Depression can lead to emotional and physical problems. Typically, people with depression find it hard to go about their day-to-day activities, and may also feel that life is not worth living.
What is Depression?
Feeling sad, or what we may call “depressed”, happens to all of us. The sensation usually passes after a while. However, people with a depressive disorder – clinical depression – find that their state interferes with daily life. Abraham Lincoln O-60 by Brady, 1862 Abraham Lincoln suffered from “melancholy”, known today as clinical depression.
For people with clinical depression, their normal functioning is undermined to such an extent that both they and those who care about them are affected by it.
Hippocrates, known as the father of Western medicine, described a syndrome of “melancholia”. He said melancholia was a distinct disease with specific physical and mental symptoms. Hippocrates characterized it as “(all) fears and despondencies if they last a long time” as being symptomatic of the illness.
According to the National Institutes of Health, a significant percentage of people with a depressive illness never seek medical help. This is unfortunate because the vast majority, even those with very severe symptoms, can improve with treatment.
A depressive disorder is a medical illness that causes a constant feeling of sadness and lack of interest.
The notion that depression is simply a “chemical imbalance” in the brain has given way to evidence that the disorder is associated with
- Disrupted neuroplasticity
- Glutamate as well as NE and 5HT receptors
- Cortical and subcortical changes
- Transition from pure pharmacology to neuromodulation (rTMS) that enhances hippocampal neurogenesis.
In short depression is truly a Brain Disease and its treatment should be multimodal to better allow those suffering from it to have their wellness restored, quality of life restored and functional capacity be fully realized. At The TMS Center of Southwest Florida we TMS as our primary treatment in treating the “Brain” illnesses our patients are suffering from.
Depression is not uniform. Signs and symptoms may be experienced by some sufferers and not by others. How severe the symptoms are, and how long they last depend on the individual person and his illness. Below is a list of the most common symptoms:
- A constant feeling of sadness, anxiety, and emptiness
- A general feeling of pessimism sets in (the glass is always half empty)
- The person feels hopeless
- Individuals can feel restless
- The sufferer may experience irritability
- Patients may lose interest in activities or hobbies they once enjoyed
- He/she may lose interest in sex
- Levels of energy feel lower, fatigue sets in
- Many people with a depressive illness find it hard to concentrate, remember details, and make decisions
- Sleep patterns are disturbed – the person may sleep too little or too much
- Eating habits may change – he/she may either eat too much or have no appetite
- Suicidal thoughts may occur – some may act on those thoughts
- The sufferer may complain more of aches and pains, headaches, cramps, or digestive problems. These problems do not get better with treatment.
There are several forms of depression (depressive disorders). Major depressive disorder and dysthymic disorder are the most common.
Major depressive disorder (major depression)
Major depressive disorder is also known as major depression. The patients suffer from a combination of symptoms that undermine their ability to sleep, study, work, eat, and enjoy activities they used to find pleasurable.
Experts say that major depressive disorder can be very disabling, preventing the patient from functioning normally. Some people experience only one episode while others have recurrences.
Dysthymic disorder (dysthymia)
Dysthymic disorder is also known as dysthymia or mild chronic depression. The patient will suffer symptoms for a long time, perhaps as long as a couple of years, and often longer. The symptoms are not as severe as in major depression – they do not disable the patient. However, people affected with dysthymic disorder may find it hard to function normally and feel well.
Some people experience only one episode during their lifetime while others may have recurrences.
When severe depressive illness includes hallucinations, delusions, and/or withdrawing from reality, the patient may be diagnosed with psychotic depression. Psychotic depression is also referred to as delusional depression.
Postpartum depression (postnatal depression)
Postpartum depression is also known as postnatal depression or PND. This is not to be confused with ‘baby blues’ which a mother may feel for a very short period after giving birth.
If a mother develops a major depressive episode within a few weeks of giving birth it is most likely she has developed postpartum depression.
Perinatal depression, defined as depression in pregnancy, around childbirth or within the first year post‐partum, is a significant problem in households around the world and often occurs comorbidly with other medical or mental health illnesses (for example, pain conditions or anxiety) affecting all members of the family while too often escaping detection and treatment.
SAD (seasonal affective disorder)
SAD is much more common the further from the equator you go, where the end of summer means the beginning of less sunlight and more dark hours. A person who develops a depressive illness during the winter months might have SAD.
Bipolar disorder (manic-depressive illness)
Bipolar disorder is also known as manic-depressive illness. It used to be known as manic depression. It is not as common as major depression or dysthymia. A patient with bipolar disorder experiences moments of extreme highs and extreme lows. These extremes are known as manias.
Nobody is sure what causes depression. Experts say depression is caused by a combination of factors, such as the person’s genes, their biochemical environment, personal experience and psychological factors.
A study published in Archives of Psychiatry found that MRI (magnetic resonance imaging) scans showed patients with clinical depression had less brain volume in several regions, including the frontal lobe, basal ganglia, and hippocampus. They also found that after treatment the hippocampus returned to normal size.
The Stanford School of Medicine says that genes do play a role in causing depression. By studying cases of major depression among identical twins (whose genes are 100% identical) and non-identical twins (whose genes are 50% identical) they found that heritability is a major contributory factor in the risk of developing depression.
