaraleengam Alagapan, PhD, a postdoctoral fellow, both in the department of psychiatry at UNC-Chapel Hill; David Rubinow, MD, the Assad Meymandi Distinguished Professor and Chair of Psychiatry at the UNC School of Medicine; former UNC postdoctoral fellow Caroline Lustenberger, PhD; and Courtney Lugo and Juliann Mellin, both study coordinators at the UNC School of Medicine.
This research was funded through grants from the Brain Behavior Research Foundation, National Institutes of Health, the BRAIN Initiative, and the Foundation of Hope.
Frohlich holds joint appointments at UNC-Chapel Hill in the department of cell biology and physiology and the Joint UNC-NC State Department of Biomedical Engineering. He is also a member of the UNC Neuroscience Center.
To summarize and systematically review the efficacy and safety of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) for depression in stroke patients.
Six databases (Wanfang, CNKI, PubMed, Embase, Cochrane Library, and Web of Science) were searched from inception until November 15, 2018.
Seventeen randomized controlled trials were included for meta-analysis.
Two independent reviewers selected potentially relevant studies based on the inclusion criteria, extracted data, and evaluated the methodological quality of the eligible trials using the Physiotherapy Evidence Database (PEDro).
We calculated the combined effect size (standardized mean difference [SMD] and odds ratio [OR]) for the corresponding effects models. Physiotherapy Evidence Database scores ranged from 7 to 8 points (mean = 7.35). The study results indicated that HF-rTMS had significantly positive effects on depression in stroke patients. The effect sizes of the SMD ranged from small to large (SMD = −1.01; 95% confidence interval [95% CI], −1.36 to −0.66; P < .001; I2 = 85%; n = 1053), and the effect sizes of the OR were large (response rates: 58.43% VS 33.59%; OR = 3.31; 95% CI, 2.25 to 4.88; P < .001; I2 = 0%; n = 529; remission rates: 26.59% VS 12.60%; OR = 2.72; 95% CI, 1.69 to 4.38; P < .001; I2 = 0%; n = 529). In terms of treatment side-effects, the HF-rTMS group was more prone to headache than the control group (OR = 3.53; 95% CI, 1.85 to 8.55; P < .001; I2 = 0%; n = 496).
HF-rTMS is an effective intervention for post-stroke depression, although treatment safety should be further verified via large sample multi-center trials.
via Efficacy and Safety of High-frequency Repetitive Transcranial Magnetic Stimulation for Post-Stroke Depression:A Systematic Review and Meta-Analysis – Archives of Physical Medicine and Rehabilitation
Current treatments for depression and PTSD only suppress symptoms, if they work at all. What if we could prevent these diseases from developing altogether? Neuroscientist and TED Fellow Rebecca Brachman shares the story of her team’s accidental discovery of a new class of drug that, for the first time ever, could prevent the negative effects of stress — and boost a person’s ability to recover and grow. Learn how these resilience-enhancing drugs could change the way we treat mental illness.
This talk was presented at an official TED conference, and was featured by our editors on the home page.
Some of these people have treatment-resistant depression, which means common prescription drugs do not alleviate the symptoms.
Recent studies have pointed to alternative treatment methods for major depression, such as non-invasive brain stimulation techniques.
For instance, a study that appeared at the end of last year showed that using small electric currents to stimulate a brain area called the orbitofrontal cortex significantly improves the mood of people who did not benefit from conventional antidepressants.
An even more recent trial of a form of brain stimulation called “transcranial alternating current stimulation” (tACS) found that the technique halved depression symptoms in almost 80 percent of the study participants.
Despite such promising results, doctors do not use these techniques widely, as there is not enough data available on their efficacy.
So, a team of researchers led by Julian Mutz at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, United Kingdom, set out to review some clinical trials that have examined the benefits of non-invasive brain stimulation techniques for people living with depression.
Specifically, Mutz and team examined the results of 113 clinical trials. Overall, these trials included 6,750 participants who were 48 years old, on average, and were living with major depressive disorder or bipolar depression.
The original clinical trials involved randomly assigning these participants to 18 treatment interventions or “sham” therapies. The reviewers focussed on the response, or “efficacy” of the treatment, as well as the “discontinuation of treatment for any reason” — or “acceptability” of the therapies. Mutz and colleagues also rated the trials’ risk of bias.