An article in Harvard Health Publications explains that depression is not caused simply by the level of one chemical being too low and another too high. Rather, several different chemicals are involved, working both within and outside nerve cells. There are “Millions, even billions, of chemical reactions that make up the dynamic system that is responsible for your mood, perceptions, and how you experience life.”
An awful experience can trigger a depressive illness. For example, the loss of a family member, a difficult relationship, physical sexual abuse.
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Virginia Beach, Va. – Rana Culotta Simpson has suffered from depression most of her adult life. “I would sleep three days, at times 2-3 days not getting out of the bed,” says Culotta. This made it hard for the 35-year-old Peninsula resident to keep her job as a newspaper reporter. “I was socially anxious. I was phobic, paranoid. It was very hard to focus,” says Culotta. She`d tried antidepressants, but she wasn`t getting better. Eventually, she was placed on work disability. Then she found Dr. Katharine Heatwole at Ocean Psychiatric Group in Virginia Beach. It’s one of only 2 or 3 clinics in Hampton Roads treating patients with transcranial magnetic stimulation or TMS. “It’s pulse magnetic energy to the front left part of the brain, and that stimulates a little electrical current to the neurons or brain cells,” says Dr. Heatwole. “During my 1st treatment, I actually felt like there was someone tinkering or tapping on my head,” says Culotta. “That has a stimulation effect on the mood circuit so that it releases the neurotransmitters that are involved in mood,” says Culotta. “It is based on neuroplasticity and training the neurons to do what they are supposed to do in […]
By the time she was 61, Martha Rhodes had spent decades battling intractable depression. Diagnosis: treatment-resistant major depressive disorder. She’d tried a variety of medications to no avail; most were ineffective or caused nausea, diarrhea, weight gain and mood swings. During one particularly low evening in 2009, she attempted suicide. And every morning when she awoke, she experienced what she describes as “an emotional nausea – it was like this feeling of, ‘Why am I still here? Why do I have to be alive?’” But four years ago, Rhodes, now 65, of Danbury, Connecticut, underwent a procedure she says saved her life: repetitive transcranial magnetic stimulation, which uses magnetic pulses to electrically stimulate nerve cells in the brain and is used by doctors to relieve symptoms of depression. “My feelings of hopelessness, wishing I were dead and that life wasn’t worth living – all of that went away,” recalls Rhodes, who chronicled her experience with TMS in her 2013 book “3,000 Pulses Later.” Rhodes says she shares her story with others to demystify the treatment – which is often misunderstood by both patients and doctors, though it’s increasingly used by medical practitioners nationwide. What Is TMS? TMS was first developed […]
When you’re depressed, literally and figuratively stuck in a dark place, with no desire to get out and experience the world, it feels like time is inching by. Seconds feel like minutes, minutes feel like hours, and hours feel like days. Apparently, though, it’s not just a feeling. It’s a very real perception of time. New research from psychologists at the Johannes Gutenberg University of Mainz in Germany shows that depressed people actually experience time differently than healthy individuals. The scientists analyzed the results of 16 different studies examining 433 depressed subjects and 485 non-depressed control subjects. For the first part of the study, subjects were surveyed on their perception of time. “Psychiatrists and psychologists in hospitals and private practices repeatedly report that depressed patients feel that time only creeps forward slowly or is passing in slow motion,” reported study author Dr. Daniel Oberfeld-Twistel. The results of the meta-analysis confirmed that this is indeed the case. Then, for the second part of the study, they asked the subjects to subjectively estimate the length of a movie in minutes, press a button for five seconds, or identify the length of different sounds. In this case, the results obtained from the depressed […]
An interesting article on the wide range of symptoms used to diagnose depression: “the standard rating scales used by healthcare professionals and researchers to diagnose this disease often differ in the symptoms they list, perhaps explaining why a one-size-fits-all treatment has to date been so ineffective.” [Read Full Article Here]
If you’re looking for information about ketamine from a scientific research perspective a terrific article was published in The Lancet and the information is still very descriptive and accurate. Click the link below to view the PDF. [Read Full Article Here]
When should you, the prescriber, conclude that your patient with depression is “treatment resistant,” and thereby eligible for alternative non-pharmacological interventions—such as vagus nerve stimulation (VNS), electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS)? There are multiple ways that the failure to agree on a standardized definition of treatment-resistant depression (TRD) impacts the clinical care of patients who do not respond to multiple medication trials. In an article appearing in the January 2017 issue of JAMA Psychiatry, Charles Conway, M.D., Mark George, M.D., and Harold Sackheim, Ph.D., wrote that the lack of a consensus definition around what constitutes TRD “limits the ability to do comparative treatment research, to understand the biological underpinnings of TRD, and produces ambiguous medical insurance coverage issues.” Drawing on data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, they proposed a definition for TRD: failure to respond to two trials of an antidepressant prescribed at an adequate dose for an adequate duration of time. Conway, a professor of psychiatry and director of the Treatment Resistant Depression and Neurostimulation Clinic at Washington University, St. Louis, said that in the absence of a consensus definition of TRD, patients often receive multiple trials of medication. “Our experience has been that […]
How Ketamine Could Cure Depression The major excitatory neurotransmitter in the central and peripheral nervous system, glutamic acid, has been known for more than 50 years to produce its actions through various ionotropic channels (NMDA and AMPA) and G-coupled metabotropic receptors (mGluR 1 to 5). The glutamate-sensitive ion channels comprise multiple protein subunits and are subject to many regulatory and modulatory controls. Such intrinsic mechanisms are most apparent in the N-methyl D-aspartate (NMDA) receptor-operated ion channel which, in turn, offers countless opportunities for drugs to selectively exploit the ubiquity of glutamate’s excitatory role. Discovery of NMDA antagonists Considerable discovery efforts in the early 90s targeted various components of the NMDA receptor complex with the aim of developing new treatments for neurodegeneration – Alzheimer’s, Parkinson’s, Huntington’s diseases, stroke, traumatic brain injury – as well as epilepsy and pain, with some interest directed to psychiatric indications like anxiety. When the undesirable CNS side effects of many of these new drug candidates became apparent much of this research was curtailed, although several compounds with weak, or non-selective effects on the NMDA receptor were subsequently approved e.g. memantine, adamantine, methadone, and dextromethorphan. Return of the NMDA antagonist – the Ketamine breakthrough Targeting NMDA receptors came back into […]
Depressive Symptoms Associated With Aggression Violence is not usually considered to be related to depression, yet findings suggest an association between violent behavior and depression or depressive symptoms in many different disorders. A Swedish study compared the criminal records of 47,158 depressed individuals with the records of 898,454 people with no history of depression matched by age and sex.1 Those in the depressed group were approximately 3 times more likely than the general population to commit violent crimes, such as homicide, attempted homicide, aggravated assault, or robbery. This association was present even when previous histories of violence, self-harm, psychosis, and substance use were taken into consideration. Furthermore, the risk of violent crime significantly increased in individuals with more depressive symptoms. [Read the Full Article Here]
Ketamine the Next-Gen Treatment “There are key questions right now concerning both the scientific understanding of ketamine and the potential future use of ketamine or ketamine-like drugs for depression,” Dr Murrough told Medscape Medical News. One question is how ketamine triggers an antidepressant response within 1 day, whereas conventional antidepressants require 2 weeks or longer to take effect. “What is the biological basis of ketamine’s antidepressant mechanism of action?” he asked. It also remains a mystery why ketamine is successful in treating symptoms of depression in patients who have not responded to conventional treatments. “What can ketamine do in the brain that is relevant to the treatment of depression, that current antidepressant drugs do not do?” asked Dr Murrough. [Read the Full Article Here]
“Special K,” a psychedelic drug popular in dance clubs, is being used to treat severe depression when nothing else works. [Read the Original Article Here]
Several research teams around the world have been trialing ketamine use in chronic and recurring depression Thomson Reuters Posted: Apr 06, 2017 5:04 PM ET Last Updated: Apr 06, 2017 5:15 PM ET The party drug ketamine can have powerful beneficial effects on severely depressed patients who have struggled for years to recover, and the drug should be developed responsibly as a psychiatric medicine, British experts said on Thursday. In a study published in the Lancet Psychiatry journal, specialists from Oxford University said there is an urgent need for ethical and innovative action by doctors to prescribe the drug under controlled conditions. “We think patients’ treatment should be in specialist centers and formally tracked in national or international registries,” said Rupert McShane, a consultant psychiatrist and researcher at Oxford who has led a series of ketamine studies. [Read the Full Article Here]
One patient says drug slows down the ‘constant, overwhelming bombardment of negative intrusive thoughts surging through your brain’ Katie Forster Health Correspondent @katieforster Ketamine can provide relief to patients with severe depression “where nothing has helped before”, researchers calling for a new approach to the drug’s medical use have said. For six years, scientists from Oxford University have been using ketamine to treat more than 100 people with treatment-resistant depression. They said patients who received a series of carefully administered intravenous infusions of the drug, followed by oral top-ups, showed sustained improvement in around 40 per cent of cases – a significant result when other antidepressants have failed. “There are lots of people who are currently resistant to antidepressant drugs and psychotherapies,” consultant psychiatrist Rupert McShane told The Independent. “We’d like to see some more centers developing expertise [about ketamine] and starting to use it.” [Read the Full Article Here]
Ketamine, introduced in 1966 as an anesthetic, is increasingly showing up in private clinics nationwide as a treatment for chronic pain. While the drug is indeed a potent pain reliever, its effect is short-lived; and use may be accompanied by headache, nausea, and fatigue, among other adverse outcomes. There also is a risk of abuse given ketamine’s euphoric properties, which have earned it a reputation as a club drug. For these and other reasons, clinicians are apprehensive about pain centers administering off-label ketamine infusions for conditions ranging from fibromyalgia to migraines. The jury is still out, they say, on whether ketamine is a viable option for pain management. While some studies have reported a benefit, the quality of the evidence is low due to the small scale, limited generalization, and lack of effective blinding in these investigations. Moreover, research evaluating ketamine for chronic pain has focused on I.V. infusion, which inflates the cost of treatment and limits its use over the long term. The American Society of Regional Anesthesia and Pain Medicine is expected to issue guidelines on ketamine use for pain management within 6 months, but University of Pittsburgh anesthesia and psychiatry professor Ajay Wasan, MD, says clinicians will […]