The therapies included in the review were “electroconvulsive therapy (ECT), transcranial magnetic stimulation (repetitive (rTMS), accelerated, priming, deep, and synchronized), theta burst stimulation, magnetic seizure therapy, transcranial direct current stimulation (tDCS), or sham therapy.”
Of these, the treatments that the researchers in the original trial examined most often were high frequency left rTMS and tDCS, which they tested against sham therapy. On the other hand, not many trials covered more recent forms of brain stimulation, such as magnetic seizure therapy and bilateral theta burst stimulation, the review found.
Kutz and his team deemed 34 percent of the trials they reviewed as having a low risk of bias. They considered half of the trials to have an “unclear” risk of bias, and finally, 17 percent to have a high risk of bias. The newer the treatments, the higher was the uncertainty of the trials’ results.
The review found that bitemporal ECT, high dose right unilateral ECT, high frequency left rTMS and tDCS were all significantly more effective than sham therapy both in terms of efficacy and acceptability.
When considering “discontinuation of treatment for any reason,” the researchers found that the participants were not any likelier to discontinue brain stimulation treatments than they were sham therapy. Mutz and colleagues conclude:
“These findings provide evidence for the consideration of non-surgical brain stimulation techniques as alternative or add-on treatments for adults with major depressive episodes.”
“These findings also highlight important research priorities in the specialty of brain stimulation, such as the need for further well-designed randomized controlled trials comparing novel treatments, and sham-controlled trials investigating magnetic seizure therapy,” the authors add.
Finally, the researchers also note that their results have clinical implications, “in that they will inform clinicians, patients, and healthcare providers on the relative merits of multiple non-surgical brain stimulation techniques.”
Like seismic sensors planted in quiet ground, hundreds of tiny electrodes rested in the outer layer of the 44-year-old woman’s brain. These sensors, each slightly larger than a sesame seed, had been implanted under her skull to listen for the first rumblings of epileptic seizures.
The electrodes gave researchers unprecedented access to the patient’s brain. With the woman’s permission, scientists at the University of California, San Francisco began using those electrodes to do more than listen; they kicked off tiny electrical earthquakes at different spots in her brain.
Most of the electrical pulses went completely unnoticed by the patient. But researchers finally got the effect they were hunting for by targeting the brain area just behind her eyes. Asked how she felt, the woman answered: “Calmer in my nerves.”
Zapping the same spot in other participants’ brains evoked similar responses: “I feel positive, relaxed,” said a 53-year-old woman. A 60-year-old man described “starting to feel a little more alive, a little more energy.” With stimulation to that one part of the brain, “participants would sit up a little straighter and seem a little bit more alert,” says UCSF neuroscientist Kristin Sellers.
Such positive mood changes in response to light neural jolts, described in the Dec. 17 Current Biology, bring researchers closer to an audacious goal: a device implanted into the brains of severely depressed people to detect a looming crisis coming on and zap the brain out of it.
It sounds farfetched, and it is. The project is “fundamental, pioneering, discovery neuroscience,” says Mark George, a psychiatrist and neurologist at the Medical University of South Carolina in Charleston. George has been studying depression for 30 years. “It’s like sending a spacecraft to the moon.”
|This video shows the location of brain regions involved in emotion processing: the orbitofrontal cortex (green), cingulate (red), insula (purple), hippocampus (yellow) and amygdala (blue). The dots show where electrodes were placed to monitor seizures in patients with epilepsy.|
Still, in the last several years, teams of scientists have made startling amounts of progress, both in their ability to spot the neural signatures that come with a low mood and to change a person’s feelings.
With powerful computational methods, scientists have recently zeroed in on some key features of depressed brains. Those hallmarks include certain types of brain waves in specific locations, like the one just behind and slightly above the eyes. Other researchers are focused on how to correct the faulty brain activity that underlies depression.
A small, implantable device capable of both learning the brain’s language and then tweaking the script when the story gets dark would be an immensely important clinical tool. Of the 16.2 million U.S. adults with severe depression, about a third don’t respond to conventional treatments. “That’s a huge number of people with a very disabling and probably underdiagnosed and underappreciated illness,” says neurologist Vikram Rao, who is working on the UCSF project with Sellers.
When George began studying depression decades ago, the field was still haunted by Sigmund Freud, who blamed the disorder on bad parenting and repressed anger. Soon after came the chemical imbalance concept, which held that the brain just needs a dash of the right chemical signal to fix itself. “It was the ‘brain is soup’ model,” George says. Toss in more of the crucial ingredient — serotonin, for instance — and the recipe would sing.