Over the past 15 years the treatment of Depression and related illnesses has undergone a myriad of changes. A milestone that had a significant impact was the effective use of Genomic testing that assisted in utilizing psychotropic medications in a systematic and scientific fashion. Here, the experience of the physicians was augmented by the genetic information about the patient and a better decision was reached in selecting the proper medication(s). This often resulted in a larger number of patients reaching greater degrees of emotional stability more rapidly and with fewer untoward effects. It has been noted that approximately 75% of patients can now reach a state of remission. The World Health Organization has stated that over 350 million people in the world suffer from Depression. In the United States in 2012, the NIMH (National Institute of Mental Health) reported 6.9% of the population (16 million) suffered from at least one major episode of Depression. If you factor in those suffering from the depressive aspects of PTSD, Chronic Pain, Bipolar Disorders and Post Partum Disorders, these numbers drastically increase. Early diagnosis and scientifically based treatment can facilitate successful treatment to reach or surpass the 75% referenced above. The remaining 25% are […]
Jesse Tahirali, CTVNews.ca Published Sunday, January 25, 2015 10:10PM EST The grey clouds of depression are difficult to shake. Approximately eight per cent of Canadian adults will experience a major depression at some point in their lives, according to Toronto’s Centre for Addiction and Mental Health. Medication often fails to temper the debilitating effects of the illness. Only one third of patients report improvement after their first round of treatment, and some fail to improve regardless of what they’re prescribed. Gail Bellissimo, a Mississauga mother of four, was one of those people who still suffer even after seeking help. “I tried just about every drug out there, antidepressant of all kinds,” Bellissimo said. “They just either didn’t work for me or the side effects were too much for me to take.” But after years of living through the lows, Bellissimo said it only took three minutes to pick her up out of her depression. She was driving home when her new treatment began to take effect. “It was so unnerving at first,” she said. “At first it was like, “Wow, is this what it feels like to be normal?’” Bellissimo participated in a four-week study for something called theta-burst stimulation, […]
Analysis of FAERS data finds less comorbid depression among pain patients on ketamine by Neel A. Duggal Contributing Writer, MedPage TodayMay 12, 2017 An analysis of data from the FDA Adverse Events Reporting System (FAERS) supported previous findings that ketamine could be an effective treatment for depression, researchers found. Given financial and ethical obstacles to a large randomized controlled trial of ketamine for depressive disorders, Ruben Abagyan, PhD, of the University of California San Diego, and colleagues decided to turn to AERS data on patients taking ketamine for pain, an FDA-approved use. They found that patients who took ketamine had significantly lower frequency of reports of depression than those taking any other drugs for pain, according to findings published in Scientific Reports. “This reduction in depression is specific to ketamine and is known to be much more rapid than current antidepressants, making this observed effect very promising for treatment of patients with acute depressive or suicidal episodes,” Abagyan and colleagues wrote. [Read the Full Article Here]
Shape Magazine Recently Covered Ketamine as a Depression Treatment By Rachel Jacoby Zoldan | May 16, 2017 Depression is more common than you might think. It affects more than 15 million Americans, and the World Health Organization estimates that number grows to 300 million when you expand globally. There are a slew of different treatment options available to help alleviate its symptoms—think anxiety, insomnia, fatigue, and loss of appetite among others—with the most common treatment being serotonin reuptake inhibitors (or SSRIs). But since about 2000, doctors and researchers have been experimenting with ketamine—originally a pain management pharmaceutical, now abused as a street drug because of its hallucinogenic effects—as another potential way to treat the condition, according to Ruben Abagyan, Ph.D., a pharmacology professor at the University of California San Diego (UCSD). You’re probably thinking, “Wait! What?” If you’ve heard of ketamine, also known as Special K, you know it’s no joke or generic OTC drug. In fact, it’s known as a dissociative anesthetic (meaning a drug that distorts perception of sight and sound, while producing literal feelings of detachment from the self and the environment). It’s primarily used by veterinarians for treating pain in animals, but it can also be […]
LOS ANGELES, July 11 — Doctors in California say magnetic stimulation can help ‘rewire’ the brains of people withdepression, offering hope for patients whose condition is not improved by medication or therapy. Depression is one of the most common forms of mental illness, affecting more than 350 million people worldwide. Bob Holmes is one of them. “I struggled with that for many years, didn’t know really what to do, tried to pull myself through it. And then ultimately when I got into my forties, I wasn’t successful.” Holmes has been receiving transcranial magnetic stimulation at the University of California Los Angeles, a treatment that beams targeted magnetic pulses deep inside his brain. Doctors say the therapy can effectively ‘rewire’ the brain by changing how brain circuits are arranged. Reuters Video: Doctors hope to ‘rewire’ depressed people’s brains: [Read the Full Article Here]
New Hope for Depression Mandy Oaklander Jul 26, 2017 TIME Health For more, visit TIME Health. Every week, when Ian Hanley sits down with his therapist, he goes through a list of depression treatments he’s been researching online. The best-known treatments at the top of the list–half a dozen antidepressants and known combinations of those drugs–are all crossed out. “My therapist says he’s never had this much difficulty with somebody,” says Hanley, “which is sort of a dubious honor.” Hanley is only 21 years old, but he’s already six years into his search for something, anything, that can help him feel better for more than a few weeks at a time. “I’ve heard people describe it as sadness, and that’s not specific enough,” he says. Numbness is closer, but it’s not like depression inures you to suffering. “It’s like not quite being alive,” he says, “but still having to go through all the crappy parts of being alive.” When he was in the 10th grade, Hanley basically lost all desire to get out of bed in the morning. He started seeing a psychiatrist and a therapist–the same one he sees today–and went on Zoloft. “I wasn’t catatonic anymore,” he says. But […]
Patrice Wendling August 03, 2017 MURRAY, UT — Depression and coronary artery disease are known to walk hand in hand, but a new study suggests that depression any time after a diagnosis of CAD is the strongest predictor of death. Among 24,137 patients identified with significant CAD, a new depression diagnosis was associated with a twofold higher risk of all-cause death after multivariable adjustment, the investigators reported in the European Heart Journal Quality of Care and Clinical Outcomes. “It was stronger than any follow-up events, stronger than diabetes, stronger than smoking, sex, prior diagnosis of high blood pressure or depression, and even whether they had a heart attack,” lead author Dr Heidi T May (Intermountain Heart Institute, Murray, UT) told theheart.org | Medscape Cardiology. “I thought it would be a significant predictor, but I didn’t anticipate it would be the strongest. “I would think most people would find that amazing.” She said the results emphasize the need for continual depression screening among all CAD patients, but an accompanying editorial notes that recommendations by the American Heart Association (AHA) for routine screening in patients with heart disease have been met with some opposition, in large part because of a lack of studies showing a survival benefit with depression treatment. “Given the […]
Published Thursday 26 October 2017 By Tim Newman Fact checked by Jasmin Collier According to a recent study, although treating major depressive disorder has benefits in the short-term, over a longer period of time, it may make the condition worse. Major depressive disorder is a serious, debilitating mental illness. In the United States, it affects more than 16.1 million people over the age of 18. Although its prevalence is high, it is still a difficult condition to treat. Treatments include medications such as selective serotonin re-uptake inhibitors and talking therapies, such as cognitive therapy. No case of depression is the same, and often, individuals receive a range of treatments across their lifetime. How well the treatment of depression works has come under scrutiny over recent years, and the debate is by no means over. The latest study, published in the journal Psychotherapy and Psychosomatics, adds another dimension to this ongoing conversation. Clinical Treatment Compared with Community Individuals with major depressive disorder who receive medication or cognitive therapy often see a reduction in their depressive symptoms and experience significantly longer times before relapse. But over the longer-term, the picture is less clear. This is primarily because studies generally only run for […]
Question: How do effects of genetics and rearing each contribute to the transmission of risk for major depression from parents to children? Findings: In this population register–based study of 2 269 552 offspring of intact, adoptive, not-lived-with father, stepfather, and triparental families from the general Swedish population, the effects of genes and rearing were approximately equal for parent-offspring resemblance for major depression. Genetic and rearing effects acted additively on offspring risk for major depression. Meaning: Genetic and rearing effects are important in the cross-generational transmission of major depression. Importance Twin studies have assessed sibling resemblance for major depression (MD) but cannot address sources of resemblance across generations. Objective To clarify the relative importance of genetic and rearing effects on the parent-offspring resemblance for MD. Design This Swedish population register–based study examined parents and children from the following 5 family types: intact (2 041 816 offspring), adoptive (14 104 offspring), not-lived-with (NLW) father (116 601 offspring), stepfather (67 826 offspring), and triparental (29 205 offspring). The 5 family types permitted quantification of parent-offspring resemblance for genes plus rearing, genes-only, and rearing-only associations. Treated MD was assessed from national primary care, specialist care, and inpatient registries. Data were collected from January 1, 1960, through […]
Significance Identifying biological targets in major depressive disorder (MDD) is a critical step for development of effective mechanism-based medications. The epigenetic agent acetyl-L-carnitine (LAC) has rapid and enduring antidepressant-like effects in LAC-deficient rodents. Here, we found that LAC levels were decreased in patients with MDD versus age- and sex-matched healthy controls in two independent study centers. In subsequent exploratory analyses, the degree of LAC deficiency reflected both the severity and age of onset of MDD. Furthermore, the lowest LAC levels were found in patients with treatment-resistant depression, whereby history of emotional neglect and being female predicted decreased LAC levels. These translational findings suggest that LAC may serve as a candidate biomarker to help the diagnosis of a clinical endophenotype of MDD. Abstract The lack of biomarkers to identify target populations greatly limits the promise of precision medicine for major depressive disorder (MDD), a primary cause of ill health and disability. The endogenously produced molecule acetyl-L-carnitine (LAC) is critical for hippocampal function and several behavioral domains. In rodents with depressive-like traits, LAC levels are markedly decreased and signal abnormal hippocampal glutamatergic function and dendritic plasticity. LAC supplementation induces rapid and lasting antidepressant-like effects via epigenetic mechanisms of histone acetylation. This mechanistic […]
WHY AREN’T SOME PATIENTS WITH MDD REACHING REMISSION? For more than 50 years, major depressive disorder (MDD) pharmacological treatment approaches have focused on increasing the level of monoamine neurotransmitters in the brain, with the hope of reducing symptoms.1 And while conventional antidepressants have helped most, the STAR*D trial* found that one-third of patients didn’t achieve remission after multiple treatment attempts.2 What’s missing? BEYOND NEUROTRANSMITTERS: SYNAPTIC CONNECTIONS One emerging theory suggests that MDD may be linked to impaired synaptic connections in areas of the brain that regulate mood.3,4 The hypothesis points to an intriguing possibility: If synaptic connections are disrupted in MDD, can this synaptic impairment be improved?5 SYNAPTIC CONNECTIVITY: THE GLUTAMATE HYPOTHESIS Scientists are honing in on the role of glutamate, a major excitatory neurotransmitter that helps regulate synaptic connectivity.6 A burst of glutamate may initiate pathways that are believed to be involved in the strengthening and formation of new synaptic connections.5 As research advances, a deeper understanding of MDD is within reach. Watch THIS video or visit Janssen Pharmaceuticals Inc. to learn more.