“We have a very different view now,” George says. Thanks to advances in brain imaging, scientists see depression as a disorder of neural circuits — altered connections between important brain regions can tip a person into a depressed state. “We’ve started to define the road map of depression,” George says.
Depression is a disorder, but one that’s tightly linked to emotion. It turns out that emotions span much of the brain. “Emotions are more widespread than we thought,” says cognitive neuroscientist Kevin LaBar. With his colleagues at Duke University, LaBar has used functional MRI scans to find signatures of certain emotions throughout the brain as people are feeling those emotions. He found the wide neural reach of sorrow, for instance, by prompting the emotion with gloomy songs and films.
Functional MRI allows scientists to see the entire scope of a working brain, but that wide view comes with the trade-off of lower resolution. And resolution is what’s needed to precisely and quickly sense — and change — brain activity. Implanting electrodes, like those used in the UCSF project, gives a more nuanced look into select brain areas. Those detailed recordings, taken from people undergoing epilepsy treatment, are what allowed neural engineer Maryam Shanechi to decode the brain’s emotions with precision.
As seven patients spent time in the hospital with electrodes monitoring brain activity, their emotions naturally changed. Every so often, the participants would answer mood-related questions on a tablet computer so that researchers could measure when the patients shifted between emotions. Then Shanechi, of the University of Southern California in Los Angeles, and her colleagues matched the brain activity data to the moods.
The task wasn’t simple. The implanted electrodes recorded an enormous pile of data, much of it irrelevant to mood. Shanechi and her team developed an algorithm to distill all that data into a few key predictive brain regions for each person. The resulting decoder could tell what mood a person was in based on brain activity alone, the team reported in the October Nature Biotechnology. “In every single individual, we can show how their mood changes in real time,” Shanechi says.[…]
Depression is a multifaceted and insidious disorder, nearly as complex as the brain itself. As research continues to suggest, the onset of depression can be attributed to an interplay of the many elements that make us human—namely, our genetics, the structure and chemistry of our brains, and our lived experience. Second only, perhaps, to the confounding mechanics of anesthesia, depression is the ultimate mind-body problem; understanding how it works could unlock the mysteries of human consciousness.
Emma Allen, a visual artist, and Dr. Daisy Thompson-Lake, a clinical neuroscientist, are fascinated by the physical processes that underlie mental health conditions. Together, they created Adam, a stop-motion animation composed of nearly 1,500 photographs. The short film illuminates the neuroscience of depression while also conveying its emotive experience.
“It was challenging translating the complicated science into an emotional visual story with scenes that would flow smoothly into each other,” Allen told The Atlantic.
“One of the most complex issues we had to deal with,” added Thompson-Lake, “is that there no single neuroscientific explanation for depression…While scientists agree that there are biological and chemical changes within the brain, the actual brain chemistry is very unique to the individual—although, of course, we can see patterns when studying large numbers of patients.” As a result, Allen and Thompson-Lake attempted a visual interpretation of depression that does not rely too heavily on any one explanation.
The film’s first sequence depicts the brain’s vast network of neuronal connections. Neurons communicate via synapses, across which electrical and chemical signals are exchanged. In a depressed patient’s brain, some of these processes are inefficient or dysfunctional, as the animation illustrates. Next, we see a positron emission tomography (PET) scan of a depressed brain, demarcated by darkened areas. Finally, the animation shows activity in the hippocampus and the frontal lobe. Abnormalities in the activity of both of these areas of the brain have been implicated in depression by recent research.
For Allen, one of the main objectives in creating Adam was to help dispel the notion that depression is a character flaw. “A common misconception is that the person is at fault for feeling this way, and that to ask for help is a weakness or embarrassing,” Allen said. “But depression has a physical component that needs treating.”
“The shame surrounding mental health still exists,” Allen continued. “In fact, in the case of Kate Spade, it was reported that she was concerned about the stigma her brand might face if this were made public.”
And who, exactly, is Adam? “Daisy lost a friend to suicide,” said Allen, “so the film is named in his memory.”
“Adam” was directed by animator Emma Allen and neuroscientist Daisy Thompson-Lake. It is part of The Atlantic Selects, an online showcase of short films from independent creators, curated by The Atlantic.