NEW YORK (Reuters Health) – A 60-hour infusion of brexanolone significantly improves symptoms in women with postpartum depression, according to results from two phase 3 trials. The results “confirm and extend the previous work showing that brexanolone has a rapid onset of action that is unlike anything else currently available,” said Dr. Samantha Meltzer-Brody from the University of North Carolina at Chapel Hill School of Medicine. “Further, the robust treatment response to a single 60-hour infusion was maintained through the 30 days of follow-up in this clinical trial,” she told Reuters Health by email. Brexanolone is a proprietary, intravenous formulation of allopregnanolone, an endogenous progesterone metabolite that appears to modulate gamma-aminobutyric acid (GABA) receptors. Brexanolone showed rapid and durable antidepressant effects during an earlier phase 2 clinical trial. Dr. Meltzer-Brody and colleagues investigated the efficacy and safety of brexanolone injection in 246 women with moderate to severe postpartum depression in two randomized, placebo-controlled phase 3 trials at 30 U.S. centers. In study 1, Hamilton Rating Scale for Depression (HAM-D) total scores decreased to a significantly greater extent at the end of the 60-hour infusion in the group receiving brexanolone 60 mcg/kg per hour (mean reduction, 19.5 points) and in the […]
For 50 years, pharmacological treatment approaches in MDD have focused on targeting monoamine receptors in the hopes of reducing symptoms. While conventional therapies have helped many, the STAR*D trial* revealed that as many as a third of patients may not achieve remission despite treatment with traditional antidepressants.¹,² Dr Rakesh Jain, clinical professor of psychiatry at Texas Tech University School of Medicine, discusses the estimated 5 million patients who aren’t reaching remission despite multiple treatment attempts in a video available on ConnectingMDD.com. THE LIKELIHOOD OF REMISSION DROPS TO 14% AFTER A SECOND TREATMENT FAILURE* In the STAR*D trial, 37% of patients reached remission after the first-line treatment step with an oral antidepressant.1 The chances for remission dropped substantially after 2 treatment attempts, even with augmentation strategies.1 WITHOUT REMISSION, THE BURDEN OF MDD GROWS REFERENCES Rush AJ, et al. Am J Psychiatry. 2006;163:1905-1917. The National Institute of Mental Health. Major depression among adults. https://www.nimh.nih.gov/health/statistics/major-depression.shtml. Updated November 2017. Accessed April 6, 2018. Uher R, et al. Depress Anxiety. 2014;(31):459-471. Feldman RL, et al. J Med Econ. 2013;16(1):62-74.
By Paul Croarkin, DO, Research Committee Co-chair and Philip Janicak, MD, Research Committee Member Introduction Perinatal depressions are serious, debilitating conditions which are often under-recognized; and, even when properly diagnosed, often sub-optimally treated. Notably, they can contribute to problematic maternal behaviors such as substance use, poor self-care, non-adherence to prenatal care, and a heightened risk for suicide. Maternal outcomes and the pathophysiology of untreated depression create challenges from conception throughout development via epigenetic mechanisms, aberrations in fetal brain development, and mother-child bonding. For example, offspring of depressed mothers are at an increased risk for future psychiatric disorders and related functional impairment.1,2 Standard treatment approaches of perinatal depression include evidence-based psychotherapies such as cognitive behavioral therapy (CBT) or interpersonal psychotherapy (IPT). Selective serotonin re uptake inhibitors (SSRIs) are the mainstay pharmacologic approach, often used in conjunction with psychotherapy. Studies consistently demonstrate that many mothers’ are hesitant about taking antidepressants while pregnant or nursing.2 As a result, both researchers and clinicians have considered the potential role for noninvasive brain stimulation modalities such as repetitive transcranial magnetic stimulation (TMS), as an alternative and possibly safer intervention for perinatal depressions. TMS is an appealing option given the lack of systemic effects that are typically associated […]
Abrupt discontinuation of an antidepressant was found to be the most likely cause of brain zaps A recently published article discusses the characteristics, symptoms, and effects on quality of life associated with brain zaps, the electrical phenomenon that can occur following antidepressant discontinuation. The study authors explained, “In some patients, stopping or reducing the dose of an antidepressant can lead to electrical sensations (or brain zaps) perceived as occurring inside the brain.” To gain more insight into this poorly understood symptom of antidepressant discontinuation, the study authors analyzed 595 unso licited posts discussing brain zaps on a mental health website, Mental Health Daily, between December 13, 2014, and December 12, 2016. Further analysis and separation of the posts yielded a total of 648 statements discussing antidepressant intake; 378 of these statements discussed symptoms experienced following the discontinuation of an antidepressant. “These posts were further analyzed for specifics of the medications involved, temporal characteristics of the medication intake, associated symptoms, specifics of the “zap” experience itself, and effect of the zaps on quality of life,” the study authors added. Compared with how often the antidepressant was prescribed in clinical practice, brain zaps were reported more frequently with venlafaxine and paroxetine and less so with fluoxetine. “This finding mirrors […]
With well over two dozen traditional antidepressants available in the US, and an ever-growing list of other psychotropic compounds with apparent antidepressant properties, pharmacological options for treating clinical depression today are broad and vast. However, recent findings suggest that the magnitude of efficacy for most antidepressants compared with placebo may be more modest than previously thought.1Most depressed patients do not respond fully to a first antidepressant trial, and with each consequent trial, there is less chance of symptom remission.2 About one-third of patients receiving long-term treatment report persistent moderate-to-severe depression.3 Hence, there remains more than a little room for improvement. Since the late 1950s, the traditional view of treating depression has focused on the role of monoamines (serotonin, norepinephrine, and dopamine) as the main targets for medications. Newer treatments are looking beyond effects on monoamines as potential strategies to leverage depressive symptoms. A major challenge for progress in novel pharmacotherapies has been our lack of a full understanding about the causes of depression. Advances in functional neuroimaging and genetic markers have begun to shed new light on brain regions and pathways associated with aberrant neural functioning in depression, but not in ways that have led to treatments aimed at remedying its pathogenesis. […]
Heart attack, conceptual computer illustration. Mild depression was a long-term independent predictor of death in patients after acute myocardial infarction (AMI), per cohort study data published in Heart, Lung and Circulation. Investigators conducted a 25-year follow-up of men who were recruited after AMI to participate in a randomized controlled trial in the 1980s. The initial trial investigated the impact of high intensity exercise on physical and psychological health; depression was assessed at baseline using the Beck Depression Inventory. Sociodemographic information, cardiovascular risk factors, and severity of AMI were also captured at baseline. During the 25-year follow-up period, investigators used the Australian National Death Index to determine mortality status of patients after their index AMI. Cox proportional-hazards modeling was used to assess the relationship between depression severity and all-cause mortality at 5, 10, 15, 20, and 25 years post-AMI. Related Articles Pharmacotherapy May Reduce Depressive Symptoms After Traumatic Brain InjuryDepression Associated With Polygenic Risk for Major Depression, Bipolar Disorder, and SchizophreniaPostnatal Paternal Depression Associated With Depression in Girls The final analysis cohort comprised 185 men, mean age 54.15 (8.54). Per the Beck Depression Inventory, 114 patients (60.4%) had low to no depression, 47 (25.2%) had mild depression, and 27 (14.3%) had moderate to severe […]
Treatment-resistant depression can be a frustrating challenge for doctor and patient alike. The trial-and-error process of trying different medications and treatments to see what alleviates patients’ depression symptoms can feel like a “shot in the dark” approach. According to Ann McDonald, former editor of the Harvard Mental Health Letter, in her blog post on the Harvard Health Blog, only about a third of patients who are diagnosed with major depressive disorder (MDD) find a medication that works for them on the first try. “When the first medication doesn’t adequately relieve symptoms, next step options include taking a new drug along with the first, or switching to another drug. With time and persistence, nearly seven in 10 adults with major depression eventually find a treatment that works. Of course, that also means that the remaining one-third of people with major depression cannot achieve remission even after trying multiple options.” The Mayo Clinic says: “If you’ve already tried an antidepressant and it didn’t work, don’t lose hope. You and your doctor simply may not have found the right dose, medication or combination of medications that works for you.” One way to find out this information is through pharmacogenomic testing, which analyzes your genes and tells your doctor what might […]
A study published this week in Depression & Anxiety suggests that among patients with cancer who are prescribed antidepressants, those who take the medication may live longer than those who are non-adherent. Patients with cancer are known to have higher rates of depression than the general public—a factor that may reduce adherence to cancer treatment and increase their risk of death. The findings “add to the pressing need to encourage adherence to [antidepressants] among cancer patients,” wrote Gal Shoval, M.D., of the Geha Mental Health Center in Tel Aviv, Israel, and colleagues. To examine the relationship between antidepressant adherence and mortality in people with cancer, Shoval and colleagues analyzed the medical records of patients with cancer who had at least one prescription for an antidepressant between January 2008 and January 2012. Patients were followed from the time of initial antidepressant prescription until death or the end of the four-year study. Patients were categorized into one of four adherence groups: Nonadherent if adherence was below 20%, poor adherence for those with 20% to 50% adherence, moderate adherence for those with 50% to 80% adherence, and good adherence for those with adherence above 80%. Of the 42,075 patients included in the analysis, 28.9% were nonadherent, […]
The glutamate blocker riluzole may have longer-term beneficial effects as adjunctive treatment for some patients with treatment-resistant depression, according to results of a trial published in the Journal of Affective Disorders. The US Food and Drug Administration approved riluzole for the treatment of amyotrophic lateral sclerosis in 1994. It inhibits presynaptic release of glutamate and acts directly on the N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, and kainate receptors. Riluzole is believed to have neuroprotective effects, possibly through increase in excitatory amino acid transporter 2 expression. Hitoshi Sakurai, MD, PhD, of the Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, and the Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan, and colleagues analyzed data from 66 patients who received adjunctive riluzole in a 12-week, open-label extension phase of an acute double-blind, placebo-controlled trial. Response was defined as a reduction of 50% or more in Montgomery-Asberg Depression Rating Scale score and relapse was defined as an increase in score of ≥22 in patients who had previously achieved a response. Two-thirds of those who responded to acute-phase treatment maintained their response at the conclusion of the 12-week extension period, while 8.3% experienced a relapse. In those who did not respond to acute-phase […]
Handan Gunduz-Bruce, M.D., Christopher Silber, M.D., Inder Kaul, M.D., Anthony J. Rothschild, M.D., Robert Riesenberg, M.D., Abdul J. Sankoh, Ph.D., Haihong Li, Ph.D., Robert Lasser, M.D., Charles F. Zorumski, M.D., David R. Rubinow, M.D., Steven M. Paul, M.D., Jeffrey Jonas, M.D., et al. Abstract BACKGROUND Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown. METHODS In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of […]
Every day last week, approximately 122 people in the United States took their lives by suicide. This week, as we recognize World Suicide Prevention Day, it’s more important than ever to help spread awareness that can save lives. The tragedy of suicide is stealing loved ones-leaving behind family and friends to navigate the tragedy of loss, emptiness, and despair. Untreated mental illnesses are often the cause of suicide. Unfortunately, the stigma surrounding mental health leaves many feeling in the dark with nowhere to turn. This is why we need to do more as a society to help end the stigma and move forward in compassion and understanding. Because depression is more than just having a bad day and it’s not just something people can shake off. Depression can be debilitating. It can interfere with every aspect of your life…making it hard to function each day. In fact, depression is currently the leading cause of disability and poor health worldwide. And, with an estimated 1 in 6 Americans affected by the darkness of depression, it’s time to put the spotlight on treatments that help people get better. The darkness of depression is something that affects an estimated 1 in 6 Americans. […]
Ketamine, Similar Compounds Emerging as Mood Disorder Treatments Sanjay J. Mathew, MD, vice chair for research at Baylor College of Medicine and staff physician at the Michael E. Debakey VA Medical Center in Houston, Texas, has long been interested in the brain’s glutamate system and how it could be manipulated with substances such as ketamine to treat conditions including depression and suicidal ideation. At this year’s Psych Congress, Dr. Mathew, who is also director of Baylor’s mood and anxiety disorders program, will share the top 5 things that mental health clinicians should know about therapy with ketamine and the esketamine nasal spray newly approved by the US Food and Drug Administration (FDA). Below, he discusses his research into ketamine, how it works in the body, ongoing research into the compound, and similar agents that are in development. Q: How did you first become involved with research into glutamatergic agents such as ketamine? A: I‘ve been involved ever since my faculty position at Mount Sinai [School of Medicine], where we were interested in the glutamate system broadly for its potential impact in neuroplasticity and we were studying agents such as riluzole, which is approved in amyotrophic lateral sclerosis (ALS), and repurposing it for depression and generalized […]
Let’s face it: we’re all stressed these days. In fact, recent polls show just how stressed out Americans are over things like politics, work, finances … the list goes on and on. It seems like we’ve adopted a new work culture where the 8-hour workday is a thing of the past. People are working 9 or 10-hour days, skipping vacation time, and slowly losing sight of priorities outside of work. With jam-packed schedules and 24/7 connection through technology, it’s easy to understand why Americans are so stressed. The problem is that chronic stress can affect your mental and physical health. So, how can you manage stress in today’s world where people wear stress like a badge of honor? Understanding Stress To start, it’s important to realize there are different types of stress in life. In many ways, stress can be a normal part of life. You might feel stressed about an upcoming deadline or major life event and that’s OK. Sometimes, this type of stress stems from excitement and anticipation and can even work as a motivator. However, chronic stress is the type of stress that lingers even after the event or deadline passes. You might feel anxious and overwhelmed […]